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Focus on 

Gastroenterologic 

Diseases 

www.uspharmacist.com 

HEALTH SYSTEMS EDITION 

DECEMBER 2009 

THE JOURNAL FOR PHARMACISTS’ EDUCATION 

Overview of Hepatitis 

Colorectal Cancer: 

Screening Guidelines 

Gastrointestinal Bleeding 

Surgical Procedures 

for Weight Loss 

2 CE Credits 

Prescription Drug Abuse 

New Products in This Issue: 

Afinitor / Novartis Pharmaceuticals Corporation • 

Authorized Generics / Greenstone LLC • Brimonidine 

Tartrate Ophthalmic Solution / Falcon Pharmaceuticals • 

Distinctive Labeling / Baxter Healthcare • Embeda / King 

Pharmaceuticals • Injectables / Pfizer Injectables • 

Kapidex / Takeda Pharmaceuticals • Methenamine 

Hippurate / CorePharma LLC • Product Labeling / Teva 

Pharmaceuticals • Uloric / Takeda Pharmaceuticals 

FOR FREE CE, GO TO: 


A JOBSON PUBLICATION

Indication 

ULORIC is a xanthine oxidase (XO) inhibitor indicated for 

the chronic management of hyperuricemia in patients 

with gout. ULORIC is not recommended for the treatment 

of asymptomatic hyperuricemia. 

Important Safety Information 

• ULORIC is contraindicated in patients being treated 

with azathioprine, mercaptopurine, or theophylline. 

• An increase in gout flares is frequently observed 

during initiation of anti-hyperuricemic agents, 

including ULORIC. If a gout flare occurs during 

treatment, ULORIC need not be discontinued. 

Prophylactic therapy (i.e. - NSAIDs or colchicine) 

upon initiation of treatment may be beneficial for 

up to six months. 

• Cardiovascular Events: In randomized controlled studies, 

there was a higher rate of cardiovascular thromboembolic 

events (cardiovascular deaths, non-fatal myocardial 

infarctions, and non-fatal strokes) in patients treated 

with ULORIC [0.74 per 100 P-Y (95% CI 0.36-1.37)] than 

allopurinol [0.60 per 100 P-Y (95% CI 0.16-1.53)]. A causal 

relationship with ULORIC has not been established. 

Monitor for signs and symptoms of MI and stroke. 

• Liver Enzyme Elevations: In randomized controlled studies, 

transaminase elevations greater than 3 times the upper 

limit of normal (ULN) were observed (AST: 2%, 2%, and 

ULORIC ® is a registered trademark of Teijin Pharma Limited and used under license by Takeda Pharmaceuticals America, Inc. 

©2009 Takeda Pharmaceuticals North America, Inc. TXF-00319 08/09

ULORIC powerfully lowers 

serum uric acid levels for long-term 

control of gout. 

Powerfully lowers serum uric acid 1 

• In the largest phase 3 study (6 months): 

- 45% of patients who received ULORIC 40 mg achieved serum uric acid 

levels of

BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION for 

ULORIC ® (febuxostat) tablets 

INDICATIONS AND USAGE 

ULORIC ® is a xanthine oxidase (XO) inhibitor indicated for the chronic management 

of hyperuricemia in patients with gout. 

ULORIC is not recommended for the treatment of asymptomatic hyperuricemia. 

CONTRAINDICATIONS 

ULORIC is contraindicated in patients being treated with azathioprine, mercaptopurine, 

or theophylline [see Drug Interactions]. 

WARNINGS AND PRECAUTIONS 

Gout Flare 

After initiation of ULORIC, an increase in gout flares is frequently observed. This 

increase is due to reduction in serum uric acid levels resulting in mobilization of 

urate from tissue deposits. 

In order to prevent gout flares when ULORIC is initiated, concurrent prophylactic 

treatment with an NSAID or colchicine is recommended. 

Cardiovascular Events 

In the randomized controlled studies, there was a higher rate of cardiovascular 

thrombo embolic events (cardiovascular deaths, non-fatal myocardial infarctions, 

and non-fatal strokes) in patients treated with ULORIC [0.74 per 100 P-Y 

(95% CI 0.36-1.37)] than allopurinol [0.60 per 100 P-Y (95% CI 0.16-1.53)] [see 

Adverse Reactions]. A causal relationship with ULORIC has not been established. 

Monitor for signs and symptoms of myocardial infarction (MI) and stroke. 

Liver Enzyme Elevations 

During randomized controlled studies, transaminase elevations greater than 3 times 

the upper limit of normal (ULN) were observed (AST: 2%, 2%, and ALT: 3%, 2% 

in ULORIC and allopurinol-treated patients, respectively). No dose-effect 

relationship for these transaminase elevations was noted. Laboratory 

assessment of liver function is recommended at, for example, 2 and 4 months 

following initiation of ULORIC and periodically thereafter. 

ADVERSE REACTIONS 

Clinical Trials Experience 

Because clinical trials are conducted under widely varying conditions, adverse 

reaction rates observed in the clinical trials of a drug cannot be directly compared 

to rates in the clinical trials of another drug and may not reflect the rates observed 

in practice. 

A total of 2757 subjects with hyperuricemia and gout were treated with ULORIC 

40 mg or 80 mg daily in clinical studies. For ULORIC 40 mg, 559 patients 

were treated for 6 months. For ULORIC 80 mg, 1377 subjects were treated for 

6 months, 674 patients were treated for 1 year and 515 patients were treated 

for 2 years. 

Most Common Adverse Reactions 

In three randomized, controlled clinical studies (Studies 1, 2 and 3), which were 

6 to 12 months in duration, the following adverse reactions were reported by 

the treating physician as related to study drug. Table 1 summarizes adverse 

reactions reported at a rate of at least 1% in ULORIC treatment groups and at 

least 0.5% greater than placebo. 

Table 1: Adverse Reactions Occurring in 1% of ULORIC-Treated 

Patients and at Least 0.5% Greater than Seen in Patients 

Receiving Placebo in Controlled Studies 

Placebo ULORIC allopurinol* 

40 mg 80 mg 

daily daily 

Adverse Reactions (N=134) (N=757) (N=1279) (N=1277) 

Liver Function 

Abnormalities 

0.7% 6.6% 4.6% 4.2% 

Nausea 0.7% 1.1% 1.3% 0.8% 

Arthralgia 0% 1.1% 0.7% 0.7% 

Rash 0.7% 0.5% 1.6% 1.6% 

* Of the subjects who received allopurinol, 10 received 100 mg, 145 received 

200 mg, and 1122 received 300 mg, based on level of renal impairment. 

The most common adverse reaction leading to discontinuation from therapy 

was liver function abnormalities in 1.8% of ULORIC 40 mg, 1.2% of ULORIC 

80 mg, and in 0.9% of allopurinol-treated subjects. 

In addition to the adverse reactions presented in Table 1, dizziness was reported 

in more than 1% of ULORIC-treated subjects although not at a rate more than 

0.5% greater than placebo. 

Less Common Adverse Reactions 

In phase 2 and 3 clinical studies the following adverse reactions occurred in less 

than 1% of subjects and in more than one subject treated with doses ranging from 

40 mg to 240 mg of ULORIC. This list also includes adverse reactions (less than 

1% of subjects) associated with organ systems from Warnings and Precautions. 

Blood and Lymphatic System Disorders: anemia, idiopathic thrombocytopenic 

purpura, leukocytosis/leukopenia, neutropenia, pancytopenia, splenomegaly, 

throm bo cytopenia; Cardiac Disorders: angina pectoris, atrial fibrillation/flutter, 

cardiac murmur, ECG abnormal, palpitations, sinus bradycardia, tachycardia; 

Ear and Labyrinth Disorders: deafness, tinnitus, vertigo; Eye Disorders: vision 

blurred; Gastrointestinal Disorders: abdominal distention, abdominal pain, 

constipation, dry mouth, dyspepsia, flatulence, frequent stools, gastritis, 

gastro esophageal reflux disease, gastrointestinal discomfort, gingival pain, 

haematemesis, hyperchlorhydria, hematochezia, mouth ulceration, pancreatitis, 

peptic ulcer, vomiting; General Disorders and Administration Site Conditions: 

asthenia, chest pain/discomfort, edema, fatigue, feeling abnormal, gait 

disturbance, influenza-like symptoms, mass, pain, thirst; Hepatobiliary 

Disorders: cholelithiasis/cholecystitis, hepatic steatosis, hepatitis, hepatomegaly; 

Immune System Disorder: hypersensitivity; Infections and Infestations: herpes 

zoster; Procedural Complications: contusion; Metabolism and Nutrition Disorders: 

anorexia, appetite decreased/increased, dehydration, diabetes mellitus, hypercholesterolemia, 

hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypokalemia, 

weight decreased/increased; Musculoskeletal and Connective Tissue Disorders: 

arthritis, joint stiffness, joint swelling, muscle spasms/twitching/tightness/weakness, 

musculoskeletal pain/stiffness, myalgia; Nervous System Disorders: altered 

taste, balance disorder, cerebrovascular accident, Guillain-Barré syndrome, headache, 

hemiparesis, hypoesthesia, hyposmia, lacunar infarction, lethargy, mental 

impairment, migraine, paresthesia, somnolence, transient ischemic attack, 

tremor; Psychiatric Disorders: agitation, anxiety, depression, insomnia, irritability, 

libido decreased, nervousness, panic attack, personality change; Renal and 

Urinary Disorders: hematuria, nephrolithiasis, pollakiuria, proteinuria, renal 

failure, renal insufficiency, urgency, incontinence; Reproductive System and 

Breast Changes: breast pain, erectile dysfunction, gynecomastia; Respiratory, 

Thoracic and Mediastinal Disorders: bronchitis, cough, dyspnea, epistaxis, 

nasal dryness, paranasal sinus hypersecretion, pharyngeal edema, respiratory 

tract congestion, sneezing, throat irritation, upper respiratory tract infection; 

Skin and Subcutaneous Tissue Disorders: alopecia, angio edema, dermatitis, 

dermographism, ecchymosis, eczema, hair color changes, hair growth abnormal, 

hyperhidrosis, peeling skin, petechiae, photosensitivity, pruritus, purpura, skin 

discoloration/altered pigmentation, skin lesion, skin odor abnormal, urticaria; 

Vascular Disorders: flushing, hot flush, hypertension, hypotension; Laboratory 

Parameters: activated partial thromboplastin time prolonged, creatine increased, 

bicarbonate decreased, sodium increased, EEG abnormal, glucose increased, 

cholesterol increased, triglycerides increased, amylase increased, potassium 

increased, TSH increased, platelet count decreased, hematocrit decreased, hemoglobin 

decreased, MCV increased, RBC decreased, creatinine increased, blood urea 

increased, BUN/creatinine ratio increased, creatine phosphokinase (CPK) increased, 

alkaline phosphatase increased, LDH increased, PSA increased, urine output 

increased/decreased, lymphocyte count decreased, neutrophil count decreased, 

WBC increased/decreased, coagulation test abnormal, low density lipoprotein 

(LDL) increased, prothrombin time prolonged, urinary casts, urine positive for 

white blood cells and protein. 

Cardiovascular Safety 

Cardiovascular events and deaths were adjudicated to one of the pre-defined 

endpoints from the Anti-Platelet Trialists’ Collaborations (APTC) (cardiovascular 

death, non-fatal myocardial infarction, and non-fatal stroke) in the randomized 

controlled and long-term extension studies. In the Phase 3 randomized controlled 

studies, the incidences of adjudicated APTC events per 100 patient-years of exposure 

were: Placebo 0 (95% CI 0.00-6.16), ULORIC 40 mg 0 (95% CI 0.00-1.08), 

ULORIC 80 mg 1.09 (95% CI 0.44-2.24), and allopurinol 0.60 (95% CI 

0.16-1.53). 

In the long-term extension studies, the incidences of adjudicated APTC events were: 

ULORIC 80 mg 0.97 (95% CI 0.57-1.56), and allopurinol 0.58 (95% CI 0.02-3.24). 

Overall, a higher rate of APTC events was observed in ULORIC than in allopurinoltreated 

patients. A causal relationship with ULORIC has not been established. 

Monitor for signs and symptoms of MI and stroke. 

DRUG INTERACTIONS 

Xanthine Oxidase Substrate Drugs 

ULORIC is an XO inhibitor. Drug interaction studies of ULORIC with drugs that 

are metabolized by XO (e.g., theophylline, mercaptopurine, azathioprine) have 

not been conducted. Inhibition of XO by ULORIC may cause increased plasma 

concentrations of these drugs leading to toxicity [see Clinical Pharmacology]. 

ULORIC is contraindicated in patients being treated with azathioprine, 

mercaptopurine, or theophylline [see Contraindications]. 

Cytotoxic Chemotherapy Drugs 

Drug interaction studies of ULORIC with cytotoxic chemotherapy have not been 

conducted. No data are available regarding the safety of ULORIC during 

cytotoxic chemotherapy. 

In Vivo Drug Interaction Studies 

Based on drug interaction studies in healthy subjects, ULORIC does not have 

clinically significant interactions with colchicine, naproxen, indomethacin, 

hydrochlorothiazide, warfarin or desipramine. Therefore, ULORIC may be used 

concomitantly with these medications.

USE IN SPECIFIC POPULATIONS 

Pregnancy 

Pregnancy Category C: There are no adequate and well-controlled studies in 

pregnant women. ULORIC should be used during pregnancy only if the potential 

benefit justifies the potential risk to the fetus. 

Febuxostat was not teratogenic in rats and rabbits at oral doses up to 48 mg per kg 

(40 and 51 times the human plasma exposure at 80 mg per day for equal body 

surface area, respectively) during organogenesis. However, increased neonatal 

mortality and a reduction in the neonatal body weight gain were observed when 

pregnant rats were treated with oral doses up to 48 mg per kg (40 times the 

human plasma exposure at 80 mg per day) during organogenesis and through 

lactation period. 

Nursing Mothers 

Febuxostat is excreted in the milk of rats. It is not known whether this drug is 

excreted in human milk. Because many drugs are excreted in human milk, caution 

should be exercised when ULORIC is administered to a nursing woman. 

Pediatric Use 

Safety and effectiveness in pediatric patients under 18 years of age have not 

been established. 

Geriatric Use 

No dose adjustment is necessary in elderly patients. Of the total number of subjects 

in clinical studies of ULORIC, 16 percent were 65 and over, while 4 percent were 

75 and over. Comparing subjects in different age groups, no clinically significant 

differences in safety or effectiveness were observed but greater sensitivity of 

some older individuals cannot be ruled out. The C max and AUC 24 of febuxostat 

following multiple oral doses of ULORIC in geriatric subjects ( 65 years) were 

similar to those in younger subjects (18-40 years). 

Renal Impairment 

No dose adjustment is necessary in patients with mild or moderate renal 

impairment (Cl cr 30-89 mL per min). The recommended starting dose of ULORIC 

is 40 mg once daily. For patients who do not achieve a sUA less than 6 mg per 

dL after 2 weeks with 40 mg, ULORIC 80 mg is recommended. 

There are insufficient data in patients with severe renal impairment (Cl cr less 

than 30 mL per min); therefore, caution should be exercised in these patients. 

Hepatic Impairment 

No dose adjustment is necessary in patients with mild or moderate hepatic 

impairment (Child-Pugh Class A or B). No studies have been conducted in 

patients with severe hepatic impairment (Child-Pugh Class C); therefore, caution 

should be exercised in these patients. 

Secondary Hyperuricemia 

No studies have been conducted in patients with secondary hyperuricemia (including 

organ transplant recipients); ULORIC is not recommended for use in patients whom 

the rate of urate formation is greatly increased (e.g., malignant disease and its 

treatment, Lesch-Nyhan syndrome). The concentration of xanthine in urine 

could, in rare cases, rise sufficiently to allow deposition in the urinary tract. 

OVERDOSAGE 

ULORIC was studied in healthy subjects in doses up to 300 mg daily for seven 

days without evidence of dose-limiting toxicities. No overdose of ULORIC was 

reported in clinical studies. Patients should be managed by symptomatic and 

supportive care should there be an overdose. 

CLINICAL PHARMACOLOGY 

Pharmacodynamics 

Effect on Uric Acid and Xanthine Concentrations: In healthy subjects, ULORIC 

resulted in a dose dependent decrease in 24-hour mean serum uric acid 

concentrations, and an increase in 24-hour mean serum xanthine concentrations. 

In addition, there was a decrease in the total daily urinary uric acid excretion. 

Also, there was an increase in total daily urinary xanthine excretion. Percent 

reduction in 24-hour mean serum uric acid concentrations was between 40% to 

55% at the exposure levels of 40 mg and 80 mg daily doses. 

Effect on Cardiac Repolarization: The effect of ULORIC on cardiac repolarization 

as assessed by the QTc interval was evaluated in normal healthy subjects and in 

patients with gout. ULORIC in doses up to 300 mg daily, at steady state, did not 

demonstrate an effect on the QTc interval. 

Special Populations 

Renal Impairment: Following multiple 80 mg doses of ULORIC in healthy subjects 

with mild (Cl cr 50-80 mL per min), moderate (Cl cr 30-49 mL per min) or severe 

renal impairment (Cl cr 10-29 mL per min), the C max of febuxostat did not change 

relative to subjects with normal renal function (Cl cr greater than 80 mL per min). 

AUC and half-life of febuxostat increased in subjects with renal impairment in 

comparison to subjects with normal renal function, but values were similar 

among three renal impairment groups. Mean febuxostat AUC values were up to 

1.8 times higher in subjects with renal impairment compared to those with 

normal renal function. Mean C max and AUC values for 3 active metabolites 

increased up to 2- and 4-fold, respectively. However, the percent decrease in 

serum uric acid concentration for subjects with renal impairment was 

comparable to those with normal renal function (58% in normal renal function 

group and 55% in the severe renal function group). 

No dose adjustment is necessary in patients with mild to moderate renal 

impairment [see Dosage and Administration and Use in Specific Populations]. 

The recommended starting dose of ULORIC is 40 mg once daily. For patients 

who do not achieve a sUA less than 6 mg per dL after 2 weeks with 40 mg, 

ULORIC 80 mg is recommended. There is insufficient data in patients with 

severe renal impairment; caution should be exercised in those patients [see Use 

in Specific Populations. 

ULORIC has not been studied in end stage renal impairment patients who are 

on dialysis. 

Hepatic Impairment: Following multiple 80 mg doses of ULORIC in patients 

with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic 

impairment, an average of 20-30% increase was observed for both C max and 

AUC 24 (total and unbound) in hepatic impairment groups compared to subjects 

with normal hepatic function. In addition, the percent decrease in serum uric 

acid concentration was comparable between different hepatic groups (62% in 

healthy group, 49% in mild hepatic impairment group, and 48% in moderate 

hepatic impairment group). No dose adjustment is necessary in patients with 

mild or moderate hepatic impairment. No studies have been conducted in 

subjects with severe hepatic impairment (Child-Pugh Class C); caution should 

be exercised in those patients [see Use in Specific Populations. 

NONCLINICAL TOXICOLOGY 

Carcinogenesis, Mutagenesis, Impairment of Fertility 

Carcinogenesis: Two-year carcinogenicity studies were conducted in F344 rats 

and B6C3F1 mice. Increased transitional cell papilloma and carcinoma of urinary 

bladder was observed at 24 mg per kg (25 times the human plasma exposure 

at maximum recommended human dose of 80 mg per day) and 18.75 mg per 

kg (12.5 times the human plasma exposure at 80 mg per day) in male rats and 

female mice, respectively. The urinary bladder neoplasms were secondary to 

calculus formation in the kidney and urinary bladder. 

Mutagenesis: Febuxostat showed a positive mutagenic response in a chromosomal 

aberration assay in a Chinese hamster lung fibroblast cell line with and without 

metabolic activation in vitro. Febuxostat was negative in the in vitro Ames assay 

and chromosomal aberration test in human peripheral lymphocytes, and L5178Y 

mouse lymphoma cell line, and in vivo tests in mouse micronucleus, rat 

unscheduled DNA synthesis and rat bone marrow cells. 

Impairment of Fertility: Febuxostat at oral doses up to 48 mg per kg per day 

(approximately 35 times the human plasma exposure at 80 mg per day) had no 

effect on fertility and reproductive performance of male and female rats. 

Animal Toxicology 

A 12-month toxicity study in beagle dogs showed deposition of xanthine crystals 

and calculi in kidneys at 15 mg per kg (approximately 4 times the human plasma 

exposure at 80 mg per day). A similar effect of calculus formation was noted in 

rats in a six-month study due to deposition of xanthine crystals at 48 mg per kg 

(approximately 35 times the human plasma exposure at 80 mg per day). 

PATIENT COUNSELING INFORMATION 

[see FDA-Approved Patient Labeling in the full prescribing information] 

General Information 

Patients should be advised of the potential benefits and risks of ULORIC. Patients 

should be informed about the potential for gout flares, elevated liver enzymes and 

adverse cardiovascular events after initiation of ULORIC therapy. 

Concomitant prophylaxis with an NSAID or colchicine for gout flares should 

be considered. 

Patients should be instructed to inform their healthcare professional if they 

develop a rash, chest pain, shortness of breath or neurologic symptoms 

suggesting a stroke. Patients should be instructed to inform their healthcare 

professional of any other medications they are currently taking with ULORIC, 

including over-the-counter medications. 

Distributed by 

Takeda Pharmaceuticals America, Inc. 

Deerfield, IL 60015 

U.S. Patent Nos. - 6,225,474; 7,361,676; 5,614,520. 

ULORIC ® is a registered trademark of Teijin Pharma Limited and used under 

license by Takeda Pharmaceuticals America, Inc. 

All other trademark names are the property of their respective owners 

©2009 Takeda Pharmaceuticals America, Inc. 

February 2009 

For more detailed information, see the full prescribing information for 

ULORIC (febuxostat) tablets (PI1114 R1; February 2009) or contact 

Takeda Pharmaceuticals America, Inc. at 1.877.825.3327. 

PI1114 R1-Brf; February 2009 

L-TXF-0209-3

Straight Talk 

Making a Difference 

Earlier this year, I announced 

the launch of a new professional 

social network exclusively 

geared to the pharmacy 

community. Since its debut, many thousands 

of pharmacists, pharmacy technicians, 

and pharmacy students have 

shared their professional and personal 

experiences. It has given pharmacy professionals 

an outlet not only to express 

their feelings but also to share professional 

information and link up with colleagues 

with like interests. For me, one 

of the best things about PharmQD 

(www.pharmqd.com) is the stories and 

blogs. A couple of months ago, I asked 

site visitors to post stories and blogs 

relating how they made a difference in 

their patients’ lives. Many of the postings 

were very heartwarming and reinforced 

why we went into pharmacy in 

the first place. As we finish out another 

year and enjoy the holiday season with 

family, friends, and colleagues, I thought I would 

briefly share some of these stories with you. 

A pharmacist from New York told of her gut-wrenching 

experience of seeing the store she owned burn to the 

ground. But, as traumatic as that was, she expressed 

thanks to competitors, manufacturers, wholesalers, and 

customers who came to her aid while she was putting 

the pieces of her life back together. She wrote, “It was 

then that I realized I was participating in a profession 

that really did care about one another.” Then there was 

the pharmacist who, like many pharmacists, gave a talk 

at a local hospital on Parkinson’s disease. “It really makes 

you appreciate your health when you see someone literally 

trapped in their body,” he wrote. “While their mind 

is active, their body is holding them hostage.” A few 

weeks later, the pharmacist received a call from a gentleman 

who had attended the talk, who told him that the 

information he provided was personally very helpful. 

“That made me feel good,” the pharmacist said. “So 

often we go through our days not realizing how much 

people appreciate what we do. We have to remind ourselves 

and others of this more often.” 

Another pharmacist tells a story to which any retailer 

can easily relate. A patient came into the pharmacy to 

fill a prescription for a thyroid product in a strength 

that was on back order. The patient was ready to go on 

vacation and was in a bit of a panic, so 

the pharmacist secured approval from the 

doctor to “adjust” her dosage with the 

strengths in stock. “The patient was very 

pleased,” said the pharmacist. “It is experiences 

like these that make the downright 

nasty patients a lot easier to deal 

with.” One pharmacist tells of his experience 

of refusing to fill a prescription for a 

patient who was an obvious addict. To 

his amazement, 6 months later that 

patient came back to the store to basically 

say thank you for not filling the prescription. 

She told the pharmacist that she 

now attends Alcoholics Anonymous and 

Narcotics Anonymous. “I just couldn’t 

believe that out of a potentially bad situation, 

something so good happened,” 

commented the pharmacist. 

And finally, there is the story about a 

particularly difficult patient who regularly 

came into the pharmacy. When he 

became too weak to make the trip, the 

pharmacist started to personally deliver prescriptions to 

the man’s home after work. Each time he went to the 

client’s apartment, the pharmacist would chat with him. 

Eventually, the embittered man started to open up, and 

he told the pharmacist that he had no family and that 

his wife had recently passed away. The pharmacist continued 

to talk with him on subsequent visits, and the 

patient would tell his friends that the pharmacist was his 

“buddy.” Sadly, the patient was found on the floor of his 

apartment one day, felled by a fatal heart attack. “Say 

what you need to say,” advises the pharmacist. “When 

you get the chance, take it. Don’t let significant 

moments pass you by. It may seem like a little thing, but 

it can make a big difference. Say it before it is too late.” 

As we enjoy this festive holiday season and begin a 

new year, let me make sure I say what I need to say. 

And that would be “thank you” for being an important 

part of the U.S. Pharmacist family. Have a wonderful 

holiday season and, most important, a very 

healthy new year. 

Harold E. Cohen, RPh 

Editor-in-Chief 

hcohen@jobson.com 

4 

U.S. Pharmacist • December 2009 • www.uspharmacist.com


Vol. 34 No. 12 

TEAR ALONG PERFORATION 

Pancreatitis 

Gallbladder 

Ga lstones 

Common 

bile duct 

Pancreatic 

duct 

Enzymes flow freely 

into the duodenum 

to aid in digestion 

PATIENT TEACHING AID 

Inflamed 

Pancreas 

Normal 

Pancreas 

DECEMBER 2009 

The Journal for Pharmacists’ Education 

U.S. Pharmacist is a Peer-Reviewed Journal 

MEDICAL ILLUSTRATION: © KRISTEN WEINANDT MARZEJON 2009 

Duodenum 

(sma l intestine) 

Acute or Chronic 

Inflammation of 

Endocrine Gland 

Ga lstones, produced 

in the ga lbladder, 

can get lodged in the 

common bile duct, 

blocking the flow of 

pancreatic enzymes 

into the sma l intestine. 

Pancreatitis occurs 

when these blocked 

enzymes irritate the 

ce ls of the pancreas 

Pancreatitis is an inflammation of the pancreas, the gland 

behind the stomach that produces insulin and enzymes 

that help digest food. The pancreas can become inflamed 

as a result of alcoholism, ga lstones, or infection, among 

other reasons. The inflammation can develop quickly over 

a period of days (acute pancreatitis) or can develop and 

continue for years (chronic pancreatitis). It can be a mild 

inflammation that heals quickly with the proper treatment, or a severe condition that can lead to 

serious diseases such as diabetes, kidney failure, or cancer of the pancreas. 

Symptoms of acute pancreatitis include pain in the abdomen that can move to the lower back area. 

The pain often feels worse with eating, but better in the fetal position. Acute pancreatitis can also cause 

nausea and vomiting. In chronic pancreatitis, the abdominal pain is also a sociated with weight lo s and 

oily, foul-sme ling bowel movements. Laboratory tests of the blood, urine, and stool are performed to look 

for signs of inflammation and abnormal amounts of pancreatic enzymes. Other tests often performed in 

the diagnosis of pancreatitis include abdominal x-ray, ultrasound testing, CT scan, and MRI. 

Treatment depends on the type of pancreatitis, its cause, and its severity. Patients may require a 

hospital stay to treat pain and a low the pancreas to rest by restricting food and fluids by mouth. 

Patients are rehydrated with intravenous fluids and nutrition is restored with special feedings. The 

specific cause of the pancreatic inflammation will determine further treatment. 

Copyright Jobson Medical Information LLC, 2009 continued 

PTA0912 Pancrea 10_14bo.indd 1 10/15/09 12:25 PM 

COVER IMAGE: 


Pancreatitis. See page 25 

Illustration: © Keith Kasnot 2009 

www.kazstudios.com 

Though prevalence is declining, infection with 

the hepatitis B or C virus is a major health 

concern because it often leads to chronic liver 

failure and even death 

CE CREDITS 

Prescription Drug Abuse: Strategies to 

Reduce Diversion. See page 61 

THIS MONTH 

Editorial Focus: Gastroenterologic Diseases 

NEXT MONTH 

Editorial Focus: Neurologic Diseases 

Earn additional CE credits online. Visit: 


CE PROGRAMS ON THE 

U.S. PHARMACIST WEB SITE 

New: 

Prescription Drug Abuse: 

Strategies to Reduce Diversion 

Recent: 

Emergency Contraception: An Update 

of Clinical and Regulatory Changes 

Ovarian Cancer: One of the Common 

Gynecologic Malignancies 

Perimenopause: Management 

of Common Symptoms During 

the Menopausal Transition 

If you have any questions about our 

CE programs, call (800) 825-4696, 

fax (212) 219-7849, or e-mail 

cecustomerservice@jobson.com. 

FEATURES 

Senior Care 

Colorectal Cancer 

Screening . . . . . . . . . . . . . . 29 

Routine examinations, beginning at age 50, 

are the key to preventing this disease. 

Mary Ann E. Zagaria, PharmD, MS, CGP 

Overview of Hepatitis 

B and C Management . . . . . . . 32 

Although much effort has been dedicated 

to the eradication of these diseases through 

education and vaccination, viral hepatitis 

is still a worldwide problem. 

Justin Hooper, PharmD, BCPS, 

and Amy Martin, PharmD, BCPS 

Probiotics and Microflora . . . . 42 

There is a new focus on the role of 

beneficial bacteria to aid digestion, 

boost natural defenses, and fight off 

bacteria that could cause health problems. 

Max Sherman, RPh 


Pharmacy Law 

Gender Discrimination 

and Its Consequences . . .56 

There is no reason to differentiate 

compensation or enforcement of 

policies based on gender alone, as 

a female pharmacist and a large 

pharmacy chain have learned. 

Jesse C. Vivian, BS Pharm, JD 

●2 CE Credits 


Strategies to 

Reduce Diversion . . . . . . . . . 61 

Pharmacists need to be aware of 

the potential for drug diversion, recognize 

the warning signs of possible misuse, 

and acknowledge a legal obligation 

to minimize drug abuse. 

Gerald Gianutsos, PhD, JD 

Law CE 

Surgical Procedures for Weight Loss . . . . . . . . . . . . . . . . . . . . . HS-2 

Bariatric surgery currently offers the best method of producing 

sustained weight reduction in morbidly obese individuals. 

Mea A. Weinberg, DMD, MSD, RPh, and Stuart L. Segelnick, DDS, MS 

In-Service Primers 

Gastrointestinal Bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . HS-12 

Early intervention to control bleeding is important in order to minimize mortality. 

Manouchehr Saljoughian, PharmD, PhD 

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6 


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Pharmacist 

A Jobson Publication 

Senior Vice President–Editor-in-Chief 


Executive Editor 

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Senior Editor 

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DECEMBER 2009 

The Journal for Pharmacists’ Education 

U.S. Pharmacist is a Peer-Reviewed Journal 

Vol. 34 No. 12 

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Marjorie Borden 

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Consulting Clinical Editor 

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DEPARTMENTS 

Straight Talk 

Making a Difference . . . . . . . . 4 


What’s News. . . . . . . . . . . . . 10 

TrendWatch 

The Burden of 

Digestive Diseases . . . . . . . . 12 

The overall incidence of gastrointestinal 

disorders has led to increased prescription 

and OTC drug use. 

Somnath Pal, BS (Pharm), MS, MBA, PhD 

Costliest Prescriptions Dispensed for Treatment of Digestive Diseases 

Lansoprazole 

Esomeprazole 

Pantoprazole 

Rabeprazole 

Omeprazole 

Ranitidine 

Mesalamine 

5.9 9.2 

1.8 3.8 

6.3 8.4 

© JUPITERIMAGES 

15.5 25.2 

14.3 23.1 

8.6 11.4 

9.7 2.6 

0 5 10 15 20 25 30 35 40 45 

Percentage 

Prescriptions 

Cost 

Visit www.uspharmacist.com for features 

and departments available only online, 

including IBS Treatment Guidelines 

Consult Your Pharmacist 

Strategies for the Relief 

of Bloating and Gas . . . . . . . . 16 

Various sources for this problem have 

been identified, including air swallowing, 

diet, lactose intolerance, and IBS. 

W. Steven Pray, PhD, DPh 

Annual Index 2009 . . . . . . . . . 50 

Contemporary 

Compounding 

Tamiflu Oral Suspension . . . . 54 

A liquid version of this influenza 

medication may be easily prepared 

using the capsule formulation. 

Loyd V. Allen, Jr, PhD 

Classified Advertising . . . . . . 71 

Career and business opportunities, 

products, and services for the pharmacist. 

Product News . . . . . . . . . . . . 73 

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New Products in This Issue 

Afinitor / Novartis Pharmaceuticals Corporation • Authorized Generics / Greenstone LLC • Brimonidine 

Tartrate Ophthalmic Solution / Falcon Pharmaceuticals • Embeda / King Pharmaceuticals • Kapidex / 

Takeda Pharmaceuticals • Methenamine Hippurate / CorePharma LLC • Uloric / Takeda Pharmaceuticals 

Health Systems Edition: Distinctive Labeling / Baxter Healthcare • Injectables / Pfizer Injectables • 

Product Labeling / Teva Pharmaceuticals 

8 


We’re about to really open it up. 

E. FOUGERA & CO. 

A division of Nycomed US Inc., Melville, NY 11747 • Toll free: 800-645-9833 • www.fougera.com 

© 2009 Fougera. All rights reserved. 

Rev. 9/09

U.S. Pharmacist 

Editorial Board of Advisors 

Joseph Bova, RPh 

Community Pharmacy Owner, 

Cary’s Pharmacy, 

Dobbs Ferry, New York; 

Member, NYS Board of Pharmacy 

Carmen Catizone, RPh 

Executive Director, National Association 

of Boards of Pharmacy 

John M. Coster, PhD, RPh 

Senior VP of Government Affairs 

National Community Pharmacists Assoc. 

Hewitt (Ted) W. Matthews, PhD 

Dean, Southern School of Pharmacy, 

Mercer University, Atlanta 

David G. Miller, RPh 

Pharmacy Affairs, Merck & Co., Inc., 

West Point, Pennsylvania 

Mario F. Sylvestri, PharmD, PhD 

Senior Director, Medical Science 

Liaisons, Amylin Pharmaceuticals 

Ray A. Wolf, PharmD 

Medical Education, Sanofi Aventis 

Mary Ann E. Zagaria, 

PharmD, MS, CGP 

Senior Care Consultant and 

President, MZ Associates, Inc., 

Norwich, New York 

Contributing Editors 

Loyd V. Allen, Jr., PhD 

Connie Barnes, PharmD 

Bruce Berger, PhD 

R. Keith Campbell, RPh, CDE 

Patrick N. Catania, PhD, RPh 

R. Rebecca Couris, PhD, RPh 

Ed DeSimone, PhD, RPh 

Ronald W. Maddox, PharmD 

Somnath Pal, BS (Pharm), MBA, PhD 


M. Saljoughian, PharmD, PhD 

Jesse C. Vivian, BS Pharm, JD 

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What’s News 

Statins May Worsen Cardiac Symptoms 

San Diego, CA — New research shows that statin drugs may negatively impact 

some patients with cardiac disorders. A new study presented at the 75th annual 

international scientific assembly of the American College of Chest Physicians found 

that statins benefit patients with systolic heart failure (SHF), but not those with 

diastolic heart failure (DHF). These patients experienced increased dyspnea, fatigue, 

and decreased exercise tolerance. “It is possible that statins would help patients with 

systolic heart failure more than patients with diastolic heart failure due to the 

cholesterol-lowering and anti-inflammatory effects of statins,” said Lawrence P. 

Cahalin, PhD, PT, Northeastern University, Boston, Massachusetts. Despite the 

new data, researchers feel that the benefits of using statins in patients with SHF 

and DHF outweigh the risks. 

Dr. Regina Benjamin Confirmed as U.S. Surgeon General 

Washington, DC — U.S. Department of Health and Human Services Secretary 

Kathleen Sebelius announced that the U.S. Senate unanimously confirmed Regina 

Benjamin, MD, MBA, as the nation’s Surgeon General. Benjamin is founder and 

CEO of the Bayou La Batre Rural Health Clinic in Bayou La Batre, Alabama. She 

is the immediate past-chair of the Federation of State Medical Boards of the U.S. 

and previously served as associate dean for Rural Health at the University of South 

Alabama College of Medicine. In 2002, she became president of the Medical Association 

of the State of Alabama, making her the first African American woman to 

hold this position at a state medical society in the U.S. “Dr. Benjamin will quickly 

become America’s doctor as our next Surgeon General. Her deep knowledge and 

strong medical skills, her commitment to her patients, and her ability to inspire the 

people she interacts with every day will serve her well as Surgeon General,” Secretary 

Sebelius said. 

FDA Expands Approved Use of H1N1 Vaccines 

Silver Spring, MD — The FDA approved the use of the CSL Limited’s 2009 

H1N1 influenza vaccine to include children ages 6 months and older. Previously, 

this vaccine was approved only for use in adults ages 18 years and older. “Because 

children are among those most vulnerable to the 2009 H1N1 virus, having a 

broader range of children’s vaccines available is an important step in responding to 

the H1N1 outbreak,” said Margaret A. Hamburg, MD, FDA commissioner. The 

expanded approval also covers the company’s seasonal flu vaccine. Because CSL’s 

seasonal and H1N1 monovalent vaccines contain a small amount of egg protein, 

they should not be administered to anyone allergic to eggs or egg products. The 

vaccines will be available in single-dose, preservative-free, prefilled syringes and in 

multidose vials that contain thimerosal, a mercury derivative, as a preservative. 

Survey: Patients Do Not Treat Cold and Flu Symptoms Early Enough 

Scottsdale, AZ — A recent survey of 505 pharmacists found that 75% of pharmacists 

say most patients should purchase OTC cold and flu products at the first sign 

of symptoms, while only 26% of their patients take this proactive approach. Nine 

out of 10 of the surveyed pharmacists believe it is important for a patient to seek 

treatment early to help shorten the duration and severity of a cold. The survey also 

found that 85% of pharmacists agree the economy has increased patient questions 

about OTC products, and that 81% of pharmacists agree that more patients are 

opting to purchase OTC medications versus filling prescriptions for economic reasons. 

The survey was sponsored by Matrixx Initiatives, Inc., an OTC health care 

company and makers of Zicam products. 

10 


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At the end of the 

20th century, 

there were changes in 

the incidence, prevalence, 

and overall 

impact of digestive diseases, 

as evidenced by 

the 2008 update to 

the National Institutes 

of Health publication 

on digestive diseases. 

Somnath Pal, BS (Pharm), MBA, PhD 

Professor of Pharmacy Administration, 

College of Pharmacy & Allied Health 

Professions, St. John’s University, 

Jamaica, New York 

Hospital and Ambulatory-Care 

Visits: 

Between 1983 and 

1988, rates of hospitalization 

for digestive 

diseases fell, a trend 

that occurred for all causes 

of hospitalization. Hospitalization 

rates were stable 

for the next 10 years and 

rose by 2004 to a rate 

equal to the previous peak 

rate in 1982. Between 

1998 and 2004, the hospitalization 

rate for all diseases 

increased to 35%. 

The largest contributions 

to the increase were made 

by gastroesophageal reflux 

disease (GERD), with an 

increase of 376 per 

100,000; viral hepatitis C 

(79/100,000); chronic constipation 

(62/100,000); 

and intestinal infection 

(41/100,000). Although 

overnight hospitalizations 

with a diagnosis of digestive 

disease decreased notably 

for peptic ulcer disease 

(PUD) and gallstones 

owing to a shift to sameday 

surgery, 25% of all 

hospital discharges in 1998 

had a diagnosis of digestive 

disease; this increased to 

30% in 2004. 

In 2004, there were 

35,684 ambulatory-care 

visits related to digestive 

diseases per 100,000 population. 

Visits were common 

for all age groups, 

with the highest rate in 

individuals aged 65 years 

and older. Rates were comparable 

between black 

patients and white patients 

and were 20% higher for 

females than for males. 

Costs: Total ambulatorycare 

costs (excluding 

ambulatory surgery) in 

2004 were $16 billion. 

Outpatient procedures 

constituted 50% of this 

TrendWatch 

The Burden of 

Digestive Diseases 

Costliest Prescriptions Dispensed for Treatment of Digestive Diseases 

Lansoprazole 

Esomeprazole 

Pantoprazole 

Rabeprazole 

Omeprazole 

Ranitidine 

Mesalamine 


5.9 9.2 

1.8 3.8 

15.5 25.2 

14.3 23.1 

8.6 11.4 

6.3 8.4 

9.7 2.6 

0 5 10 15 20 25 30 35 40 45 

Percentage 

Prescriptions 

Cost 

amount. Abdominal-wall 

hernia (AWH), GERD, 

chronic constipation, gallstones, 

and diverticular disease 

were the biggest contributors 

to ambulatory 

costs. Diseases costing 

more than $1 billion were 

(in descending order) gallstones, 

AWH, diverticular 

disease, pancreatitis, 

colorectal cancer, appendicitis, 

liver disease, GERD, 

and PUD. The total cost 

of prescription drugs written 

during office visits was 

$12.3 billion, and more 

than half of this cost ($7.7 

billion) was associated with 

drugs prescribed for 

GERD. PUD, hepatitis C 

virus (HCV), and irritable 

bowel syndrome (IBS) 

were major contributors to 

the remaining drug cost. 

The chart shows the 

seven costliest prescription 

drugs for digestive diseases 

from retail pharmacies. 

The five proton pump 

inhibitors (prescribed 

for GERD) constituted 

51% of the total 

number of prescriptions, 

amounting to 

77% of total cost; 

mesalamine (inflammatory 

bowel disease) 

and ranitidine were 

the other top contributors. 

Other drugs adding 

to the cost were 

tegaserod (IBS, constipation), 

ribavirin, and 

peginterferon alpha 2a 

(HCV). The Consumer 

Healthcare Products 

Association estimates 

expenditures for OTC 

drugs for GERD, constipation, 

and diarrhea at $2.1 

billion, excluding complementary 

and alternative 

medicines. 

In 2004, the costliest 

prescriptions (n = 938,000) 

filled at retail pharmacies 

were for gastrointestinal 

(GI) infections; most were 

antimicrobials or GI-motility 

agents (e.g., promethazine). 

The next costliest 

prescriptions were for viral 

hepatitis (n = 637,000), 

but these were represented 

by a few drugs. 

Continued progress in 

improving the health of 

the population requires 

continued investment in 

digestive disease research, 

public-health initiatives, 

the health care system, and 

education of the public. 

12 


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Please see brief summary 

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Lansoprazole Delayed-Release 

Capsules USP 

STRENGTH SIZE NDC# 

15 mg 30 00093-7350-56 

30 mg 30 00093-7351-56 

*Prevacid ® is a registered trademark of Takeda Pharmaceuticals, Inc. 

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8498A

BRIEF SUMMARY 

LANSOPRAZOLE DELAYED-RELEASE CAPSULES 

USP 

4 CONTRAINDICATIONS 

Lansoprazole delayed-release capsules are contraindicated in 

patients with known severe hypersensitivity to any component of the 

formulation of lansoprazole delayed-release capsules. 

5 WARNINGS AND PRECAUTIONS 

Symptomatic response to therapy with lansoprazole does not 

preclude the presence of gastric malignancy. 

6 ADVERSE REACTIONS 

6.1 Clinical 

Worldwide, over 10,000 patients have been treated with lansoprazole in 

Phase 2 or Phase 3 clinical trials involving various dosages and durations 

of treatment. The adverse reaction profiles for lansoprazole delayedrelease 

capsules and lansoprazole for delayed-release oral suspension are 

similar. In general, lansoprazole treatment has been well-tolerated in both 

short-term and long-term trials. 

Because clinical trials are conducted under widely varying conditions, 

adverse reaction rates observed in the clinical trials of a drug cannot be 

directly compared to rates in the clinical trials of another drug and may 

not reflect the rates observed in clinical practice. 

The following adverse reactions were reported by the treating physician 

to have a possible or probable relationship to drug in 1% or more 

of lansoprazole-treated patients and occurred at a greater rate in 

lansoprazole-treated patients than placebo-treated patients in Table 1. 

Table 1: Incidence of Possibly or Probably Treatment-Related 

Adverse Reactions in Short-Term, Placebo-Controlled 

Lansoprazole Studies 

Body System/Adverse 

Event 

Body as a Whole 

Lansoprazole 

(N = 2768) % 

Placebo 

(N = 1023) % 

Abdominal Pain 2.1 1.2 

Digestive System 

Constipation 1.0 0.4 

Diarrhea 3.8 2.3 

Nausea 1.3 1.2 

Headache was also seen at greater than 1% incidence but was more 

common on placebo. The incidence of diarrhea was similar between 

patients who received placebo and patients who received 15 mg and 

30 mg of lansoprazole, but higher in the patients who received 60 mg 

of lansoprazole (2.9%, 1.4%, 4.2%, and 7.4%, respectively). 

The most commonly reported possibly or probably treatment-related 

adverse event during maintenance therapy was diarrhea. 

In the risk reduction study of lansoprazole for NSAID-associated 

gastric ulcers, the incidence of diarrhea for patients treated with 

lansoprazole, misoprostol, and placebo was 5%, 22%, and 3%, 

respectively. 

Another study for the same indication, where patients took either a 

COX-2 inhibitor or lansoprazole and naproxen, demonstrated that 

the safety profile was similar to the prior study. Additional reactions 

from this study not previously observed in other clinical trials with 

lansoprazole included contusion, duodenitis, epigastric discomfort, 

esophageal disorder, fatigue, hunger, hiatal hernia, hoarseness, 

impaired gastric emptying, metaplasia, and renal impairment. 

Additional adverse experiences occurring in less than 1% of patients 

or subjects who received lansoprazole in domestic trials are shown 

below: 

Body as a Whole - abdomen enlarged, allergic reaction, asthenia, back 

pain, candidiasis, carcinoma, chest pain (not otherwise specified), chills, 

edema, fever, flu syndrome, halitosis, infection (not otherwise specified), 

malaise, neck pain, neck rigidity, pain, pelvic pain 

Cardiovascular System - angina, arrhythmia, bradycardia, 

cerebrovascular accident/cerebral infarction, hypertension/ 

hypotension, migraine, myocardial infarction, palpitations, shock 

(circulatory failure), syncope, tachycardia, vasodilation 

Digestive System - abnormal stools, anorexia, bezoar, cardiospasm, 

cholelithiasis, colitis, dry mouth, dyspepsia, dysphagia, enteritis, 

eructation, esophageal stenosis, esophageal ulcer, esophagitis, fecal 

discoloration, flatulence, gastric nodules/fundic gland polyps, gastritis, 

gastroenteritis, gastrointestinal anomaly, gastrointestinal disorder, 

gastrointestinal hemorrhage, glossitis, gum hemorrhage, hematemesis, 

increased appetite, increased salivation, melena, mouth ulceration, 

nausea and vomiting, nausea and vomiting and diarrhea, gastrointestinal 

moniliasis, rectal disorder, rectal hemorrhage, stomatitis, tenesmus, 

thirst, tongue disorder, ulcerative colitis, ulcerative stomatitis 

Endocrine System - diabetes mellitus, goiter, hypothyroidism 

Hemic and Lymphatic System - anemia, hemolysis, lymphadenopathy 

Metabolic and Nutritional Disorders – avitaminosis, gout, 

dehydration, hyperglycemia/hypoglycemia, peripheral edema, weight 

gain/loss 

Musculoskeletal System - arthralgia, arthritis, bone disorder, joint 

disorder, leg cramps, musculoskeletal pain, myalgia, myasthenia, 

ptosis, synovitis 

Nervous System - abnormal dreams, agitation, amnesia, anxiety, 

apathy, confusion, convulsion, dementia, depersonalization, 

depression, diplopia, dizziness, emotional lability, hallucinations, 

hemiplegia, hostility aggravated, hyperkinesia, hypertonia, 

hypesthesia, insomnia, libido decreased/increased, nervousness, 

neurosis, paresthesia, sleep disorder, somnolence, thinking 

abnormality, tremor, vertigo 

Respiratory System - asthma, bronchitis, cough increased, dyspnea, 

epistaxis, hemoptysis, hiccup, laryngeal neoplasia, lung fibrosis, 

pharyngitis, pleural disorder, pneumonia, respiratory disorder, upper 

respiratory inflammation/infection, rhinitis, sinusitis, stridor 

Skin and Appendages - acne, alopecia, contact dermatitis, dry skin, 

fixed eruption, hair disorder, maculopapular rash, nail disorder, 

pruritus, rash, skin carcinoma, skin disorder, sweating, urticaria 

Special Senses - abnormal vision, amblyopia, blepharitis, blurred 

vision, cataract, conjunctivitis, deafness, dry eyes, ear/eye disorder, 

eye pain, glaucoma, otitis media, parosmia, photophobia, retinal 

degeneration/disorder, taste loss, taste perversion, tinnitus, visual 

field defect 

Urogenital System - abnormal menses, breast enlargement, breast 

pain, breast tenderness, dysmenorrhea, dysuria, gynecomastia, 

impotence, kidney calculus, kidney pain, leukorrhea, menorrhagia, 

menstrual disorder, penis disorder, polyuria, testis disorder, urethral 

pain, urinary frequency, urinary retention, urinary tract infection, 

urinary urgency, urination impaired, vaginitis. 

6.2 Postmarketing Experience 

Additional adverse experiences have been reported since lansoprazole 

has been marketed. The majority of these cases are foreign-sourced 

and a relationship to lansoprazole has not been established. Because 

these reactions were reported voluntarily from a population of 

unknown size, estimates of frequency cannot be made. These events 

are listed below by COSTART body system. 

Body as a Whole - anaphylactic/anaphylactoid reactions; Digestive 

System - hepatotoxicity, pancreatitis, vomiting; Hemic and Lymphatic 

System - agranulocytosis, aplastic anemia, hemolytic anemia, 

leukopenia, neutropenia, pancytopenia, thrombocytopenia, and 

thrombotic thrombocytopenic purpura; Musculoskeletal System - 

myositis; Skin and Appendages - severe dermatologic reactions including 

erythema multiforme, Stevens-Johnson syndrome, toxic epidermal 

necrolysis (some fatal); Special Senses - speech disorder; Urogenital 

System - interstitial nephritis, urinary retention. 

6.4 Laboratory Values 

The following changes in laboratory parameters in patients who 

received lansoprazole were reported as adverse reactions: 

Abnormal liver function tests, increased SGOT (AST), increased SGPT 

(ALT), increased creatinine, increased alkaline phosphatase, increased 

globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal 

AG ratio, abnormal RBC, bilirubinemia, blood potassium increased, blood 

urea increased, crystal urine present, eosinophilia, hemoglobin decreased, 

hyperlipemia, increased/decreased electrolytes, increased/decreased 

cholesterol, increased glucocorticoids, increased LDH, increased/ 

decreased/abnormal platelets, increased gastrin levels and positive fecal 

occult blood. Urine abnormalities such as albuminuria, glycosuria, and 

hematuria were also reported. Additional isolated laboratory abnormalities 

were reported. 

In the placebo controlled studies, when SGOT (AST) and SGPT 

(ALT) were evaluated, 0.4% (4/978) and 0.4% (11/2677) patients, 

who received placebo and lansoprazole, respectively, had enzyme 

elevations greater than three times the upper limit of normal range 

at the final treatment visit. None of these patients who received 

lansoprazole reported jaundice at any time during the study. 

7 DRUG INTERACTIONS 

Drugs With pH-Dependent Absorption Kinetics 

Lansoprazole causes long-lasting inhibition of gastric acid secretion. 

Lansoprazole and other PPIs are likely to substantially decrease the 

systemic concentrations of the HIV protease inhibitor atazanavir, 

which is dependent upon the presence of gastric acid for absorption, 

and may result in a loss of therapeutic effect of atazanavir and the 

development of HIV resistance. Therefore, lansoprazole and other 

PPIs should not be coadministered with atazanavir [see Clinical 

Pharmacology (12.5)]. 

It is theoretically possible that lansoprazole and other PPIs may interfere 

with the absorption of other drugs where gastric pH is an important 

determinant of oral bioavailability (e.g., ampicillin esters, digoxin, iron 

salts, ketoconazole) [see Clinical Pharmacology (12.5)]. 

Warfarin 

In a study of healthy subjects, coadministration of single or multiple 

60 mg doses of lansoprazole and warfarin did not affect the 

pharmacokinetics of warfarin nor prothrombin time [see Clinical 

Pharmacology (12.5)]. However, there have been reports of increased 

INR and prothrombin time in patients receiving PPIs and warfarin 

concomitantly. Increases in INR and prothrombin time may lead to 

abnormal bleeding and even death. Patients treated with PPIs and 

warfarin concomitantly may need to be monitored for increases in INR 

and prothrombin time [see Clinical Pharmacology (12.5)]. 

Tacrolimus 

Concomitant administration of lansoprazole and tacrolimus may 

increase whole blood levels of tacrolimus, especially in transplant 

patients who are intermediate or poor metabolizers of CYP2C19. 

Theophylline 

A minor increase (10%) in the clearance of theophylline was observed 

following the administration of lansoprazole concomitantly with 

theophylline. Although the magnitude of the effect on theophylline 

clearance is small, individual patients may require additional titration 

of their theophylline dosage when lansoprazole is started or stopped 

to ensure clinically effective blood levels [see Clinical Pharmacology 

(12.5)]. 

8 USE IN SPECIFIC POPULATIONS 

8.1 Pregnancy 

Teratogenic Effects 

Pregnancy category B 

Reproduction studies have been performed in pregnant rats at oral 

doses up to 40 times the recommended human dose and in pregnant 

rabbits at oral doses up to 16 times the recommended human dose 

and have revealed no evidence of impaired fertility or harm to the fetus 

due to lansoprazole. There are, however, no adequate or well-controlled 

studies in pregnant women. Because animal reproduction studies are 

not always predictive of human response, this drug should be used 

during pregnancy only if clearly needed [see Nonclinical Toxicology 

(13.2)]. 

8.3 Nursing Mothers 

Lansoprazole or its metabolites are excreted in the milk of rats. It is 

not known whether lansoprazole is excreted in human milk. Because 

many drugs are excreted in human milk, because of the potential for 

serious adverse reactions in nursing infants from lansoprazole, and 

because of the potential for tumorigenicity shown for lansoprazole 

in rat carcinogenicity studies, a decision should be made whether to 

discontinue nursing or to discontinue lansoprazole, taking into account 

the importance of lansoprazole to the mother. 

8.4 Pediatric Use 

The safety and effectiveness of lansoprazole have been established 

in pediatric patients 1 to 17 years of age for short-term treatment of 

symptomatic GERD and erosive esophagitis. 

One to 11 Years of Age 

In an uncontrolled, open-label, U.S. multicenter study, 66 pediatric 

patients (1 to 11 years of age) with GERD were assigned, based on 

body weight, to receive an initial dose of either lansoprazole 15 mg 

daily if ≤ 30 kg or lansoprazole 30 mg daily if greater than 30 kg 

administered for 8 to 12 weeks. The lansoprazole dose was increased 

(up to 30 mg twice daily) in 24 of 66 pediatric patients after 2 or more 

weeks of treatment if they remained symptomatic. At baseline 85% 

of patients had mild to moderate overall GERD symptoms (assessed 

by investigator interview), 58% had non-erosive GERD and 42% had 

erosive esophagitis (assessed by endoscopy). 

After 8 to 12 weeks of lansoprazole treatment, the intent-to-treat 

analysis demonstrated an approximate 50% reduction in frequency 

and severity of GERD symptoms. 

Twenty-one of 27 erosive esophagitis patients were healed at 8 

weeks and 100% of patients were healed at 12 weeks by endoscopy 

(Table 2). 

Table 2: GERD Symptom Improvement and Erosive Esophagitis 

Healing Rates in Pediatric Patients Age 1 to 11 

GERD 

Final Visit a % (n/N) 

Symptomatic GERD 

Improvement in Overall GERD 

76% (47/62 

Symptoms b 

c ) 

Erosive Esophagitis 


81% (22/27) 

Symptoms b 

Healing Rate 100% (27/27) 

a 

At Week 8 or Week 12 

b 

Symptoms assessed by patients diary kept by caregiver. 

c 

No data were available for 4 pediatric patients. 

In a study of 66 pediatric patients in the age group 1 year to 11 years 

old after treatment with lansoprazole given orally in doses of 15 mg 

daily to 30 mg twice daily, increases in serum gastrin levels were 

similar to those observed in adult studies. Median fasting serum 

gastrin levels increased 89% from 51 pg/mL at baseline to 97 pg/ 

mL [interquartile range (25 th to 75 th percentile) of 71 to 130 pg/mL] 

at the final visit. 

The pediatric safety of lansoprazole delayed-release capsules has 

been assessed in 66 pediatric patients aged 1 to 11 years of age. Of 

the 66 patients with GERD 85% (56/66) took lansoprazole for 8 weeks 

and 15% (10/66) took it for 12 weeks. 

The most frequently reported (2 or more patients) treatment-related 

adverse reactions in patients 1 to 11 years of age (N = 66) were 

constipation (5%) and headache (3%). 

Twelve to 17 Years of Age 

In an uncontrolled, open-label, U.S. multicenter study, 87 adolescent 

patients (12 to 17 years of age) with symptomatic GERD were treated 

with lansoprazole for 8 to 12 weeks. Baseline upper endoscopies 

classified these patients into two groups: 64 (74%) nonerosive GERD 

and 23 (26%) erosive esophagitis (EE). The nonerosive GERD patients 

received lansoprazole 15 mg daily for 8 weeks and the EE patients 

received lansoprazole 30 mg daily for 8 to 12 weeks. At baseline, 89% of 

these patients had mild to moderate overall GERD symptoms (assessed 

by investigator interviews). During 8 weeks of lansoprazole treatment, 

adolescent patients experienced a 63% reduction in frequency and a 

69% reduction in severity of GERD symptoms based on diary results. 

Twenty-one of 22 (95.5%) adolescent erosive esophagitis patients 

were healed after 8 weeks of lansoprazole treatment. One patient 

remained unhealed after 12 weeks of treatment (Table 3). 

Table 3: GERD Symptom Improvement and Erosive Esophagitis 

Healing Rates in Pediatric Patients Age 12 to 17 

GERD 

Final Visit % (n/N) 

Symptomatic GERD (All Patients) 


73.2% (60/82) 

Symptoms a 

b 

Nonerosive GERD 


71.2% (42/59) 

Symptoms a 

b 

Erosive Esophagitis 


78.3% (18/23) 

Symptoms a 

Healing Rate c 

95.5% (21/22) c 

a 

Symptoms assessed by patient diary (parents/caregivers as 

necessary). 

b 

No data available for 5 patients. 

c 

Data from one healed patient was excluded from this analysis due 

to timing of final endoscopy. 

In these 87 adolescent patients, increases in serum gastrin levels 

were similar to those observed in adult studies, median fasting serum 

gastrin levels increased 42% from 45 pg/mL at baseline to 64 pg/ 

mL [interquartile range (25 th to 75 th percentile) of 44 to 88 pg/mL] 

at the final visit. (Normal serum gastrin levels are 25 to 111 pg/mL.) 

The safety of lansoprazole delayed-release capsules has been 

assessed in these 87 adolescent patients. Of the 87 adolescent 

patients with GERD, 6% (5/87) took lansoprazole for less than 6 

weeks, 93% (81/87) for 6 to 10 weeks, and 1% (1/87) for greater 

than 10 weeks. 

The most frequently reported (at least 3%) treatment-related adverse 

reactions in these patients were headache (7%), abdominal pain 

(5%), nausea (3%) and dizziness (3%). Treatment-related dizziness, 

reported in this package insert as occurring in less than 1% of 

adult patients, was reported in this study by 3 adolescent patients 

with nonerosive GERD, who had dizziness concurrently with other 

reactions (such as migraine, dyspnea, and vomiting). 

8.5 Geriatric Use 

No dosage adjustment of lansoprazole is necessary in geriatric 

patients. The incidence rates of lansoprazole-associated adverse 

reactions and laboratory test abnormalities are similar to those seen 

in younger patients [see Clinical Pharmacology (12.4)]. 

8.6 Renal Impairment 

No dosage adjustment of lansoprazole is necessary in patients with 

renal impairment. The pharmacokinetics of lansoprazole in patients 

with various degrees of renal impairment were not substantially 

different compared to those in subjects with normal renal function 

[see Clinical Pharmacology (12.4)]. 

8.7 Hepatic Impairment 

In patients with various degrees of chronic hepatic impairment, an 

increase in the mean AUC of up to 500% was observed at steady state 

compared to healthy subjects. Consider dose reduction in patients with 

severe hepatic impairment [see Clinical Pharmacology (12.4)]. 

8.8 Gender 

Over 4,000 women were treated with lansoprazole. Ulcer healing 

rates in females were similar to those in males. The incidence rates 

of adverse reactions in females were similar to those seen in males 

[see Clinical Pharmacology (12.4)]. 

8.9 Race 

The pooled mean pharmacokinetic parameters of lansoprazole from 

twelve U.S. Phase 1 studies (N = 513) were compared to the mean 

pharmacokinetic parameters from two Asian studies (N = 20). The 

mean AUCs of lansoprazole in Asian subjects were approximately 

twice those seen in pooled U.S. data; however, the inter-individual 

variability was high. The C max values were comparable.

12 CLINICAL PHARMACOLOGY 

12.4 Specific Populations 

Pediatric Use 

One to 17 years of age 

The pharmacokinetics of lansoprazole were studied in pediatric patients 

with GERD aged 1 to 11 years and 12 to 17 years in two separate 

clinical studies. In children aged 1 to 11 years, lansoprazole was dosed 

15 mg daily for subjects weighing ≤ 30 kg and 30 mg daily for subjects 

weighing greater than 30 kg. Mean C max and AUC values observed on 

Day 5 of dosing were similar between the two dose groups and were 

not affected by weight or age within each weight-adjusted dose group 

used in the study. In adolescent subjects aged 12 to 17 years, subjects 

were randomized to receive lansoprazole at 15 mg or 30 mg daily. 

Mean C max and AUC values of lansoprazole were not affected by body 

weight or age; and nearly dose-proportional increases in mean C max and 

AUC values were observed between the two dose groups in the study. 

Overall, lansoprazole pharmacokinetics in pediatric patients aged 1 

to 17 years were similar to those observed in healthy adult subjects. 

Geriatric Use: The clearance of lansoprazole is decreased in the 

elderly, with elimination half-life increased approximately 50% to 

100%. Because the mean half-life in the elderly remains between 

1.9 to 2.9 hours, repeated once daily dosing does not result in 

accumulation of lansoprazole. Peak plasma levels were not increased 

in the elderly. No dosage adjustment is necessary in the elderly [see 

Use in Specific Populations (8.5)]. 

Renal Impairment: In patients with severe renal impairment, plasma 

protein binding decreased by 1.0% to 1.5% after administration of 60 

mg of lansoprazole. Patients with renal impairment had a shortened 

elimination half-life and decreased total AUC (free and bound). The AUC 

for free lansoprazole in plasma, however, was not related to the degree 

of renal impairment; and the C max and t max (time to reach the maximum 

concentration) were not different than the C max and t max from subjects 

with normal renal function. No dosage adjustment is necessary in 

patients with renal impairment [see Use in Specific Populations (8.6)]. 

Hepatic Impairment: In patients with various degrees of chronic hepatic 

impairment, the mean plasma half-life of lansoprazole was prolonged 

from 1.5 hours to 3.2 to 7.2 hours. An increase in the mean AUC of up 

to 500% was observed at steady state in hepatically-impaired patients 

compared to healthy subjects. Consider dose reduction in patients with 

severe hepatic impairment [see Use in Specific Populations (8.7)]. 

Gender: In a study comparing 12 male and 6 female human subjects 

who received lansoprazole, no gender differences were found in 

pharmacokinetics and intragastric pH results [see Use in Specific 

Populations (8.5)]. 

12.5 Drug-Drug Interactions 

It is theoretically possible that lansoprazole may interfere with 

the absorption of other drugs where gastric pH is an important 

determinant of bioavailability (e.g., ketoconazole, ampicillin esters, 

iron salts, digoxin). 

Lansoprazole is metabolized through the cytochrome P 450 system, 

specifically through the CYP3A and CYP2C19 isozymes. Studies have 

shown that lansoprazole does not have clinically significant interactions 

with other drugs metabolized by the cytochrome P 450 system, such as 

warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, 

prednisone, diazepam, or clarithromycin in healthy subjects. These 

compounds are metabolized through various cytochrome P 450 

isozymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A. 

Atazanavir: Lansoprazole causes long-lasting inhibition of gastric 

acid secretion. Lansoprazole substantially decreases the systemic 

concentrations of the HIV protease inhibitor atazanavir, which is 

dependent upon the presence of gastric acid for absorption, and may 

result in a loss of therapeutic effect of atazanavir and the development of 

HIV resistance. Therefore, lansoprazole, or other proton pump inhibitors, 

should not be coadministered with atazanavir. 

Theophylline: When lansoprazole was administered concomitantly 

with theophylline (CYP1A2, CYP3A), a minor increase (10%) in the 

clearance of theophylline was seen. Because of the small magnitude 

and the direction of the effect on theophylline clearance, this 

interaction is unlikely to be of clinical concern. Nonetheless, individual 

patients may require additional titration of their theophylline dosage 

when lansoprazole is started or stopped to ensure clinically effective 

blood levels. 

Warfarin: In a study of healthy subjects neither the pharmacokinetics 

of warfarin enantiomers nor prothrombin time were affected 

following single or multiple 60 mg doses of lansoprazole. However, 

there have been reports of increased International Normalized Ratio 

(INR) and prothrombin time in patients receiving proton pump 

inhibitors, including lansoprazole, and warfarin concomitantly. 

Increases in INR and prothrombin time may lead to abnormal 

bleeding and even death. Patients treated with proton pump 

inhibitors and warfarin concomitantly may need to be monitored for 

increases in INR and prothrombin time. 

Methotrexate and 7-hydromethotrexate: In an open-label, singlearm, 

eight-day, pharmacokinetic study of 28 adult rheumatoid 

arthritis patients (who required the chronic use of 7.5 to 15 mg of 

methotrexate given weekly), administration of 7 days of naproxen 

500 mg twice daily and lansoprazole 30 mg daily had no effect on the 

pharmacokinetics of methotrexate and 7-hydroxymethotrexate. While 

this study was not designed to assess the safety of this combination 

of drugs, no major adverse reactions were noted. 

Amoxicillin: Lansoprazole has also been shown to have no clinically 

significant interaction with amoxicillin. 

Sucralfate: In a single-dose crossover study examining lansoprazole 

30 mg and omeprazole 20 mg each administered alone and 

concomitantly with sucralfate 1 gram, absorption of the proton 

pump inhibitors was delayed and their bioavailability was reduced 

by 17% and 16%, respectively, when administered concomitantly 

with sucralfate. Therefore, proton pump inhibitors should be taken 

at least 30 minutes prior to sucralfate. In clinical trials, antacids 

were administered concomitantly with lansoprazole and there was no 

evidence of a change in the efficacy of lansoprazole. 

13 NONCLINICAL TOXICOLOGY 

13.1 Carcinogenesis, Mutagenesis, Impairment of 

Fertility 

In two 24 month carcinogenicity studies, Sprague-Dawley rats were 

treated with oral lansoprazole doses of 5 to 150 mg/kg/day - about 

1 to 40 times the exposure on a body surface (mg/m 2 ) basis of a 50 

kg person of average height [1.46 m 2 body surface area (BSA)] given 

the recommended human dose of 30 mg/day. Lansoprazole produced 

dose-related gastric enterochromaffin-like (ECL) cell hyperplasia and 

ECL cell carcinoids in both male and female rats. It also increased 

the incidence of intestinal metaplasia of the gastric epithelium in 

both sexes. In male rats, lansoprazole produced a dose-related 

increase of testicular interstitial cell adenomas. The incidence of these 

adenomas in rats receiving doses of 15 to 150 mg/kg/day (4 to 40 

times the recommended human dose based on BSA) exceeded the 

low background incidence (range = 1.4 to 10%) for this strain of rat. 

In a 24 month carcinogenicity study, CD-1 mice were treated with 

oral lansoprazole doses of 15 to 600 mg/kg/day, 2 to 80 times the 

recommended human dose based on BSA. Lansoprazole produced 

a dose-related increased incidence of gastric ECL cell hyperplasia. It 

also produced an increased incidence of liver tumors (hepatocellular 

adenoma plus carcinoma). The tumor incidences in male mice treated 

with 300 and 600 mg/kg/day (40 to 80 times the recommended 

human dose based on BSA) and female mice treated with 150 to 

600 mg/kg/day (20 to 80 times the recommended human dose 

based on BSA) exceeded the ranges of background incidences in 

historical controls for this strain of mice. Lansoprazole treatment 

produced adenoma of rete testis in male mice receiving 75 to 

600 mg/kg/day (10 to 80 times the recommended human dose 

based on BSA). 

A 26 week p53 (+/-) transgenic mouse carcinogenicity study was 

not positive. 

Lansoprazole was not genotoxic in the Ames test, the ex vivo rat 

hepatocyte unscheduled DNA synthesis (UDS) test, the in vivo 

mouse micronucleus test, or the rat bone marrow cell chromosomal 

aberration test. It was positive in in vitro human lymphocyte 

chromosomal aberration assays. 

Lansoprazole at oral doses up to 150 mg/kg/day (40 times the 

recommended human dose based on BSA) was found to have no 

effect on fertility and reproductive performance of male and female rats. 

13.2 Animal Toxicology and/or Pharmacology 

Reproductive Toxicology Studies 

Reproduction studies have been performed in pregnant rats at oral 

lansoprazole doses up to 150 mg/kg/day [40 times the recommended 

human dose (30 mg/day) based on body surface area (BSA)] and 

pregnant rabbits at oral lansoprazole doses up to 30 mg/kg/day 

(16 times the recommended human dose based on BSA) and have 

revealed no evidence of impaired fertility or harm to the fetus due 

to lansoprazole. 

17 PATIENT COUNSELING INFORMATION 

Patients should be informed of the following: 

17.1 Information for Patients 

Lansoprazole is available as a capsule and is available in 15 mg and 

30 mg strengths. Directions for use specific to the route and available 

methods of administration for this dosage form is presented below 

[see Dosage and Administration (2.3)]. 

• Lansoprazole delayed-release capsules should be taken before 

eating. 

• Lansoprazole delayed-release capsules SHOULD NOT BE 

CRUSHED OR CHEWED. 

Administration Options 

Lansoprazole Delayed-Release Capsules 

• Lansoprazole delayed-release capsules should be swallowed 

whole. 

• Alternatively, for patients who have difficulty swallowing capsules, 

lansoprazole delayed-release capsules can be opened and 

administered as follows: 

• Open capsule. 

• Sprinkle intact granules on one tablespoon of either applesauce, 

ENSURE ® pudding, cottage cheese, yogurt or strained pears. 

• Swallow immediately. 

• Lansoprazole delayed-release capsules may also be emptied into 

a small volume of either apple juice, orange juice or tomato juice 

and administered as follows: 

• Open capsule. 

• Sprinkle intact granules into a small volume of either apple juice, 

orange juice or tomato juice (60 mL — approximately 2 ounces). 

• Mix briefly. 

• Swallow immediately. 

• To ensure complete delivery of the dose, the glass should be 

rinsed with two or more volumes of juice and the contents 

swallowed immediately. 

USE IN OTHER FOODS AND LIQUIDS HAS NOT BEEN STUDIED 

CLINICALLY AND IS THEREFORE NOT RECOMMENDED. 

ENSURE ® is a registered trademark of Abbott Laboratories. 

Manufactured In Israel By: 

TEVA PHARMACEUTICAL IND. LTD. 

Jerusalem, 91010, Israel 

Manufactured For: 

TEVA PHARMACEUTICALS USA 

Sellersville, PA 18960 

Rev. B 11/2009


Strategies for the 

Relief of Bloating and Gas 

Patients often consider 

pharmacists as 

professionals to whom 

they can confide embarrassing 

medical problems 

in the hope that the 

pharmacist will provide 

some assistance. One 

such problem is abdominal 

bloating, often 

thought to be due to 

excess intestinal gas. 

However, patients may 

also experience abdominal 

discomfort they attribute 

to gas, but can be caused 

by several serious medical 

conditions. 

Prevalence of 

Bloating and Gas 

The prevalence of intestinal 

gas and bloating is 

unknown, as reliable 

large-scale studies do not 

exist. However, bloating 

and flatulence (defined as 

excessive air or other gas 

in the stomach and/or 

intestines) are two of the 

most common complaints 

for which patients seek 

medical care. 1 

Manifestations of 


Bloating and gas can 

cause several complaints 

or coexist with them. 


Bernhardt Professor, Nonprescription 

Products and Devices 

College of Pharmacy, Southwestern 

Oklahoma State University 

Weatherford, Oklahoma 

Undigested food passes from the small intestine into the large 

intestine, where bacteria break it down, producing gas that 

eventually exits through the rectum. 

Patients complain of 

excessive belching (eructation). 

2 Belching is a normal 

response during or 

after a meal, especially 

one that was eaten so rapidly 

that the patient also 

swallowed air. However, 

some patients swallow air 

intentionally to facilitate 

belching, a practice that 

can develop into an 

unconscious habit. Thus, 

if people burp excessively, 

they may be chronic air 

swallowers. Patients may 

deny that they swallow air 

as a nervous habit, forcing 

physicians to give them a 

mirror to observe the episodes 

themselves. 

Flatulence is a common 

and logical consequence 

of intestinal gas. 

Average patients with no 

© JOHN M. DAUGHERTY / PHOTO RESEARCHERS, INC 

pathology or underlying 

medical condition produce 

1 to 4 pints of 

intestinal gas per day and 

flatulate 14 to 23 times 

daily. 2,3 

Abdominal distention 

is an increase in abdominal 

girth that is frequently 

ascribed to excessive intestinal 

gas. 2,4 This perception 

is often incorrect, as 

many such patients have 

normal amounts of gas. 

Rather, investigators 

believe that these patients 

have a heightened awareness 

of intestinal gas. 

Thus, even normal volumes 

of gas cause troublesome 

symptoms. 

Abdominal pain is 

another complaint often 

thought to be due to 

gas. 2,3 It may arise from 

either side of the colon, 

mimicking such conditions 

as heart disease, gallstones, 

and appendicitis. 

Possible Causes of 


Various sources of excess 

gas have been identified, 

including air swallowing, 

diet, lactose intolerance, 

and irritable bowel syndrome 

(IBS). 

Aerophagia: Aerophagia, 

or air swallowing, has 

long been thought to be 

responsible for bloating 

and gas, as previously 

described. 5,6 But there 

had been little evidence 

to support the hypothesis, 

as logical as it sounds. 

However, in 2009, investigators 

confirmed the 

hypothesis by assessing 

swallowing frequency in 

general and air swallowing 

frequency in particular 

in patients with suspected 

aerophagia. 5 They 

identified a group of 

patients with typical 

complaints of bloating, 

abdominal distention, 

flatulence, and/or excessive 

belching. Abdominal 

x-rays confirmed the 

presence of excessive 

abdominal gas, the presumed 

source of the 

complaints. The researchers 

carried out 24-hour 

pH-impedance monitor- 

16 


✁ 

PATIENT INFORMATION 

Bloating and Gas: Not a Laughing Matter 

Bloating and intestinal gas are not considered polite subjects 

for discussion. Rather, they are very often a source of humor 

and ridicule. This aversion to discussing such subjects means 

that many patients suffer needlessly, when just a little advice 

can go a long way in improving their quality of life. 


Swallowing Air 

When you swallow air, it 

must either be burped 

up or expelled as gas. 

Several problems can 

cause one to swallow air. 

Dentures that do not fit 

well cause you to 

swallow more saliva, 

which is mixed with air 

bubbles. If this is a 

possible cause, you 

should see the dental 

professional who fitted 

your dentures to have 

them adjusted. If you 

have postnasal discharge, 

you tend to swallow 

more than normal, 

allowing more air to 

enter your stomach. 

Judicious use of a nasal 

decongestant (e.g., 

Sudafed, Afrin) may 

help. Smoking cigarettes, 

cigars, or pipes and 

using chewing tobacco 

can increase salivation 

and contribute to 

excessive bloating, as can 

talking too much. 

Some people belch 

excessively, either as a 

nervous habit or perhaps 

as a source of humor. To 

accomplish intentional 

belching, the person 

often first swallows 

air, followed by the 

belching. However, he or 

she seldom releases all of 

the swallowed air, and it 

becomes flatulence. 

Dietary Issues 

Eating too rapidly causes 

you to swallow extra air. 

You should slow your 

eating and chew the 

food thoroughly before 

swallowing it. Chewing 

gum and sucking on 

hard candy also increase 

the amount of swallowed 

air, so these practices 

should be reduced. 

An easy way to help 

minimize bloating and 

gas is to focus on 

carbonated beverages 

(e.g., Coke, Pepsi). 

Manufacturers 

intentionally add 

carbonation to all of 

these sodas to give the 

products their “fizz.” 

When the bottle or can 

is agitated before being 

opened, everyone knows 

what the result will 

PHARMACY STAMP 

be—a great deal of 

bubbly drink on the 

floor. As a person drinks 

the beverage, the 

carbonation bubbles 

enter the stomach. If 

they are not belched out, 

they become excess 

flatulence. Many people 

could reduce gas 

problems dramatically by 

simply eliminating all 

carbonated beverages. If 

a person refuses to take 

this simple step, perhaps 

he or she can be 

convinced to allow the 

drinks to sit out on the 

counter at room 

temperature for several 

hours, which allows 

them to go flat and thus 

reduces the amount of 

swallowed gas. 

The same advice can 

be given to beer 

drinkers. Beer contains 

gas, as indicated by the 

frothy head that 

develops when it is 

poured. You should 

completely eliminate it 

from your diet to see if 

your symptoms improve. 

A major dietary cause 

of gas is beans, as well as 

other foods with 

indigestible components, 

such as cabbage, 

cauliflower, and broccoli. 

Your intestinal bacteria 

use these components as 

foods, producing gas as a 

by-product. 

Lactose intolerance 

also contributes to gas 

and bloating. It is best 

to avoid dairy products 

or to take supplements 

that contain lactase, such 

as Lactaid. 

Consult Your 

Pharmacist 

There are several OTC 

products you can take to 

help relieve symptoms. 

Your pharmacist can 

assist you by advising on 

the use of simethicone 

(e.g., Gas-X, Mylanta 

Gas, Phazyme), which 

eases elimination of gas. 

Beano, a product that 

reduces the amount of 

gas, is a liquid solution 

that can be applied 

directly to food or taken 

as a tablet prior to 

eating. 

Remember, if you have questions, Consult Your Pharmacist. 

17 


YOU’RE USED TO ANSWERING JUST ABOUT ANY QUESTION CUSTOMERS COME UP WITH. 

Teaching customers about Humalog ® KwikPen doesn’t change that. Humalog KwikPen is part of the Humalog ® approach, 

designed to help fit mealtime therapy into a patient’s life. And now, the maker of Humalog is offering a complimentary Humalog 

KwikPen Pharmacy Kit with a demonstration pen to help educate your customers and information to answer 

their questions. 

For more details or to order a kit, visit www.kwikpenpharmkit.com. 

Humalog is for use in patients with diabetes mellitus for the control of hyperglycemia. 

Hypoglycemia is the most common adverse effect associated with insulins, including Humalog. 

For complete safety profile, please see Important Safety Information on adjacent page and accompanying 

Brief Summary of full Prescribing Information. 

Please see full user manual that accompanies the pen.

Indication 

Humalog (insulin lispro injection [rDNA origin]) is for use in patients with diabetes mellitus for the control 

of hyperglycemia. Humalog should be used with longer-acting insulin, except when used in combination 

with sulfonylureas in patients with type 2 diabetes. 


Humalog is contraindicated during episodes of hypoglycemia and in patients sensitive to Humalog or one 

of its excipients. 

Humalog differs from regular human insulin by its rapid onset of action as well as a shorter duration of 

action. Therefore, when used as a mealtime insulin, Humalog should be given within 15 minutes before or 

immediately after a meal. 

Due to the short duration of action of Humalog, patients with type 1 diabetes also require a longeracting 

insulin to maintain glucose control (except when using an insulin pump). Glucose monitoring is 

recommended for all patients with diabetes. 

The safety and effectiveness of Humalog in patients less than 3 years of age have not been established. 

There are no adequate and well-controlled clinical studies of the use of Humalog in pregnant or 

nursing women. 

Starting or changing insulin therapy should be done cautiously and only under medical supervision. 

Hypoglycemia 

Hypoglycemia is the most common adverse effect associated with insulins, including Humalog. 

Hypoglycemia can happen suddenly, and symptoms may be different for each person and may change 

from time to time. Severe hypoglycemia can cause seizures and may be life-threatening. 

Other Side Effects 

Other potential side effects associated with the use of insulins include: hypokalemia, weight gain, 

lipodystrophy, and hypersensitivity. Systemic allergy is less common, but may be life-threatening. 

Because of the difference in action of Humalog, care should be taken in patients in whom hypoglycemia 

or hypokalemia may be clinically relevant (eg, those who are fasting, have autonomic neuropathy or renal 

impairment, are using potassium-lowering drugs, or taking drugs sensitive to serum potassium level). 

For additional safety profile and other important prescribing considerations, see accompanying Brief 

Summary of full Prescribing Information. 

Please see full user manual that accompanies the pen. 

Humalog ® is a registered trademark of Eli Lilly and Company and is available by prescription only. 

Humalog ® KwikPen is a trademark of Eli Lilly and Company and is available by prescription only. 

HI59613 0909 PRINTED IN USA ©2009, LILLY USA, LLC. ALL RIGHTS RESERVED.

HUMALOG ® 

INSULIN LISPRO INJECTION (rDNA ORIGIN) 

BRIEF SUMMARY: Consult package insert for complete prescribing information. 

INDICATIONS AND USAGE: Humalog is an insulin analog that is indicated in the treatment of patients with 

diabetes mellitus for the control of hyperglycemia. Humalog has a more rapid onset and a shorter duration of 

action than regular human insulin. Therefore, in patients with type 1 diabetes, Humalog should be used in 

regimens that include a longer-acting insulin. However, in patients with type 2 diabetes, Humalog may be used 

without a longer-acting insulin when used in combination therapy with sulfonylurea agents. 

Humalog may be used in an external insulin pump, but should not be diluted or mixed with any other 

insulin when used in the pump. Humalog administration in insulin pumps has not been studied in patients 

with type 2 diabetes. 

CONTRAINDICATIONS: Humalog is contraindicated during episodes of hypoglycemia and in patients sensitive to 

Humalog or any of its excipients. 

WARNINGS: This human insulin analog differs from regular human insulin by its rapid onset of action as well 

as a shorter duration of activity. When used as a mealtime insulin, the dose of Humalog should be given 

within 15 minutes before or immediately after the meal. Because of the short duration of action of Humalog, 

patients with type 1 diabetes also require a longer-acting insulin to maintain glucose control (except when 

using an external insulin pump). 

External Insulin Pumps: When used in an external insulin pump, Humalog should not be diluted or mixed 

with any other insulin. Patients should carefully read and follow the external insulin pump manufacturer’s 

instructions and the “PATIENT INFORMATION” leaflet before using Humalog. 

Physicians should carefully evaluate information on external insulin pump use in the Humalog physician 

package insert and in the external insulin pump manufacturer’s instructions. If unexplained hyperglycemia or 

ketosis occurs during external insulin pump use, prompt identification and correction of the cause is necessary. 

The patient may require interim therapy with subcutaneous insulin injections (see PRECAUTIONS, For Patients 

Using External Insulin Pumps, and DOSAGE AND ADMINISTRATION). 

Hypoglycemia is the most common adverse effect associated with the use of insulins, including Humalog. 

As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. Glucose 

monitoring is recommended for all patients with diabetes and is particularly important for patients using an 

external insulin pump. 

Any change of insulin should be made cautiously and only under medical supervision. Changes in insulin 

strength, manufacturer, type (eg, regular, NPH, analog), species, or method of manufacture may result in the 

need for a change in dosage. 

PRECAUTIONS: General—Hypoglycemia and hypokalemia are among the potential clinical adverse effects 

associated with the use of all insulins. Because of differences in the action of Humalog and other insulins, care 

should be taken in patients in whom such potential side effects might be clinically relevant (eg, patients who are 

fasting, have autonomic neuropathy, or are using potassium-lowering drugs or patients taking drugs sensitive to 

serum potassium level). Lipodystrophy and hypersensitivity are among other potential clinical adverse effects 

associated with the use of all insulins. 

As with all insulin preparations, the time course of Humalog action may vary in different individuals or at 

different times in the same individual and is dependent on site of injection, blood supply, temperature, and 

physical activity. 

Adjustment of dosage of any insulin may be necessary if patients change their physical activity or their usual 

meal plan. Insulin requirements may be altered during illness, emotional disturbances, or other stress. 

Hypoglycemia—As with all insulin preparations, hypoglycemic reactions may be associated with the 

administration of Humalog. Rapid changes in serum glucose concentrations may induce symptoms of 

hypoglycemia in persons with diabetes, regardless of the glucose value. Early warning symptoms of 

hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, 

diabetic nerve disease, use of medications such as beta-blockers, or intensified diabetes control. 

Renal Impairment—The requirements for insulin may be reduced in patients with renal impairment. 

Hepatic Impairment—Although impaired hepatic function does not affect the absorption or disposition of 

Humalog, careful glucose monitoring and dose adjustments of insulin, including Humalog, may be necessary. 

Allergy—Local Allergy—As with any insulin therapy, patients may experience redness, swelling, or itching 

at the site of injection. These minor reactions usually resolve in a few days to a few weeks. In some instances, 

these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor 

injection technique. 

Systemic Allergy—Less common, but potentially more serious, is generalized allergy to insulin, which may 

cause rash (including pruritus) over the whole body, shortness of breath, wheezing, reduction in blood pressure, 

rapid pulse, or sweating. Severe cases of generalized allergy, including anaphylactic reaction, may be lifethreatening. 

Localized reactions and generalized myalgias have been reported with the use of cresol as an 

injectable excipient. In Humalog-controlled clinical trials, pruritus (with or without rash) was seen in 17 patients 

receiving Humulin R ® (N=2969) and 30 patients receiving Humalog (N=2944) (P=.053). 

Antibody Production—In large clinical trials, antibodies that cross-react with human insulin and insulin lispro 

were observed in both Humulin R- and Humalog-treatment groups. As expected, the largest increase in the 

antibody levels during the 12-month clinical trials was observed with patients new to insulin therapy. 

Usage of Humalog in External Insulin Pumps—The infusion set (reservoir syringe, tubing, and catheter), 

Disetronic ® D-TRON ®2,3 or D-TRONplus ®2,3 cartridge adapter, and Humalog in the external insulin pump 

reservoir should be replaced and a new infusion site selected every 48 hours or less. Humalog in the external 

insulin pump should not be exposed to temperatures above 37°C (98.6°F). 

In the D-TRON ®2,3 or D-TRONplus ®2,3 pump, Humalog 3 mL cartridges may be used for up to 7 days. However, 

as with other external insulin pumps, the infusion set should be replaced and a new infusion site should be 

selected every 48 hours or less. 

When used in an external insulin pump, Humalog should not be diluted or mixed with any other insulin (see 

INDICATIONS AND USAGE, WARNINGS, PRECAUTIONS, For Patients Using External Insulin Pumps, Mixing of 

Insulins, DOSAGE AND ADMINISTRATION, and Storage). 

Information for Patients—Patients should be informed of the potential risks and advantages of Humalog and 

alternative therapies. Patients should also be informed about the importance of proper insulin storage, injection 

technique, timing of dosage, adherence to meal planning, regular physical activity, regular blood glucose 

monitoring, periodic hemoglobin A1C testing, recognition and management of hypoglycemia and hyperglycemia, 

and periodic assessment for diabetes complications. 

Patients should be advised to inform their physician if they are pregnant or intend to become pregnant. 

Refer patients to the “PATIENT INFORMATION” leaflet for timing of Humalog dosing (


ing on subjects, discovering 

that swallowing frequency 

for the 24-hour 

period was normal (741 

+/- 71 episodes), but the 

number of air swallows 

and gastric belches was 

excessive (521 +/- 63 and 

126 +/-37, respectively). 

Thus, the advice presented 

in this month’s 

Patient Information section 

regarding air swallowing 

may be beneficial 

for these patients. 

Diet: Diet is a major 

cause of bloating and gas. 

One of the most common 

dietary issues is eating 

foods that cannot be 

digested in the gastrointestinal 

(GI) tract due to 

a lack of the necessary 

enzymes. 1,2 

If certain food residues 

(mostly carbohydrates) 

reach the large intestine, 

normal bacterial residents 

utilize them as food 

sources, producing carbon 

dioxide, hydrogen, and 

sometimes methane as byproducts. 

1,2 Exactly which 

foods cause gas varies 

from person to person. 

Some patients’ bowel 

microorganisms destroy 

hydrogen, lessening their 

intestinal gas burden. 2 

Nevertheless, some foods 

are universally identified 

as gas producers. 

Carbohydrate-containing 

foods are among the 

most common culprits in 

causing intestinal gas, 

whereas fatty foods and 

proteins are seldom 

responsible. 1,2,7 Raffinose 

A Dictator and His Flatulence 

It is remarkable how often flatulence is used for its shock 

value. In 1945, a high-ranking Nazi officer communicated 

a candid portrait of Adolf Hitler to a British agent. 16 The 

top-secret papers were to have been destroyed immediately, 

but they were not. Their discovery in 2009 after a 

house clearance gave new insights into Hitler’s habits and 

behaviors. Although the papers also contained critically 

important insights into the tyrant’s personality, the headlines 

focused on Hitler’s flatulence, a relatively minor matter 

presumably of little interest to historians. 

is one such complex 

sugar, being found in the 

indigestible seed coatings 

of beans, cabbage, brussels 

sprouts, broccoli, asparagus, 

other vegetables, and 

whole grains. 2 Fructose is 

another offender, found 

in onions, artichokes, 

pears, and wheat; it is also 

used as an artificial sweetener. 

Sorbitol is also an 

artificial sweetener, but it 

is a naturally occurring 

component of apples, 

pears, peaches, and 

prunes. Sorbitol is a cause 

of “Halloween diarrhea,” 

a phenomenon experienced 

by many children 

who consume large 

amounts of candy on 

Halloween night. Numerous 

patients also report 

that psyllium ingested to 

ensure regularity causes 

gas (e.g., Metamucil, 

Konsyl). These patients 

may benefit by switching 

to methylcellulose, an 

FDA-approved fiber supplement 

that is not fermented 

by colonic bacteria 

(e.g., Citrucel). 

Lactose Intolerance: 

Lactose intolerance (LI) 

is another type of carbohydrate 

malabsorption, 

discussed separately 

because of its different 

etiologies. 1 Lactase found 

in the brush border cells 

of the small intestine is 

essential for breaking lactose 

down into its component 

sugars for absorption. 

Lactase deficiency is 

the underlying defect 

behind LI. 

There are two major 

types of LI. They share 

the same consequences, in 

that undigested lactose 

reaches the intestinal tract, 

where the colonic microbiota 

digest it, producing 

gas, diarrhea, bloating, 

borborygmus, and a host 

of other complaints, 

beginning as early as 30 

minutes after ingestion. 8,9 

The more common type 

of LI is the primary form, 

experienced by most of 

the world’s peoples, 

including those of African, 

Native American, and 

Asian heritage. In primary 

LI, lactase activity drops 

sharply after weaning 

from breast milk, until it 

is virtually absent. Drinking 

milk or ingesting dairy 

products causes the symptoms 

to begin. 

Some people also suffer 

from secondary LI. They 

normally produce lactase 

as adults, but an environmental 

insult or surgical 

procedure compromises 

their ability to do so. Possible 

causes of secondary 

LI include chemotherapy, 

diarrheal diseases, small 

intestine resection, or 

celiac disease. 1 Pharmacists 

can direct patients with 

suspected LI to lactasecontaining 

supplements 

(e.g., Lactaid) or lactosefree 

dairy products. 

Irritable Bowel Syndrome: 

IBS causes abdominal 

pain, cramping, bloating, 

constipation, and diarrhea. 

10-12 About 20% of 

Americans suffer from 

IBS, perhaps due to 

colonic hypersensitivity to 

specific foods or in 

response to stressful situations. 

11 Pharmacists should 

refer patients with suspected 

IBS to a physician 

for a full evaluation, but 

they can also advise 

patients to keep a food 

diary to help identify 

dietary causes of IBS. 

Elimination of certain 

foods and drinks (e.g., 

chocolate, alcohol, caffeine, 

cola, tea, peppers, 

onions) may be all that is 

needed to provide relief. 

Nonprescription 

Products 

Pharmacists can recommend 

two types of nonprescription 

products 

other than lactose-intolerance 

products. One 

21 



group of products contains 

simethicone, a nontoxic 

and hypoallergenic 

ingredient that is FDA 

approved as safe and 

effective in breaking 

down bubbles or froth in 

the GI tract, although 

the total amount of gas 

remains the same. 1 

Simethicone’s usefulness 

may be due to several 

factors. Some patients 

may experience abdominal 

discomfort as normal 

amounts of intestinal gas 

move through them. 

Reducing froth may 

allow the gas to pass 

through more readily. 

Further, patients using 

simethicone may be able 

to eliminate gas in several 

larger episodes, reducing 

the perception of excessive 

gas. Products with 

simethicone include 

Mylanta Gas, Phazyme, 

and Gas-X. The dosage is 

typically 1 or 2 units as 

needed after meals and at 

bedtime. 

Alpha-galactosidase is 

another means to prevent 

bloating and gas. 1,13 This 

is an enzyme derived 

from Aspergillus niger, and 

it has the ability to break 

down the oligosaccharide 

linkages that humans cannot 

digest. The patient is 

then able to absorb the 

single-component sugar 

residues. In research 

exploring the enzyme’s 

efficacy, subjects ingested 

two meals of meatless 

chili composed of several 

types of beans, cabbage, 

cauliflower, and onions. 14 

They were given either a 

placebo or the commercially 

available alphagalactosidase 

product, 

known as Beano. Beano 

reduced the number of 

flatulence events at all 

times except for 2 hours 

postingestion. The effect 

was most pronounced 5 

hours after the meal. 14 

To use Beano solution, 

the patient places approximately 

5 drops on the 

first bite of troublesome 

food, such as beans, cabbage, 

cauliflower, broccoli, 

grains, cereals, nuts, 

seeds, and whole-grain 

breads. 13 That amount 

usually covers a half-cup 

serving of food. If the 

meal consists of two or 

three servings of the food, 

the patient should place 

10 to 15 drops on the 

meal. However, if the 

patient still experiences 

flatulence, the amount 

can be adjusted upward 

until an effective dose is 

reached. The patient may 

also swallow or chew a 

Beano tablet with the 

first bite of food or crumble 

it onto the first bite. 

One tablet usually digests 

a half-cup serving; more 

tablets can be used for 

larger portions. Patients 

cannot cook with Beano 

because of heat-induced 

enzyme degradation. 

Patients with galactosemia 

should consult a 

physician prior to use 

since enzymatic degradation 

of oligosaccharides 

produces galactose. Beano 

is labeled only for 

patients aged 12 years 

and above. While it 

appears to be safe during 

pregnancy and breastfeeding, 

there are no studies 

to confirm that observation. 

At one time, the 

manufacturer recommended 

that patients 

allergic to molds not use 

Beano, but the present 

view is that the caution is 

not supported by medical 

literature. 13 

Addition Diets 

Pharmacists can also 

advise patients to undergo 

an addition diet. 15 With 

this method, the patient 

eliminates all foods and 

drinks that are thought to 

produce symptoms. If 

symptoms improve, the 

patient continues the diet 

for several days until 

reaching a perceived normal 

level, a state known 

as normoflatulence. 15 Then 

one new food or drink is 

added, and the patient 

records the results in a 

diary, paying particular 

attention to the intensity 

of the symptoms. 

Patients should discontinue 

any troublesome 

food for the duration of 

the addition diet and 

add another suspected 

food or drink after 48 

hours. After several 

weeks of following this 

simple procedure, the 

patient begins to build a 

profile of difficult foods. 

Eventually all suspected 

foods will be identified, 

and the patient will have 

a much better idea of 

how to choose foods and 

drinks, even when visiting 

a restaurant. 

REFERENCES 

1. Pray WS. Nonprescription Product Therapeutics. 

2nd ed. Baltimore, MD: Lippincott 

Williams & Wilkins; 2006. 

2. Gas in the digestive tract. NIDDK. 

http://digestive.niddk.nih.gov/ddiseases/pubs/ 

gas/. Accessed October 29, 2009. 

3. Gas—flatulence. MedlinePlus. www.nlm.nih. 

gov/medlineplus/ency/article/003124.htm. 

Accessed October 29. 2009. 

4. Agrawal A, Whorwell PJ. Review article: 

abdominal bloating and distension in functional 

gastrointestinal disorders—epidemiology and 

explorations of possible mechanisms. Aliment 

Pharmacol Ther. 2008;27:2-10. 

5. Hemmink GJ, Weusten BL, Bredenoord AJ, 

et al. Aerophagia: excessive air swallowing demonstrated 

by esophageal impedance monitoring. 

Clin Gastroenterol Hepatol. 2009;7:1127-1129. 

6. Azpiroz F. Intestinal gas dynamics: mechanisms 

and clinical relevance. Gut. 2005;54: 

893-895. 

7. Hernot DC, Boileau TW, Bauer LL, et al. 

In vitro fermentation profiles, gas production 

rates, and microbiota modulation as affected by 

certain fructans, galactooligosaccharides, and 

polydextrose. J Agric Food Chem. 2009;57: 

1354-1361. 

8. Saulnier DM, Kolida S, Gibson GR. 

Microbiology of the human intestinal tract and 

approaches for its dietary modulation. 

Curr Pharm Des. 2009;15:1403-1414. 

9. Ozdemir O, Mete E, Catal F, et al. Food 

intolerances and eosinophilic esophagitis in 

childhood. Dig Dis Sci. 2009;54:8-14. 

10. Gasbarrini A, Lauritano EC, Garcovich M, 

et al. New insights into the pathophysiology of 

IBS: intestinal microflora, gas production and 

gut motility. Eur Rev Med Pharmacol Sci. 

2008;12(suppl 1):111-117. 

11. Irritable bowel syndrome. NIDDK. 

http://digestive.niddk.nih.gov/ddiseases/pubs/ 

ibs/. Accessed October 29, 2009. 

12. Rana SV, Sharma S, Sinha SK, et al. Incidence 

of predominant methanogenic flora in 

irritable bowel syndrome patients and apparently 

healthy controls from North India. Dig 

Dis Sci. 2009;54:132-135. 

13. Beano FAQs. GlaxoSmithKline. 

www.beanogas.com/FAQ.aspx. Accessed 

October 29, 2009. 

14. Ganiats TG, Norcross WA, Halverson AL, 

et al. Does Beano prevent gas? A double-blind 

crossover study of oral alpha-galactosidase to 

treat dietary oligosaccharide intolerance. J Fam 

Pract. 1994;39:441-445. 

15. Clearfield HR. Clinical intestinal gas syndromes. 

Prim Care. 1996;23:621-628. 

16. Adolf Hitler had poor table manners and 

suffered flatulence. Telegraph. February 17, 

2009. www.telegraph.co.uk/news/newstopics/ 

howaboutthat/4678840/Adolf-Hitler-had-poortable-manners-and-suffered-flatulence.html. 

Accessed October 29, 2009. 

22 


Brimonidine Tartrate Ophthalmic Solution, 0.15% 

Sterile 

DESCRIPTION 

Brimonidine Tartrate Ophthalmic Solution, 0.15% (1.5 mg brimonidine tartrate per mL equivalent to 1.0 mg 

brimonidine free base per mL) is a relatively selective alpha-2-adrenergic agonist for ophthalmic use. The 

chemical name of brimonidine tartrate is 5-bromo-6-(2-imidazolidinylideneamino) quinoxaline L-tartrate. It is an 

off-white to pale yellow powder. It has a molecular weight of 442.24 as the tartrate salt, and is both soluble in 

water (1.5 mg/mL) and in the product vehicle (3.0 mg/mL) at pH 7.2. The structural formula is: 

Formula: C 11 

H 10 

BrN 5 

4 

H 6 

O 6 

CAS Number: 59803-98-4 

HN 

N 

NH 

Br 

In solution, Brimonidine Tartrate Ophthalmic Solution, 0.15% has a clear, greenish-yellow color. It has an 

osmolality of 250 – 350 mOsmol/kg and a pH of 6.6-7.4. 

Each mL of Brimonidine Tartrate Ophthalmic Solution, 0.15% contains: Active ingredient: brimonidine tartrate 

0.15% (1.5 mg/mL) Inactives: povidone; boric acid; sodium borate; calcium chloride; magnesium chloride; 

potassium chloride; mannitol; sodium chloride; POLYQUAD* 0.001% (0.01 mg/mL); purified water; with 

hydrochloric acid and/or sodium hydroxide to adjust pH. 


Mechanism of Action: Brimonidine Tartrate Ophthalmic Solution, 0.15% is an alpha-2 adrenergic receptor 

agonist. It has a peak ocular hypotensive effect occurring at two hours post-dosing. Fluorophotometric studies 

in animals and humans suggest that brimonidine tartrate has a dual mechanism of action by reducing aqueous 

humor production and increasing uveoscleral outflow. 

Pharmacokinetics: 

In a pharmacokinetic study, 14 healthy subjects (4 males and 10 females) received a single topical ocular 

administration of Brimonidine Tartrate Ophthalmic Solution, 0.15%, one drop per eye. The peak plasma 

concentrations (C max 

) and AUC 0-inf 

max 

was 1.7 ± 0.7 

hours after dosing. The systemic half-life was approximately 2.1 hours. 

Brimonidine is metabolized primarily by the liver. In vitro metabolism data from human microsomal fractions and 

liver slices indicate that brimonidine undergoes extensive hepatic metabolism. 

Urinary excretion is the major route of elimination of brimonidine and its metabolites. Approximately 87% 

of an orally administered radioactive dose of brimonidine was eliminated within 120 hours, with 74% of the 

radioactivity recovered in the urine. 

Special Populations 

Brimonidine Tartrate Ophthalmic Solution, 0.15% has not been studied in patients with hepatic or renal impairment. 

Because of the low systemic drug exposure following topical ocular administration of Brimonidine Tartrate Ophthalmic 

Solution, 0.15%, no dose adjustment is necessary when treating patients with hepatic or renal impairment. 

Clinical Evaluations: 

Elevated IOP presents a major risk factor in glaucomatous field loss. The higher the level of IOP, the greater the 

likelihood of optic nerve damage and visual field loss. Brimonidine tartrate has the action of lowering intraocular 

pressure with minimal effect on cardiovascular and pulmonary parameters. 

A clinical study was conducted to evaluate the safety and efficacy of Brimonidine Tartrate Ophthalmic Solution, 

0.15% compared to Alphagan ® P** administered three-times-daily in patients with open-angle glaucoma or 

ocular hypertension. The results indicated that Brimonidine Tartrate Ophthalmic Solution, 0.15% is equivalent in 

IOP-lowering effect to Alphagan ® P (brimonidine tartrate ophthalmic solution), 0.15%, and effectively lowers IOP 

in patients with open-angle glaucoma or ocular hypertension by 2 - 6 mm Hg. 


Brimonidine Tartrate Ophthalmic Solution, 0.15% is indicated for the lowering of intraocular pressure in patients 

with open-angle glaucoma or ocular hypertension. 


Brimonidine Tartrate Ophthalmic Solution, 0.15% is contraindicated in patients with hypersensitivity to 

brimonidine tartrate or any component of this medication. It is also contraindicated in patients receiving 

monoamine oxidase (MAO) inhibitor therapy. 

PRECAUTIONS 

General: 

Although Brimonidine Tartrate Ophthalmic Solution, 0.15% had minimal effect on the blood pressure of patients 

in clinical studies, caution should be exercised in treating patients with severe cardiovascular disease. 

Brimonidine Tartrate Ophthalmic Solution, 0.15% has not been studied in patients with hepatic or renal 

impairment; caution should be used in treating such patients. 

Brimonidine Tartrate Ophthalmic Solution, 0.15% should be used with caution in patients with depression, 

cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, or thromboangiitis 

obliterans. Patients prescribed IOP-lowering medication should be routinely monitored for IOP. 

N 

N 

COOH 

H 

HO 

C 

C 

OH 

H 

COOH 

Information for Patients: 

As with other drugs in this class, Brimonidine Tartrate Ophthalmic Solution, 0.15% may cause fatigue and/or 

drowsiness in some patients. Patients who engage in hazardous activities should be cautioned of the potential 

for a decrease in mental alertness. 

Drug Interactions: 

Although specific drug interaction studies have not been conducted with Brimonidine Tartrate Ophthalmic 

Solution, 0.15%, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, 

opiates, sedatives, or anesthetics) should be considered. Alpha-2 agonists, as a class, may reduce pulse and 

blood pressure. Caution in using concomitant drugs such as beta-blockers (ophthalmic and systemic), antihypertensives 

and/or cardiac glycosides is advised. 

Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not 

known whether the concurrent use of these agents with Brimonidine Tartrate Ophthalmic Solution, 0.15% in 

humans can interfere with its IOP-lowering effect. No data on the level of circulating catecholamines after 

Brimonidine Tartrate Ophthalmic Solution, 0.15% administration are available. Caution, however, is advised in 

patients taking tricyclic antidepressants, which can affect the metabolism and uptake of circulating amines. 

Carcinogenesis, Mutagenesis, and Impairment of Fertility: 

No compound-related carcinogenic effects were observed in either mice or rats following a 21-month and a 

24-month study, respectively. In these studies, dietary administration of brimonidine tartrate at doses up to 

2.5 mg/kg/day in mice and 1.0 mg/kg/day in rats achieved 60 and 50 times, respectively, the plasma drug 

concentration estimated in humans treated with one drop of Brimonidine Tartrate Ophthalmic Solution, 0.15% 

into both eyes. 

Brimonidine tartrate was not mutagenic or cytogenic in a series of in vitro and in vivo studies including the Ames 

test, chromosomal aberration assay in Chinese hamster ovary (CHO) cells, a host-mediated assay and cytogenic 

studies in mice, and dominant lethal assay. 

Pregnancy: Teratogenic Effects: Pregnancy Category: B 

Reproductive studies performed in rats and rabbits with oral doses of 0.66 mg base/kg revealed no evidence 

of harm to the fetus due to Brimonidine Tartrate Ophthalmic Solution, 0.15%. Dosing at this level produced an 

exposure in rats and rabbits that is 80 and 40 times higher than the exposure seen in humans, respectively. 

There are no adequate and well-controlled studies in pregnant women. In animal studies, brimonidine crossed 

the placenta and entered into the fetal circulation to a limited extent. Brimonidine Tartrate Ophthalmic Solution, 

0.15% should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to 

the fetus. 

Nursing Mothers: 

It is not known whether this drug is excreted in human milk. In animal studies, brimonidine tartrate was excreted 

in breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into 

account the importance of the drug to the mother. 

Pediatric Use: 

In a well-controlled clinical study conducted in pediatric glaucoma patients (ages 2 to 7 years) the most 

commonly observed adverse events with brimonidine tartrate ophthalmic solution 0.2% dosed three-timesdaily 

were somnolence (50%-83% in patients ages 2 to 6 years) and decreased alertness. In pediatric patients 

7 years of age or older (>20 kg), somnolence appears to occur less frequently (25%). Approximately 16% of 

patients on brimonidine tartrate ophthalmic solution discontinued from the study due to somnolence. 

The safety and effectiveness of brimonidine tartrate ophthalmic solution have not been studied in pediatric 

patients below the age of 2 years. Brimonidine tartrate ophthalmic solution is not recommended for use in 

pediatric patients under the age of 2 years. (Also refer to ADVERSE REACTIONS section.) 

Geriatric Use: 

No overall differences in safety or effectiveness have been observed between elderly and other adult patients. 


Adverse events occurring in approximately 10-20% of the subjects included: allergic conjunctivitis, conjunctival 

hyperemia, and eye pruritis. 

Adverse events occurring in approximately 5-9% of the subjects included: burning sensation, conjunctival 

folliculosis, hypertension, ocular allergic reaction, oral dryness, and visual disturbance. 

Events occurring in approximately 1-4% of subjects included: allergic reaction, arthralgia, arthritis, asthenia, 

blepharitis, blepharoconjunctivitis, blurred vision, bronchitis, cataract, chest pain, conjunctival edema, 

conjunctival hemorrhage, conjunctivitis, cough, dizziness, diabetes mellitus, dyspepsia, dyspnea, epiphora, eye 

discharge, eye dryness, eye irritation, eye pain, eyelid edema, eyelid erythema, fatigue, flu syndrome, follicular 

conjunctivitis, foreign body sensation, gastrointestinal disorder, headache, hypercholesterolemia, hypotension, 

infection, insomnia, joint disorder, keratitis, lid disorder, osteoporosis, pharyngitis, photophobia, rash, rhinitis, 

sinus infection, sinusitis, somnolence, stinging, superficial punctate keratopathy, tearing, visual field defect, 

vitreous detachment, vitreous disorder, vitreous floaters, and worsened visual acuity. 

The following events were reported in less than 1% of subjects: corneal erosion, nasal dryness, and taste 

perversion. 

The following events have been identified during post-marketing use of brimonidine tartrate ophthalmic 

solutions in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates 

of frequency cannot be made. The events, which have been chosen for inclusion due to either their seriousness, 

frequency of reporting, possible causal connection to brimonidine tartrate ophthalmic solutions, or a combination 

of these factors, include: bradycardia; iritis; miosis; skin reactions (including erythema, eyelid pruritis, rash, and 

vasodilation); and tachycardia. Apnea, bradycardia, hypotension, hypothermia, hypotonia, and somnolence have 

been reported in infants receiving brimonidine tartrate ophthalmic solutions. 

OVERDOSAGE 

No information is available on overdosage in humans. Treatment of an oral overdose includes supportive and 

symptomatic therapy; a patent airway should be maintained. 

DOSAGE AND ADMINISTRATION 

The recommended dose is one drop of Brimonidine Tartrate Ophthalmic Solution, 0.15% in the affected eye(s) 

three-times-daily, approximately 8 hours apart. 

Brimonidine Tartrate Ophthalmic Solution, 0.15% may be used concomitantly with other topical ophthalmic drug 

products to lower intraocular pressure. If more than one topical ophthalmic product is being used, the products 

should be administered at least 5 minutes apart. 

HOW SUPPLIED 

Brimonidine Tartrate Ophthalmic Solution, 0.15% is supplied sterile in opaque white LDPE plastic bottles and 

natural tips with purple polypropylene caps as follows: 

5 mL in 8 mL bottle NDC 61314-144-05 



Storage: Store at 15°-25° C (59° - 77°F). 

Rx Only 

Distributed by: 

Falcon Pharmaceuticals, Ltd. 

Fort Worth, Texas 76134 

Manufactured by: 

Alcon Laboratories, Inc. 

Fort Worth, Texas 76134 

Printed in USA 

*POLYQUAD is a registered trademark of Alcon Research, Ltd. 

**ALPHAGAN P is a registered trademark of Allergan, Inc. 

349040-1008

Brimonidine Tartrate Ophthalmic Solution, 0.15% 

(compares to Alphagan ® P Ophthalmic Solution, 0.15%)* 

First-Time Generic 

NEW STRENGTH 

Seeing is Believing. 

Introducing Brimonidine Tartrate Ophthalmic Solution, 0.15%. 

A lower price alternative that is AT Rated and therapeutically 

equivalent to Alphagan® P* Ophthalmic Solution, 0.15%. 

Available 5 mL, 10 mL, and 15 mL DROP-TAINER®** dispensers. 

© 2009 Falcon Pharmaceuticals, Ltd. 

PLEASE SEE FULL PRESCRIBING INFORMATION ON ADJACENT PAGE 

*Alphagan ® P is a registered trademark of Allergan, Inc. 

** DROP-TAINER is a registered trademark of Alcon Research, Ltd.


Pancreatitis 

Enzymes flow freely 

into the duodenum 

to aid in digestion 

Gallbladder 

Normal 

Pancreas 

TEAR ALONG PERFORATION 

MEDICAL ILLUSTRATION: © KRISTEN WEINANDT MARZEJON 2009 

Gallstones 

Common 

bile duct 

Pancreatic 

duct 

Duodenum 

(small intestine) 

Acute or Chronic 

Inflammation of 

Endocrine Gland 

Pancreatitis is an inflammation of the pancreas, the gland 

behind the stomach that produces insulin and enzymes 

that help digest food. The pancreas can become inflamed 

as a result of alcoholism, gallstones, or infection, among 

other reasons. The inflammation can develop quickly over 

a period of days (acute pancreatitis) or can develop and 

continue for years (chronic pancreatitis). It can be a mild 

inflammation that heals quickly with the proper treatment, or a severe condition that can lead to 

serious diseases such as diabetes, kidney failure, or cancer of the pancreas. 

Symptoms of acute pancreatitis include pain in the abdomen that can move to the lower back area. 

The pain often feels worse with eating, but better in the fetal position. Acute pancreatitis can also cause 

nausea and vomiting. In chronic pancreatitis, the abdominal pain is also associated with weight loss and 

oily, foul-smelling bowel movements. Laboratory tests of the blood, urine, and stool are performed to look 

for signs of inflammation and abnormal amounts of pancreatic enzymes. Other tests often performed in 

the diagnosis of pancreatitis include abdominal x-ray, ultrasound testing, CT scan, and MRI. 

Treatment depends on the type of pancreatitis, its cause, and its severity. Patients may require a 

hospital stay to treat pain and allow the pancreas to rest by restricting food and fluids by mouth. 

Patients are rehydrated with intravenous fluids and nutrition is restored with special feedings. The 

specific cause of the pancreatic inflammation will determine further treatment. 

Copyright Jobson Medical Information LLC, 2009 

Inflamed 

Pancreas 

Gallstones, produced 

in the gallbladder, 

can get lodged in the 

common bile duct, 

blocking the flow of 

pancreatic enzymes 

into the small intestine. 

Pancreatitis occurs 

when these blocked 

enzymes irritate the 

cells of the pancreas 

continued


Alcohol Abuse and Smoking Are 

Major Risk Factors for the Disease 

The pancreas is responsible for producing hormones and 

enzymes that help regulate blood sugar and food digestion. 

The digestive enzymes produced in the pancreas are not activated 

until after they are released by the pancreas into the 

small intestine. If these enzymes become active while they are 

still in the pancreas, they can irritate the pancreatic tissue and 

lead to inflammation. Conditions that can cause the digestive 

enzymes to inflame the pancreas include excess alcohol, gallstones, 

infections, trauma to the abdomen, or pancreatic 

Inflammation occurs when 

pancreatic enzymes irritate 

the cells of the organ. 

cancer. People with ulcers, elevated triglycerides, cystic fibrosis, or a family history of pancreatitis 

and those who smoke are also at higher risk. People with frequent bouts of acute pancreatitis 

can develop scar tissue in the pancreas, leading to chronic pancreatitis. 

Presentation and Diagnosis 

Symptoms of acute pancreatitis include significant upper abdominal pain, nausea, and vomiting. 

In severe cases, patients may become dehydrated and go into shock when other organs begin to 

fail or the pancreas begins to bleed internally. Chronic pancreatitis also causes abdominal pain, but 

it is more often associated with digestive problems and oily, foul-smelling bowel movements. Patients 

with long-standing pancreatitis often lose weight due to a lack of digestive enzymes needed to break 

down nutrients from food. Diabetes can also result from chronic inflammation of the pancreas, 

since the scar tissue in the pancreas means that there are fewer healthy cells to produce insulin. 

Pancreatitis can also lead to infection of the inflamed tissue in the pancreas, requiring surgery. 

Diagnosis is based on a series of tests to measure the effect of the inflammation in blood, 

urine, and stool samples. Studies that allow a view of the pancreas include x-rays, CT scans, 

ultrasound procedures, and MRIs. 

Treatment Options 

Treatment of an acute episode of pancreatitis usually means stabilizing the patient in the hospital 

to allow the pancreas to rest. This means that no food or liquids can be taken by mouth for 

several days, during which time fluids are administered intravenously and abdominal pain is 

treated. When the inflammation and pain begin to subside, the patient can begin drinking and 

eating soft foods, and eventually resume a more normal diet. In cases of chronic pancreatitis, a 

low-fat, highly nutritious diet is necessary, and pancreatic enzyme supplements may be prescribed 

for use before meals to help break down food into useful nutrients. Alcohol is a significant cause 

of pancreatitis and should be avoided completely. Smoking is another risk factor for pancreatitis, 

and smoking cessation is an important way to help prevent future attacks. Patients with a history 

of pancreatitis should drink plenty of fluids daily to prevent dehydration. 

Depending on the cause of pancreatitis, other procedures may be needed to avoid future bouts 

of inflammation and the development of chronic pancreatitis. If a bile duct blockage or gallstones 

were a cause of the condition, surgery may be indicated to correct the problem. If alcohol was 

the cause, an abstinence program may be needed to help prevent future damage. Infected tissue 

or pockets of fluid known as pseudocysts may require surgical removal. 

Diagnosis and treatment of acute or chronic pancreatitis can also be performed using a procedure 

known as endoscopic retrograde cholangiopancreatography (ERCP). ERCP uses a tiny camera 

on the end of a tube to view the pancreas without a surgical incision. The tube is inserted down 

the throat and through the stomach and small intestine to the pancreas, where the area can be 

seen and minor surgical procedures can be performed to correct the cause of the pancreatitis. 

If you have questions about pancreatic enzyme supplements or pain medications prescribed 

for pancreatitis, ask your pharmacist.

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Surgical 

Procedures for 

Weight Loss 

Obesity is a chronic condition characterized by 

an extreme accumulation of fat that exceeds the 

body’s skeletal and physical standards. 1 It is 

insidious, with symptoms slowly becoming evident over 

a prolonged period of time. Morbid (clinically severe) 

obesity, which involves an increased risk of coexisting 

disease, is defined as having at least 100 lb. of excess 

weight, being 20% or more above ideal body weight, or 

having a body-mass index (BMI) of 35 kg/m 2 or higher. 2,3 

(BMI, a measure of body fat based on height and weight, 

is calculated as weight [kg]/height [m] 2 . 3,4 ) At this stage, 

obesity becomes a health risk and treatment options must 

be contemplated. 5 Weight-loss, or bariatric, surgery is 

considered for the morbidly obese patient when all conventional 

therapy—including behavioral modification, 

diet therapy, exercise, and medication—has failed. 

Obesity: Epidemiology and Screening 

In the last 20 years, there has been a dramatic increase 

in the prevalence of obesity in the United States. 2 In 

1991, no state had an obesity rate higher than 20%. 4 

According to 2008 statistics, obesity prevalence in adults 

increased in 37 states, with Mississippi having the highest 

rate (31.7%) and Colorado having the lowest rate 

(18.4%). In every state except Colorado, more than 20% 

of adults are obese. 4 

In 1994, according to the National Health and Nutrition 

Examination Survey III, approximately 55% of U.S. 

adults (about 97 million) were obese. 6 In 2007, it was 

estimated that about 66% of adults are overweight or obese; 

16% of children and adolescents are overweight and 34% 

are at risk for becoming overweight. 7 The prevalence of 

severe obesity in the U.S. between 1999 and 2002 was 

greater in women than in men. 8 In the U.S., approximately 

280,000 deaths are attributed to obesity, which will soon 

exceed smoking as the primary preventable cause of death. 9 

Mea A. Weinberg, DMD, MSD, RPh 

Clinical Associate Professor 

Stuart L. Segelnick, DDS, MS 

Clinical Associate Professor 

Department of Periodontology and Implant Dentistry 

New York University College of Dentistry 

New York, New York 


Surgical Treatment Options 

Introduced in the 1950s, bariatric 

surgery currently offers the best 

method of producing sustained weight 

loss in morbidly obese individuals. 10 

A consensus statement by the American 

Society for Metabolic and Bariatric 

Surgery (ASMBS) concluded that bariatric surgery 

is the most effective treatment for morbid obesity and 

that it can result in improvement or complete resolution 

of obesity comorbidities. 11-13 In 2002, 63,000 bariatric 

surgeries were performed in the U.S.; in 2006, an estimated 

177,600 patients underwent the procedure, according 

to the ASMBS. Fewer than 1% of individuals who 

meet the criteria for weight-loss surgery actually undergo 

the procedure. It is advisable for severely obese patients 

to have surgery early to prevent the development of other 

medical conditions, such as diabetes and hypertension. 14 

Three types of bariatric surgery exist (TABLE 1). Restrictive 

surgery limits food intake by making the stomach 

smaller. Malabsorptive surgery hinders calorie absorption 

by shortening the duodenum and/or altering where the 

duodenum connects to the stomach, thereby limiting 

the amount of food digested or absorbed. The third type 

of surgery is a combination of the first two. Restrictive 

procedures, which are performed least often, result in 

the most significant weight loss by reducing the amount 

of food eaten and slowing the speed of gastric emptying. 15 

The mechanism by which weight 

loss occurs after bariatric surgery is 

most likely an interplay between 

mechanical effects of the surgery and 

neurohormonal feedback loops 

involved in body-weight homeostasis. 

16,17 The amount of weight loss 

HS-2 


IN THE TREATMENT OF MRSA BACTEREMIA AND MRSA COMPLICATED SKIN INFECTIONS 

INSIDE.OUTSIDE.ON HIS SIDE. 

n Landmark clinical trial of CUBICIN 6 mg/kg once daily demonstrated 

efficacy in S. aureus bacteremia caused by MRSA and MSSA 

n Proven clinical success of CUBICIN 4 mg/kg once daily in S. aureus 

complicated skin infections —both MRSA and MSSA 

INDICATIONS AND IMPORTANT SAFETY INFORMATION 

CUBICIN is indicated for the following infections: 

Complicated skin and skin structure infections caused by susceptible 

isolates of the following Gram-positive microorganisms: S. aureus (including 

methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus 

agalactiae, Streptococcus dysgalactiae subspecies equisimilis, and 

Enterococcus faecalis (vancomycin-susceptible isolates only). Combination 

therapy may be clinically indicated if the documented or presumed 

pathogens include Gram-negative or anaerobic organisms. 

S. aureus bloodstream infections (bacteremia), including those with 

right-sided infective endocarditis, caused by methicillin-susceptible and 

methicillin-resistant isolates. Combination therapy may be clinically indicated 

if the documented or presumed pathogens include Gram-negative or 

anaerobic organisms. 

The efficacy of CUBICIN in patients with left-sided infective endocarditis due 

to S. aureus has not been demonstrated. The clinical trial of CUBICIN in 

patients with S. aureus bloodstream infections included limited data from 

patients with left-sided infective endocarditis; outcomes in these patients 

were poor. CUBICIN has not been studied in patients with prosthetic valve 

endocarditis or meningitis. 

Patients with persisting or relapsing S. aureus infection or poor clinical 

response should have repeat blood cultures. If a culture is positive for 

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©2007 Cubist Pharmaceuticals, Inc. 

3974071907 September 2007 

CUBICIN is a registered trademark of Cubist Pharmaceuticals,Inc. 

S. aureus, MIC susceptibility testing of the isolate should be performed 

using a standardized procedure, as well as diagnostic evaluation to rule 

out sequestered foci of infection. Appropriate surgical intervention (eg, 

debridement, removal of prosthetic devices, valve replacement surgery) 

and/or consideration of a change in antibiotic regimen may be required. 

CUBICIN is not indicated for the treatment of pneumonia. 

Clostridium difficile-associated diarrhea (CDAD) has been reported with the 

use of nearly all antibacterial agents, including CUBICIN, and may range in 

severity from mild diarrhea to fatal colitis. CDAD has been reported to occur 

over 2 months post-antibiotic treatment. If CDAD is suspected, antibiotic 

treatment may need to be suspended. 

Patients receiving CUBICIN should be monitored for the development of 

muscle pain or weakness, particularly of the distal extremities. In patients 

who receive CUBICIN, creatine phosphokinase (CPK) levels should be 

monitored weekly, and more frequently in patients who received recent prior 

or concomitant therapy with an HMG-CoA reductase inhibitor. In patients 

with renal insufficiency, both renal function and CPK should be monitored 

more frequently. Patients who demonstrate unexplained elevations in CPK 

while receiving CUBICIN should be monitored more frequently. 

CUBICIN should be discontinued in patients with unexplained signs and 

symptoms of myopathy in conjunction with CPK elevation >1000 U/L 

(~5X ULN), or in patients without reported symptoms who have marked 

elevations in CPK >2000 U/L (≥10X ULN). 

Most adverse events reported in CUBICIN clinical trials were mild to moderate 

in intensity. The most common CUBICIN adverse events were anemia, 

constipation, diarrhea, nausea, 

vomiting, injection-site reactions, 

and headache. 

Please see Brief Summary 

of Prescribing Information 

on adjacent page.

Brief summary of prescribing information. 

INDICATIONS AND USAGE CUBICIN (daptomycin for injection) is indicated 

for the following infections (see also DOSAGE AND ADMINISTRATION and 

CLINICAL STUDIES in full prescribing information): Complicated skin 

and skin structure infections (cSSSI) caused by susceptible isolates 

of the following Gram-positive microorganisms: Staphylococcus aureus 

(including methicillin-resistant isolates), Streptococcus pyogenes, S. agalactiae, 

S. dysgalactiae subsp equisimilis, and Enterococcus faecalis (vancomycin-susceptible 

isolates only). Combination therapy may be clinically 

indicated if the documented or presumed pathogens include Gram-negative 

or anaerobic organisms. Staphylococcus aureus bloodstream infections 

(bacteremia), including those with right-sided infective endocarditis, 

caused by methicillin-susceptible and methicillin-resistant isolates. Combination 

therapy may be clinically indicated if the documented or presumed 

pathogens include Gram-negative or anaerobic organisms. The efficacy of 

CUBICIN in patients with left-sided infective endocarditis due to S. aureus 

has not been demonstrated. The clinical trial of CUBICIN in patients with 

S. aureus bloodstream infections included limited data from patients with 

left-sided infective endocarditis; outcomes in these patients were poor (see 

CLINICAL STUDIES in full prescribing information). CUBICIN has not been 

studied in patients with prosthetic valve endocarditis or meningitis. Patients 

with persisting or relapsing S. aureus infection or poor clinical response 

should have repeat blood cultures. If a culture is positive for S. aureus,MIC 

susceptibility testing of the isolate should be performed using a standardized 

procedure, as well as diagnostic evaluation to rule out sequestered foci 

of infection (see PRECAUTIONS). CUBICIN is not indicated for the treatment 

of pneumonia. Appropriate specimens for microbiological examination 

should be obtained in order to isolate and identify the causative pathogens 

and to determine their susceptibility to daptomycin. Empiric therapy may 

be initiated while awaiting test results. Antimicrobial therapy should be 

adjusted as needed based upon test results. To reduce the development 

of drug-resistant bacteria and maintain the effectiveness of CUBICIN and 

other antibacterial drugs, CUBICIN should be used only to treat or prevent 

infections that are proven or strongly suspected to be caused by susceptible 

bacteria.When culture and susceptibility information are available, they 

should be considered in selecting or modifying antibacterial therapy. In the 

absence of such data, local epidemiology and susceptibility patterns may 

contribute to the empiric selection of therapy. 

CONTRAINDICATIONS CUBICIN is contraindicated in patients with 

known hypersensitivity to daptomycin. 

WARNINGS Clostridium difficile–associated diarrhea (CDAD) has been 

reported with use of nearly all antibacterial agents, including CUBICIN, 

and may range in severity from mild diarrhea to fatal colitis. Treatment 

with antibacterial agents alters the normal flora of the colon, leading to 

overgrowth of C. difficile. C. difficile produces toxins A and B, which contribute 

to the development of CDAD. Hypertoxin-producing strains of C. 

difficile cause increased morbidity and mortality, since these infections 

can be refractory to antimicrobial therapy and may require colectomy. 

CDAD must be considered in all patients who present with diarrhea following 

antibiotic use. Careful medical history is necessary because CDAD 

has been reported to occur over 2 months after the administration of 

antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic 

use not directed against C. difficile may need to be discontinued. 

Appropriate fluid and electrolyte management, protein supplementation, 

antibiotic treatment of C. difficile, and surgical evaluation should be instituted 

as clinically indicated. 

PRECAUTIONS General The use of antibiotics may promote the selection 

of non-susceptible organisms. Should superinfection occur during therapy, 

appropriate measures should be taken. Prescribing CUBICIN in the absence 

of a proven or strongly suspected bacterial infection is unlikely to provide 

benefit to the patient and increases the risk of the development of drugresistant 

bacteria. Persisting or Relapsing S. aureus Infection Patients 

with persisting or relapsing S. aureus infection or poor clinical response 

should have repeat blood cultures. If a culture is positive for S. aureus,MIC 

susceptibility testing of the isolate should be performed using a standardized 

procedure, as well as diagnostic evaluation to rule out sequestered foci 

of infection. Appropriate surgical intervention (eg, debridement, removal of 

prosthetic devices, valve replacement surgery) and/or consideration of a 

change in antibiotic regimen may be required. Failure of treatment due to 

persisting or relapsing S. aureus infections was assessed by the Adjudication 

Committee in 19/120 (15.8%) CUBICIN-treated patients (12 with 

MRSA and 7 with MSSA) and 11/115 (9.6%) comparator-treated patients 

(9 with MRSA treated with vancomycin and 2 with MSSA treated with antistaphylococcal 

semi-synthetic penicillin). Among all failures, 6 CUBICINtreated 

patients and 1 vancomycin-treated patient developed increasing 

MICs (reduced susceptibility) by central laboratory testing on or following 

therapy. Most patients who failed due to persisting or relapsing S. aureus 

infection had deep-seated infection and did not receive necessary surgical 

intervention (see CLINICAL STUDIES in full prescribing information). 

Skeletal Muscle In a Phase 1 study examining doses up to 12 mg/kg 

q24h of CUBICIN for 14 days, no skeletal muscle effects or CPK elevations 

were observed. In Phase 3 cSSSI trials of CUBICIN at a dose of 4 mg/kg, 

elevations in CPK were reported as clinical adverse events in 15/534 

(2.8%) CUBICIN-treated patients, compared with 10/558 (1.8%) comparator-treated 

patients. In the S. aureus bacteremia/endocarditis trial, at a 

dose of 6 mg/kg, elevations in CPK were reported as clinical adverse 

events in 8/120 (6.7%) CUBICIN-treated patients compared with 1/116 

(500 U/L) at baseline, 2/19 (10.5%) treated with CUBICIN and 4/24 

(16.7%) treated with comparator developed further increases in CPK while 

on therapy. In this same population, no patients developed myopathy. 

CUBICIN-treated patients with baseline CPK >500 U/L (N=19) did not experience 

an increased incidence of CPK elevations or myopathy relative to 

those treated with comparator (N=24). In the S. aureus bacteremia/endocarditis 

study, 3 (2.6%) CUBICIN-treated patients, including 1 with trauma 

associated with a heroin overdose and 1 with spinal cord compression, had 

an elevation in CPK >500 U/L with associated musculoskeletal symptoms. 

None of the patients in the comparator group had an elevation in CPK 

>500 U/L with associated musculoskeletal symptoms. CUBICIN should be 

discontinued in patients with unexplained signs and symptoms of myopathy 

in conjunction with CPK elevation >1,000 U/L (~5x ULN), or in patients 

without reported symptoms who have marked elevations in CPK >2,000 

U/L (10x ULN). In addition, consideration should be given to temporarily 

suspending agents associated with rhabdomyolysis, such as HMG-CoA 

reductase inhibitors, in patients receiving CUBICIN. In a Phase 1 study examining 

doses up to 12 mg/kg q24h of CUBICIN for 14 days, no evidence 

of nerve conduction deficits or symptoms of peripheral neuropathy was 

observed. In a small number of patients in Phase 1 and Phase 2 studies at 

doses up to 6 mg/kg, administration of CUBICIN was associated with 

decreases in nerve conduction velocity and with adverse events (eg, paresthesias, 

Bell’s palsy) possibly reflective of peripheral or cranial neuropathy. 

Nerve conduction deficits were also detected in a similar number of comparator 

subjects in these studies. In Phase 3 cSSSI and communityacquired 

pneumonia (CAP) studies, 7/989 (0.7%) CUBICIN-treated patients 

and 7/1,018 (0.7%) comparator-treated patients experienced paresthesias. 

New or worsening peripheral neuropathy was not diagnosed in any of 

these patients. In the S. aureus bacteremia/endocarditis trial, a total of 

11/120 (9.2%) CUBICIN-treated patients had treatment-emergent adverse 

events related to the peripheral nervous system. All of the events were 

classified as mild to moderate in severity; most were of short duration and 

resolved during continued treatment with CUBICIN or were likely due to an 

alternative etiology. In animals, effects of CUBICIN on peripheral nerve were 

observed (see ANIMAL PHARMACOLOGY in full prescribing information). 

Therefore, physicians should be alert to the possibility of signs and symptoms 

of neuropathy in patients receiving CUBICIN. Drug Interactions 

Warfarin Concomitant administration of CUBICIN (6 mg/kg q24h for 5 

days) and warfarin (25 mg single oral dose) had no significant effect on the 

pharmacokinetics of either drug, and the INR was not significantly altered. 

As experience with the concomitant administration of CUBICIN and warfarin 

is limited, anticoagulant activity in patients receiving CUBICIN and warfarin 

should be monitored for the first several days after initiating therapy with 

CUBICIN (see CLINICAL PHARMACOLOGY, Drug-Drug Interactions in 

full prescribing information). HMG-CoA Reductase Inhibitors Inhibitors 

of HMG-CoA reductase may cause myopathy, which is manifested as 

muscle pain or weakness associated with elevated levels of CPK. There 

were no reports of skeletal myopathy in a placebo-controlled Phase 1 trial 

in which 10 healthy subjects on stable simvastatin therapy were treated 

concurrently with CUBICIN (4 mg/kg q24h) for 14 days. In the Phase 3 S. 

aureus bacteremia/endocarditis trial, 5/22 CUBICIN-treated patients who 

received prior or concomitant therapy with an HMG-CoA reductase inhibitor 

developed CPK elevations >500 U/L. Experience with co-administration of 

HMG-CoA reductase inhibitors and CUBICIN in patients is limited; therefore, 

consideration should be given to temporarily suspending use of HMG-CoA 

reductase inhibitors in patients receiving CUBICIN (see ADVERSE 

REACTIONS, Post-Marketing Experience). Drug-Laboratory Test 

Interactions There are no reported drug-laboratory test interactions. 

Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term 

carcinogenicity studies in animals have not been conducted to evaluate the 

carcinogenic potential of daptomycin. However, neither mutagenic nor 

clastogenic potential was found in a battery of genotoxicity tests, including 

the Ames assay, a mammalian cell gene mutation assay, a test for chromosomal 

aberrations in Chinese hamster ovary cells, an in vivo micronucleus 

assay, an in vitro DNA repair assay, and an in vivo sister chromatid exchange 

assay in Chinese hamsters. Daptomycin did not affect the fertility or 

reproductive performance of male and female rats when administered 

intravenously at doses up to 150 mg/kg/day, which is approximately 9 

times the estimated human exposure level based upon AUCs. Pregnancy 

Teratogenic Effects: Pregnancy Category B Reproductive and teratology 

studies performed in rats and rabbits at doses of up to 75 mg/kg, 2 and 

4 times the 6 mg/kg human dose, respectively, on a body surface area 

basis, have revealed no evidence of harm to the fetus due to daptomycin. 

There are, however, no adequate and well-controlled studies in pregnant 

women. Because animal reproduction studies are not always predictive of 

human response, this drug should be used during pregnancy only if clearly 

needed. Nursing Mothers It is not known if daptomycin is excreted in 

human milk. Caution should be exercised when CUBICIN is administered to 

nursing women. Pediatric Use Safety and efficacy of CUBICIN in patients 

under the age of 18 have not been established. Geriatric Use Of the 534 

patients treated with CUBICIN in Phase 3 controlled clinical trials of cSSSI, 

27.0% were 65 years of age or older and 12.4% were 75 years of age or 

older. Of the 120 patients treated with CUBICIN in the Phase 3 controlled 

clinical trial of S. aureus bacteremia/endocarditis, 25.0% were 65 years of 

age or older and 15.8% were 75 years of age or older. In Phase 3 clinical 

studies of cSSSI and S. aureus bacteremia/endocarditis, lower clinical success 

rates were seen in patients 65 years of age compared with those 

SURGICAL PROCEDURES FOR WEIGHT LOSS 

Table 1 

Different Types of Bariatric Surgical Procedures 

Surgical 

Procedure Type Features Advantages Disadvantages/Risks 

Roux-en-Y Restrictive/ Pouch created with staples/band High percentage Heartburn, nausea, 

gastric bypass malabsorptive on stomach; section of duodenum of weight loss diarrhea, infection, 

attached to pouch; food bypasses 

abdominal hernia, 

much of duodenum, resulting in 

abdominal obstruction, 

inability to absorb calories and 

gallstones (rare) 

nutrients. Pouch size: 1 oz. 

Laparoscopic Restrictive Inflatable silicone band placed Adjustable, reversible, Less weight loss than 

adjustable around upper end of stomach, minimally invasive, with gastric bypass 

gastric band creating small pouch and narrow less pain, outpatient, surgery, harder to 

surgery passage into rest of stomach. fewer nutritional maintain loss, vomiting, 

Pouch size:


Table 2 

NIH Guidelines for Patient 

Selection for Bariatric Surgery 

• ≥100 lb. excess weight 

• BMI ≥40 kg/m 2 without obesity-associated 

comorbidities (e.g., diabetes, cardiovascular disease, 

arthritis, obstructive sleep apnea) 

• BMI 35.0-39.9 kg/m 2 with 1 or more associated 


• Previous failed weight-loss attempts (e.g., nonsurgical 

interventions: diet control, behavioral modification, 

exercise) 

BMI: body-mass index; NIH: National Institutes of Health. 

Source: Reference 29. 

and the patient’s weight is considered to be stable. 

Combined surgery is more likely to result in long-term 

nutritional deficiencies, so it is important to monitor 

patients. Deficiencies of the fat-soluble vitamins (A, D, 

E, and K) and calcium, zinc, and selenium are common 

after gastric bypass. 23 There is an increased incidence of 

anemia owing to decreased levels of iron, vitamin B 12 

, 

and folic acid. 24 Patients should take a supplemental 

multivitamin containing B 12 

and folic acid. 

Purely Restrictive Surgery: Approved by the FDA in 

June 2001 for patients over 18 years of age, laparoscopic 

adjustable gastric band surgery (LAGBS) is a minimally 

invasive procedure for the severely obese that, unlike 

gastric bypass surgery, offers the advantages of being 

adjustable and reversible (band can be removed). LAGBS 

seems to be increasing in popularity in the U.S. 25 This 

type of surgery is easier to perform and has a lower 

complication rate than malabsorptive surgery. The surgery, 

which usually takes about 1 hour, is done on an outpatient 

basis or involves an overnight stay. 

After small incisions are made, a laparoscope is used 

to visualize placement and to suture an adjustable/ 

inflatable hollow silicone gastric band around the top 

5% of the stomach, creating a small upper pouch and 

a large lower pouch. No staples are used. The band is 

connected to a port that is placed subcutaneously in 

the stomach via small incisions; the port can be accessed 

to inflate or deflate the balloon in the band, which 

changes the size of the band accordingly. The diameter 

of the band obstructs or restricts the passage of food. 

The band is inflated or adjusted by adding saline to or 

removing it from the port. As the patient eats, the upper 

pouch fills and the patient feels full sooner. The pouch 

initially can hold only about 1 oz. of food, but later 

expands to hold up to 3 oz. The normal digestive process 

is not altered. Most patients return to normal 

activities within a few weeks. 22 


Postsurgical instructions include a liquid diet for about 

2 weeks, followed by soft foods and then solid foods. It 

is highly recommended that the patient follow a personalized 

nutrition plan and exercise program. Within the 

first 2 years, there is a weight loss of about 50% to 60%. 26 

LABGS is also safe and effective as reoperative surgery 

in obese patients who require additional weight loss after 

previous bariatric surgery. 27 

Weight loss is not as dramatic as with restrictive/ 

malabsorptive surgery, and some patients regain weight 

quickly. Vomiting results from poor chewing, rapid eating, 

exceeding pouch capacity, or drinking shortly after 

eating; repeated vomiting may cause the pouch to stretch, 

enabling weight gain. 28 Because adjustments involve 

needle puncture of the access port, there is an increased 

chance of infection. The procedure is contraindicated in 

patients with Crohn’s disease, large hiatal hernia, or a 

history of gastric ulcers. 

Vertical banded gastroplasty (VBG) uses both a band 

and staples to create a small stomach pouch that empties 

into the lower pouch. Once the most common restrictive 

operation, VBG is not often used today because longterm 

weight loss is minimal. 

Purely Malabsorptive Surgery: In biliopancreatic bypass 

with duodenal switch, the stomach is reduced and the 

small pouch that remains is connected directly to the 

end of the ileum, thus bypassing the duodenum and 

jejunum entirely. This procedure is performed infrequently 

because of the high risk of nutritional deficiencies. 

Criteria for Surgery 

The patient-selection guidelines for bariatric surgery 

developed by the National Institutes of Health (NIH) 

are listed in TABLE 2. A candidate for weight-loss surgery 

must meet these criteria. 29 The risk of death if a patient 

does not undergo the surgery may outweigh the risks 

Table 3 

Adverse Effects and 

Complications of Bariatric Surgery 

Adverse Effects 

Nausea 

Vomiting 

Diarrhea 

Nutritional/vitamin 

deficiencies 

Gallstones 


Complications 

Internal hernia 

Leakage from staples 

Wound infection from band/port 

Gastric bleeding 

Stomal stenosis 

Small-bowel obstruction 

Marginal ulcer 

HS-6 


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Baxter Healthcare Corporation, Route 120 and Wilson Road, Round Lake, IL 60073 www.baxter.com 111085 03/09



from possible complications of the procedure. 

Mortality from bariatric surgery is relatively rare. 38 

In 2007, a survey of 1,343 U.S. bariatric surgeons The mortality rate differs according to the type of surgical 

procedure: 0.15% for VBG and 0.54% for gastric 

was published. A questionnaire examining clinical predictors 

of patient selection was mailed to participants. The bypass. 38 The most common cause of death is pulmonary 

survey concluded that the influences of patient age, embolism. 38 

gender, insurance status, social support, and functional A recent study documented a 30-day mortality rate 

status on the decision to operate were mitigated by of 0.9% postsurgery and a 6.4% mortality rate at 5 years. 

comorbidities and BMI. 30 

Mortality increased substantially with age (>65 years), 

The patient must be prepared to make significant and coronary heart disease was the leading cause of death 

lifestyle changes after having bariatric surgery. These include overall. 39 Another study found that rates of hospitalization 

doubled in the first 3 years after gastric bypass 

proper diet, physical activity, and health care practices 

necessary for any surgical weight-loss system to work. surgery and that many admissions were directly related 

to the procedure, including ventral hernia repair and 

Considerations in Adolescents and Older Adults gastric revision (e.g., surgery for staple-line failure). 40 

Bariatric surgery is an option for obese adolescents. Assessment of the risks of weight-loss surgery should 

However, emotional and physical long-term effects of include operative, perioperative, and long-term complications. 

The rate of complications in the early post- 

the surgery on the adolescent patient should be considered. 

Although weight-loss surgery can yield outstanding operative period (wound infection; leaking from stomach 

into abdominal cavity [peritonitis]; leaking from 

improvements in comorbid conditions in adults, it is not 

clear whether similar improvements occur in adolescents. 31 staple lines or from Y connection; saline solution leaking 

from port; stomal stenosis; marginal ulcers; consti- 

Bariatric surgery has not been a common therapy in 

adolescents, largely because the long-term effects (e.g., pation; staple-line dehiscence; pulmonary problems; 

nutritional deficiencies) are unknown. Within the last deep thrombophlebitis) may be as high as 10% or 

few years, many hospitals have been conducting FDAapproved 

studies of LABGS. Currently, only gastric bypass be necessary to control operative bleeding. Sometimes 

more. 41 In fewer than 1% of patients, splenectomy may 

surgery is approved for patients under 18 years of age. 32 a second operation may be necessary, which increases 

Bariatric surgery should be considered for an adolescent 

only after the patient has unsuccessfully tried to lose A recent study found that patients who undergo 

mortality and morbidity rates. 

weight for least 6 months. The candidate should have a LAGBS may have lower short-term morbidity than those 

BMI of 40 or more, be at least 13 years old (girls) or 15 treated with RGB, but reoperation rates may be higher 

years old (boys), and have serious comorbid conditions. 32 among LAGBS patients. 42 

Bariatric surgery in adults aged 60 years and older is 

effective. However, older patients may develop more Postoperative Drug-Absorption Alterations 

pre- and postoperative problems and achieve less weight Considering the changes made to the upper GI-tract 

loss than younger patients. 33 

anatomy in bariatric surgery, specific nutritional and 

absorptive side effects should be expected and managed 

Complications, Risks, and Adverse Effects appropriately to avoid complications and decreased drug 

Negative effects of bariatric surgery may be classified into efficacy. 43 All weight-loss procedures reduce the size and 

true complications associated with the operation and surface area of the stomach, which decreases the amount 

adverse effects related to alterations in upper-gastrointestinal 

(GI) anatomy (TABLE 3). 34 

the drug to remain in contact with the GI mucosal lin- 

of drug absorption and increases transit time; this causes 

Nausea and vomiting are common adverse effects. ing longer. Patients should not take drugs with the 

The patient can minimize their occurrence by eating a potential to cause ulcers (nonsteroidal anti-inflammatories, 

aspirin, oral bisphosphonates). 44 Alternative analge- 

meal without interruption, chewing meticulously, never 

drinking with meals, and waiting 2 hours after consuming 

solid food before drinking. 34 

agents (e.g., calcitonin nasal spray) should be recomsics 

(e.g., acetaminophen, narcotics) and osteoporosis 

The prevention of secondary complications of morbid 

obesity is an important goal of management. In the intestine, reducing the surface area for drug absorption. 

mended. 43 RGB bypasses a major portion of the small 

majority of cases, the results of surgery outweigh the Therefore, a drug’s route of administration, formulation 

risks, and the consensus is that surgery is the most (liquid vs. tablet/capsule), or dosage must be altered. 43 

effective treatment for severe obesity. 35 However, successful 

postsurgical weight loss does not preclude com- 

intestine for extended periods are likely to exhibit decreased 

Drugs with long absorptive phases that remain in the 

plications, and questions persist regarding efficacy and bioavailability in bypass-surgery patients. For that reason, 

safety. 1,34,35 In 2006, approximately 40% of patients products with prolonged dissolution times, such as extendedrelease 

formulations, should be avoided in this group. 43 

who underwent bariatric surgery developed complications 

within 6 months. 36,37 Iron must be absorbed in the ferrous state in the acidic 

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stomach, but because bypass patients have reduced acid 

production, iron must be taken with vitamin C. This 

acidifies the stomach contents, allowing for better absorption. 

43,45 The small stomach pouch created during the 

bypass procedure produces less gastric acid and hydrochloric 

acid; this may reduce the absorption of calcium 

carbonate, but the citrate salt is unaffected. 43 

Drugs that may potentially cause decreased absorption 

in these patients include enalapril and ketoconazole, for 

which an alternative agent should be prescribed. With 

ramipril, metoprolol, metformin, olanzapine, quetiapine, 

ramipril, simvastatin, and zolpidem, the patient should 

be monitored for reduced drug efficacy. 43 

Conclusion and Future Trends 

The growing epidemic of overweight and obesity is a 

serious health problem in the U.S., with more than 5 

million Americans having a BMI exceeding 35. 46 Severe 

obesity is a chronic condition that is difficult to treat, 

and weight loss can be hard to maintain. There are many 


different approaches to weight management; bariatric 

surgery should be considered only when all other methods 

have failed. 

Surgery can result in profound weight loss in adults, 

which in turn may spur a significant improvement in 

comorbid conditions. Methods of bariatric surgery have 

improved over the past 25 years, but questions about 

safety and efficacy remain. Although concerns exist 

regarding bariatric procedures in adolescents, surgery is 

gaining acceptance as a treatment option in this population. 

Preoperatively, it is essential to stress to the bariatric 

surgical candidate the importance of healthy eating 

and exercise behaviors. 47 

In 2003, the National Institute of Diabetes and Digestive 

and Kidney Diseases of the NIH formed a partnership 

with researchers called the Longitudinal Assessment 

of Bariatric Surgery. The goal of this consortium is to 

plan and conduct studies that will lead to a better understanding 

of bariatric surgery and its impact on the health 

and well-being of patients with extreme obesity. 

REFERENCES 

1. Schwartz MW, Brunzell JD. Regulation of body adiposity and the problem of obesity. 

Arterioscler Thromb Vasc Biol. 1997;17:233-238. 

2. Centers for Disease Control and Prevention. U.S. obesity trends. www.cdc.gov/nccdphp/ 

dnpa/obesity/trend/maps/index.htm. Accessed August 14, 2009. 

3. U.S. Preventive Services Task Force. Screening for obesity in adults: recommendations and 

rationale. Ann Intern Med. 2003;139:930-932. 

4. Trust for America’s Health. F as in fat 2008: how obesity policies are failing in America. 

www.healthyamericans.org. Accessed August 14, 2009. 

5. Pentin PL, Nashelsky J. What are the indications for bariatric surgery? J Fam Pract. 

2005;54:633-634. 

6. Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL. Overweight and obesity in the 

United States: prevalence and trends, 1960-1994. Int J Obes Relat Metab Disord. 1998;22: 

39-47. 

7. Wang Y, Beydoun MA. The obesity epidemic in the United States—gender, age, socioeconomic, 

racial/ethnic, and geographic characteristics: a systematic review and meta-regression 

analysis. Epidemiol Rev. 2007;29:6-28. 

8. Hedley AA, Ogden CL, Johnson CL, et al. Prevalence of overweight and obesity among 

US children, adolescents, and adults, 1999-2002. JAMA. 2004;291:2847-2850. 

9. Allison DB, Fontaine KR, Manson JE, et al. Annual deaths attributable to obesity in the 

United States. JAMA. 1999;282:1530-1538. 

10. Brolin RE. Bariatric surgery and long-term control of morbid obesity. JAMA. 

2002;288:2793-2796. 

11. Buchwald H. Consensus conference statement. Bariatric surgery for morbid obesity: 

health implications for patients, health professionals, and third-party payers. Surg Obes Relat 

Dis. 2005;1:371-381. 

12. Christou NV, Sampalis JS, Liberman M, et al. Surgery decreases long-term mortality, 

morbidity, and health care use in morbidly obese patients. Ann Surg. 2004;240:416-424. 

13. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and 

meta-analysis. JAMA. 2004;292:1724-1737. 

14. Sugerman H, Wolfe LG, Sica DA, Clore JN. Diabetes and hypertension in severe obesity 

and effects of gastric bypass-induced weight loss. Ann Surg. 2003;237:751-758. 

15. Wyles SM, Ahmed AR. Tips and tricks in bariatric surgical procedures: a review article. 

Minerva Chir. 2009;64:253-264. 

16. Duell PB. Bariatric surgery for morbid obesity [letter]. JAMA. 2003;289:1779. 

17. Schwartz MW, Woods SC, Porte D, et al. Central nervous system control of food intake. 

Nature. 2000;404:661-667. 

18. Olbers T, Björkman S, Lindroos A, et al. Body composition, dietary intake, and energy 

expenditure after laparoscopic Roux-en-Y gastric bypass and laparoscopic vertical banded gastroplasty: 

a randomized clinical trial. Ann Surg. 2006;244:715-722. 

19. Santry HP, Lauderdale DS, Cagney KA, et al. Predictors of patient selection in bariatric 

surgery. Ann Surg. 2007;245:59-67. 

20. Puzziferri N, Austrheim-Smith IT, Wolfe BM, et al. Three-year follow-up of a prospective 

randomized trial comparing laparoscopic versus open gastric bypass. Ann Surg. 2006;243: 

181-188. 

21. Johansson H-E, Öhrvall M, Haenni A, et al. Gastric bypass alters the dynamics and metabolic 

effects of insulin and proinsulin secretion. Diabet Med. 2007;24:1213-1220. 

22. Matarasso A, Roslin MS, Kurian M. Bariatric surgery: an overview of obesity surgery. 

Plast Reconstr Surg. 2007;119:1357-1362. 

23. Gong K, Gagner M, Pomp A, et al. Micronutrient deficiencies after laparoscopic gastric 

bypass: recommendations. Obes Surg. 2008;18:1062-1066. 

24. Slater GH, Ren CJ, Siegel N, et al. Serum fat-soluble vitamin deficiency and abnormal 

calcium metabolism after malabsorptive bariatric surgery. J Gastrointest Surg. 2004;8:48-55. 

25. Favretti F, Ashton D, Busetto L, et al. The gastric band: first-choice procedure for obesity 

surgery. World J Surg. 2009;33:2039-2048. 

26. Zinzindohoue F, Chevallier JM, Douard R, et al. Laparoscopic gastric banding: a minimally 

invasive surgical treatment for morbid obesity: prospective study of 500 consecutive 

patients. Ann Surg. 2003;237:1-9. 

27. Gentileschi P, Lirosi F, Benavoli D, et al. Laparoscopic reoperative approach after open 

bariatric surgery. Chir Ital. 2009;61:137-141. 

28. Kral JG. ABC of obesity. Management: part III—surgery. BMJ. 2006;333:900-903. 

29. NHLBI Obesity Education Initiative. Clinical Guidelines on the Identification, Evaluation, 

and Treatment of Overweight and Obesity in Adults: The Evidence Report. Bethesda, MD: 

National Heart, Lung, and Blood Institute; 1998. NIH Publication No. 98-4083. 

30. Santry HP, Lauderdale DS, Cagney KA, et al. Predictors of patient selection in bariatric 

surgery. Ann Surg. 2007;245:59-67. 

31. Inge TH. Bariatric surgery for morbidly obese adolescents: is there a rationale for early 

intervention? Growth Horm IGF Res. 2006;(suppl A):S15-S19. 

32. Inge TH, Krebs NF, Garcia VF, et al. Bariatric surgery for severely overweight adolescents: 

concerns and recommendations. Pediatrics. 2004;114:217-223. 

33. Sugerman HJ, DeMaria EJ, Kellum JM, et al. Effects of bariatric surgery in older 

patients. Ann Surg. 2004;240:243-247. 

34. Pandolfino JE, Krishnamoorthy B, Lee TJ. Gastrointestinal complications of obesity surgery. 

MedGenMed. 2004;6:15. 

35. Mitka M. Surgery useful for morbid obesity, but safety and efficacy questions linger. 

JAMA. 2006;296:1575-1577. 

36. Encinosa WE, Bernard DM, Chen CC, Steiner CA. Healthcare utilization and outcomes 

after bariatric surgery. Med Care. 2006;44:706-712. 

37. Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. 

N Engl J Med. 2007;357:753-761. 

38. Morino M, Toppino M, Forestieri P, et al. Mortality after bariatric surgery: analysis of 

13,871 morbidly obese patients from a national registry. Ann Surg. 2007;246:1002-1009. 

39. Omalu BI, Buhari AM, Schauer PR, Kuller LH. Death rates and causes of death after 

bariatric surgery for Pennsylvania residents, 1995 to 2004. Arch Surg. 2007;142:923-928. 

40. Zingmond DS, McGory ML, Ko CY. Hospitalization before and after gastric bypass surgery. 

JAMA. 2005;294;1918-1924. 

41. Virji A, Murr MM. Caring for patients after bariatric surgery. Am Fam Physician. 

2006;73:1403-1408. 

42. Tice JA, Karliner L, Walsh J, et al. Gastric banding or bypass? A systematic review comparing 

the two most popular bariatric procedures. Am J Med. 2008;1221:885-893. 

43. Miller AD, Smith KM. Medication and nutrient administration considerations after bariatric 

surgery. Am J Health Syst Pharm. 2006;63:1852-1857. 

44. Sapala JA, Wood MH, Sapala MA, Flake TM. Marginal ulcer after gastric bypass: a prospective 

3-year study of 173 patients. Obes Surg. 1998;8:505-516. 

45. Rhode BM, Shustik C, Christou NV, MacLean LD. Iron absorption and therapy after 

gastric bypass. Obes Surg. 1999;9:17-21. 

46. Dalla Vecchia CF, Susin C, Rösing CK, et al. Overweight and obesity as risk indicators 

for periodontitis in adults. J Periodontol. 2005;76:1721-1728. 

47. Balduf LM, Kohn GP, Galanko JA, Farrell TM. The impact of socioeconomic factors on 

patient preparation for bariatric surgery. Obes Surg. 2009;19:1089-1095. 

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Early intervention to 

control bleeding is 

important in order to 

minimize mortality, 

particularly in 

elderly patients. 

Gastrointestinal (GI) bleeding 

can originate anywhere 

from the pharynx to the 

rectum and can be occult or overt. It 

differs from internal bleeding, where 

blood leaks from the blood vessels in 

such a way that the bleeding cannot 

be seen outside of the body. GI 

bleeding has a variety of causes, and 

a review of patient medical history 

and a physical examination can distinguish 

between the macroscopic 

and microscopic forms. The manifestations 

depend on the location 

and rate of bleeding, from nearly 

undetectable to acute and life-threatening. 

Upper endoscopy or colonoscopy 

are generally considered the 

best methods to identify the source 

of bleeding. 1 

History of present illness should 

be reviewed to ascertain quantity 

and frequency of blood passage. 

However, quantity can be difficult to 

assess because even small amounts 

(5-10 mL) of rectal bleeding or 

modest amounts of vomited blood 

are alarming to a patient. Wh ether 

blood was passed with initial emesis 

Manouchehr Saljoughian, PharmD, PhD 

Department of Pharmacy Services 

Alta Bates Summit Medical Center 

Berkeley, California 

Gastrointestinal 

Bleeding 

AN ALARMING SIGN 

or only after several nonbloody vomiting 

episodes could indicate different 

causes. 1 

To evaluate the patient, there are 

a number of symptoms that need to 

be reviewed after GI bleeding. These 

include presence of abdominal discomfort, 

weight loss, easy bleeding 

or bruising, previous colonoscopy 

results, and symptoms of anemia 

(weakness, fatigue, dizziness). Past 

medical history should also inquire 

about previously diagnosed or undiagnosed 

GI bleeding, inflammatory 

bowel disease (IBD), bleeding diatheses, 

and liver disease. 

Several drugs increase the likelihood 

of bleeding, including nonsteroidal 

anti-inflammatory drugs 

(NSAIDs), warfarin, and heparin. 

Chronic liver disease due to excessive 

use of alcohol can also cause bleeding. 

GI bleeding may also precipitate 

hepatic encephalopathy (brain and 

nervous system damage caused by 

liver failure) or hepatorenal syndrome 

(kidney failure secondary to 

liver disease). 2 

Types of GI Bleeding 

Upper GI Bleeding: Hematemesis is 

vomiting of red-colored blood and 

indicates upper GI bleeding, usually 

from an arterial source or varix. It is 

considered a medical emergency, and 

the most vital distinction is whether 

there is blood loss sufficient to cause 

shock. The bleeding is similar to 

dark brown emesis, with granular 

material that resembles coffee 

grounds. This results from upper GI 

bleeding that has slowed or stopped, 

with conversion of red hemoglobin 

to brown hematin by gastric acid. 3 

There are many causes for 

hematemesis, including irritation or 

erosion of the lining of the esophagus 

or stomach; bleeding ulcer 

located in the stomach, duodenum, 

or esophagus; vomiting of ingested 

blood after hemorrhage in the oral 

cavity, nose, or throat; vascular malfunctions 

of the GI tract; and 

tumors of the stomach or esophagus. 

Minimal Blood Loss: In this case, 

the patient is administered a proton 

pump inhibitor such as omeprazole, 

given a blood transfusion, and kept 

nil per os (Latin, “nothing by 

mouth”) until endoscopy can be 

arranged for further investigation. 

Significant Blood Loss: In a hemodynamically 

significant case of 

hematemesis (e.g., hypovolemic 

shock), resuscitation is an immediate 

priority to prevent cardiac arrest. 

Fluids and/or blood are administered, 

preferably by central venous 

catheter, and the patient is prepared 

for emergency endoscopy. If the 

source of bleeding cannot be identified 

endoscopically, a surgical option 

is usually sought for laparotomy. 3 

Lower GI Bleeding: Hematochezia 

is the passage of gross blood 

from the rectum and usually indicates 

lower GI bleeding. It is distinguished 

from melena, which is stool 

with blood that has been altered by 

the gut flora and appears “tarry” 

black. It is also different from bright 

red blood per rectum, which is 

caused by hemorrhoidal or fissure 

problems and is a local rectal bleeding. 

Hematochezia might also result 

from vigorous upper GI bleeding 

with rapid transit of blood through 

the intestines. Most common causes 

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GASTROINTESTINAL BLEEDING 


in adults are diverticulosis and hemorrhoids, 

both relatively benign, 

although this bleeding might be a 

warning sign for colorectal cancer. 

Hematochezia in newborn infants 

may be due to swallowed maternal 

blood at the time of delivery. In the 

most serious cases, it can also be an 

initial symptom of necrotizing 

enterocolitis, a serious condition 

affecting premature infants. In 

young adults, IBD, particularly 

ulcerative colitis, is a serious cause of 

hematochezia that must be further 

investigated for rapid treatment. 1-3 

Melena: Melena is a black, tarry 

stool that is caused by GI bleeding. 

The black color is due to the oxidation 

of blood hemoglobin during 

the bleeding in the ileum and colon. 

Melena also refers to stools or vomit 

stained black by blood pigment or 

dark blood products and may indicate 

upper GI bleeding. Bleeding 

from a lower source that occurs 

slowly enough to allow for oxidation 

is also associated with melena. About 

100 to 200 mL of blood in the 

upper GI tract is required to cause 

melena, which can remain for several 

days after bleeding has stopped. 4 

Black stool that does not contain 

occult blood may result from ingestion 

of iron, bismuth, or various 

foods and should not be mistaken 

for melena. Peptic ulcer disease is the 

main cause of melena, but secondary 

causes include bleeding from the 

upper GI tract as in gastritis or 

esophageal varices or even from the 

ascending colon. Overdosing of certain 

drugs (e.g., warfarin, clopidogrel, 

or long-term use of NSAIDS) 

may also be a cause. Melena is not 

considered a medical emergency, but 

patients should be carefully monitored 

to find the cause and assessed 

for further treatment. 3 

Etiology 

GI bleeding of any cause is more 

likely and severe in patients with 

chronic liver disease from alcohol 

abuse or hepatitis. It also occurs 

more commonly in patients with 

hereditary coagulation disorders or 

in those taking certain drugs. Drugs 

associated with GI bleeding include 

heparin, warfarin, aspirin, certain 

NSAIDs, clopidogrel, and selective 

serotonin reuptake inhibitors, which 

cause platelet depletion and reduce 

the ability to form clots. About 20% 

to 30% of GI bleeding is due to 

duodenal ulcers and gastric or duodenal 

erosions. 4 

Varices and erosive esophagitis are 

responsible for 10% to 20% of 

upper GI bleeds. For the lower GI, 

the bleeding depends on the age 

group, but it is mainly due to anal 

fissures, diverticulitis, irritable bowel 

syndrome, colitis, Crohn’s disease, 

and colonic polyps or carcinoma. 5 

Evaluation and Diagnosis 

The first step in the diagnosis of GI 

bleeding is to stabilize the patient’s 

airways and administer IV fluids or 

transfuse blood. Bloody nasogastric 

aspirate indicates active upper GI 

bleeding, but about 10% of patients 

have no blood in the nasogastric 

aspirate. 4 Then the focus should be 

on vital signs and any indication for 

hypovolemia (e.g., tachycardia, 

tachypnea, oliguria, confusion) or 

anemia (e.g., fatigue, pale skin, 

headache, coldness in the hands and 

feet, diaphoresis). In cases of lesser 

bleedings, the tachycardia and orthostatic 

changes (i.e., pulse, blood pressure) 

are milder but need immediate 

attention, especially in the elderly. 6 

When the patient is stable, the 

signs and symptoms of external 

bleeding disorders, such as black and 

blue spots on the skin (petechiae, 

ecchymoses), are sought. Other signs 

to look for are ascites and erythema 

(chronic liver disease) and splenomegaly 

and dilated abdominal wall 

veins (portal hypertension). 

In all patients with GI bleeding, a 

digital rectal examination is necessary 

to search for stool color, masses, 

and fissures. Anoscopy is done to 

diagnose hemorrhoids. Chemical 

testing of a stool specimen for occult 

blood completes the examination if 

gross blood is not present. In about 

50% of patients, peptic ulcer can be 

the cause of GI bleeding. 4 Epigastric 

abdominal discomfort that is 

relieved by food or antacids suggests 

peptic ulcer disease. These patients 

may or may not have pain. 6 

Bloody diarrhea, fever, and 

abdominal pain suggest ischemic 

colitis, ulcerative colitis, Crohn’s disease, 

or an infectious colitis. Fresh 

blood only on stools suggests rectal 

hemorrhoids or fissures, whereas 

blood mixed with the stool indicates 

bleeding from a distal or farthest 

area of the colon. Occult blood in 

the stool may be the first sign of a 

polyp, particularly in middle-aged 

patients. A CBC should be obtained 

in patients with occult blood loss. 6 

With more significant bleeding, 

coagulation monitoring such as 

platelet count, prothrombin time 

(PT), and partial thromboplastin 

time (PTT), and liver function tests 

such as aspartate aminotransferase 

(AST), alanine aminotransferase 

(ALT), bilirubin, alkaline phosphatase 

(ALP), and albumin, are done 

in certain patients. In most cases , 

one or more diagnostic procedures 

are required. 

Although endoscopy is therapeutic 

as well as diagnostic, it should be 

done rapidly for significant upper 

GI bleeding. Angiography is useful 

in the diagnosis of upper GI bleeding 

and permits certain therapeutic 

maneuvers (e.g., embolization, vasoconstrictor 

infusion). 

Flexible sigmoidoscopy and anoscopy 

may be all that is required 

acutely for patients with symptoms 

typical of hemorrhoidal bleeding. All 

other patients with hematochezia 

should have a colonoscopy, which 

can be done electively after routine 

preparation unless there is significant 

ongoing bleeding. If colonoscopy 

cannot visualize the source and 

ongoing bleeding is sufficiently rapid 

(>0.5 to 1 mL/min), angiography 

may localize the source. 5,6 

Endoscopy is the preferred choice 

for occult bleeding, because diagno- 

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GASTROINTESTINAL BLEEDING 


sis of this type of bleeding may be 

difficult, due to heme-positive stools 

from bleeding anywhere in the GI 

tract. Double-contrast barium enema 

and sigmoidoscopy can also be used 

for the lower tract when colonoscopy 

is unavailable or the patient 

refuses the procedure. 4 

Treatment 

Both hematemesis and hematochezia 

should be considered an emergency. 

Admission to an intensive care unit, 

with consultation by a gastroenterologist 

and a surgeon, is recommended 

for all patients with severe GI bleeding. 

General treatment is directed at 

maintenance of the airway and restoration 

of circulating volume. Hemostasis 

and other treatments depend 

on the cause of the bleeding. 7,8 

Airway: A major cause of morbidity 

and mortality in patients with 

active upper GI bleeding is aspiration 

of blood with subsequent respiratory 

problems. To prevent these 

issues, endotracheal intubation 

should be considered in patients 

who have inadequate gag reflexes or 

are obtunded or unconscious—particularly 

if they will be undergoing 

upper endoscopy. 4 

Fluid Replacement: IV fluids are 

initiated for any patient with hypovolemia 

or hemorrhagic shock. 

Patients requiring further resuscitation 

should receive transfusion with 

packed red blood cells (RBCs). 

Transfusions continue until intravascular 

volume is restored and then are 

given as needed to replace ongoing 

blood loss. Platelet count should be 

monitored closely, since platelet 

transfusion may be required with 

severe bleeding. Patients who a re 

taking antiplatelet drugs (e.g., 

clopid ogrel) and aspirin may have 

platelet dysfunction, often resulting 

in increased bleeding. Platelet transfusion 

should be considered when 

patients taking these drugs have 

severe, ongoing bleeding. Fresh frozen 

plasma should be transfused 

after every 4 units of packed RBCs. 4 

Hemostasis: Early intervention to 

control bleeding is important in 

order to minimize mortality, particularly 

in elderly patients. Specific 

therapy depends on the bleeding 

site. Fo r peptic ulcer, ongoing bleeding 

or rebleeding is treated with 

endoscopic coagulation. Nonbleeding 

vessels that are visible within an 

ulcer crater are also treated. If endoscopy 

does not stop the bleeding and 

medical management does not control 

gastric acid secretion, then surgery 

is performed. 4 

Severe, ongoing hematochezia 

from diverticula or angiomas can 

sometimes be controlled colonoscopically 

by electrocautery, coagulation 

with a heater probe, or injection 

with dilute epinephrine. Polyps can 

be removed by snare or cautery. If 

these methods are ineffective or 

unfeasible, angiography with embolization 

or vasopressin infusion may 

be successful. 4 Angiography can also 

be used to localize the source of 

bleeding more accurately. Surgery 

may be used in patients with continued 

bleeding, but localization of the 

bleeding site is very important. 

Acute or chronic bleeding of internal 

hemorrhoids stops spontaneously in 

most cases. Patients with refractory 

bleeding are treated via anoscopy 

with rubber band ligation, injection, 

coagulation, or surger y. 8 

Typically, a healthy person can 

endure a loss of 10% to 15% of the 

total blood volume without serious 

medical difficulties, and blood donation 

typically takes 8% to 10% of 

the donor’s blood volume. 4 

GI Bleeding in the Elderly 

I n the elderly (age ≥65 years), hemorrhoids 

and colorectal cancer are 

the most common causes of minor 

bleeding. Peptic ulcer, diverticular 

disease, and angiodysplasia are the 

most common causes of major 

bleeding. Approximately 35% to 

45% of all cases of acute upper GI 

hemorrhage occur in elderly persons. 

These patients increasingly account 

for the 10% of deaths that result 

from a bleeding episode each year. 4 

El derly patients tolerate massive 

GI bleeding poorly. Diagnosis must 

be made quickly, and treatment 

must be started sooner than in 

younger patients, who can better tolerate 

repeated episodes of bleeding. 9 

Endoscopic Safety 

Although upper endoscopy and 

colonoscopy are generally considered 

to be safe in the elderly, the risk of 

complications (including hemorrhage, 

aspiration pneumonia, myocardial 

infarction, and perforation) is 

greater than that with younger 

patients. Approximately 30% to 

40% of patients who undergo GI 

endoscopy are older than 70 years. 4 

On an emergency basis, therapeutic 

endoscopy is generally riskier than 

diagnostic endoscopy. Therefore, 

elderly patients—especially those 

with such comorbidities as obesity 

and cardiovascular, pulmonary, renal, 

hepatic, metabolic, or neurologic disorders—require 

careful evaluation 

before, and intensive monitoring 

during, the procedure. Endoscopy 

can be done in patients taking aspirin 

or NSAIDs who do not have a 

preexisting bleeding disorder. 

REFERENCES 

1. Ghosh S, Watts D, Kinnear M. Management of 

gastrointestinal haemorrhage. Postgrad Med J. 

2002;78:4-14. 

2. Rockey DC, Auslander A, Greenberg PD. Detection 

of upper gastrointestinal blood with fecal occult 

blood tests. Am J Gastroenterol. 1999;94:344-350. 

3. Marignani M, Angeletti S, Filippi L, et al. Occult and 

obscure bleeding, iron deficiency anemia, and other gastrointestinal 

stories. Int J Mol Med. 2005;15:129-135. 

4. Gastrointestinal bleeding. MedlinePlus. www.nlm. 

nih.gov/medlineplus/gastrointestinalbleeding.html. 

Accessed November 4, 2009. 

5. Raju GS, Nath SK. Capsule endoscopy. Curr 

Gastroenterol Rep. 2005;7:358-364. 

6. Triester SL, Leighton JA, Leontiadis GI, et al. A 

meta-analysis of the yield of capsule endoscopy compared 

to other diagnostic modalities in patients with 

obscure gastrointestinal bleeding. Am J Gastroenterol. 

2005;100:2407-2418. 

7. Carey EJ, Fleischer DE. Investigation of the small 

bowel in gastrointestinal bleeding—enteroscopy and 

capsule endoscopy. Gastroenterol Clin North Am. 

2005;34:719-734. 

8. Gastrointestinal bleeding. Mayo Clinic. 

www.mayoclinic.org/gastrointestinal-bleeding. 


9. Allison JE, Tekawa IS, Ransom LJ, Adrain AL. A 

comparison of fecal occult-blood tests for colorectalcancer 

screening. N Engl J Med. 1996;334:155-159. 

HS-16 


TOUGH AS EVER, BUT 

A BIT MORE REFINED 

Now, patients who use colchicine for gout flares can get 

the efficacy they need from gentle COLCRYS. 


COLCRYS (colchicine, USP) tablets are 

indicated for prophylaxis and the treatment 

of gout fl ares. 

COLCRYS is contraindicated in patients 

with renal or hepatic impairment who are 

concurrently prescribed P-gp inhibitors 

or strong inhibitors of CYP3A4 as lifethreatening 

or fatal toxicity has been 

reported. Dose adjustments of COLCRYS 

may be required when co-administered 

with P-gp or CYP3A4 inhibitors. The most 

common adverse events in clinical trials 

for the prophylaxis and treatment of gout 

were diarrhea and pharyngolaryngeal 

pain. Rarely, myelosuppression, thrombocytopenia, 

and leukopenia have been 

reported in patients taking colchicine. 

Rhabdomyolysis has been occasionally 

observed, especially when colchicine is 

prescribed in combination with other drugs 

known to cause this effect. Monitoring is 

recommended for patients with a history 

of blood dyscrasias or rhabdomyolysis. 

You are encouraged to report negative 

side effects of prescription drugs to the 

FDA. Visit www.fda.gov/medwatch or call 

1.800.FDA.1088. 

You may also report negative side effects 

to the manufacturer of COLCRYS by calling 

1.888.351.3786. 

Please see brief summary on adjacent 

page. 

Distributed by AR Scientific, Inc. 

A URL Pharma company. Philadelphia, PA 

www.urlpharma.com 

©2009 URL Pharma, Inc. All rights reserved. 

COL-097 Nov 2009 Printed in USA. 

www.COLCRYS.com | 1.888.351.3786

COLCRYS (colchicine, USP) tablets for oral use 

Brief Summary of full Prescribing Information 

The following is a brief summary only. Please see full Prescribing 

Information for complete product information. 


COLCRYS TM (colchicine, USP) tablets are indicated for prophylaxis and 

the treatment of gout flares. 

Prophylaxis of Gout Flares: COLCRYS is indicated for prophylaxis of 

gout flares. 

Treatment of Gout Flares: COLCRYS is indicated for treatment of acute 

gout flares when taken at the first sign of a flare. 

Familial Mediterranean fever (FMF): COLCRYS is indicated in adults 

and children 4 years or older for treatment of familial Mediterranean 

fever (FMF). 


Patients with renal or hepatic impairment should not be given COLCRYS in 

conjunction with P-gp or strong CYP3A4 inhibitors. In these patients, 

life-threatening and fatal colchicine toxicity has been reported with colchicine 

taken in therapeutic doses. 


Fatal Overdose: Fatal overdoses, both accidental and intentional, have 

been reported in adults and children who have ingested colchicine. 

COLCRYS should be kept out of the reach of children. 

Blood Dyscrasias: Myelosuppression, leukopenia, granulocytopenia, 

thrombocytopenia, pancytopenia, and aplastic anemia have been reported 

with colchicine used in therapeutic doses. 

Drug Interactions: Colchicine is a P-gp and CYP3A4 substrate. Lifethreatening 

and fatal drug interactions have been reported in patients 

treated with colchicine given with P-gp and strong CYP3A4 inhibitors. 

If treatment with a P-gp or strong CYP3A4 inhibitor is required in 

patients with normal renal and hepatic function, the patient’s dose of 

colchicine may need to be reduced or interrupted [see DRUG 

INTERACTIONS]. Use of COLCRYS in conjunction with P-gp or strong 

CYP3A4 inhibitors is contraindicated in patients with renal or hepatic 

impairment [see CONTRAINDICATIONS]. 

Monitor for toxicity and if present consider temporary interruption or 

discontinuation of COLCRYS. 

Neuromuscular Toxicity: Colchicine-induced neuromuscular toxicity 

and rhabdomyolysis have been reported with chronic treatment in 

therapeutic doses. Patients with renal dysfunction and elderly patients, 

even those with normal renal and hepatic function, are at increased risk. 

Concomitant use of atorvastatin, simvastatin, pravastatin, fluvastatin, 

gemfibrozil, fenofibrate, fenofibric acid, or benzafibrate (themselves 

associated with myotoxicity) or cyclosporine with COLCRYS may potentiate 

the development of myopathy [see DRUG INTERACTIONS]. Once 

colchicine is stopped, the symptoms generally resolve within 1 week to 

several months. 


Prophylaxis of Gout Flares: The most commonly reported adverse reaction 

in clinical trials of colchicine for the prophylaxis of gout was diarrhea. 

Treatment of Gout Flares: The most common adverse reactions reported 

in the clinical trial with COLCRYS for treatment of gout flares were diarrhea 

(23%) and pharyngolaryngeal pain (3%). 

FMF: Gastrointestinal tract adverse effects are the most frequent side 

effects in patients initiating COLCRYS, usually presenting within 24 hours, 

and occurring in up to 20% of patients given therapeutic doses. Typical 

symptoms include cramping, nausea, diarrhea, abdominal pain, and 

vomiting. These events should be viewed as dose-limiting if severe as they 

can herald the onset of more significant toxicity. 


COLCRYS is a substrate of the efflux transporter P-glycoprotein (P-gp). Of 

the cytochrome P450 enzymes tested, CYP3A4 was mainly involved in the 

metabolism of colchicine. If COLCRYS is administered with drugs that 

inhibit P-gp, most of which also inhibit CYP3A4, increased concentrations 

of colchicine are likely. Fatal drug interactions have been reported. 

Physicians should ensure that patients are suitable candidates for 

treatment with COLCRYS and remain alert for signs and symptoms of 

toxicities related to increased colchicine exposure as a result of a drug 

interaction. Signs and symptoms of COLCRYS toxicity should be evaluated 

promptly and, if toxicity is suspected, COLCRYS should be discontinued 

immediately. See full Prescribing Information for a complete list of reported 

potential interactions. 


• In the presence of mild to moderate renal or hepatic impairment, adjustment 

of dosing is not required for treatment of gout flare, prophylaxis of gout 

flare, and FMF but patients should be monitored closely. 

• In patients with severe renal impairment for prophylaxis of gout flares the 

starting dose should be 0.3 mg/day, for gout flares no dose adjustment is 

required but a treatment course should be repeated no more than once 

every 2 weeks. In FMF patients, start with 0.3 mg/day and any increase in 

dose should be done with close monitoring. 

• In patients with severe hepatic impairment, a dose reduction may be 

needed in prophylaxis of gout flares and FMF patients; while a dose 

reduction may not be needed in gout flares, a treatment course should be 

repeated no more than once every 2 weeks. 

• For patients undergoing dialysis, the total recommended dose for 

prophylaxis of gout flares should be 0.3 mg given twice a week with close 

monitoring. For treatment of gout flares, the total recommended dose 

should be reduced to 0.6 mg (1 tablet) x 1 dose and the treatment course 

should not be repeated more than once every two weeks. For FMF 

patients the starting dose should be 0.3 mg per day and dosing can be 

increased with close monitoring. 

• Pregnancy: Use only if the potential benefit justifies the potential risk to 

the fetus. 

• Nursing Mothers: Caution should be exercised when administered to a 

nursing woman. 

• Geriatric Use: The recommended dose of colchicine should be based on 

renal function. 

Manufactured for: 

AR SCIENTIFIC, INC. Philadelphia, PA 19124 USA 

by: 

MUTUAL PHARMACEUTICAL COMPANY, INC. 

Philadelphia, PA 19124 USA 

Rev 02, September 2009 

Distributed by AR Scientifi c, Inc. 

A URL Pharma company. 

Philadelphia, PA 

www.urlpharma.com 

COL-088 Nov 09


Screening 

LIFESAVING GUIDELINES 

Routine examinations, 

beginning at age 50, 

are key to preventing 

this disease. 

Colorectal (colon) cancer is 

extremely common. Of all 

the cancers that affect both 

men and women, colorectal cancer is 

the second-leading cancer killer in 

the United States. 1 The disease manifests 

in the colon or rectum, with 

70% of colorectal cancer occurring 

specifically in the sigmoid colon and 

rectum. 2,3 While colorectal cancer 

affects men and women of all racial 

and ethnic groups, cancer of the 

colon is more common in women, 

whereas cancer of the rectum is more 

common in men. 2,3 The disease is 

most often found in adults aged 50 

years or older, with incidence beginning 

to rise at age 40 and peaking at 

age 60 to 75. 3 According to United 

States Cancer Statistics, in 2005 there 

were 141,405 people diagnosed with 

colorectal cancer in the U.S., and 

53,005 deaths were attributed to it. 1,4 

Remarkably, up to 60% of deaths 

from this condition could be prevented. 

2 Routine screening, beginning 

at age 50, is the key to preventing 

colorectal cancer. 5 Screening saves 

lives (TABLE 1). 3 

Mary Ann E. Zagaria, PharmD, MS, CGP 

Senior Care Consultant Pharmacist and 

President of MZ Associates, Inc. 

Norwich, New York 

www.mzassociatesinc.com 

Recipient of the Excellence in Geriatric Pharmacy 

Practice Award from the Commission for 

Certification in Geriatric Pharmacy 

Clinical Features and Metastasis 

Symptoms of colorectal cancer 

develop insidiously and often are 

present for months, even years, 

before diagnosis. 6 Symptoms include 

blood in the stool or a change in 

bowel habits. 3 Colorectal tumors 

spread into adjacent structures (i.e., 

by direct extension) and metastasize 

through the lymphatics and blood 

vessels. 6 Sites of metastatic spread 

are, preferentially, the regional lymph 

nodes and the liver, lungs, and 

bones; many other sites may follow. 6 

Carcinomas of the anal region are 

locally invasive and involve metastasis 

to regional lymph nodes and distant 

sites. 6 

Staging, Prognosis, 

and Treatment 

The extent of the tumor at time of 

diagnosis is the most important 

prognostic indicator of colorectal 

cancer. 6 Staging designates the 

extent of the disease regarding tumor 

penetration, regional lymph node 

metastasis, and distant metastasis. 7 

Treatment for colorectal cancer is by 

surgical resection and chemotherapy 

(for lymph node involvement). 3 Typical 

chemotherapeutic agents utilized are 

5-fluorouracil and leucovorin; survival 

is improved by 10% to 30% when 

used in patients with colorectal cancer 

with positive lymph nodes. 3 Combined 

radiation and chemotherapy may be 

beneficial in patients with rectal cancer 

with one to four positive lymph 

nodes. 3 For improving the rate of 

resectability in rectal cancer or reducing 

lymph node metastasis, preoperative 

radiation and chemotherapy may be 

employed. 3 


Screening Saves Lives 

The premise for the utility of cancer 

screening, in general, is that early 

diagnosis may reduce cancer mortality, 

result in less radical therapy, and 

decrease costs. 3 Colorectal cancer 

screening, in particular, is capable of 

detecting precancerous polyps in the 

colon or rectum for removal and can 

detect early-stage cancer so that 

treatment may be initiated when it is 

more effective, often leading to a 

cure. 4,8 It is predicted that if all 

individuals aged 50 or older had 

regular colorectal screening tests 

resulting in the removal of all precancerous 

polyps, up to 90% of 

deaths from colorectal cancer could 

be prevented. 4 

Screening for colorectal cancer 

begins soon after an individual turns 

50 years of age, then continues at 

regular intervals (TABLE 1). 8,9 People 

at higher risk for colorectal cancer 

should be tested at a younger age 

and/or more frequently, including 

individuals who 1) have a personal 

or close family history of colorectal 

polyps or colorectal cancer; 2) have 

inflammatory bowel disease; 3) have 

genetic syndromes such as familial 

adenomatous polyposis (FAP) or 

hereditary nonpolyposis colorectal 

cancer. 8,10 Patients should be encouraged 

to speak to their health care 

provider to ascertain when they 

should begin screening and how 

often they should be tested. 8 

Screening Tests and Guidelines 

There are several screening tests 

that can be used to detect polyps 

or colorectal cancer; while each can 

29 


COLORECTAL CANCER 

Table 1 

Routine Colorectal Cancer–Screening 

Schedule in Average-Risk Adults 

Recommendation ACS/USMSTF/ACR USPSTF 

Age to commence Commence at age 50 and Commence screening at 

and cease cease screening at point age 50. Routine screening 

screening in in time where curative between ages 76-85 and 

average-risk therapy would not be screening after age 85 is 

adults offered secondary to not recommended 

life-limiting comorbidity 

Stool testing Annual screening with Annual screening with 

(gFOBT) high-sensitivity guaiac- high-sensitivity guaiacbased 

tests 

based tests 

Flexible Screening every 5 years. Screening every 5 years, 

sigmoidoscopy Screening every 5 years, with gFOBT every 3 years 

with annual gFOBT or 

FIT optional 

Colonoscopy Screening every 10 years Screening every 10 years 

ACS/USMSTF/ACR: American Cancer Society, the U.S. Multi-Society Task Force on 

Colorectal Cancer, and the American College of Radiology; FIT: fecal immunochemical test; 

gFOBT: guaiac-based fecal occult blood test; USPSTF: U.S. Preventive Services Task Force. 

Source: References 13-15. 

be used alone, they are sometimes 

employed in combination. 11 The 

U.S. Preventive Services Task Force 

(USPSTF) recommends colorectal 

cancer screening in average-risk 

men and women aged 50 to 75 

years using high-sensitivity fecal 

occult blood testing, sigmoidoscopy, 

or colonoscopy (TABLE 1). 11 

A high-sensitivity fecal occult 

blood test (FOBT) checks for 

occult blood in three consecutive 

stool samples. 10,12 There are two 

types of FOBT: 1) guaiac based 

and 2) fecal immunochemical 

using antibodies. A test kit for 

home use can be provided by a 

health care practitioner. The 

patient employs a stick or brush to 

obtain a small amount of stool to 

be checked for an abnormality by 

the doctor or a laboratory. 11 Routine 

schedule: annually. 10,12 

A flexible sigmoidoscopy is a 

procedure in which a physician 

uses a short, thin, flexible, lighted 

tube (sigmoidoscope) to visually 

inspect the interior walls of the 

rectum and only a portion of the 

colon; Routine schedule: every 5 

years. 10,12 

A colonoscopy involves a flexible, 

lighted tube (colonoscope) 

with which the physician visually 

inspects the interior walls of the 

rectum and the entire colon; samples 

of tissue may be collected 

during the test for closer examination, 

and polyps may be removed 

as well. The colonoscopy is also 

used as a follow-up test if any previous 

result from one of the other 

screening tests is unusual. 10-12 Routine 

schedule: every 10 years. 10,12 

Other screening tests not recommended 

by the USPSTF may be 

used in some settings, may be recommended 

by other groups, or are 

being studied. 11 Health insurance 

plans usually do not cover these 

tests; additionally, if any unusual 

findings are noted, a follow-up 

colonoscopy is required. 11 Examples 

include a double-contrast barium 

enema, consisting of a liquid barium 

enema followed by an air enema, 

which allows for a visual outline of 

the colon on an x-ray; a virtual colonoscopy, 

creating images of the entire 

colon on a computer screen through 

the use of x-rays and computer technology 

(while no sedation is necessary, 

bowel preparation is still 

required; lesions cannot be biopsied 

during this diagnostic procedure as 

in the optical colonoscopy); and a 

stool DNA test, requiring the collection 

of an entire bowel movement to 

be sent to a laboratory to test for 

cancer cells. 7,11 

A consensus guideline for 

colorectal cancer screening was 

released in March 2008 by the 

American Cancer Society, the U.S. 

Multi-Society Task Force on 

Colorectal Cancer, and the American 

College of Radiology (ACS/ 

USMSTF/ACR), while the USPSTF 

updated its screening recommendations 

in October 2008. 13-15 A concise 

and summarized version of the 

most current recommendations is 

available in TABLE 1; for complete 

and detailed coverage of the recommendations, 

refer to Reference 13 

online. Ongoing studies drive the 

constantly evolving recommended 

screening schedules. 3 The involved 

organizations promote a message 

for adults: Choose a test and get 

screened if you are 50 or older. 13 

The CDC indicates that the 

decision to be screened after age 

75 should be made on an individual 

basis; patients older than 75 

Resources 


Screening Basic Fact Sheet 

www.cdc.gov/cancer/Colorectal 


Activities Across the Nation 

States, tribes, and territories that have 

screening programs or laws related to 

colorectal cancer. 

www.cdc.gov/cancer/Colorectal 

(800) 4-CANCER 

or (800) ACS-2345 

Learn about screening options in 

your community. 

Colorectal Cancer Fact Sheet 

Learn how to reduce colon cancer risk 

by following screening guidelines, 

increasing activity levels, and eating a 

low-fat, healthy diet. 

www.cancer.org/docroot/PRO/content/ 

PRO_1_1_2002_Fact_Sheets.asp? 

30 


COLORECTAL CANCER 

are instructed to consult their 

physician as to whether they 

should be screened. 11 The USP- 

STF suggests that routine screening 

between ages 76 and 85 years 

is not recommended; screening 

after age 85 is also not recommended. 

13 According to the ACS/ 

USMSTF/ACR consensus guideline 

for colorectal cancer screening, 

screening should end at a 

point where curative therapy 

would not be offered due to lifelimiting 

comorbidity. 13 

Demonstration Project 

Partnerships have been built by 

the CDC to encourage screening, 

REFERENCES 

1. Centers for Disease Control and Prevention. Colorectal 

(colon) cancer. www.cdc.gov/cancer/Colorectal. Accessed 

November 16, 2009. 

2. Centers for Disease Control and Prevention. 

Basic information about colorectal (colon) cancer. 

www.cdc.gov/cancer/colorectal/basic_info/index.htm. 


3. Beers MH, Porter RS, Jones TV, et al. The Merck 

Manual of Diagnosis and Therapy. 18th ed. Whitehouse 

Station, NJ: Merck Research Laboratories; 2006:89- 

94,173-178,1147-1150. 


Cancer Control Program. www.cdc.gov/cancer/crccp. 


5. U.S. Preventive Services Task Force. Screening for Colorectal 

Cancer: U.S. Preventive Services Task Force Recommendation 

Statement. Rockville, MD: Agency for Healthcare 

Research and Quality; October 2008. AHRQ publication 

08-05124-EF-3. 

support education and training, 

and conduct surveillance and 

research. 4 One particular program 

developed by the CDC is the 

Colorectal Cancer Control Program, 

which provides funding to 

26 states and tribes across the 

U.S. 4 It provides colorectal cancer–screening 

services to lowincome 

men and women aged 50 

to 64 years who do not have 

insurance or are underinsured for 

screening when no other insurance 

options are available. States and 

tribes in the CDC’s Colorectal 

Cancer Control Program can be 

found in the map provided in 

Reference 4 online. 

6. Cotran RS, Kumar V, Collins T. Robbins Pathologic Basis of 

Disease. 6th ed. Philadelphia, PA: WB Saunders Company; 

1999:834-835. 

7. The Merck Manuals Online Library. Colorectal cancer. 

Table 2. Staging colorectal cancer. Revised December 2007. 

www.merck.com/mmpe/sec02/ch021/ch021h.html. Accessed 



cancer screening. www.cdc.gov/cancer/colorectal/basic_info/ 

screening. Accessed November 16, 2009. 

9. Comparison of 2008 ACS/USMSTF/ACR guidelines 

with those of the USPSTF. www.cancer.org/docroot/PRO/ 

content/PRO_4_1x_ColonMD_Comparison_Guidelines. 

asp. Accessed November 16, 2009. 


cancer screening guidelines. www.cdc.gov/cancer/ 

colorectal/basic_info/screening/guidelines.htm. Accessed 



cancer screening tests. www.cdc.gov/cancer/colorectal/basic_ 

Conclusion 

Symptoms of colorectal cancer 

develop insidiously and often are 

present for months, and maybe 

years, before they are diagnosed. 

While screening for colorectal cancer 

saves lives, the disease remains 

extremely common. Pharmacists, 

in the name of health promotion, 

disease prevention, and patient 

advocacy, should encourage individuals 

who are aged 50 or older 

or who think they may be at 

higher-than-average risk for 

colorectal cancer to speak to their 

doctor about getting screened. 

Routine screening is the key to 

preventing colorectal cancer. 

info/screening/tests.htm. Accessed November 16, 2009. 

12. U.S. Preventive Services Task Force. Guide to Clinical 

Preventive Services: Recommendations of the U.S. Preventive 

Services Task Force. Rockville, MD: Agency for Healthcare 

Research and Quality; September 2008. AHRQ publication 

08-05122. 

13. Comparison of 2008 ACS/USMSTF/ACR guidelines 

with those of the USPSTF. www.cancer.org/docroot/PRO/ 

content/PRO_4_1x_ColonMD_Comparison_Guidelines. 

asp. Accessed November 16, 2009. 

14. Levin B, Lieberman D, McFarland B, et al. Screening 

and surveillance for the early detection of colorectal cancer 

and adenomatous polyps, 2008: a joint guideline from the 

American Cancer Society, the US Multi-Society Task Force 

on Colorectal Cancer, and the American College of Radiology. 

CA Cancer J Clin. 2008;58:130-160. 

15. U.S. Preventive Services Task Force. Screening for 

colorectal cancer: U.S. Preventive Services Task Force 

recommendation statement. Ann Intern Med. 

2008;149:627-637. 

Season’s Greetings 

Wishing you and your 

loved ones a joyous 

holiday season and a 

happy and healthy new year. 

From the staff of 

31 


Overview of 

Hepatitis B and C Management 

Hepatitis is an inflammation of the liver that is 

often caused by one of five hepatitis viruses: 

A, B, C, D, or E. Hepatitis A and E are commonly 

contracted by ingestion of contaminated food 

or water, while transmission of hepatitis B and C occurs 

by parenteral contact with infected body fluids. No 

specific drug therapy is available for the treatment of 

hepatitis A or E. Hepatitis B and C infections are 

worldwide concerns because they often lead to chronic 

liver disease and even death. Much effort has been 

dedicated to global eradication of these diseases through 

education and vaccination. Still, viral hepatitis is a major 

public health concern. While both hepatitis B and C 

are associated with significant morbidity and mortality, 

the therapeutic approach to treatment varies by virus 

type, and each will be discussed separately. 

Hepatitis B 

In the United States, only 4,519 new acute hepatitis B 

(HBV) cases were reported to the Centers for Disease 

Control in 2007. 1 This represents a significant decrease 

from the early 1980s, when the number of reported 

cases of HBV each year was generally greater than 

25,000. A national immunization strategy instituted in 

the early 1990s was largely responsible for the sharp 

decline in new HBV cases. The incidence of HBV in 

the U.S. is now 1.5 cases per 100,000 persons, which 

is an all-time low. 1 Still, HBV remains an important 

worldwide public health concern, with an estimated 1 

million deaths each year due to HBV sequelae. 

HBV is a DNA virus transmitted by percutaneous 

or mucosal contact with infectious blood or body fluids. 

Accordingly, intravenous drug users and those who 

practice unprotected sex are at increased risk of HBV 

infection. Infants born to infected mothers are also at 

greater risk of becoming infected with HBV. Morbidity 

and mortality associated with chronic HBV infection 

are connected to the development of 

cirrhosis or hepatocellular carcinoma 

(HCC). Worldwide, approximately 

75% of HCC cases are due to chronic 

HBV infection. 2 

Justin Hooper, PharmD, BCPS 

Pharmacy Clinical Manager, CompleteRx 

Trinity Mother Frances Hospital 

Tyler, Texas 

Amy Martin, PharmD, BCPS 

Clinical Staff Pharmacist, CompleteRx 

Trinity Mother Frances Hospital 

Tyler, Texas 

Clinical Characteristics and Diagnosis: 

HBV infection is often characterized 

by acute hepatitis, with approximately 5% of 

these infections progressing to chronic disease. The 

presence of serum hepatitis B surface antigen (HBsAg) 

indicates infection with HBV, and antibodies against 

HBsAg indicate recovery. Hepatitis B e antigen (HBeAg) 

is elevated during periods of active viral replication, but 

may be absent in chronic hepatitis due to a DNA mutation 

of the virus responsible for hepatitis B. In fact, 

HBeAg-negative chronic HBV is generally linked to 

more serious liver disease and a limited sustained response 

to antiviral therapy. The presence of anti-HBc (core 

antibody) indicates HBV infection at some point in 

time as opposed to positivity for HBV surface antibody, 

which may indicate humoral immunity in response to 

HBV vaccination. 3 Signs and symptoms of infection 

depend on the age of the patient, and many patients 

may be asymptomatic initially. Symptoms may be 

nonspecific and do not aid in differentiating HBV from 

other forms of acute hepatitis. Patients may complain 

of fever, fatigue, and abdominal pain. Other findings 

may include anorexia, nausea, vomiting, dark urine, 

clay-colored stools, joint pain, and jaundice. 

Management: The goals of treating chronic HBV are 

to achieve sustained suppression of viral replication and 

prevent progression of liver disease. 4 Response to treatment 

can be measured using biochemical (normalization 

of alanine aminotransferase [ALT]), virologic (clearance 

of HBV DNA), serologic (loss of HBeAg, HBeAg 

seroconversion), or histologic markers. All available 

treatment options have advantages and disadvantages, 

and drug therapy selection should take into account 

cost, efficacy, safety, risk of drug resistance, and method 

of administration. 

Antiviral Treatment: For the minority of patients who 

develop chronic HBV infection, there are currently 

eight drugs approved by the FDA 

for the treatment of chronic hepatitis 

B: conventional interferon (IFN) 

alpha-2b, lamivudine, adefovir dipivoxil, 

pegylated interferon (pegIFN) 

alpha-2a, entecavir, telbivudine, and 

tenofovir disoproxil fumarate. The 

prototype antiviral used for the treat- 

32 


© KEITH KASNOT 2009 

www.kazstudios.com 

OVERVIEW OF HEPATITIS B AND C MANAGEMENT 

Though prevalence is declining, infection with the hepatitis B or C virus is a major 

health concern because it often leads to chronic liver failure and even death. 

ment of HBV is IFN. IFN is effective at inducing a 

virologic, histologic, and biochemical response at a dose 

of 10 million international units (IU) three times weekly 

or 5 million IU daily. Adverse reactions classified as 

severe were reported in 21% to 44% of patients, the 

most common being fever, fatigue, bone marrow suppression, 

and alopecia. 5 As a result, pegIFN has largely 

replaced IFN alpha-2b due to its longer half-life and 

improved tolerability. IFN alpha-2b is administered as 

a once-weekly subcutaneous injection for a duration of 

48 weeks. 

While treatment with IFN yields a highly durable 

viral response, nucleoside/nucleotide analogues have 

become the primary treatment modality for chronic 

HBV due to their ease of use and tolerability. Lamivudine 

(LAM) is a convenient oral therapy for treatment 

of chronic HBV with modest efficacy and minimal side 

effects. Unfortunately, LAM has been associated with a 

high rate of resistance (up to 70% after 5 years) and 

virologic breakthrough, thus limiting its usefulness as a 

first-line agent for chronic HBV. 6 Conversely, LAM is 

well tolerated and may be used in select circumstances 

such as HIV coinfection. For patients in whom LAM 

resistance is suspected or who have received therapy for 

more than 2 years, alternative therapies such as entecavir 

(ETV) and tenofovir disoproxil fumarate (TDF) 

have proven effective. 7 

Adefovir dipivoxil (ADV) is another 

well-tolerated oral therapy for treatment 

of chronic HBV with slightly less viral 

resistance than LAM. Primary nonresponse 

to ADV occurs at a rate of 20% to 50%, 

presumably due to the low dosage used 

in chronic HBV treatment. 8 ADV may 

cause nephrotoxicity at higher doses, thus 

limiting its utility as a first-line agent. It 

should be avoided in combination with 

TDF due to the additive risk of nephrotoxicity. 

Monitoring of serum creatinine 

every 3 months is recommended for 

patients with medical conditions that 

may lead to renal dysfunction and for 

patients receiving treatment with ADV 

for more than 1 year. 6 

ETV is a nucleoside analogue with 

excellent potency that is associated with 

minimal viral resistance in untreated 

patients. ETV has been used successfully 

in patients with LAM-resistant disease, 

though efficacy is reduced when compared 

to treatment of nucleoside analogue-naïve 

patients for whom a higher dosing strategy 

is used. 9 Like other nucleoside/ 

nucleotide analogues, ETV must be dose 

adjusted in renal dysfunction. 

Telbivudine (LdT) is more potent than 

LAM at HBV suppression, but it has a 

high level of cross-resistance with LAM. Additionally, 

resistance to LdT develops rapidly, especially with treatment 

duration beyond 1 year. 6 Though this drug is 

generally well tolerated, myopathy and peripheral neuropathy 

have also been associated with its use. These 

safety and viral resistance concerns have caused LdT to 

have an uncertain role in contemporary management 

of HBV. 

The most recently approved therapy for treatment 

of chronic HBV is TDF. When compared to ADV, 

treatment with TDF yielded a significantly greater 

histologic response and normalization of ALT. 7 TDF is 

useful for treatment of LAM-resistant HBV. Renal 

dysfunction and decreases in bone mineral density have 

been reported infrequently. 7 

Hepatitis C 

Viral hepatitis C (HCV) affects approximately 4 million 

persons in the U.S. alone, with a worldwide disease 

burden estimated at 180 million. 10 Of those infected 

in the U.S., the vast majority have active disease. While 

some individuals may clear the disease, 75% develop 

chronic infection. Infection with HCV is often insidious, 

and affected individuals are often asymptomatic 

during much of the course of the disease. Significant 

morbidity is related to the development of cirrhosis, 

33 



which currently affects over 600,000 individuals. HCVrelated 

mortality is attributed to complications of 

end-stage liver disease as well as death from development 

of HCC. The rate of newly diagnosed HCV 

infection has fortunately declined to about 17,000 

cases annually, mainly due to improved screening for 

HCV in blood products, which began around 1992. 

Additionally, heightened awareness of the risks of 

needle-sharing among injection drug users has reduced 

the transmission of HCV; still, acquisition of new 

HCV continues to occur primarily in injection drug 

abusers. 11 Despite the decline in new cases, HCVassociated 

mortality continues to rise due to clinical 

progression of HCV. 

Clinical Characteristics and Diagnosis: Acute HCV 

infection usually goes undetected, as symptoms are 

nonspecific in nature and may include anorexia, abdominal 

discomfort, and nausea and vomiting, along with 

elevated hepatic transaminases and, less commonly, 

jaundice. 11,12 For this reason, diagnosis cannot be made 

based on risk factors and clinical presentation. Specific 

serologic testing for the presence of anti-HCV antibodies 

is indicated in any at-risk individual (TABLE 1) and 

establishes exposure to the disease. 13 Virologic testing 

for the presence of HCV-ribonucleic acid (HCV-RNA) 

along with viral genotyping is also indicated in all 

patients who test positive for HCV, particularly in those 

patients being considered for antiviral therapy. 13 

Management of Patients With HCV: Determining a 

patient’s specific HCV genotype is mandatory because 

it aids in predicting the likelihood of response to drug 

therapy and determines optimal treatment duration as 

well. 12,13 There are a total of six distinct, numbered 

HCV genotypes. Genotype 1 accounts for about 70% 

of the disease in the U.S., followed by genotypes 2 and 

3. Genotype 1 is generally more refractory to antiviral 

drug therapy, and comparative studies have demonstrated 

substantially lower treatment response rates when compared 

to rates among those infected with genotypes 2 

or 3. 11,13 Genotyping is therefore valuable in evaluating 

the risk-to-benefit ratio of antiviral therapy. Because 

anti-HCV medications put patients at risk for significant 

treatment toxicities, a thorough assessment of a patient’s 

overall medical and mental health is necessary to determine 

if contraindications to treatment are present. 

Contraindications to combination HCV treatment 

Table 1 

Antiviral Therapies for Treatment-Naïve Patients With HBeAg-Positive Chronic HBV 

Pegylated 

Interferon Alpha-2a Lamivudine a Adefovir a Entecavir a Telbivudine a Tenofovir a 

Brand name Pegasys Epivir Hepsera Baraclude Tyzeka Viread 

Manufacturer Roche GlaxoSmithKline Gilead Bristol-Myers Squibb Novartis Gilead 

Dosage 180 mcg/wk 100 mg/day 10 mg/day 0.5 mg/day 600 mg/day 300 mg/day 

Route of SC PO PO PO PO PO 

administration 

Adverse Flulike symptoms, Minimal Minimal, Minimal Minimal Minimal, 

effects bone marrow but suggest but suggest 

suppression, monitoring monitoring 

depression, creatinine creatinine 

anxiety, autoimmune 

disorders 

Duration of 48 >48 >48 >48 >52 >48 

therapy (wk) 

Viral resistance None 15%-30% None None 6% None 

(1 y) 

Histologic 38% at Wk 72 49%-62% 53%-68% 72% 65% 74% 

improvement 

ALT normalization 39% 41%-75% 48%-61% 68% 60% 77% 

at end of Y 1 

a 

Requires dosage adjustment for renal dysfunction. 

ALT: alanine aminotransferase; HBeAg: hepatitis B e antigen; HBV: viral hepatitis B. 

Source: Adapted from Reference 8. 

34 



Eligible patient 

HCV-antibody positive 

Genotype 1 

Obtain quantitative 

HCV-RNA and genotype 

Genotype 2,3 

Liver biopsy 

Liver biopsy 

(optional) 

No fibrosis = 

no treatment 

Fibrosis 

= treat 

Begin pegIFN plus ribavirin 

1,000 mg/day if 75 kg 

Check HCV-RNA at Week 12 

Treat with pegIFN 

plus ribarivin 800 mg/day 

× 24 weeks 

Check HCV-RNA level 

to establish end-oftreatment 

response 

Complete 

early response 

(no HCV- 

RNA)? 

Continue 

treatment for 

total of 48 

weeks 

Partial response 

(HCV-RNA ↓ >2 

log)? Continue 

treatment and 

repeat HCV-RNA 

at 24 weeks 

HCV-RNA 

negative? 

No early 

response 

(HCV-RNA 

↓ >2 log) 

Stop treatment 

HCV-RNA 

positive? 

HCV-RNA 

positive 

Treatment 

failed 

HCV-RNA 

negative 

Repeat 

HCV-RNA 

at Week 48 

to establish 

SVR 

Source: Adapted from Reference 13. 

Figure 1. HCV management strategy. HCV: viral hepatitis C; HCV-RNA: viral hepatitis C-ribonucleic acid; pegIFN: pegylated interferon; 

SVA: sustained virologic response. 

include decompensated liver disease; pregnancy; uncontrolled 

depression or neuropsychiatric illness; history 

of autoimmune hepatitis; severe uncontrolled comorbid 

illnesses such as seizure disorders, thyroid disorders, 

diabetes, and active coronary disease; age less than 2 

years; anemia; post solid-organ transplantation; or 

unwillingness to use adequate contraception. 13 

In general, patients who are considered candidates 

for combined anti-HCV therapy include adult patients 

with chronic HCV infection (≥6 months) who have 

evidence of chronic hepatitis based on liver biopsy 

with compensated liver disease and acceptable laboratory 

values on serum chemistry. In addition, due to 

high rates of neuropsychiatric side effects of combination 

ribavirin-INF (i.e., depression, and anxiety in up 

to one-thid of patients), it is advisable to screen for 

any occult psychiatric illness prior to therapy. Patients 

must also be willing and able to adhere to treatment. 

Antiviral Treatment: Subcutaneous pegIFN alpha 

combined with oral ribavirin is the mainstay of treatment 

of HCV virus infection with no clear evidence 

that one product is superior to the other (see FIGURE 

1). While monotherapy with IFN may be used in 

individualized cases where ribavirin is contraindicated, 

ribavirin should never be used as monotherapy. Goals 

of treatment include early virologic response (EVR; 

undetectable HCV-RNA after 12 weeks of treatment), 

end-of-treatment response (ETR), and a sustained 

virologic response (SVR), defined as undetectable HCV- 

RNA 24 weeks after cessation of antiviral therapy. 13 

Additional goals are to minimize treatment-related 

37 


Day 1 

Day 2 Day 3 Day 4 Day 5 

TAKE Z-PAK ® FOR 5 DAYS 1 OR... 

(azithromycin) 250 mg 

TAKE AZITHROMYCIN TO 

1 DAY. 1 DOSE.2 

Please see accompanying Zmax brief summary. 

Zmax is indicated for mild to moderate acute bacterial 

sinusitis in adults due to Haemophilus influenzae, Moraxella 

catarrhalis, or Streptococcus pneumoniae and is also indicated 

for community-acquired pneumonia due to Chlamydophila 

pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae,or 

or Streptococcus pneumoniae in adult and pediatric patients 

aged 6 months and over, deemed appropriate for oral therapy. 

Zmax and Zithromax are contraindicated in patients with 

known hypersensitivity to azithromycin, erythromycin, or any 

macrolide or ketolide antibiotic. If an allergic reaction occurs, 

appropriate therapy should be instituted. Physicians should be 

aware that reappearance of the allergic symptoms may occur 

when symptomatic therapy is discontinued. 

There have been rare reports of serious allergic reactions including 

angioedema, anaphylaxis, Stevens Johnson syndrome, and toxic 

epidermal necrolysis in patients on other formulations of 

azithromycin therapy. Rarely, fatalities have been reported. 

Clostridium difficile associated diarrhea (CDAD) has been 

reported with use of nearly all antibacterial agents, including 

azithromycin, and may range in severity from mild diarrhea 

to fatal colitis. CDAD must be considered in all patients who 

present with diarrhea following antibiotic use. Careful 

medical history is necessary since CDAD has been reported to 

occur over two months after the administration of 

antibacterial agents. If CDAD is suspected or confirmed, 

ongoing antibiotic use not directed against C. difficile may need 

to be discontinued, and appropriate management and treatment 

of C. difficile should be instituted as clinically indicated. 

As with all macrolides, including Zmax, exacerbations of 

myasthenia gravis have been reported.

Zmax: 1 product — indicated for both 

adult and pediatric patients 2 

Pediatric 

patients 

Adult 

patients 

A higher incidence of gastrointestinal adverse events (8 of 19 

subjects) was observed when Zmax was administered to a 

limited number of subjects with GFR

Zmax ® (azithromycin extended release) for oral suspension 

Brief Summary of Prescribing Information 


Zmax is indicated for the treatment with mild to moderate infections caused by susceptible isolates 

of the designated microorganisms in the specific conditions listed below. 

Acute bacterial sinusitis in adults due to Haemophilus influenzae, Moraxella catarrhalis or 

Streptococcus pneumoniae. 

Community-acquired pneumonia in adults and pediatric patients six months of age or older due to 

Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus 

pneumoniae, in patients appropriate for oral therapy. Pediatric use in this indication is based on 

extrapolation of adult efficacy. 

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Zmax and other 

antibacterial drugs, Zmax should be used only to treat infections that are proven or strongly suspected 

to be caused by susceptible bacteria. When culture and susceptibility information are available, they 

should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local 

epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. 

Appropriate culture and susceptibility tests should be performed before treatment to determine the causative 

organism and its susceptibility to Zmax.Therapy with Zmax may be initiated before results of these tests are 

known; once the results become available, antimicrobial therapy should be adjusted accordingly. 


Zmax is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin or any 

macrolide or ketolide antibiotic. 


Allergic and skin reactions 

Serious allergic reactions, including angioedema, anaphylaxis, Stevens Johnson syndrome, and toxic 

epidermal necrolysis have been reported rarely in patients on azithromycin therapy using other 

formulations. Although rare, fatalities have been reported. Despite initially successful symptomatic 

treatment of the allergic symptoms, when symptomatic therapy was discontinued, the allergic symptoms 

recurred soon thereafter in some patients without further azithromycin exposure.These patients 

required prolonged periods of observation and symptomatic treatment. The relationship of these 

episodes to the long tissue half-life of azithromycin and subsequent exposure to antigen has 

not been determined. 

If an allergic reaction occurs, appropriate therapy should be instituted. Physicians should be aware 

that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued. 

Clostridium difficile-associated diarrhea 

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial 

agents, including Zmax, and may range in severity from mild diarrhea to fatal colitis. Treatment with 

antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. 

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing 

strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to 

antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present 

with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been 

reported to occur over two months after the administration of antibacterial agents. 

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need 

to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic 

treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. 

Exacerbation of myasthenia gravis 

Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been 

reported in patients receiving azithromycin therapy. 

Gastrointestinal Disturbances 

A higher incidence of gastrointestinal adverse events (8 of 19 subjects) was observed when Zmax 

was administered to a limited number of subjects with GFR


toxicities, which may emerge on therapy while maintaining 

efficacy. 

Both pegIFN products approved for use in the U.S., 

pegINF alpha-2b and pegINF alpha-2a, have demonstrated 

superior efficacy to standard interferon plus 

ribavirin. 13 These products are similar in that both 

drugs have added various polyethylene glycol side 

chains to the parent molecule to increase the duration 

of pharmacologic activity. It is important to note that 

there are differences with respect to dosing, frequency, 

and how each product is combined with ribavirin. 

PegINF alpha-2b is given, in combination with ribavirin, 

as a weight-based dose of 1.5 mcg/kg, while a 

fixed dose of 180 mcg is used with pegINF alpha-2a. 

Both are given as weekly subcutaneous injections. 

Standard INF alphacon-1 is also approved for treatment 

in HCV in a fixed dosage given subcutaneously 

three times weekly alone or in combination with 

ribavirin. Adverse reactions to INF products are common 

and may lead to patient intolerance as well as 

reduced efficacy due to the need for dose reductions. 

Commonly experienced side effects attributable to 

INF include flulike symptoms, myelosuppression 

(anemia, neutropenia, and/or thrombocytopenia), 

psychiatric adverse effects, injection-site reactions, 

alopecia, anorexia, and sleep abnormalities. 14 Toxicities 

generally associated with ribavirin include hemolytic 

anemia, fatigue, dermatologic reactions, and precipitation 

of gout. Ribavirin is also an abortifacient and 

is carcinogenic and teratogenic. As a result, adequate 

contraception must be present with female patients as 

well as female partners of male patients who are of 

childbearing age and should be continued for 6 months 

following treatment cessation. 15 

Monitoring and Follow-up: Duration of therapy 

and disease monitoring are dependent on HCV 

genotype, with genotype 1 generally requiring a 

longer course of therapy. In genotype 1–infected 

patients started on pegIFN/ribavirin, quantitative 

HCV-RNA is measured at baseline and at 12 weeks 

after treatment (see FIGURE 1). Patients with an EVR 

should continue treatment for a total of 48 weeks 

and then be assessed for an ETR. HCV-RNA testing 

is repeated 24 weeks following treatment cessation 

to determine presence of an SVR. If partial EVR is 

attained at Week 12 (HCV-RNA reduction of ≥2 

log), treatment should be continued for an additional 

12 weeks. A negative HCV-RNA test at 24 weeks 

means treatment should be continued for a total of 

48 weeks. If no response is seen after 12 or 24 weeks, 

then treatment should be discontinued as the benefit 

is unlikely. In genotype 2 or 3 patients, HCV- 

RNA is not assessed until 24 weeks of therapy are 

complete. 13 If HCV-RNA is not detected, then assessment 

for SVR is performed at 48 weeks. If HCV is 

still detectable, treatment failure has occurred. Efficacy 

defined by attainment of SVR is roughly 75% 

for genotypes 2 and 3 and 50% for genotype 1. 13 

Ongoing monitoring for both INF and ribavirin 

toxicity is indicated during treatment. Baseline CBC, 

serum creatinine, transaminases, thryoid-stimulating 

hormone (TSH), and pregnancy testing should be assessed 

at baseline. TSH should be monitored every 12 weeks 

on therapy, while other chemistries may be assessed 

monthly for the first 12 weeks, then every 2 months 

until the end of treatment unless specific toxicity issues 

warrant more frequent visits. Specific dosage reductions 

or treatment cessation for ribavirin is necessary with the 

development of anemia and or severe renal failure. 15 

Dosage reductions of pegIFN may also be necessary 

with elevated liver enzymes or renal insufficiency. 

Patient Counseling 

Pharmacists play an important role in the care of patients 

infected with viral hepatitis. The pharmacist may provide 

medication counseling and follow-up to ensure 

adherence or identify problems (e.g., drug toxicities) 

that emerge during therapy. All patients should be 

counseled to abstain from alcohol and avoid OTC drugs 

or supplements that may be hepatotoxic (e.g., high 

doses of acetaminophen). Counseling should include 

strategies to minimize disease prevention, such as use 

of barrier contraceptive methods or avoidance of highrisk 

behaviors. Immunization against HBV also plays 

a key role in primary prevention of HBV infection, and 

hepatitis B vaccination may be provided directly by 

pharmacists in many states. 

REFERENCES 

1. Centers for Disease Control and Prevention. Hepatitis B: FAQs for health professionals. 

www.cdc.gov/hepatitis/HBV/HBVfaq.htm#overview. Accessed October 

2, 2009. 

2. Marcellin P. Hepatitis B and hepatitis C in 2009. Liver Int. 2009;29(supp1):1-8. 

3. Liaw YF. Natural history of chronic hepatitis B virus infection and long-term 

outcome under treatment. Liver Int. 2009;29(supp1):100-107. 

4. Corey RL. Update on pharmacotherapy of chronic Hepatitis B and C. In: 

Richardson M, Chant C, Cheng JW, et al, eds. Pharmacotherapy Self-Assessment 

Program. 6th ed. Gastroenterology and Nutrition. Lenexa, KS: American College 

of Clinical Pharmacy; 2009:1-20. 

5. Intron A [package insert]. Kenilworth, NJ: Schering-Plough; 2008. 

6. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 

2009;50(3):661-662. 

7. Jenh AM, Thio CL, Pham PA. Tenofovir for the treatment of hepatitis B virus. 

Pharmacother. 2009;29(10):1212-1227. 

8. Dienstag JL. Hepatitis B virus infection. N Engl J Med. 2008;359:1486-1500. 

9. Liaw YF, Leung N, Kao JH, et al. Asian-Pacific consensus statement on the management 

of chronic hepatitis B: a 2008 update. Hepatol Int. 2008;2(3):263-283. 

10. Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C 

virus infection in the United States, 1999 through 2002. Ann Intern Med. 

2006;144:705-714. 

11. Centers for Disease Control and Prevention. Hepatitis C: FAQs for health 

professionals. www.cdc.gov/hepatitis/HCV/HCVfaq.htm#section1. Accessed September 

7, 2009. 

12. Kowdley KV. Hepatitis C. In: Floch MH, Floch NR, Kowdley KV, et al, eds. 

Netter’s Gastroenterology. Carlstadt, NJ: Icon Learning Systems; 2005. 

13. Ghany MG, Strader DB, Thomas D, et al. AASLD practice guideline: diagnosis, 

management, and treatment of hepatitis C: an update. Hepatology. 

2009;49:1335-1373. 

14. Peg-intron [package insert]. Kenilworth, NJ: Schering-Plough; 2009. 

15. Copegus [package insert]. Nutley, NJ: Roche Laboratories; 2009. 

41 


Probiotic foods have recently become popular in the 

United States, although such products have been 

marketed for decades in Europe and Asia. 1 Probiotics 

are defined as living organisms that, when administered 

in sufficient numbers, are beneficial to the host. One 

probiotic food is Activia. It is a line of yogurt containing 

Lactobacillus, Streptococcus thermophilus, and Bifidobacterium 

animalis bacteria, and it is advertised to aid regularity. 

While new to the U.S., Activia has been sold in Europe 

since 1987. 1 Most probiotic products can be found in the 

dairy case of supermarkets or as dietary supplements. There 

are probiotic frozen yogurts and dairy-based drinks such 

as DanActive, a probiotic yogurt drink that contains 

Lactobacillus casei immunitas cultures. Its manufacturer 

(Dannon) indicates that the product is clinically proven 

to “help strengthen your body’s defenses.” 2 Products sold 

in the pharmacy include, among others, Culturelle (Lactobacillus 

GG), Florastor (Saccharomyces boulardii) and 

Lactinex (Lactobacillus acidophilus, Lactobacillus bulgaricus), 

which are indicated to reduce the chance of developing 

diarrhea due to antibiotics. 3 The FDA takes a neutral 

position on probiotics, policing food packages to ensure 

that companies do not try to equate probiotic products 

with disease-curing drugs. 

The growth of probiotics comes as many scientists are 

now focused on the role of beneficial bacteria to aid digestion, 

boost natural defenses, and fight off bacteria that 

could cause health problems. Intestinal bacteria can benefit 

health by breaking down toxins, synthesizing vitamins, 

and defending against infection. They may also play a role 

in preventing such diseases as peptic ulcers, colorectal 

cancer, and inflammatory bowel disease. 4 This article will 

describe the genesis and evolution of our indigenous microbial 

community, the size and makeup of its inhabitants, its 

effects, its benefits, and new research. 

Genesis and Evolution 

Most of us are aware that bacteria are a part of a healthy 

human ecosystem (i.e., an assembly of species and the 

organic and inorganic constituents characterizing a particular 

site). According to one author, the armies of bacteria 

that sneak into our bodies the moment we are born 

are the “primal illegal immigrants.” 5 Most are industrious 

and friendly, minding their own business in tight-knit, 

long-lived communities, doing the grunt biochemical work 

we all rely on to stay alive. 5 The ecosystem forms at birth, 

but the human-microbe alliance begins months before. 

Midway through pregnancy, a hormonal shift directs the 

cells lining the vagina to begin stockpiling sugary glycogen, 

the favorite food of sausage-shaped bacteria called lactobacilli. 

By fermenting the sugar into lactic acid, these 

bacteria lower the pH of the vagina to levels that discourage 

the growth of potentially dangerous invaders. 6 

Max Sherman, RPh 

President, Sherman Consulting Services, Inc. 

Warsaw, Indiana 

Probiotics 

and 

Microflora 

The infant mouth’s first inoculation 

of bacteria includes a generous sampling 

of the lactobacilli present in the mother’s 

birth canal. With the first gulp of breast milk, these 

lactobacilli are joined by millions of bifidobacteria, a related 

group of acid-producing microbes. 6 The source of these 

bacteria is the mother’s nipples, where the bacteria appear 

during the eighth month of pregnancy. Bifidobacteria secrete 

acids and antibiotic chemicals that repel potentially dangerous 

organisms, including Staphylococcus aureus. Bifidobacteria 

and lactobacilli are soon joined by acid-tolerant Streptococcus 

salivarius bacteria, which appear on a baby’s tongue 

during the first day of life. Bifidobacteria are anaerobic, 

pleomorphic rods that break down dietary carbohydrate 

and synthesize and excrete water-soluble vitamins. 7 Their 

name is derived from the observation that they often exist 

in a Y-shaped, or bifid, form. 8 These organisms predominate 

in the colons of breastfed babies, account for up to 95% 

of all culturable bacteria, and protect against infection. 9 

Strangely, they do not occur in such high numbers in 

adults. 8 Several other streptococci, along with one or more 

kinds of Neisseria bacteria, settle in during the first week. 

The vast majority emanate from the mother’s mouth, which 

is always within reach of a nursing baby’s fingers. 10 

As the baby begins nursing or drinking formula, the 

bacterial population inside the mouth increases. These 

bacteria consume enough oxygen to create a zone where 

anaerobic bacteria can thrive. By the time the baby is 2 

months old, a microscopic close-up of the gums will reveal 

clusters and chains of bacteria and fungi. Another wave of 

bacteria arrive when the first teeth appear. The first is 

Streptococcus sanguis, followed by Streptococcus mutans. By 

middle childhood, the diversity inside the mouth surpasses 

a hundred species, and their total number is greater than 

10 billion. 6 Bacteria also settle in the nasal cavities, which 

are connected to the mouth via the upper respiratory tract. 

The bacteria eventually lodge in the intestinal tract. In the 

small intestine, incoming microbes engage the infant’s 

dormant immune system. Pits on the surface of the Peyer’s 

patches (aggregated lymphoid tissue in the ileum) capture 

passing bacteria, where they are ushered 

into the underlying lymph tissue. Interaction 

on the Peyer’s patches triggers 


42 


the production of an abundance of immunoglobulin A 

(IgA) antibodies. Instead of marking the bacteria for destruction, 

IgA clusters across the bacterial surface, preventing 

the bacteria from attaching to the intestinal wall. This 

action also leads to the proliferation of T and B cells that 

will marshal an attack against these same bacteria should 

they turn up in the blood or other forbidden areas. 6 The 

small intestine must provide a platform for nutrient absorption, 

but at the same time the epithelium and its associated 

immune cells must keep out pathogens that escape the 

inhospitable environment of the stomach. To satisfy these 

responsibilities, small intestinal epithelial cells divide at a 

rate of 13 to 16 cells every hour. 6 

When the child reaches adulthood, his or her intestine 

becomes home to an almost inconceivable number of 

microorganisms. The size of the population—up to 100 

trillion—far exceeds all other microbial communities associated 

with the body’s surfaces and is more than 10 times 

greater than the total number of our somatic and germ 

cells combined. 11 (There is a significant variation in both 

the total number of bacteria and the composition of the 

bacterial flora in different body regions. 12 ) Since humans 

depend on their microbial inhabitants (microbiome) for 

various essential services, a person should really be considered 

a superorganism, consisting of his or her own cells 

and those of all the commensal bacteria. 

Humans are not inherently endowed with a healthy 

immune or digestive system. Fortunately, the microbiome 

in our intestinal tract provides us with genetic and metabolic 

attributes we have not been required to evolve on our own, 

including the ability to harvest otherwise inaccessible 

nutrients and to modify host immune reactivity. 11 

Inhabitants 

The adult human gastrointestinal (GI) tract contains all 

three domains of life—bacteria, archaea, and eukaryotes. 11 

Archaea are a group of prokaryotic and single-celled microorganisms, 

and while similar to bacteria, have evolved 

differently. Archaea were originally described in extreme 

environments but have since been found in all habitats 

including the digestive tracts of animals such as ruminants, 

termites, and humans. 13 Eukaryotes are organisms whose 

cells contain a limiting membrane around the nuclear 

material (the nucleus). Bacteria living in the human gut 

achieve the highest cell densities recorded for any ecosystem. 

14 The vast majority belong to two divisions, the 

Bacteroidetes (48%) and the Firmicutes (51%). Bacteroidetes 

include a number of Bacteroides genera, which have yet 

to be encountered in any environment other than animal 

GI tracts. Firmicutes include the genera Clostridium, Lactobacillus, 

Eubacterium, Ruminococcus, and several others. 

In the first comprehensive molecular survey of the gut 

microbiota (normal microflora), 395 bacterial and one 

archaeal phylotype (bacteria defined by their ribosomal 

RNA gene sequence) were identified. 14 Thus, the gut 

microbiota is a tremendously diverse bioreactor. Eight 

PROBIOTICS AND MICROFLORA 

divisions with divergent lineages are represented. This 

diversity is desirable for ecosystem stability. There appears 

to be a strong host selection for specific bacteria whose 

behavior is beneficial to the host. Cooperative activity by 

bacteria is required to break down nutrients and provide 

the host with energy. Populations of bacteria are remarkably 

stable within the human gut, which implies that mechanisms 

exist to suppress undesirable bacteria and promote the 

abundance of those that are needed. 11 

Bacteroides thetaiotaomicron is the prominent and remarkable 

bacterial species in the distal intestinal tract of adult 

humans. It is a very successful anaerobic glycophile (“sugarloving” 

microbe) whose prodigious capacity for digesting 

otherwise indigestible dietary polysaccharides is reflected 

in its genome. It encodes 241 glycoside hydrolases and 

polysaccharide lyases. This means that the organism has 

the ability to break down xylan-, pectin- and arabinosecontaining 

polysaccharides that are common components 

of dietary fiber. 15 When dietary polysaccharides are scarce, 

B thetaiotaomicron turns to host mucus by deploying a 

different set of polysaccharide-binding proteins and glycoside 

hydrolases. Other Bacteroides species include B 

vulgatus, B distasonis, and B fragilis. All play a role in the 

digestive process. 

New Research 

Microbiologists from Louis Pasteur (1822-1895) and Ilya 

Mechnikov (1845-1916) to present-day scientists have 

emphasized the importance of understanding the contributions 

of our microbiota to human health and disease. 

Mechnikov, who won the Nobel Prize for Physiology and 

Medicine in 1908, was one of the first researchers to study 

the flora of the human intestine. 16 He developed a theory 

that senility is due to poisoning of the body by the products 

of these bacteria. To prevent them from multiplying, he 

suggested a diet containing milk fermented by bacilli, which 

produce large quantities of lactic acid. 16 

Today, science is on the verge of understanding how 

the body maintains a state of equilibrium with its incredibly 

complex enteric microflora. 17 Appropriate immune 

recognition is also essential to host-bacteria symbiosis (i.e., 

the biological association of two individuals or populations 

of different species). It has recently been shown that the 

recognition of commensal bacteria by epithelial cells protects 

against intestinal injury. 17 Other research indicates 

that use of antibiotics reduces the capacity of intestinal 

microflora to metabolize phytochemicals into compounds 

that may protect against cancer. 18 However, antibiotic use 

also disrupts the intestinal microflora metabolism of 

estrogens, which results in lower levels that might decrease 

the risk of some hormonal cancers. Use of antibiotics may 

be associated with cancer risk through effects on immune 

function and inflammation, although little is known about 

these mechanisms. 19,20 

Intestinal bacteria release chemical signals recognized 

by specific receptors—called toll-like receptors (TLRs)—of 

43 


the innate immune system. The 

interaction helps to maintain the 

architectural integrity of the intestinal 

surface and enhance the ability 

of the epithelial surface to 

withstand injury. A deficiency in 

any of the numerous signaling 

molecules can induce intestinal 

inflammation, which may be a 

precursor of inflammatory bowel 

disease. Research is now ongoing 

to understand various types of TLR 

activation to ascertain how this 

information can be used to treat 

irritable bowel syndrome, Crohn’s 

disease, and other types of intestinal 

inflammatory conditions. 21 

A group of medical researchers 

in Ireland recently identified five 

probiotic bacteria than can prevent Salmonella infection 

in pigs and, if translatable to humans, could potentially 

reduce Salmonella-induced foodborne illnesses, which cause 

between 500 and 1,000 deaths every year in the U.S. 4 

This same group is also investigating the human microbiome 

for antimicrobials against pathogens. They have 

isolated a compound called lacticin 3147 from the harmless 

bacterium Lactococcus lactis, which is used to make 

cheese. Recently, lacticin 3147 has demonstrated antimicrobial 

activity against a range of genetically distinct 

Clostridium difficile strains isolated from the human gut. 

This indicates that lacticin 3147 may offer a new treatment 

for C difficile–associated diarrhea, a serious condition that 

affects 3 million people per year in the U.S. and is a major 

problem in hospitals. 4 

There is evidence confirming the effects of Lactobacillus 

GG in preventing diarrhea and atopy in children. 22,23 These 

organisms are thought to occupy binding sites in the gut 

mucosa that prevent pathogenic bacteria from adhering. 

Lactobacilli also produce bacteriocins that act as local 

antibiotics. Diarrhea associated with antibiotics may result 

PROBIOTICS AND MICROFLORA 

Table 1 

Strain-Specific Organisms 

Researched in the 

Prevention and Treatment of 

Antibiotic-Associated Diarrhea 

Bifidobacterium 

Lactobacillus GG (LGG) a 

Lactobacillus casei 

Lactobacillus plantarum 299v 

Enterococcus faecium (SF68) 

Saccharomyces boulardii a 

Saccharomyces cerevisiae 

Bacillus clausii 

Clostridium butyricum 

Lactobacillus acidophilus 

a 

S boulardii and LGG are the most promising. 


when the antibiotics disrupt the 

normal flora in the gut of a healthy 

person. Such disruptions cause 

dysfunction of the gut’s ecosystem 

and allow pathogens to colonize 

the gut and gain access to the 

mucosa. A number of organisms 

have been studied as probiotics to 

prevent antibiotic- and C difficile– 

associated diarrhea (TABLE 1). 24 

Whether probiotic supplements 

stop this process by reducing the 

disruption or by acting as substitutes 

for healthy flora is unclear. 

Final Thoughts 

Recent evidence has shown that 

microbes and their genes play 

important roles in the development 

of our immune systems, in the production of fatty acids 

that enhance healthy intestinal cell growth, in elaborating 

molecules that inhibit the growth and virulence of enteric 

bacterial pathogens, and in the detoxification of ingested 

substances that could otherwise lead to cancerous cell 

growth or alter our ability to metabolize medicines. 25,26 

Pharmacists will thus become more involved in counseling 

patients interested in taking probiotics. In Europe, probiotics 

are regarded as medicines and prescribed along with 

antibiotics. 27 In the U.S., pharmacists can advise patients 

to take such probiotic products as Culturelle, Florastor, 

or Lactinex while on antibiotics and for 3 to 7 days thereafter. 

3 The same products can be taken to help prevent 

traveler’s diarrhea. They should be taken a few days before 

the trip and continued through its duration. Instruct 

patients to separate any probiotic and antibiotic doses by 

2 hours to prevent the antibiotic from destroying the 

probiotic organisms. 3 Immunocompromised patients should 

be advised not to use probiotics because of the potential 

for systemic infections. Other side effects can include GI 

upset (e.g., flatulence, discomfort). 

REFERENCES 

1. Martin A. In live bacteria, food makers see a bonanza. NY Times. 

January 22, 2007. www.nytimes.com/2007/01/22/business/ 

22yogurt.html. Accessed September 2, 2009. 

2. DanActive. Dannon. www.danactive.com. Accessed 

September 10, 2009. 

3. Probiotics for digestive health. Pharmacist’s Letter. 

2006;7(22):220704. 

4. Friedrich MJ. Benefits of gut microflora under study. JAMA. 

2008;299:162. 

5. Zuger A. Separating friend from foe among the body’s invaders. 

NY Times. November 27, 2007. www.nytimes.com/2007/11/27/ 

health/27book.html. Accessed September 2, 2009. 

6. Sacks JS. Good Germs, Bad Germs. New York, NY: Hill & 

Wang; 2007. 

7. Macfarlane GT, Cummings JH. Probiotics and prebiotics: can 

regulating the activities of intestinal bacteria benefit health? BMJ. 

1999;318:999-1003. 

8. Intestinal flora. http://tuberose.com/Intestinal_Flora.html. 

Accessed September 2, 2009. 

9. Bullen CL, Willis AT. Resistance of the breast-fed infant to 

gastroenteritis. BMJ. 1971;3:338-343. 

10. Berkowitz RJ, Turner J, Green P. Maternal salivary levels of 

Streptococcus mutans and primary oral infection of infants. 

Arch Oral Biol. 1981;26:147-149. 

11. Backhed F, Ley RE, Sonnenburg JL, et al. Host-bacterial mutualism 

in the human intestine. Science. 2005;307:1915-1920. 

12. Leyden JJ, McGinley KJ, Nordstrom KM, Webster GF. Skin 

microflora. J Invest Dermatol. 1987;88(suppl 3):65s-72s. 

13. Introduction to the archaea. University of California Museum of 

Paleontology. www.ucmp.berkeley.edu/archaea/archaea.html. 

Accessed September 2, 2009. 

14. Whitman WB, Coleman DC, Wiebe WJ. Prokaryotes: the 

unseen majority. Proc Natl Acad Sci USA. 1998;95:6578-6583. 

15. Gordon JI, Ley RE, Wilson R, et al. Extending our view of self: 

the human gut microbiome initiative. Center for Genome Sciences. 

www.genome.gov/Pages/Research/Sequencing/SeqProposals/ 

HGMISeq.pdf. Accessed September 2, 2009. 

16. Ilya Mechnikov. The Nobel Prize in Physiology or Medicine 

1908. Biography. http://nobelprize.org/nobel_prizes/medicine/ 

laureates/1908/mechnikov-bio.html. Accessed September 2, 2009. 

17. Fiocchi C. One commensal bacterial molecule—all we need for 

health? N Eng J Med. 2005;353:2078-2080. 

18. Velicer CM, Heckbert SR, Lampe JW, et al. Antibiotic use in 

relation to the risk of breast cancer. JAMA. 2004;291:827-835. 

19. Velicer CM, Lampe JW, Heckbert SR, et al. Hypothesis: is antibiotic 

use associated with breast cancer? Cancer Causes Control. 

2003;14:739-747. 

20. Reed MJ, Purohit A. Aromatase regulation and breast cancer. 

Clin Endocrinol. 2001;54:563-571. 

21. Madara J. Building an intestine—architectural contributions of 

commensal bacteria. N Eng J Med. 2004;351:1685-1686. 

22. Szajewska H, Mrukowicz JZ. Probiotics in the treatment and 

prevention of acute infectious diarrhea in infants and children: a systematic 

review of published, randomized, double-blind placebo-controlled 

trials. J Pediatr Gastroenterol Nutr. 2001;33(suppl):S17-S25. 

23. Kalliomaki M, Salminen S, Arvilommi H, et al. Probiotics in 

primary prevention of atopic disease: a randomized placebo-controlled 

trial. Lancet. 2001;357:1076-1079. 

24. Rohde CL, Bartolini V, Jones N. The use of probiotics in the 

prevention and treatment of antibiotic-associated diarrhea with special 

interest in Clostridium difficile-associated diarrhea. Nutr Clin 

Pract. 2009;24:33-40. 

25. Mindell DP. Evolution in the everyday world. Sci Am. 

2009;300:82-89. 

26. Sherman PM, Ossa JC, Johnson-Henry K. Unraveling mechanisms 

of action of probiotics. Nutr Clin Pract. 2009;24:10-14. 

27. Berger A. Science commentary: probiotics. BMJ. 

2002;324:1364. 

44 


Annual Index 2009 

Title, Month:page 


Appropriate Use of 


Hydrocortisone, 4:12 

Automated External 

Defibrillators in the 

Community Setting, 

2:12 

Fatigue and Drowsiness: 

Everyday Exhaustion 

and Beyond, 11:12 

Getting to the Bottom of 

Common Foot 

Problems, 10:11 

Minor Eye Problems in the 

Elderly, 6:12 

Patients With Headaches: 

The Pharmacist’s Role, 

1:12 

Pediatric Otitis Media: 

Managing Ear Infections 

in Children, 3:12 

Recent Developments in 

Birth Control and STD 

Prevention for Men, 

8:12 

Recommending Analgesics 

for Common 

Conditions, 5:12 

Strategies for the Relief of 

Bloating and Gas, 

12:16 

Treating Common 

Problems in the 

Pregnant Patient, 9:12 

Why Patients Need 

Protection From the 

Sun, 7:14 

Contemporary 

Compounding 

Buprenorphine 2 mg/mL 

Sublingual Drops, 2:40 

Coal Tar 0.4% Alcohol 

Gel, 1:40 

Dexamethasone 0.2% 

With Tetracycline 2.4% 

or Metronidazole 10% 

Periodontal Gel, 3:42 

Gentamicin, Polymyxin, 

Neomycin, and 

Hydrocortisone in 50% 

Alcohol Otic Drops, 

8:70 

Ketamine Hydrochloride 

10-mg Troches, 11:58 

Ketoprofen 2% Oral Gel, 

10:48 

Metronidazole 2%, 

Misoprostol 0.0024%, 

and Phenytoin 5% 

Topical Gel, 6:50 

Myristyl Nicotinate 5% 

Topical Cream, 7:42 

Naproxen Sodium 100- 

mg/mL Injection, 5:48 

Ondansetron 

Hydrochloride 0.8 mg/ 

mL Oral Liquid, 4:38 

Tamiflu Oral Suspension, 

12:54 

Vitamin E 200-IU 

Suppositories, 9:56 

Continuing Education 

An Update on the Current 

Treatment of HIV, 

8:76* 

Drug Information 

Resources for the 

Community 

Pharmacist, 2:45* 

Emergency Contraception: 

An Update of Clinical 

and Regulatory 

Changes, 11:70* 

Herpes Zoster (Shingles) 

and Postherpetic 

Neuralgia Management, 

5:53* 

Ovarian Cancer: One of 

the Common 

Gynecologic 

Malignancies, 10:61* 

Pediatric and Adolescent 

Sports-Related Injuries 

and Ailments, 3:44* 

Perimenopause: 

Management of 

Common Symptoms 

During the Menopausal 

Transition, 9:73* 


Strategies to Reduce 

Diversion, 12:61* 

Tetrabenazine for the 

Treatment of Huntington’s 

Chorea, 1:47* 

The Prevention and 

Treatment of Pressure 

Ulcers, 4:44* 

Treatment Options in 

Acute Lung Injury and 

Acute Respiratory 

Distress Syndrome, 

7:52* 

Urinalysis: A Guide for 

Pharmacists, 6:52* 

Diagnostic Spotlight 

At-Home Test for Tobacco-Product 

Use, 7:36 

Malaria Test Kit, 8:46 

Novel Device for 

Medication 

Management, 6:Epub 

Features 

Alcohol-Induced 

Pancreatitis, 8:26 

Assisting Seniors With 

Insomnia: A 

Comprehensive 

Approach, 6:38 

Cardiovascular Risk: What 

Should We Measure?, 

2:25 

Evaluating the Link 

Between Diet and 

Acne, 4:26 

Food and Lifestyle 

Interactions With 

Warfarin: A Review, 

2:28 

Gestational Diabetes 

Mellitus, 9:43 

High Cholesterol in 

Childhood, 3:27 

IBS Treatment Guidelines, 

12:Epub 

Influenza Update: Seasonal 

and H1N1 Vaccines, 

10:Epub 

Managing Chronic 

Diabetic Peripheral 

Neuropathy in the 

Elderly, 1:30 

Massage Therapy: 

Implications for 

Pharmaceutical Care, 

5:Epub 

Medications Used in 

Opioid Maintenance 

Treatment, 11:40 

New Drug Review 2009, 

10:37 

Osteoporosis: A 

Preventable Part of 

Aging, 6:27 

Overview of Hepatitis B 

and C Management, 

12:32 

Pediatric OTC Cough and 

Cold Product Safety, 

6:39 

Pharmacists’ Role in 

Preventing Vaccine- 

Preventable Diseases, 

8:39 

Pharmacologic Management 

of Alcohol 

Dependence, 11:60 

Pharmacotherapy of 

Diabetes in the Elderly, 

7:44 

Pharmacy Students 

Providing Patient 

Medication Discharge 

Counseling in 

Pennsylvania, 8:49 

Probiotics and Microflora, 

12:42 

Psychotropic Medication 

During Pregnancy, 9:58 

Recent Advances in the 

Treatment of Pain 

Associated With 

Fibromyalgia, 9:49 

Recommendations for the 

Use of OTC Cough 

50 



and Cold Medications 

in Children, 3:33 

Restless Legs Syndrome: 

A Common, 

Underdiagnosed 

Disorder, 1:24 

Solutions to Male 

Infertility, 8:58 

So Many Options, So 

Little Difference in 

Efficacy: What Is the 

Appropriate 

Antidepressant?, 11:26 

The Diagnosis and Treatment 

of Gout, 5:40 

The Relationship Between 

GERD and Asthma, 

7:30 

The Use of 

Antidepressants for 

Chronic Pain, 5:26 

The Use of OTC 

Medications in Older 

Adults, 6:44 

Understanding 

Breastfeeding: Beyond 

Medication, 9:25 

Updates in 


Therapy for Heartburn 

and GERD, 10:52 

ISMP: Medication 

Safety 

A Warning About Warning 

Labels, 2:Epub 

Health Literacy— 

¿Comprende? Not 

Necessarily, 6:11 

Transdermal Patches and 

Burns, 4:43 

Patient Teaching Aids 

Bipolar Disorder, 11:17 

Fibromyalgia, 5:17 

Insomnia, 1:17 

Knee Replacement 

Surgery, 6:19 

Melanoma, 4:17 

Meningitis, 10:29 

Pancreatitis, 12:25 

Prostatitis, 8:17 

Smoking Cessation, 7:21 

Sudden Infant Death 

Syndrome, 3:17 

Tubal Ligation, 9:17 

Ventricular Tachycardia, 

2:17 

Pharmacy Law 

Criminalization of 

Medication Errors, 

11:66 

Disposal of Controlled 

Substances, 3:38 

Federal Preemption of 

States’ Drug Product 

Liability Laws DOA, 

5:50 


and Its Consequences, 

12:56 

HIPAA Breach 

Notification Rule, 

10:56 

Pharmacists Beware: Data 

Mining Unlawful, 6:48 

Pharmacy Robberies, 

7:49 

Recusal of Judges, 4:40 

Right of Conscience: 

Federal Developments, 

2:43 

Rogue Internet 

Pharmacies, 1:42 

The Price of Living: Endof-Life 

Costs, 8:72 

Unraveling Plan B’s Legal 

Status, 9:69 

Senior Care 

Amyloidosis: Interference 

With Organ Structure 

and Function, 8:21 

Assessing Pain in the 

Cognitively Impaired, 

5:21 

Caring for the Aging: Key 

Health Care 

Legislation, 6:22 


Screening, 12:29 

Dermatologic Signs of 

Rheumatoid Arthritis, 

4:22 

Obesity: Reality and 

Relevance to Health, 

9:20 

Progressive Supranuclear 

Palsy, 11:20 

Raising Awareness About 

Pulmonary Embolism, 

7:24 

The Dying Patient: 

Choices, Control, and 

Communication, 10:32 

Venous Thrombosis: 

Pathogenesis and 

Potential for Embolism, 

2:22 

Vitamin D Deficiency and 

Bone Pain, 3:22 

Wrist and Thumb Pain in 

Seniors: Focus on De 

Quervain’s 

Tenosynovitis, 1:20 

TrendWatch 

Acute Negative Feelings 

Among Adults, 11:10 

Cancer Trends in Women, 

9:10 

Dietary Behaviors and 

Weight-Control 

Practices Among 

Youths, 3:11 

Disparities in Respiratory 

Diseases, 7:13 

Drugs Used for Pain 

Relief, 5:10 

FDA Postmarketing 

Surveillance, 10:10 

Health Status and Health 

Care of Elderly 

Americans, 6:Epub 

Incidence and Prevalence 

of Prostate Cancer, 8:10 

Neurologic Visits to 

Ambulatory-Care 

Settings, 1:Epub 

Prevalence of Selected 

Cardiovascular Diseases, 

2:8 

The Burden of Digestive 

Diseases, 12:12 

Trends in the Practice of 

Dermatology, 4:10 

Supplements 

Diabetes & 

Pharmaceutical Care, 

May 

CE Article: Addressing 

Patient Challenges to 

Diabetes Treatment 

Through the Use of 

Incretin-Based 

Therapies* 

Glucose Sensors: The New 

Frontier of Diabetes 

Technology 

Hypertriglyceridemia 

Management in 

Patients with Diabetes 

Osteoporosis: An Understated 

Complication of 

Diabetes 

Generic Drug Review, 

June 

Follow-On Biologics: The 

Controversy Continues 

Generic Drug Use: Survey 

Results 

Generic Drugs: History, 

Approval Process, and 

Current Challenges 

Generic Substitution of 

Narrow Therapeutic 

Index Drugs 

How Is the Quality of a 

Generic Drug 

Evaluated? 

Q&A With GPhA 

President and CEO 

Kathleen Jaeger 

Oncology/Hematology 

Breast Cancer Pathology 

Report: What 

52 



Pharmacists Need to 

Know, May 

Concepts in Cancer Pain 

Management, 

November 

Drug Interactions With 

Newer Oral 

Chemotherapy Agents, 

July 

Management of 

Chemotherapy 

Extravasations, 

September 

Mantle Cell Lymphoma, 

September 

Pharmacological 

Management of Colon 

Cancer, March 

Oral Mucositis: Update on 

Prevention and 

Management Strategies, 

January 

Sickle Cell Disease and 

Stroke Prevention in 

Children, January 

The Expanded Role of 

Bisphosphonates in 

Survivors of Breast 

Cancer, March 

Treatment Options in the 

Management of 

Nonmuscle-Invasive 

Bladder Cancer, July 

OTC Trends, April 

OTCs & Seniors: Risks 

and Safeguards 

Pharmacist Consultation 

for Self-Care With 

NSAIDs 

Insomnia and Its 

Treatment With 


Products 

Sponsored Supplements 

CE Article: Initiating and 

Monitoring 

Pharmacotherapy in 

Patients with 

Parkinson’s Disease, 

February* 

CE Article: Optimizing 

Individualized 

Management of 

Osteoarthritis, June* 

CE Article: The Rx for 

Gout: The Pharmacist’s 

Role in Improving 

Clinical Outcomes for 

Patients, April* 

Disease State Information 

Guide: Irritable Bowel 

Syndrome: Overview of 

Diagnosis and Management 

of IBS: Focus on 

Probiotics, May 

Generic Pharmaceuticals 

2009: The Road Ahead, 

January 

Patient Counseling Aid: 

Contact Lens Care, July 

Product Information 

Guide: AMITIZA 

(lubiprostone) 8 mcg 

Twice Daily in the 

Management of 

Irritable Bowel 

Syndrome with 

Constipation in 

Women 18 Years of Age 

and Older, April 


Guide: The Future of 

Hazardous IV Drug 

Preparation Is Here, 

May 


Guide: Update on 

Respiratory Syncytial 

Virus Infection in 

Children With 

Emphasis on 

Immunoprophylaxis, 

February 


Guide: What 

Pharmacists Should 

Know About Caring for 

Contact Lenses, May 

Health Systems 

Edition Features 

Antiplatelet Therapy for 

the Secondary 

Prevention of Acute 

Coronary Syndrome, 

2:HS-1 

A Review of Testicular 

Cancer, 8:HS-3 

Diagnosis and Treatment 

of Acute Inflammatory 

Dermatoses, 4:HS-1 

Evidence-Based Medicine 

in Pharmacy Practice, 

10:HS-14 

Hypothyroidism, 9:HS-3 

Immunizations in the 

Older Population, 

6:HS-1 

Management of 

Hypertensive Crises, 

5:HS-8 

Management Strategies in 

Stable COPD, 1:HS-10 

Managing Acute 

Exacerbations of 

COPD, 7:HS-11 

Metabolic Syndrome and 

Cardiovascular Risk 

Factors, 2:HS-12 

Methicillin-Resistant 

Staphylococcus aureus 

Skin and Soft Tissue 

Infections, 4:HS-8 

Multiple Sclerosis: A 

Therapeutic Overview, 

1:HS-3 

Newly Approved mTOR 

Inhibitors for the 

Treatment of Metastatic 

Renal Cell Carcinoma, 

11:HS-20 

Optimal Management of 

Hyperglycemia in 

Hospitalized Patients, 

5:HS-14 

Polymyalgia Rheumatica, 

6:HS-7 

Prophylactic Therapies in 

Traumatic Brain Injury 

Management, 

11:HS-10 

Prostate Cancer: Updates 

in Pharmacotherapy, 

8:HS-15 

Rapid Molecular Testing in 

Bloodstream Infections, 

9:HS-9 

Reducing Medication 

Errors Using 

Technological 

Innovations, 3:HS-15 

Refractory Epilepsy, 

3:HS-8 

Review of Selected NMEs 

2009, 10:HS-3 

Schizophrenia: A Review 

of Pharmacologic and 

Nonpharmacologic 

Treatments, 11:HS-2 

Surgical Procedures for 

Weight Loss, 12:HS-2 

The Management of 

Amyotrophic Lateral 

Sclerosis, 8:HS-10 

Topical Anesthesia Use in 

Children, 3:HS-4 

Treatment of Hypertension 

in the Elderly, 6:HS-12 

Tuberculosis: Insidious But 

Treatable, 7:HS-2 

Understanding the 

Pharmacologic Therapy 

for Patients Afflicted 

with Complex Regional 

Pain Syndrome, 

5:HS-3 


Adaptogenic or Medicinal 

Mushrooms, 4:HS-16 

Capsaicin, 7:HS-17 

Gastrointestinal Bleeding, 

12:HS-12 

Nutrition and Clinical 

Depression, 11:HS-28 

Whey Protein, 9:HS-14 

*Available as online CEs. 

Visit www.uspharmacist.com. 

53 


Contemporary Compounding 

Tamiflu Oral Suspension 

A liquid version of this influenza medication may 

be easily prepared using the capsule formulation. 

●FORMULA 

Tamiflu Oral Suspension 1,2 

Rx: Ingredient 12 mg/mL 15 mg/mL 

Tamiflu (as 1.2 g 1.5 g 

75-mg capsules) (16 caps) (20 caps) 

Vehicle qs 100 mL qs 100 mL 

A preferred vehicle may be chosen from the following: 

Cherry syrup (Humco) 

Ora-Sweet SF 

If neither of the above is available, one of the following 

alternative vehicles may be used: 

PCCA-Plus 

Acacia syrup 

Methylcellulose 1% solution 

Other a 

a 

Other suitable vehicles are available commercially, or the following 

products from the USP Pharmacists’ Pharmacopeia, 2nd edition, 

may be used: Vehicle for Oral Solution, Sugar Free USP or Vehicle 

for Oral Suspension. These products are compounded vehicles using 

routine compounding ingredients. 

Method of Preparation: 

Calculate the quantity of 

each ingredient for the 

amount to be prepared. 

Accurately weigh or measure 

each ingredient. 

Carefully separate the 

capsule body and cap 

and transfer the contents 

of the required number 

of Tamiflu 75-mg capsules 

into a clean mortar. 

Triturate the granules to 

a fine powder. Add about 

one-third of the specified 

amount of vehicle to the 

Loyd V. Allen, Jr, PhD 

Professor Emeritus, College of 

Pharmacy, University of Oklahoma, 

Oklahoma City 

mortar, and triturate the 

powder until a uniform 

suspension is achieved. 

Transfer the suspension 

to an amber glass or 

polyethylene terephthalate 

bottle that has been 

properly calibrated for 

the final volume. Add 

another one-third 

(approximate) of the 

vehicle to the mortar, 

rinse the pestle and mortar, 

and transfer the contents 

to the bottle. 

Repeat the rinsing with 

the sufficient vehicle, 

adding it to final volume 

in the calibrated container. 

Place a child-resistant 

cap on the bottle. 

Shake well, then package 

and label. 

Use: Tamiflu oral suspension 

is indicated for prophylaxis 

and treatment 

of uncomplicated influenza 

infection in patients 

aged ≥1 year. 3 

Packaging: Package in 

tight, light-resistant 

containers. 

Labeling: Shake well 

before use. Keep out of 

the reach of children. 

Discard after ____ [time 

period]. 

Stability: Cherry syrup 

(Humco) and Ora-Sweet 

SF formulations—Refrigeration: 

stable for 5 

weeks (35 days) when 

stored in a refrigerator at 

2°C to 8°C (36°F to 

46°F). Room temperature: 

cherry syrup stable 

for 5 days when stored at 

room temperature of 

25°C (77°F); Ora-Sweet 

SF stable for 35 days 

when stored at room 

temperature. 

PCCA-Plus, acacia 

syrup, and methylcellulose 

1% solution formulations—Refrigeration: 

stable 

for 90 days when 

stored in a refrigerator at 

2°C to 8°C (36°F to 

46°F). Room temperature: 

stable for 90 days 

when stored at room 

temperature of 25°C 

(77°F). 

Note: The time periods 

listed above are recommended 

by Ford et 

al. 2 Shorter dating is suggested, 

however, as this 

preparation is intended 

for short-term storage 

and use. 

Other vehicles—Stability 

information is not 

available for other vehicles. 

Therefore, the USP 

General Chapter 

standard would be to 

assign a beyond-use date 

of 14 days for the preparation 

when stored in a 

refrigerator at 2°C to 

8°C (36°F to 46°F). 

Quality Control: Quality-control 

assessment 

can include weight/volume, 

pH, specific gravity, 

active drug assay, 

color, rheologic properties/pourability, 

physical 

observation, and physical 

stability (discoloration, 

foreign materials, gas formation, 

mold growth). 4 

Discussion: It has been 

announced that Tamiflu 

54 


Contemporary Compounding 

capsules will be manufactured 

to meet current 

demands and that pharmacists 

will compound 

the oral suspension for 

consumers. The manufacturer 

can mass-produce 

many more capsules 

than the oral 

suspension formulation 

in a given time period. 

The labeling for Tamiflu 

includes instructions on 

how to prepare an oral 

suspension using two 

different vehicles, as presented 

above. 1 

Different vehicles 

may be used and different 

concentrations may 

be compounded, according 

to the needs of the 

physician or patient and 

the availability of vehicles. 

The stability implications 

must be considered 

in the event that 

other concentrations are 

compounded. 

Oseltamivir phosphate 

(C 16 

H 28 

N 2 

O 4 

. 

H 3 

PO 4 

, MW 420.40) is 

an ethyl ester prodrug 

available as a capsule 

containing 75 mg oseltamivir 

for oral use as 

an antiviral (influenza). 

It is manufactured as a 

capsule and as a powder 

for oral suspension. The 

suspension, when reconstituted 

according to 

labeling instructions, 

contains 12 mg/mL 

oseltamivir. Oseltamivir 

phosphate occurs as a 

white crystalline solid. 

The capsules also contain 

pregelatinized 

starch, talc, povidone 

K30, croscarmellose 

sodium, and sodium 

stearyl fumarate; the 

capsule shells contain 

gelatin and coloring 

agents. 

REFERENCES 

1. Tamiflu.com. Dosing, 

administration and storage: 

extemporaneous preparation. 

www.tamiflu.com/hcp/dosing/ 

extprep.aspx. Accessed November 

13, 2009. 

2. Ford SM, Kloesel LG, 

Grabenstein JD. Stability of 

oseltamivir in various extemporaneous 

liquid preparations. IJPC. 

2007;11:162-174. 

3. Physicians’ Desk Reference. 63rd 

ed. Montvale, NJ: Thomson 

Reuters; 2009:2649-2654. 

4. Allen LV Jr. Standard operating 

procedure for performing physical 

quality assessment of oral and 

topical liquids. IJPC. 1999;3: 

146-147. 

Report Six of Six in a series 

Problem: 

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medications must not contain any 

gluten, casein, dye, sugar, or flavorings. 

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gluten-free, casein-free, dye-free, and sugarfree. 

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GALLIPOT ® 

The Art Of Compounding ®


and Its Consequences 

There is no reason 

to differentiate 

compensation or 

enforcement of 

policies based on 

gender alone, as a 

female pharmacist 

and a large pharmacy 

chain have learned. 

Legislation to apply the principle 

of equal pay for equal work without 

discrimination because of sex is 

a matter of simple justice. 

President Dwight D. Eisenhower, 1956 1 

A 

recent case from the 

Supreme Judicial Court of 

Massachusetts affirmed a 

jury verdict in favor of a female 

pharmacist who claimed she was 

paid less than her male counterparts. 

2 With interests, costs, and 

attorney fees, the recovery from the 

defendant chain store corporation 

will be well over $3.5 million. 3,4 

Facts of the Case 

Cynthia Haddad worked as a pharmacist 

for Wal-Mart for 10 years, 7 

of those years in the Pittsfield, Massachusetts, 

store. For the majority of 

this time, she worked as a staff pharmacist 

and consistently had excellent 

evaluations. In March 2003, the 

Jesse C. Vivian, RPh, JD 

Professor, Department of Pharmacy Practice 

College of Pharmacy and Health Sciences 

Wayne State University 

Detroit, Michigan 

plaintiff accepted the position of 

pharmacy manager. From that point 

until her involuntary termination 13 

months later, she was paid at an 

hourly rate considerably lower than 

any male pharmacy manager in the 

geographic region. Although she was 

told that she would receive the additional 

hourly pay that was paid to all 

pharmacy managers, she did not 

receive this differential. After numerous 

complaints, on April 9, 2004, 

she finally received a check for the 

pharmacy manager bonus that others 

received in February, but she 

never received the 13 months’ worth 

of differential hourly pay. 

On April 14, 2004, a district 

manager, who was not a pharmacist, 

and two other supervisors met with 

Ms. Haddad. They questioned her 

about two prescriptions that had 

been fraudulently written and filled 

by a pharmacy technician. One of 

the prescriptions, for Prevacid (lansoprazole), 

had been written in 

October 2002, while the female 

pharmacist was on duty (well before 

she had been promoted to manager), 

and one was written on March 20, 

2004, while a male pharmacist was 

working. The pharmacy technician 

on duty immediately admitted that 

she had falsified the October 2002 

prescription. The female pharmacist 

denied any knowledge of the fraudulent 

prescriptions, but told the district 

manager that it could have been 

written when she briefly left the 

pharmacy area to purchase a soda at 

a nearby counter, when she was in 

the restroom, when she was in the 

front of the pharmacy talking to customers, 

or when she was in the back 

of the pharmacy eating lunch or 

counting narcotics. There was no 

written policy prohibiting a pharmacist 

from leaving the pharmacy for 

short periods of time while the pharmacist 

remained inside the store. 

Ms. Haddad’s employment was 

terminated that day. She was told 

that the reason for her dismissal was 

based on her statement during the 

interview that she failed to secure 

the pharmacy, in violation of an 

unspecified policy, and that she had 

briefly left the pharmacy area unsecured 

while a technician was unattended 

in the pharmacy area. A written 

form filled out by the district 

manager indicated she was terminated 

for “gross misconduct, misappropriation.” 

The technician was 

also fired the same day. 

The other fraudulent prescription 

contained the male pharmacist’s initials. 

Neither he, who was on duty 

when the second fraudulent prescription 

was written, nor any other 

pharmacist was questioned about it 

or disciplined for it. Employees testified 

that the pharmacy did not further 

investigate the second fraudulent 

prescription because the 

technician did not admit to having 

forged it. Ironically, the same male 

pharmacist was appointed to be 

pharmacy manager on the day that 

the female pharmacist was fired. The 

male pharmacist testified at trial that 

he commonly left the pharmacy area 

unsecured to talk to a customer in 

the OTC area, to go to the restroom, 

or to get a snack. He also 

stated that he was unaware of any 

policy prohibiting this practice and 

was never disciplined for doing so. 

56 


GENDER DISCRIMINATION AND ITS CONSEQUENCES 

He also admitted that within 3 

months of assuming the manager 

position, he was earning substantially 

more per hour than the female 

pharmacist had ever earned during 

the 13 months that she held the 

position. 

At the time of the female pharmacist’s 

termination, in the geographic 

district containing the store 

she worked at, 20 of the 21 managers 

above the pharmacy manager 

level were male, and all of the pharmacy 

technicians were female. Only 

two of the pharmacy managers were 

females. 

Law and Evidence 

Under Massachusetts law, every 

pharmacy must have a pharmacist 

“manager of record,” who is responsible 

for complying with state and 

federal reporting requirements and 

supervising the pharmacy staff, and a 

registered pharmacist must be on 

duty during a pharmacy’s hours of 

operation. 5 During the period at 

issue, the pharmacy employed one 

pharmacist at its Pittsfield store who 

was designated the pharmacy manager 

to serve as the manager of 

record. A staff pharmacist generally 

worked under the pharmacy manager, 

and several pharmacy technicians 

assisted the staff pharmacist. At 

most times, only one pharmacist 

would be on duty. 

On appeal, Wal-Mart argued that 

there was no evidence to support the 

jury’s finding that it discriminated 

against the female pharmacist on the 

basis of her gender. In its defense, 

the pharmacy offered several facially 

valid reasons for the plaintiff’s termination. 

According to this court, 

however, there was ample evidence 

from which a jury could have 

inferred that the pharmacy’s stated 

reasons were pretexts, and consequently 

that it acted with discriminatory 

intent. A pretext in law is the 

reason assigned to justify an act, 

which only has the appearance of 

truth but is without foundation. 6 

The court concluded that the jury 

could have justifiably decided that 

all of the pharmacy’s proffered reasons 

for terminating the plaintiff’s 

employment were false. 

The district manager had previously 

given a variety of conflicting 

reasons for the termination. He testified 

that the female pharmacist was 

terminated because she failed to 

secure the pharmacy area and that 

she disclosed her computer sign-on 

code to a technician. This statement 

could be construed as false for several 

reasons. The pharmacist testified 

that she had never disclosed her 

password to anyone, and the sign-on 

code was known by everyone to be 

the pharmacist on duty’s first, middle, 

and last initials. A number of 

pharmacy employees testified that it 

was routine practice for pharmacists 

to log on to the computer in the 

morning and to stay logged on all 

day, so that a technician could easily 

use the pharmacist’s computer 

account. In addition, there was substantial 

evidence that similarly situated 

male pharmacists were treated 

differently than the female pharmacist 

for similar infractions of pharmacy 

policies. There was evidence 

that male pharmacists routinely left 

the pharmacy area unsecured in 

order to purchase snacks or drinks, 

and that no other pharmacist had 

been terminated for such a reason. 

There was also evidence that the 

policy on lunch breaks did not mandate 

that a pharmacist secure the 

pharmacy before leaving the pharmacy 

area. The policy stated that a 

pharmacist may close and lock the 

pharmacy if only one pharmacist 

was on duty and was going on a 

meal break, and that the pharmacist 

may leave the pharmacy area, but 

should not leave the building. Additionally, 

evidence showed that the 

incident had occurred 18 months 

prior to the termination. There was 

testimony that male pharmacists 

routinely left the pharmacy to purchase 

food or beverages in the store 

or to assist customers. The reason 

initially checked on the exit interview 

form—“gross misconduct, misappropriation”—could 

have been 

erroneous because there was no evidence 

or even any allegation that the 

plaintiff misappropriated assets. 

In circumstances virtually identical 

to the purported incident for 

which the female pharmacist was 

terminated, a male pharmacist was 

neither questioned about nor disciplined 

for the second fraudulent prescription 

filled by the technician, 

even though his initials were on the 

prescription, he was on duty at the 

time it was filled, the prescription 

appeared suspicious on its face, and 

the incident had occurred only a few 

weeks, rather than 18 months, 

before the plaintiff’s termination. 

The evidence indicated that the 

store’s investigation of the second 

fraudulent prescription was limited 

to questioning the plaintiff about it 

and thereafter asking the technician 

whether she had written it. 

The pharmacy claimed that its 

decision to investigate only the 

plaintiff and none of the male pharmacists 

regarding the fraudulent prescriptions 

is “legally irrelevant, and 

cannot support an inference of discrimination.” 

The pharmacy asserted 

that it did not investigate or discipline 

the male pharmacist on duty 

when the tech wrote the second 

fraudulent prescription because it 

had no reason to suspect the male 

pharmacist had engaged in wrongdoing. 

This argument was considered 

meritless because the evidence 

showed that the pharmacy questioned 

the female pharmacist about 

both the prescription the technician 

wrote when the female pharmacist 

was on duty and the one written 

when the male pharmacist was on 

duty, but did not question the male 

pharmacist about either prescription. 

Given the evidence of the fraudulent 

prescription with the male pharmacist’s 

initials, the pharmacy should 

have had as much reason to suspect 

that the male pharmacist was 

engaged in wrongdoing as it did to 

suspect the female pharmacist. 

57 



Notwithstanding the proffered 

reason that the female pharmacist 

was terminated for leaving the pharmacy 

area unattended in October 

2002, at that time she was a staff 

pharmacist and not the pharmacy 

manager legally responsible for seeing 

that the pharmacy was secure. 

Moreover, terminating her employment 

for a single policy infraction 

did not comport with the corporation’s 

stated policy of progressive discipline, 

with employees first 

“coached” about proper procedures, 

then suspended, and then, in 

extreme circumstances, terminated 

from employment. 

Perhaps even more telling, there 

was evidence that Ms. Haddad’s termination 

had been planned in 

advance. Her termination notice was 

originally dated on the day before 

the interview, and the district supervisor 

testified that he told the 

regional manager the day before that 

he intended to interview and then 

terminate the pharmacist on the following 

day. In addition, without the 

female pharmacist’s prior knowledge, 

the male pharmacist was registered 

with the Board of Pharmacy to 

become the manager of record 3 

days prior to her termination. 

There was also evidence of other 

incidents in which male pharmacists 

were not disciplined for far more 

serious infractions of pharmacy policies, 

or even for actions that violated 

state and federal law. For instance, a 

videotape from a surveillance camera 

showed the technician placing drugs 

in her purse while a male pharmacist 

on duty was standing near her. The 

store policy prohibited bringing 

purses into the pharmacy area. That 

male pharmacist, who remained 

employed by the pharmacy at the 

time of trial, testified that he was 

not questioned or disciplined about 

the incident. In August 2003, the 

pharmacy discovered that another 

male pharmacist had been writing 

prescriptions for himself for a Schedule 

II narcotic. A district manager 

instructed that pharmacist to have a 

prescription written by his physician, 

and no disciplinary action was taken 

against him for these forged prescriptions. 

That pharmacist was also 

later observed taking drugs from the 

pharmacy. His employment was not 

terminated for this conduct. 

Most difficult for the pharmacy 

to justify, the undisputed evidence 

showed that the female pharmacist’s 

base pay was significantly less per 

hour than all the male pharmacy 

managers in the region. In addition, 

despite her repeated requests for the 

additional hourly pay and bonus 

that the male pharmacy managers 

received, the pharmacy failed to pay 

her the bonus until just before her 

termination. 

Damages 

The jury awarded $17,700 in special 

damages, $125,000 in emotional 

distress damages, back pay of 

$95,000, and front pay of $733,307 

based on an estimated 19 years of 

continued employment if not for the 

wrongful termination. On appeal, 

the pharmacy contested only the 

front pay award. It argued that a) 

the front pay award is excessive and 

speculative; b) the judge failed to 

consider evidence of the pharmacist’s 

future earning ability; and c) a 

19-year award is too long. The jury 

also awarded $1 million in punitive 

damages. However, the trial court 

judge reversed the punitive damages 

award and entered a verdict for the 

compensatory amount. The pharmacist 

appealed for reinstatement of 

this award. 

Front pay is intended to compensate 

a plaintiff for the loss of 

future earnings caused by the defendant’s 

discriminatory conduct. The 

judge properly instructed the jury 

that front pay damages must be 

“proven with reasonable certainty;” 

that in awarding such damages they 

should consider the “amount of 

future earnings, including salary, 

bonuses and benefits that the plaintiff 

would have received but for the 

defendant’s unlawful discrimination;” 

that they should not overcompensate 

the plaintiff; and that 

the plaintiff had a duty to mitigate 

her damages by reasonable efforts to 

secure other employment. The 

judge also correctly instructed the 

jury to consider and weigh five factors 

in determining the amount of 

any front pay award: 1) the amount 

of earnings, including salary and 

benefits, that the plaintiff would 

have received between the time of 

trial and the plaintiff’s projected 

retirement date; 2) the plaintiff’s 

probable retirement date; 3) the 

amount of earnings that the plaintiff 

would probably have received from 

another employer until her retirement, 

which would reduce any 

front pay award; 4) the availability 

of other employment opportunities; 

and 5) the possibility of future wage 

increases and inflation. The judge 

further instructed that any award of 

front pay damages must be based on 

the present discounted value of the 

income stream, and he provided an 

explanation of how that value was 

to be calculated. Notably, the female 

pharmacist hired a PhD economist 

as an expert to testify about front 

pay damages, and the pharmacy did 

not offer any contradictory testimony 

or evidence. 

Ms. Haddad testified to her difficulty 

in obtaining a new job. After 

more than 6 months of seeking 

employment, she eventually secured 

a position at a small pharmacy that 

was owned by a relative of her inlaws 

with less advancement potential, 

significantly fewer benefits, and 

fewer available hours. She remained 

in that position at the time of trial; 

the evidence suggested that the 

plaintiff intended to stay in the 

Pittsfield area and to continue working 

at her present type of job as a 

pharmacist. Her tendency to job 

stability was supported by evidence 

that she had worked at the defendant 

pharmacy for 10 years. While 

the pharmacy emphasizes that the 

pharmacist’s hourly pay in the new 

job is higher, it ignores the fact that 

58 


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the pharmacist earns less money 

than she did before termination of 

her employment because fewer 

hours are available in her new position 

than had been available to her 

during her employment with the 

defendant. 

The pharmacy contends that a 

19-year award is excessive. However, 

the award of lost income of 19 years 

is consistent with the pharmacist’s 

anticipated retirement age of 65 

years. Based on her 10-year employment 

history with the pharmacy, 

her testimony that she had planned 

to continue working there for the 

remainder of her career, and with 

the limited number of pharmacies 

in the area around Pittsfield, the 

jury permissibly could have concluded 

that an award of 19 years 

was appropriate. 

As to the punitive damages, the 

pharmacy claimed there was insufficient 

evidence to justify the award. 

Concluding that the pharmacy had 

presented no evidence that it knowingly 

or intentionally violated the 

antidiscrimination statute, 7 and that 

there was no evidence that its conduct 

was otherwise outrageous, evil 

in motive, or could be viewed as 

exhibiting a reckless indifference for 

the pharmacist’s rights, the judge 

reversed the jury’s finding on the 

punitive damages award. 

Under existing Massachusetts law, 

punitive damages may be awarded 

for conduct that is outrageous, 

because of the defendant’s evil 

motive or his reckless indifference to 

the rights of others. These cases have 

held that if a defendant knows that 

it has acted unlawfully by interfering 

with the legally protected rights of 

the plaintiff, such “reckless indifference” 

to the rights of others constituted 

conduct warranting “condemnation 

and deterrence,” sufficient to 

support an award of punitive damages. 

That the defendant acted with 

the knowledge that it was interfering 

with the plaintiff’s right to be free of 

unlawful discrimination, however, 

has been only one circumstance warranting 

an award of punitive damages. 

If the defendant’s act was otherwise 

outrageous, egregious, evil in 

motive, or undertaken with reckless 

indifference to the rights of others, 

an award of punitive damages has 

been allowed. 

There was evidence that the pharmacy 

had policies prohibiting harassment, 

from which a jury could infer 

that the pharmacy was aware that 

gender discrimination was not 

legally permitted. In addition, there 

was sufficient evidence of reprehensible 

or recklessly indifferent conduct 

to support an award of punitive 

damages. The pharmacy maintained 

policies prohibiting harassment and 

“inappropriate conduct.” The pharmacy 

training manuals provided for 

“coaching” on “harassment/inappropriate 

conduct.” The pharmacy considered 

“serious harassment/inappropriate 

conduct” to be “gross 

misconduct” justifying immediate 

termination without the possibility 

of future rehire. 

The pharmacy contended that 

the award of $1 million in punitive 

damages was excessive. In considering 

whether an award of punitive 

damages is excessive in a gender discrimination 

case, Massachusetts law 

requires consideration of three factors: 

1) the degree of reprehensibility 

of the defendant’s conduct; 2) 

the ratio of the punitive damage 

award to the actual harm inflicted 

on the plaintiff; and 3) a comparison 

of the punitive damages award 

and the civil or criminal penalties 

that could be imposed for comparable 

misconduct. An award of punitive 

damages also requires a heightened 

finding beyond mere liability 

and also beyond a knowing violation 

of the statute. Punitive damages 

may be awarded where the defendant’s 

conduct is outrageous or egregious. 

Punitive damages are warranted 

where the conduct is so 

offensive that it justifies punishment 

and not merely compensation. In 

making an award of punitive damages, 

the jury must find that the 

award is needed to deter such 

behavior toward the class of which 

the plaintiff is a member, or that the 

defendant’s behavior is so egregious 

that it warrants public condemnation 

and punishment. According to 

this court, the jury was justified in 

concluding that the pharmacy’s pattern 

of unequal treatment of male 

and female pharmacists was outrageous 

and reprehensible. For these 

reasons, the punitive damage award 

for Ms. Haddad was reinstated. 

Conclusion 

In this day and age, there is no reason 

to differentiate compensation or 

enforcement of policies based on 

gender alone. As the court found, the 

facts of this case were so egregious as 

to be without any reasonable explanation. 

This conduct not only justified 

compensatory damages due the 

female pharmacist for her disparate 

treatment but punitive damages to 

deter such discrimination in the 

future. It took a long time against 

formidable odds for this pharmacist 

to be vindicated. In the end, maybe 

this case will make pharmacy a better 

profession for all its practitioners, 

male and female alike. 

Author’s Note: At the time this article was 

submitted for publication, the defendant corporation 

had not paid the judgment. According 

to the plaintiff’s attorney, Richard E. 

Fradette, RPh, JD, the company was haggling 

over the payment of pre- and postjudgment 

interest and attorney fees. According to 

his estimate, those fees are accumulating at 

approximately $900 per day that the judgment 

remains unpaid. This is just further 

evidence of how difficult it is to bring and 

prevail in cases like this one. 

REFERENCES 

1. Eisenhower DD. Quotations Book. http://quotationsbook.com/ 

quote/45318/. Accessed November 5, 2009. 

2. Haddad v. Wal-Mart, Slip Op No SJC-10261 (October 5, 2009), 

2009 Mass Lexis 654. 

3. The trial was discussed in an earlier column. Vivian JC. 

David victorious over Goliath. US Pharm. 2007;32(10):58-60. 

www.uspharmacist.com/content/d/pharmacy_law/c/10228/. 

Accessed October 13, 2009. 

4. The final judgment estimate was provided by Richard E. 

Fradette, RPh, JD, counsel for the plaintiff, in an e-mail to the 

author dated October 29, 2009. 

5. GL c 112, §§ 24, 39; 247 Code Mass Regs §§ 6.01, 6.02, 6.07. 

6. Pretext. Law Dictionary. www.law-dictionary.org/PRETEXT. 

asp?q=PRETEXT. Accessed October 13, 2009. 

7. GL c 151B. 

60 


2 CE Credits 



Law CE 

Imagine a cocktail of 

morphine, Demerol 

(meperidine), codeine, 

chlorpheniramine, Placidyl 

(ethchlorvynol), and Valium 

(diazepam). These and other 

drugs were found in “significant 

quantities” in the 

tissues of Elvis Presley upon 

his death in 1977 from a 

suspected drug overdose. 1 

More than 30 years later, 

the actor Heath Ledger, who 

was found dead from a drug 

overdose, had Vicodin 

(hydrocodone), OxyContin 

(oxycodone), diazepam, and 

alprazolam in his bloodstream. 2 What is especially noteworthy 

in these two high-profile cases was that none of 

these substances are illegal drugs, but rather medications 

that can be readily obtained by almost anyone through 

normal, legal channels with a prescription. Although the 

abuse of legal prescription drugs may garner headlines when 

well-known celebrities like these are involved, most of the 

lay public and many health professionals equate drug abuse 

with illegal street drugs. However, the problem of prescription 

drug abuse has become increasingly prevalent. 

A number of reports have shown that the abuse of 

prescription drugs, especially opiates, stimulants, and 

sedatives, has reached alarming proportions, particularly 

among teenagers. 3 In fact, prescription drugs have become 

the second most abused drug, behind only marijuana, 

among young people aged 12 to 17 years, and the gap is 

shrinking. 3 Teen abuse of prescription drugs has become 

so pervasive that the Partnership for a Drug-Free America 

has introduced the term “Generation Rx” to refer to these 

adolescents. 4 Helping to fuel the rise in this trend of drug 

abuse is the perception among young people and their 

parents that legal prescription drugs provide a safer high 

than street drugs. Health professionals, especially pharmacists, 

need to be aware of the potential 

for prescription drug abuse and to 

recognize their responsibility to limit 

the diversion of legitimate, beneficial 

U.S. Pharmacist Continuing Education 

GOAL: To provide pharmacists with an understanding of the 

diversion and abuse of prescription drugs and the legal issues 

designed to limit diversion. 

OBJECTIVES: After completing this activity, participants 

should be able to: 

1. Describe the demographics of prescription drug abuse.* 

2. Identify the dangers associated with the nonmedical use of 

prescription drugs.* 

3. Recognize the patient characteristics and techniques that 

may suggest the possibility of diversion.* 

4. Discuss the legal risks and responsibilities that arise from 

the diversion of drugs.* 

5. Implement strategies to reduce diversion. 

* Also applies to pharmacy technicians. 

Gerald Gianutsos, PhD, JD 

Associate Professor of Pharmacology 

University of Connecticut School of Pharmacy 

Storrs, Connecticut 

medications to those who 

would misuse them. 

This review will examine 

the problem of prescription 

drug abuse and what 

the pharmacist can do to 

recognize and minimize 

the problem of drug diversion. 

Pharmacists should 

also be aware that abuse 

of legal drugs does not end 

with prescription medications; 

OTC drugs are also 

widely prone to abuse, 

especially by adolescents, 

and the interested pharmacist 

is directed to other 

resources for further information. 5 

Patterns of Prescription Drug Abuse 

Demographics: It is undeniable that the abuse of prescription 

medications is on the rise. Recent surveys report that 

the number of Americans abusing prescription drugs is 

approaching 7 million. From 2000 to 2006, there was an 

80% increase in prescription drug abuse, and it has now 

become more common than the number of individuals 

who are abusing street drugs like cocaine, heroin, hallucinogens, 

Ecstasy, and inhalants combined. 6 The use of 

illegal drugs has generally tended to show a gradual decline 

over the past decade, but the misuse of prescription drugs, 

especially sedatives, opiates, and stimulants, has grown 

over the same period. 7 

The age group most likely to abuse prescription drugs 

is individuals between 18 and 25 years of age, although 

younger groups and even the elderly are not immune. 8 

Among adolescents, opiates are the most popular prescription 

drugs. 9 OxyContin use increased for all grades from 

2002 to 2007. The annual prevalence of use in 2007 was 

1.8%, 3.9%, and 5.2% in grades 8, 10, and 12, respectively. 

Vicodin abuse occurred at higher levels but remained fairly 

constant over the same time period, 

with prevalence rates of 2.7%, 7.2%, 

and 9.6% in grades 8, 10, and 12, 

respectively. 9 High rates of use of pre- 

61 


PRESCRIPTION DRUG ABUSE: STRATEGIES TO REDUCE DIVERSION 

scription drugs are also noted in college students and young 

adults. 10 Other classes of prescription drugs frequently 

diverted by adolescents include tranquilizers and stimulants. 

10,11 Among teens, 10% have abused Adderall (amphetamine 

and dextroamphetamine) or Ritalin (methylphenidate) 

compared with 9% having tried crack cocaine. 11 

While white males are the most common demographic 

among prescription abusers overall, in the younger 12- 

to 17-year-old age group, girls are more likely to abuse 

prescription drugs than boys, with stimulants and 

sedatives being the most popular among adolescent 

girls. 8,9 Across all age groups, women are more likely 

to abuse prescription drugs than illegal drugs. 12 Data 

suggest that prescription abuse is highest in small metropolitan 

areas compared with larger metropolitan or 

rural areas, which may be related to the availability, 

purity, and cost of heroin in a local region. 13 

A significant factor in the growth of prescription 

drug abuse is the ease with which these drugs can be 

obtained. Young people are readily able to secure prescription 

drugs; 40% of 12th-graders reported that painkillers 

are “fairly” or “very” easy to get, and more than half 

say the same thing for stimulants. 14 The majority of teens 

indicate that prescription drugs are easier to obtain than 

illicit dugs, and more than half say they abuse prescription 

painkillers because they are not illegal. Teens also 

believe that there is less shame attached to using these 

drugs (33%) and that their parents would not be as 

concerned if they got caught (21%). This mirrors the 

perception among parents that prescription drug abuse 

is a safer alternative to street drug use. 

Nearly two-thirds (64%) of teenagers who have abused 

prescription drugs reported receiving, buying, or stealing 

them from friends or relatives; almost half (46%) say they 

got prescription pain relievers for free from a relative or 

friend. 14 Thus, in many cases, the procuring of prescription 

drugs does not entail the same risks and consequences 

associated with traditional drug dealing. Another 9% said 

they bought pain relievers from a friend or relative, while 

5% took the drugs without asking. Only 4% had to resort 

to buying them from a drug dealer. 14 

Relationship to Increased Use of Prescription Drugs: 

Pharmacists are well aware that total prescription volume 

is on the rise. Could the escalating abuse of prescription 

drugs be a reflection of the increased prescribing of drugs 

in the population generally and not an unusual phenomenon? 

Data fail to support this view. Between 1992 and 

2002, the increase in the number of prescriptions written 

for scheduled drugs outpaced the rate of increase in nonscheduled 

drugs and the growth in the population by 3- 

and 12-fold, respectively. 13 

Overall, opiates represent three-fourths of the volume 

of prescription drugs that are abused. 8 The number of 

people using analgesics for nonmedical reasons increased 

four-fold from 1980 to 1998 and shows little sign of abating. 

8 Retail sales of methadone increased almost 10-fold 

between 1997 and 2005, 11 while the number of prescriptions 

for hydrocodone and oxycodone increased 376% and 

380%, respectively, from 1992 to 2002. 15 This compares 

with an overall increase in prescription volume of 61% and 

a population growth of 12% over the same time frame. 15 

It is clear that the prescribing of scheduled drugs in general, 

and opiates in particular, has far outpaced the increase in 

use of most other drug classes. Part of this growth is related 

to an appropriate increased emphasis on and recognition 

of pain management, and reflects a legitimate expansion 

of prescription use. However, the disproportionate increase 

in the availability of opiate drugs in the supply chain can 

also lead to increased diversion into the hands of abusers. 

Dangers of Prescription Drug Abuse 

The increased misuse of prescription drugs has coincided 

with increased risks and mortality. Death from drugs is 

the second leading cause of accidental death in the U.S., 

exceeded only by motor vehicle accidents. 16 According to 

the CDC, unintentional drug overdose deaths increased 

68% between 1999 and 2004. 17 In a recent study from 

West Virginia, 63% of deaths due to unintentional overdose 

of prescription drugs were associated with diversion 

of the drug (i.e., there was no documented prescription 

for the deceased person), while another 21% involved 

persons who had obtained prescriptions for controlled 

substances from five or more physicians (representing 

probable “doctor shopping”). 18 These data indicate that 

the primary cause of overdose death from prescription 

drugs results from their nonmedical use. Prescription drug 

overdose associated with diversion most closely resembles 

the profile of traditional abusers of street drugs, being 

highest in unmarried men and in the 18- to 24-year-old 

group. 17 This group was also more likely to have a history 

of other substance abuse and to combine prescription 

drugs with illicit drugs. In contrast, overdose linked to 

doctor shopping was highest in the group aged 35 to 44 

years and was more likely to involve women. 18 

Nationally, the number of opioid analgesic poisonings 

listed on death certificates increased 91% between 1999 

and 2002, while poisonings due to heroin and cocaine 

increased by much smaller percentages (12.4% and 22.8%, 

respectively). 11 Emergency room admissions for prescription 

opioid use increased 74% from 2002 to 2006, and 

the misuse of opioid analgesics now results in more drug 

overdose deaths than cocaine and heroin combined. 16 

Overall, the nonmedical use of controlled prescription 

drugs is estimated to cost the health care system more 

than $72 billion annually. 16 

Nearly one-third of new drug abusers report that their 

first experience involved a prescription drug, with 19% 

citing opioids. 16 These data highlight the risks associated 

with the intentional misuse of prescription drugs and are 

contrary to the belief among adolescents and their parents 

that prescription drug abuse represents a safer alternative 

62 



Table 1 

Methods Used to Obtain Prescription 

Drugs for Purposes of Abuse 

• “Doctor shopping” (i.e., seeing more than one 

physician for the same prescription) 

• Traditional drug dealing 

• Theft from pharmacies or homes, including family 

members taking someone else’s drugs from a 

medicine cabinet 

• Acquiring prescription drugs via the Internet without 

a physician visit 

• Receiving drugs from friends or relatives 

• Buying drugs from patients leaving clinics 

• Feigning legitimate illness (e.g., sports injuries, 

anxiety) to obtain a prescription 

Source: References 6, 20. 

to street drug use. Criminal activity, including thefts and 

robberies from pharmacies, is an additional risk. 19 

Methods of Prescription Drug Diversion 

Surveys by the National Center on Addiction and Substance 

Abuse (CASA) at Columbia University asked health care 

professionals and the public what they perceive to be 

responsible for diversion of prescription drugs from legitimate 

uses. 20 Individuals who may inappropriately acquire 

prescription drugs employ a variety of different means to 

obtain them (TABLE 1). 6,20 

Physicians: Among physicians, the main reason cited for 

diversion (96%) is doctor shopping, followed by patient 

manipulation or deception of the physician, and forged 

or altered prescriptions. 20 Clearly, physicians place the 

primary blame for diversion on patients who, they believe, 

either seek drugs from multiple sources, mislead the physician 

into making an inappropriate medical decision, or 

commit outright theft. Increased access to medical information 

on the Internet has facilitated the faking of apparently 

appropriate physical symptoms that can deceive the 

busy physician into issuing a prescription when it is not 

necessary to treat the patient. Nearly half the surveyed 

physicians, especially younger physicians, admitted that 

patients try to pressure them into prescribing a controlled 

drug. However, not all patients receiving prescriptions use 

the drugs themselves; some individuals may collect thousands 

of pills each year and sell them on the street, and 

there are also reports of patients supplementing Social 

Security income by selling all or part of their prescriptions. 9 

Physicians also admit to gaps in their medical school 

training that complicate their ability to detect misuse. 

Only 40% were trained in identifying prescription abuse 

and addiction. 20 Almost half of primary care physicians 

report that they find it difficult to discuss prescription 

drug abuse with patients for whom they prescribe the 

medications; fewer than half of the surveyed physicians 

asked about prescription drug abuse when taking a patient 

history, and one-third do not regularly call or obtain records 

from other treating physicians before prescribing controlled 

drugs on a long-term basis. 20 

Pharmacists: Almost half (46%) of the pharmacists in 

one survey viewed diversion and abuse of prescription 

opioid analgesics as a problem in their community, and 

10% of these considered the problem as serious. 21 

Pharmacists surveyed by CASA agreed with physicians 

on the three most common methods of diversion, but the 

order was slightly different. 20 Pharmacists also felt that 

doctor shopping is the most common mechanism, followed 

by forged or altered prescriptions and patient manipulation 

of physicians. Less common methods were believed to be 

theft of prescription pads from physicians and deliberate 

diversion by physicians. In all, more than 60% of pharmacists 

believed that physicians bear the primary responsibility 

for preventing prescription abuse and addiction. 

Only half of the surveyed pharmacists agreed that they 

had received training in identifying prescription drug abuse 

and addiction, and less than half had received instruction 

in preventing diversion. 20 However, more than 25% of 

the pharmacists admitted that when a patient presents a 

prescription for a controlled drug, they “somewhat” or 

“very often” think it is for purposes of abuse or diversion. 

More than three-fourths of pharmacists said that they 

become somewhat or very concerned about abuse and 

diversion if a patient asks for a controlled drug by its brand 

name, believing that a brand name would have a higher 

resale value on the black market. Other circumstances that 

raise suspicions among pharmacists include a prescription 

with apparent irregularities; the patient’s lack of familiarity 

with the prescribing physician; a patient and/or prescribing 

physician from out of town; the patient’s demeanor 

(overly friendly, nervous, or aberrant); or the patient trying 

to pay in cash instead of using insurance. Some pharmacists 

admit to relying on their “gut instinct.” 

Although pharmacists may believe that physicians bear 

the primary responsibility for preventing prescription abuse, 

pharmacists are reminded that they share the responsibility 

for preventing diversion. The Controlled Substance Act 

(CSA) mandates that only prescription orders for controlled 

substances that are for a “legitimate medical purpose” and 

issued in the “usual course of professional practice” may 

be dispensed by a pharmacist. 22 The Drug Enforcement 

Agency (DEA) reminds pharmacists that while the primary 

responsibility for proper prescribing rests with the physician, 

the pharmacist who dispenses the prescription has a corresponding 

responsibility. A pharmacist who “knowingly” 

fills a prescription that is not issued in the usual course of 

professional treatment is subject to the penalties of the 

CSA. 22 The pharmacist is required to exercise sound professional 

judgment when determining the legitimacy of a 

prescription for a controlled substance. The pharmacist 

63 



who “looks the other way” and fills a prescription for a 

controlled substance that he or she knew or should have 

known was not for a legitimate purpose may be prosecuted. 

Merely contacting the physician for verification that the 

prescription was written by that prescriber may not be 

sufficient to fulfill the pharmacist’s duty, and the pharmacist 

should refuse to fill the prescription if there is reasonable 

suspicion that it is not valid. The DEA has established 

criteria that can serve as guidelines for a pharmacist to 

potential prescribing for illegitimate purposes or prescriptions 

that are not legitimate (TABLE 2). Of course, these are 

guidelines, and nothing can substitute for the pharmacist’s 

own experience and knowledge of the community. Recently, 

a major national pharmacy chain was fined $5 million by 

the DEA for CSA violations. 23 

Pharmacists are also reminded that under federal and 

state laws, a controlled-substance prescription issued to an 

addict or habitual user for the purpose of keeping him or 

her comfortable (i.e., avoiding withdrawal) is not considered 

to be a valid prescription, since this is outside of the 

scope of legitimate medical purpose (except for patients 

enrolled in a licensed treatment program). 22 

Studies suggest that many pharmacists do not know 

what constitutes legitimate dispensing practices for controlled 

substances under federal or state policy in emergencies 

or for patients with terminal illnesses, especially 

for noncancer patients. 21 Only 29% of pharmacists 

“strongly agreed” that their knowledge of relevant controlled-substance 

regulation was adequate. 21 Pharmacists, 

like physicians, also believe that there are gaps in their 

Table 2 

DEA Criteria That Indicate a 

Prescription May Not Be for a 

Legitimate Medical Purpose 

• A prescriber’s prescription pattern is different 

from that of other prescribers in the area (e.g., 

more prescriptions for controlled substances or 

prescriptions for larger quantities of controlled drugs) 

• Prescriber writes for antagonistic drugs (e.g., 

stimulant and depressant at the same time) 

• Patient returns to the pharmacy more frequently than 

expected (e.g., prescription quantities do not last as 

long as expected) 

• Patient presents multiple prescriptions for the same 

drug written for different people 

• A number of people appear within a short time period 

for the same controlled drug from the same physician, 

or a large number of previously unknown patrons 

show up with prescriptions from the same physician 

• The patron presents a prescription that shows 

evidence of possible forgery (e.g., unusual directions 

or quantities, no abbreviations, apparent erasures, 

unusual legibility, evidence of photocopying) 

DEA: Drug Enforcement Agency. Source: Reference 22. 

education with respect to drug abuse. More than twothirds 

of pharmacists reported that they received 2 hours 

or less of addiction and substance abuse education in 

pharmacy school, and almost 30% received no addiction 

education. 24 Many pharmacists are also unaware of the 

important distinctions among addiction, physical dependence, 

and tolerance. Significantly, more than half of the 

pharmacists said that they had never referred a patient 

to a drug treatment program. 

Pharmacists also need to be on the lookout for fraudulent 

prescriptions. Patients may alter a legitimate prescription, 

steal prescription pads, copy prescriptions (or 

scan and print legitimate prescriptions), or create authentic-looking 

prescription blanks with a real physician’s 

name but a fake phone number, which would be answered 

if the pharmacist called to verify. 22 Modern technology 

has made these fraudulent prescriptions even more difficult 

to detect. 

When pharmacists were asked what they would do if 

they suspected a patient of abusing or diverting a controlled 

prescription drug, the most common responses 

were to call the prescribing physician (93%) or refuse to 

dispense the prescription (76.6%). 20 Less than half would 

call the police. Only 1.7% said they would take no action, 

justifying their inaction as due to fear of reprisal by the 

patient or their employer. 20 

Patients may not obtain their drugs from a pharmacy 

by fraudulent means but may resort to theft. The CASA 

survey revealed that 29% of pharmacists had experienced 

a theft or robbery of prescription drugs in the preceding 

5 years, most commonly involving OxyContin. 20 Moreover, 

21% of pharmacies would not stock certain controlled 

drugs, including OxyContin, Percocet, and Percodan, in 

an effort to reduce diversion. 20 

Data from the DEA reveal that in the period from 

2000 through 2003, nearly 28 million dosage units of 

controlled substances were diverted by theft or loss from 

lawful channels, including pharmacies, of which 24% 

were opioid analgesics (primarily hydrocodone, oxycodone, 

morphine, methadone, meperidine, hydromorphone, 

and fentanyl); these figures are believed to represent 

underreporting of the true incident rate. 25 These data 

provide evidence that a considerable volume of drug 

diversion occurs through criminal actions even before 

being prescribed. 12,25 

Approximately 6,500 pharmacy thefts occur annually 

in the U.S. 25 Among retail pharmacies, about half the 

thefts are attributed to employees, with the remainder 

being attributed to individuals who break into pharmacies 

or clinics or commit armed robberies to acquire the drugs. 

Individuals also steal pharmaceuticals from friends or 

relatives who possess legitimate prescriptions. 19 

Role of the Internet 

The Internet has brought many changes to the practice 

of pharmacy and medicine. Among them is the strongly 

64 



held belief that it is a source of diversion for prescription 

drugs, especially for Schedule III and IV drugs. 26 A report 

from CASA states that “drugs continue to be as easy to 

buy over the Internet as candy.” 27 According to the report, 

89% of sites selling controlled drugs have no prescription 

requirement; and of the 11% that do require a prescription, 

70% only require a faxed copy that can be easily 

forged. Many Internet sites dispense drugs after a patient 

completes an online questionnaire, which may or may not 

have been reviewed by a physician. The most commonly 

sold drugs on these sites are anxiolytics like diazepam and 

lorazepam, followed closely by OxyContin and Vicodin. 27 

Of the total sites identified in 2006, slightly less than half 

were portal sites (acting as a conduit to a retailer) and the 

rest were anchor sites (which sell the drug to and receive 

payment from the consumer). The anchor site may or 

may not operate the pharmacy where the prescription is 

actually filled and may not even be located in the same 

geographic area as the dispensing pharmacy. Indeed, many 

sites operate beyond the borders of the U.S. 

Many of the illegitimate Internet sites are run by non- 

DEA registrants without medical or pharmacy training. 26 

These sites typically work with physicians who approve 

the prescription, frequently targeting young graduates with 

significant debt or retired practitioners looking for additional 

sources of income. In many cases, the prescriber 

reviews an online questionnaire, bypassing the accepted 

patient-prescriber relationship and contrary to the accepted 

standard of medical care. In one documented case, a Texas 

physician authorized over 20,000 prescriptions without 

ever meeting a single patient or verifying any medical 

information. 12 Some of the rogue Internet pharmacy sites 

claim that a physician may contact the patient via telephone 

or e-mail while others attempt to distance themselves from 

the requirement for consultation by claiming that they are 

merely providing a referral service. 27 The DEA also noted 

an absence of protection against minors obtaining potentially 

dangerous drugs through this process, citing an 

example of a 13-year-old who obtained methylphenidate 

after accurately filling out the form with his correct height, 

weight, and age. 26 

The Internet facilitators also recruit pharmacies, often 

targeting small, struggling independents. 26,27 The facilitator 

will tell the pharmacist that all he or she has to do 

is prepare and ship prescriptions to customers, and provide 

reassurance to the pharmacist that the prescriptions 

are only for Schedule III or Schedule IV substances and 

have been “approved” by a physician. In addition to 

paying the pharmacy for the cost of the drug, the Internet 

facilitator will pay the pharmacy an agreed-upon 

amount that may total into the millions of dollars. The 

DEA has seen pharmacies close their doors completely 

to walk-in patients and convert their entire business to 

filling Internet orders. The DEA estimates that controlled 

substances represent 11% of prescription volume at a 

typical brick-and-mortar pharmacy, but may constitute 

Table 3 

Behavioral Traits That Might 

Trigger Suspicion of Drug Abuse 

• Depression 

• Loss of interest in personal appearance or activities 

that used to bring enjoyment 

• Low self-esteem 

• Feelings that the individual does not fit in or 

is not popular 

• Feeling sluggish or exhibiting sleep disturbances 

• An aggressive or rebellious attitude toward 

authority figures 

• Difficulty paying attention 

• A shift in pattern of attending social functions 

• Vague physical complaints that the subject indicates 

need to be treated by drugs or exaggeration of 


• A family history of substance or alcohol abuse 

• Seeing multiple physicians for prescriptions 

(“doctor shopping”) 

• Frequently borrowing money or having unexpected 

extra cash 

Source: References 6, 14, 20, 29. 

as much as 95% at rogue Internet pharmacies. 26 With a 

typically higher prescription volume, the DEA estimates 

that rogue Internet pharmacies may sell 20-fold more 

prescriptions for controlled substances each day than the 

normal brick-and-mortar pharmacy. 26 At least one study, 

however, suggests that the Internet is overestimated as a 

direct source for illicit drug procurement. 28 

Warning Signs 

What can a concerned parent, pharmacist, or other 

health professional do to prevent or stop prescription 

drug abuse? Individuals who are prone to abusing prescription 

drugs do not advertise the fact but often exhibit 

certain traits that can be signals to health professionals 

or loved ones that the person is at risk and may need 

monitoring or intervention. Some behavioral traits that 

experts believe might trigger suspicion of drug abuse are 

listed in TABLE 3. 6,14,20,29 Patients may also employ various 

deceptive practices when dealing with health professionals 

in order to procure prescriptions or products for 

illicit purposes (TABLE 4). 20 

Patients who are concerned about their own risk of 

abuse and are seeking guidance can be directed by the 

pharmacist to the CAGE questionnaire, first proposed 

more than 25 years ago as a screening mechanism to detect 

alcoholism. 30 The questionnaire has been adapted for 

prescription drug abuse, where patients ask themselves 

four questions (TABLE 5). 31 The patient who answers two 

or more questions affirmatively may be showing indications 

of a probable drug addiction. Even a single affirmative 

65 



Table 4 

Deceptive Practices Used 

to Procure Prescriptions 

• The patient must be seen right away 

• The patient is visiting friends or relatives or is 

passing through town and cannot see his or her 

regular physician 

• The individual claims to be a patient of a practitioner 

who is unavailable, or will not name the practitioner 

• The individual requests only specific drug brand 

names and is reluctant to try an alternative or 

claims to be “allergic” or nonresponsive to 

nonopiate alternatives 

• The patient shows unusual knowledge of controlled 

substances 

• The patient claims that his or her prescription has 

been lost or stolen 

• The patient pressures the practitioner by eliciting 

sympathy or guilt or uses direct threats 

• The patient uses a surrogate, such as a child, when 

seeking methylphenidate, or an elderly person when 

seeking opiates 


answer may deserve further evaluation and should be 

referred to a health care professional. 

Prescription Drug Monitoring Programs 

Regulators have taken several steps in an attempt to minimize 

the diversion of prescription products and the 

proliferation of prescription drug abuse. One measure that 

has grown over the past decade is the institution of national 

or local prescription monitoring programs that attempt 

to detect suspicious patterns of controlled-substance use. 

Federal Programs: Nationally, the National All Schedules 

Prescription Electronic Reporting (NASPER) Act was 

signed into law in August 2005. 32 The intent of NASPER 

was to establish a national electronic system that would 

monitor Schedule II, III, and IV controlled-substance 

prescriptions. It would be administered by the states and 

would enable health care providers to have timely and 

accurate access to prescription history information that 

could be used in the early identification of patients at risk 

for addiction or diversion and would encourage appropriate 

medical intervention. 32,33 

Under this law, each time a controlled substance was 

dispensed, the pharmacist would be required to report 

to Health and Human Services (HHS) specific information 

about the controlled substance, including: 1) identifying 

the patient; 2) name, date, and quantity of the 

drug dispensed; 3) number of refills ordered; 4) practitioner 

who signed the prescription; and 5) identity of 

the dispenser. Compilations of this information would 

be provided to practitioners (i.e., physicians, pharmacists, 

other licensed persons) who certify that they need this 

information to provide care to a current patient. HHS 

would also be permitted to provide compilations of this 

information to any local, state, or federal law enforcement, 

narcotics control, licensure, or disciplinary authority 

requesting the information as part of an ongoing drug 

diversion investigation. 32 

NASPER attempts to minimize doctor shopping, 

particularly by users who cross state lines, a limitation of 

individual state programs (discussed later). In order to 

receive funding under the Act, a state must collect data 

on Schedules II, III, and IV drugs and must meet standards 

that enable data sharing. 34 In this way, users who try to 

circumvent local monitoring by presenting prescriptions 

in multiple locations would be subject to detection; this 

would be more difficult to monitor when done on a stateby-state 

basis. In 2007, the first pilot project was initiated 

for sharing of information between states (Nevada and 

California). 34 The measure was also supported by the 

National Association of Chain Drug Stores (NACDS), 

which favored uniform standards that would apply in all 

states where a chain operates pharmacies. The Act authorized 

$60 million from 2006 to 2010 for grants to establish 

or improve state-run prescription drug monitoring 

programs; however, funding has yet to be committed. 34 

State Programs: Although the federal program has been 

slow to launch, as of November 2008, 38 states had enacted 

legislation that would require prescription drug monitoring 

programs (32 are currently in operation and 6 are in 

the start-up phase). 34 However, the state programs vary in 

their design and requirements. A current summary of state 

programs can be found on the DEA Web site. 34 All of the 

states track Schedule II drugs and most, but not all, also 

track Schedule III and IV; some also include Schedule V 

drugs. An additional 11 states are reportedly considering 

legislation; the only holdouts at this time are Wisconsin 

and the District of Columbia. Every state program contains 

safeguards to protect patient confidentiality. Only those 

Table 5 

CAGE Questionnaire for 


1 Have you ever felt the need to Cut down on your use 

of prescription drugs? 

2. Have you ever felt Annoyed by remarks your friends or 

loved ones made about your use of prescription drugs? 

3. Have you ever felt Guilty or remorseful about your use 

of prescription drugs? 

4. Have you Ever used prescription drugs as a way to 

“get going” or to “calm down”? 


66 



individuals who are authorized by statute or regulation 

can access the controlled-substance prescription information. 

34 Some state programs proactively notify physicians 

when their patients are seeing multiple prescribers for the 

same class of drugs, which should assist health care professionals 

in managing patients. 

One of the advantages noted by the DEA in an electronic 

information system is that it would eliminate the 

need for investigators to visit each location to obtain 

prescription information. 34 Some of the expected benefits 

of these programs include deterrence and identification of 

illegal activity such as prescription forgery, indiscriminate 

prescribing, and doctor shopping; the agency believes that 

it has already been successful in thwarting diversion in a 

number of states. 

The first state program, which many other states have 

used as a model, is the KASPER (Kentucky All Schedule 

Prescription Electronic Reporting) program, established 

in 1998 in Kentucky. 31 KASPER is a reporting system 

designed to be both a source of information for practitioners 

and pharmacists and an investigative tool for law 

enforcement personnel. KASPER tracks controlledsubstance 

prescriptions dispensed within the state and 

shows all scheduled prescriptions for an individual over 

a specified time period, the prescriber, and the dispenser. 

KASPER specifically indicates that it is not intended to 

prevent people from obtaining needed drugs or to decrease 

the number of doses dispensed. The state also claims that 

access to KASPER reports are carefully controlled through 

identity and credential checks and secure Web access. 

KASPER reports are available only to prescribers and 

dispensers for medical treatment of a current or prospective 

patient; law enforcement officers for a bona fide 

drug-related investigation; licensure boards for an investigation 

of a licensee; Medicaid for utilization review on 

a recipient; a grand jury by subpoena; and a judge, 

probation, or parole officer administering a drug diversion 

or probation program. 

Some states have approached the diversion problem 

in a different way. For example, a few states mandate the 

use of state-issued multiple-part prescription forms for 

Schedule II drugs that can be monitored. 35 Pharmacists 

are cautioned to stay up to date on their state’s current 

requirements. 

Effects on Legitimate Use for Pain 

Although the abuse of prescription drugs has become a 

serious problem, the response by law enforcement and 

other concerned agencies to limit diversion has also created 

a therapeutic dilemma. At stake is whether the concern 

over diversion and the possibility of addiction impacts the 

legitimate treatment of pain by making prescribers reluctant 

to provide analgesic drugs or stigmatizing patients 

who receive chronic pain medications. 8 

In general, attitudes towards opioids in pain management 

have undergone cyclical changes over the past few 

decades. In the middle of the 20th century, irrational fear 

of addiction resulted in the withholding of opioids from 

patients until they were close to death, a position even 

held by the president of the American Medical Association 

(AMA) in the 1940s. 36 In the latter part of the 20th 

century, the pendulum swung in the opposite direction 

with the emergence of the apparently erroneous belief that 

chronic pain patients were immune to the risks of aberrant 

drug-seeking behavior. 36 The dilemma between appropriate 

pain management and the concern over the risk of 

addiction and diversion continues to influence the prescribing 

of opioid drugs today. 

In 2007, the American Pain Foundation conducted a 

survey of health care practitioners including primary care 

physicians, pain specialists, nurse practitioners, and physician 

assistants. 37 It found that more than three-fourths of 

the respondents felt that moderate-to-severe noncancer 

pain is undertreated in the U.S. The reasons for any 

undertreatment include many factors. Nearly 75% of 

surveyed physicians refrained from prescribing controlled 

drugs because of concern over addiction, and physicians 

were especially wary about prescribing controlled drugs 

to a patient with a history of drug or alcohol abuse. 11,37 

Nevertheless, 77% said that current drug control laws and 

policies impact their opioid-prescribing practices, and most 

practitioners felt that many of their patients face prejudices 

while filling their prescriptions for opioids. 

In a survey of pharmacists, a large number of respondents 

did not view the chronic prescribing or dispensing 

of opioids for more than several months to patients with 

chronic pain of malignant or nonmalignant origin as a 

lawful and acceptable medical practice, especially when 

the patient had a history of opioid abuse. 21 

Federal and state law and policy can also influence 

prescribing practices. For example, DEA regulations 

require that all prescriptions for controlled substances 

“be dated as of, and signed on, the day when issued.” 38 

However, longstanding federal law and DEA regulations 

provide no express requirement that a prescription be 

filled within a certain time frame after it was issued. In 

2007, the DEA issued a revised rule allowing practitioners 

to provide individual patients with multiple prescriptions 

to be filled sequentially for the same Schedule II controlled 

substance, with such multiple prescriptions having the 

effect of allowing a patient to receive up to a 90-day 

supply of the controlled substance, a benefit for the 

terminally ill. 38 

Individual states, however, can have more restrictive 

policies, and pharmacists need to be aware of the policies 

in their state. Currently, 47 states and the District 

of Columbia have pain management policies (i.e., from 

a medical or pharmacy board), the exceptions being 

Alaska, Delaware, Illinois, and Indiana at the time this 

lesson was prepared. 39 For example, pain policies in 

eight states restrict the quantity of prescription medications 

that can be prescribed and dispensed at one time, 

67 



stipulating either a maximum number of dosage units 

(100-120) or duration (30-day or 1-month supply) 

irrespective of patient need. 39 Similarly, the number of 

days within which a prescription for a controlled substance 

must be dispensed following its issuance is not 

regulated by federal law or the laws of most states. 

However, policies in some states restrict the length of 

time that a Schedule II prescription is valid to less than 

2 weeks; the state of Hawaii limits the period of validity 

to as little as 3 days. These policies are established 

in an apparent effort to prevent “uncashed,” although 

valid, prescriptions from being used as a possible source 

of diversion. 39 

Other policies that can affect pain management include 

statutes in 14 states and regulations in two states that 

classify physical dependence as synonymous with addiction, 

effectively making a prescription that is being used 

to reduce withdrawal in a terminally ill patient an invalid 

prescription. 39 Other state policies reserve opioids as a 

treatment of last resort, recommend drug holidays as a 

part of prescribing, or limit the off-label use of certain 

drugs. Other polices exist that impact pharmacy practice; 

for example, Michigan and Oregon have legislation 

mandating continuing education about pain management 

for pharmacists. 39 

Summary and Conclusions 

It is clear that many of the prescriptions dispensed by 

pharmacists each year are diverted for inappropriate 

use and that this problem is growing, particularly 

among adolescents. Patients may receive prescriptions 

from multiple physicians or deceive physicians into 

writing prescriptions for the wrong reasons. Other 

individuals receive or purchase unwanted drugs from 

family or friends, while some resort to outright theft 

from family or pharmacies. 

The pharmacist needs to be aware of the potential 

for drug diversion, recognize the warning signs of possible 

misuse, and acknowledge a legal obligation to 

minimize the use of prescription drugs for improper 

purposes. Pharmacists also need to proactively disabuse 

the public of the notion that prescription drug abuse 

represents a safe alternative to street drugs, since statistics 

show that drug-induced morbidity and mortality 

continue to rise. In addition, pharmacists need to 

be aware of their state (and possible multistate or 

federal) prescription drug monitoring programs. By 

taking an active role in reducing the incidence of 

prescription drug abuse, the pharmacist makes a valuable 

contribution to society. 

References available online at www.uspharmacist.com. 

■ Disclosure Statements: 

Dr. Gianutsos has no actual or potential conflict of interest in relation to 

this activity. 

U.S. Pharmacist does not view the existence of relationships as an implication 

of bias or that the value of the material is decreased. The content of the activity 

was planned to be balanced, objective, and scientifically rigorous. Occasionally, 

authors may express opinions that represent their own viewpoint. Conclusions 

drawn by participants should be derived from objective analysis of 

scientific data. 

■ Disclaimer: 

Participants have an implied responsibility to use the newly acquired information 

to enhance patient outcomes and their own professional development. The information 

presented in this activity is not meant to serve as a guideline for patient 

management. Any procedures, medications, or other courses of diagnosis or treatment 

discussed or suggested in this activity should not be used by clinicians 

without evaluation of their patients’ conditions and possible contraindications or 

dangers in use, review of any applicable manufacturer’s product information, 

and comparison with recommendations of other authorities. 

EXAMINATION 

Select one correct answer for each question and record 

your responses on the examination answer sheet. Mail 

it to U.S. Pharmacist, address shown on the answer 

sheet (photocopies are acceptable). Please allow four 

weeks for processing. Alternatively, this exam can be 

taken online at www.uspharmacist.com. Please 

contact CE Customer Service at (800) 825-4696 or 

cecustomerservice@jobson.com with any questions. 

2 CE Credits 



1. The abuse of prescription drugs by teenagers 

and young adults: 

A. Has become the second most common form of 

drug abuse 

B. Is common but less frequent than the abuse of 

cocaine or heroin 

C. Has gradually declined over the past decade 

D. Is less frequent than abuse in the 40- to 50-yearold 

age group 

2. The class of prescription drugs most commonly 

abused is: 

A. Stimulants C. Antianxiety drugs 

B. Opiates D. Steroids 

3. The percentage of teens who reported 

improperly receiving prescription pain relievers 

from friends and relatives for free is 

approximately: 

A. 10% C. Nearly half 

B. 25% D. Less than 1% 

4. The incidence of prescription drug abuse has 

increased: 

A. At the same rate as the growth of prescription 

volume 

B. Proportionally to the increase in the U.S. population 

68 



C. Much faster than both the increase in prescription 

volume and the population 

D. But has declined relative to population growth 

5. Death from drug overdose: 

A. Rarely occurs from accidental misuse 

B. Is the second leading cause of accidental death 

in the U.S. 

C. Occurs with either street drugs or prescription 

drugs, but is rarely seen as a combination 

of these 

D. Has declined in the past decade due to more 

available information on the dangers of drug use 

11. If a pharmacist has reason to believe that a 

prescription for a controlled substance has been 

written for a nonmedical purpose, he/she: 

A. May wish to take some action but is under no 

obligation to do so 

B. Fulfills his/her obligation if he/she contacts the 

physician and documents that the physician wrote 

the suspicious prescription 

C. Must fill the suspicious prescription if he/she can 

verify that it was written by a legitimate physician 

D. Should refuse to fill the prescription even if the 

physician verifies that he/she wrote the 

prescription 

6. Overdose from prescription drugs: 

A. Leads to more deaths than from heroin 

B. Is common, but trails far behind deaths attributed 

to heroin 

C. Is rare because the standardization of prescription 

drugs and dosing leads to greater safety 

D. Costs the U.S. health care system between 

$10 and $20 billion annually 

7. ______ of pharmacists surveyed considered 

prescription drug diversion a problem in their 

community. 

A. 10% 

B. 25% 

C. Nearly half 

D. More than 90% 

8. Pharmacists believe that the biggest cause of 

prescription drug diversion is: 

A. Obtaining prescriptions for the same drug from 

different physicians 

B. Theft of prescription pads 

C. Theft from pharmacies 

D. Sale of illegitimate prescriptions by physicians 

9. When pharmacists were asked what 

they would do if they suspected a patient 

of abusing or diverting a controlled 

prescription drug, the most common 

answer was: 

A. Call the police or the DEA 

B. Refuse to fill the prescription 

C. Call the physician for verification 

D. Take no action 

10. The percentage of surveyed pharmacies 

experiencing thefts of prescription drugs over a 

5-year period is approximately: 

A. 5% 

B. 10% 

C. 30% 

D. 50% 

12. Which statement about Internet pharmacies 

is true? 

A. Internet pharmacies cannot supply Schedule II 

drugs 

B. Internet pharmacies using a patient 

questionnaire are complying with standard 

medical practice 

C. Many Internet pharmacies operate outside of the 

U.S. and are beyond the reach of the DEA 

D. The volume of controlled drug prescriptions from 

Internet pharmacies is roughly comparable to a 

traditional brick-and-mortar pharmacy 

13. Applying DEA guidelines, which of the 

following situations would not be a reason to 

question the legitimacy of a controlled drug 

prescription? 

A. A prescription is written too legibly 

B. A patient presents multiple prescriptions for the 

same drug for different people 

C. A patient is receiving large quantities of an opiate 

drug on a regular basis 

D. A patient presents prescriptions for an opiate and 

a stimulant at the same time 

14. “Doctor shopping” refers to: 

A. Seeking out a physician who will write a 

prescription for a controlled drug for a fee 

B. Obtaining prescriptions for the same controlled 

drug from multiple prescribers 

C. Paying other individuals to obtain a prescription 

for a controlled drug from a physician 

D. Buying prescriptions from unlicensed physicians 

operating on the Internet 

15. Which of the following situations has been 

cited as potentially raising a suspicion that a 

patient is misusing prescription drugs? 

A. The patient claims to be “allergic” to 

noncontrolled alternative medications 

B. The patient demands only a brand name of a 

controlled drug 

69 


Examination Answer Sheet 

Credits: 2.0 hours (0.20 ceu) 

Expires: December 31, 2011 

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Lesson 106448 Type of Activity: Knowledge 0430-0000-09-030-H03-T 

✁ 

PRESCRIPTION DRUG ABUSE 

C. The patient, who has insurance, wants to pay cash 

for the drug 

D. All of the above 

16. State prescription drug monitoring programs: 

A. Have been established in all 50 states 

B. Are uniform in all states 

C. Monitor the prescribing of Schedule II–V drugs in 

all states that have programs 

D. Do not yet permit nationwide sharing of 

information between all states 

17. The KASPER prescription drug monitoring 

program in Kentucky: 

A. Is the first state program in the U.S. 

B. Permits physicians to access reports but not 

pharmacists 

C. Requests the name of the prescriber of each 

controlled-substance prescription on reports but 

does not identify where prescriptions were filled 

D. Is intended to decrease the number of dosages 

dispensed for opiates 

18. In a typical prescription drug monitoring 

program, a report of controlled substances 

dispensed is available to: 

A. State licensing boards during an investigation 

B. Medicaid 

C. A patient’s parole officer 

D. All of the above 

19. Physicians and pharmacists surveyed about 

prescription opiates: 

A. Are wary of prescribing or dispensing opiates 

to patients, especially if they have a history 

of abuse 

B. Feel that prescribing or dispensing chronic opiates 

to patients with nonmalignant pain is appropriate 

C. Do not feel that current regulations have an effect 

on prescribing opiates 

D. Do not believe that patients receiving opiates are 

stigmatized 

20. Which statement is false with respect to 

prescriptions for opioid drugs? 

A. The number of opioid doses that can be prescribed 

by a physician is limited to a 30-day supply by 

the DEA 

B. The number of opioid doses that can be dispensed 

by a pharmacist is limited by the laws and policies 

of some states 

C. Some states restrict the period that an unfilled 

prescription for a Schedule II drug is valid, and 

this can be as short as 3 days 

D. Some state policies equate addiction with 

physical dependence 

70 


U.S. Pharmacist Classifieds 

CAREER OPPORTUNITIES 

We are currently hiring for the following positions: 

● Director of Pharmacy 

DE – Smyrna 

IA – Sheldon 

KY – Prestonburg 

● Assistant Director of Pharmacy 

NC – Wilmington 

● System Clinical Manager 

LA – Shreveport 

● Clinical Staff Pharmacist 

TX - Odessa; San Antonio 

● Staff Pharmacist 

AZ - Mesa 

CT – Sharon 

DE – Smyrna 

FL– Tampa (PRN) 

NV – N. Las Vegas (PRN) 

● Pharmacy Technicians 

AZ – Mesa; Phoenix 

DE – Smyrna 

LA – Shreveport (2) 

MD – Rockville 

RI – Westerly 

● Clinical Manager 

TX – Bryan 

PA – Waynesburg 

TX – Sulphur Springs (PRN); 

San Antonio (1) F/T, 

(1) PRN; 

TX – The Woodlands (PRN) 

TX – Bryan; Odessa 

UT – Layton 

WV – Princeton 

UT – Salt Lake City (PRN) 

WV – Bluefield (P/T) 

WY – Rocksprings 

● R x e-source SM (Staff Pharmacists at Remote Centers, 7on/7 off Overnight) 

CA – Glendale NC – Cary MA – Marlborough 

● Senior Consultant, Clinical Operations 

IN – Indianapolis 

● Clinical Specialist, Critical Care 

NY – Valhalla 

VA – Newport News 

MI – Grand Rapids 


● Quality Training Manager 

TX – Houston 

FL – Port St. Lucie 

TX – The Woodlands 

Nome, Alaska 

Where else might you see musk oxen and sled dogs 

on your way to work and still pan for gold on the beach? 

Serve the people of northwest Alaska in a unique, comprehensive health system 

in a vast, stark and fiercely beautiful yet surprisingly livable Seward Peninsula. 

Director of Pharmacy: $140,000+ DOE, benefits, relocation allowance 

and potential for student loan repayment from the Indian Health Service. 

Norton Sound Health Corporation 

Steve Brock 

sbrock@nshcorp.org | 877-538-3142 

(NO Recruitment firms or agency reps) 

Who is Cardinal Health? 

• Leading, global provider of information, products, services 

and technologies for the health care industry 

• Ranked 18th in Fortune 500 

• 30,000 employees worldwide 

• $87 billion global company 

Who is Pharmacy Solutions? 

• We bring 40 years of expertise in helping hospitals and healthcare 

systems improve both the financial predictability of pharmacies 

and the quality of patient care. 

• 1,000 pharmacists employed, including 110 clinical specialists 

• Participate in more than 140 accreditation survey reviews each year 

• We process four million order lines remotely each year and identified 

20,000 patient safety events through our R x e-source SM centers 

in 2008 

• R x e-view TM solution is an automated medication order management 

and clinical intervention tracking tool 

• We also offer a customized portfolio of drug contracts 

For information or to apply, 

call 800-231-9807 ext. 1315 

or fax 281-749-2026 


To place a classified ad, call: 

Toll Free: (800) 983-7737 

Phone: (610) 854-3770 

Fax: (610) 854-3780 

PRODUCTS AND SERVICES 

FILL RXS FASTER- TIME IS LIFE phone or fax NOW: 

1-800-487-5024 

Improved...Shake & Roll speedy tab/cap counter. 

Durable, maintenance-free, over 20,000 sold. 

$129. 85 + frght, 30-day free trial. (eliminate Count- 

Fatigue forever - be happy). 

Chem-Pharm Corp 

Box 6246, West Palm Beach, FL 33405.

U.S. Pharmacist Classifieds 


To place a classified ad, call: 

Toll Free: (800) 983-7737 

Phone: (610) 854-3770 

Fax: (610) 854-3780 

A D 

I NDEX 

National 

Coca-Cola Co. . . . . . . . . . . . . . . . . . 5 

CorePharma LLC . . . . . . . . . . . CV4 

Eli Lilly and Company . . . . . . . . . . 18 

Falcon Pharmaceuticals . . . . . . . . 24 

Fougera . . . . . . . . . . . . . . . . . . . . . . 9 

Gallipot . . . . . . . . . . . . . . . . . . . . . 55 

Greenstone LLC . . . . . . . . . . . . . . 11 

King Pharmaceuticals, Inc. . . . . . . 45 

Mylan Pharmaceuticals Inc. . . . . . . 7 

Novartis Pharmaceuticals . . . . . . . 35 

Pfizer Inc. . . . . . . . . . . . . . . . . . . . 38 

Takeda Pharmaceuticals 

North America . . . . . . . . . . . CV2, 76 

Teva Pharmaceuticals . . . . . . . . . . 13 

URL Pharma . . . . . . . . . . . . . . . . . 27 

Health Systems 

Baxter Healthcare . . . . . . . . . . HS07 

Cubist Pharmaceuticals . . . . . . HS03 

Dr. Reddy's . . . . . . . . . . . . . . . HS09 

Eli Lilly and Company . . . . . . . HS13 

Medi-Dose Group . . . . . . . . . . 51-HS 

Pfizer Injectables . . . . . . HS01, HS15 

Teva Pharmaceuticals . . . . . . . .HS11 

New Products - National 

Authorized Generics / 

Greenstone LLC . . . . . . . . . . . . . . . . . 11 

Afinitor / Novartis Pharmaceuticals . .35 

Brimonidine Tartrate Ophthalmic Solution / 

Falcon Pharmaceuticals . . . . . . . . . .24 

Embeda / King Pharmaceuticals, Inc. . 45 

New Products - National 

Kapidex / Takeda Pharmaceuticals 

North America . . . . . . . . . . . . . . . . . . .76 

Methenamine Hippurate / 

CorePharma LLC . . . . . . . . . . . . . . CV4 

Uloric / Takeda Pharmaceuticals 

North America . . . . . . . . . . . . . . . . . CV2 

New Products - Health Systems 

Distinctive Labeling / Baxter 

Healthcare . . . . . . . . . . . . . . . . HS07 

Product Labeling / 

Teva Pharmaceuticals . . . . . . . .HS11 

Injectables / 

Pfizer Injectables . . . . . . HS01, HS15

Product News 

Mirixa Corporation 

Announces MirixaEdge 

Mirixa Corporation, a pharmacybased 

patient care service, has 

announced the launch of Mirixa- 

Edge. MirixaEdge enables pharmacists 

to design their own patient 

care programs for any of their 

patients, regardless of health plan, 

employer, or age. MirixaEdge 

helps set in motion the process of 

personalized program creation by 

providing pharmacists with predefined 

templates for conditions 

such as asthma, diabetes, and cardiovascular 

disease. Templates for 

medication therapy management 

also are available. 

Teva Introduces 

Extended-Release Tablets 

Teva Pharmaceuticals has 

announced the introduction and 

availability of fexofenadine hydrochloride 

(HCl) and pseudoephedrine 

HCl extended-release (ER) 

tablets. This product is the same 

as Allegra-D (sanofi-aventis U.S.) 

12 Hour (fexofenadine HCl 60 

mg/pseudoephedrine HCl 120 

mg) ER Tablets. Fexofenadine 

HCl and pseudoephedrine HCl 

ER tablets are available in 

60-mg/120-mg strength, in bottle 

sizes of 100 and 500. 

FDA Approves 

Pennsaid Topical Solution 

Covidien, a global health care 

products company, and Nuvo 

Research Inc., a Canadian drug 

development company, has 

announced FDA approval of 

Pennsaid Topical Solution (diclofenac 

sodium topical solution) 

1.5% w/w. Pennsaid Topical Solution 

is a nonsteroidal anti-inflammatory 

drug used for the treatment 

of the signs and symptoms 

of osteoarthritis of the knee. 

Sandoz Launches Authorized 

Generic Prevacid Capsules 

Sandoz, a division of Novartis, has 

introduced lansoprazole delayedrelease 

(DR) capsules, an authorized 

generic equivalent of 

Prevacid, in the U.S. Lansoprazole 

is a proton pump inhibitor indicated 

for the treatment of active 

duodenal and gastric ulcers and 

the common symptoms of gastroesophageal 

reflux disease, including 

heartburn and erosive esophagitis. 

Lansoprazole DR capsules 

offer the same efficacy and 

strength as Prevacid. 

Genzyme Launches Renvela 

Genzyme Corporation has 

announced the U.S. launch of 

Renvela (sevelamer carbonate) for 

oral suspension, a powder dosing 

option for the control of serum 

phosphorus in patients with 

chronic kidney disease who are on 

dialysis. Renvela is a next-generation 

version of Renagel (sevelamer 

HCl) and is the only phosphate 

binder available in both tablet and 

powder form. 

Prasco Partners With sanofiaventis 

to Market Generics 

Prasco Laboratories has entered 

into agreements with Winthrop 

U.S., a business of sanofi-aventis 

U.S., to provide sales support and 

distribution services to Winthrop 

U.S. for authorized generic versions 

of Allegra-D 12 Hour ER 

tablets and Drisdol (ergocalciferol) 

capsules in the U.S. under the 

Winthrop label. 

Medi-Dose Releases New 

Addition to Packaging Line 

To complement its existing products, 

Medi-Dose, Inc., has introduced 

new Deeper Oval Medi-Cup 

Blisters. The deeper capacity 

accommodates larger medications, 

including most 

fish oil tablets, 

AIDS medications, 

and veterinary medicines. 

Produced in green Nultraviolet 

plastic, the Deeper Oval Medi-Cup 

Blister provides the same tamper 

evidence, moisture resistance, and 

ultraviolet inhibitance as other 

Medi-Dose products. 

FDA Approves New Drug 

Treatment for Shingles 

NeurogesX, Inc., has announced 

FDA approval of Qutenza (capsaicin) 

8%, a medicated skin patch 

that relieves the pain of postherpetic 

neuralgia, a serious complication 

that can occur after an 

attack of shingles. Qutenza delivers 

a synthetic form of capsaicin 

through a topical delivery system, 

providing up to 12 weeks of 

reduced pain following a single 

1-hour application. 

73 


KAPIDEX WORKS A 

SECOND SHIFT 

TO HELP SHUT DOWN ACID PUMPS

KAPIDEX is the first and only PPI with a 

Dual Delayed Release (DDR) formulation, 

which provides a second release of drug 

1200 

Mean plasma concentration (in healthy subjects; day 5; ng/mL) 1 

1000 

800 

600 

400 

200 

KAPIDEX 60 mg 

KAPIDEX 30 mg 

0 

0 6 12 18 24 

Time (h) 

• KAPIDEX 30 mg provided full 24-hour heartburn relief in a majority of symptomatic 

non-erosive gastroesophageal reflux disease patients at week 4 1 

• KAPIDEX 60 mg provided consistently high erosive esophagitis healing rates 

at week 8 1 

• KAPIDEX offers a safety and tolerability profile similar to lansoprazole 1 

• KAPIDEX can be taken without regard to food 1 

KAPIDEX should be swallowed whole. Alternatively, capsules can be opened, 

sprinkled on 1 tablespoon of applesauce, and swallowed immediately. While 

KAPIDEX can be taken without regard to food, some patients may benefit from 

administering the dose prior to a meal if post-meal symptoms do not resolve 

under post-fed conditions. 

Conclusions of comparative efficacy cannot be drawn from this information. 

Indications 

KAPIDEX is indicated for healing all grades of erosive esophagitis (EE) for 

up to 8 weeks, maintaining healing of EE for up to 6 months, and treating 

heartburn associated with symptomatic non-erosive gastroesophageal reflux 

disease (GERD) for 4 weeks. 


KAPIDEX is contraindicated in patients with known hypersensitivity to any 

component of the formulation. Hypersensitivity and anaphylaxis have been reported 

with KAPIDEX use. Symptomatic response with KAPIDEX does not preclude the 

presence of gastric malignancy. Most commonly reported treatment-emergent 

adverse reactions (≥2%): diarrhea (4.8%), abdominal pain (4.0%), nausea (2.9%), 

upper respiratory tract infection (1.9%), vomiting (1.6%), and flatulence (1.6%). 

Do not co-administer atazanavir with KAPIDEX because atazanavir systemic 

concentrations may be substantially decreased. KAPIDEX may interfere with 

absorption of drugs for which gastric pH is important for bioavailability (e.g., 

ampicillin esters, digoxin, iron salts, ketoconazole). Patients taking concomitant 

warfarin may require monitoring for increases in international normalized ratio 

(INR) and prothrombin time. Increases in INR and prothrombin time may lead to 

abnormal bleeding, which can lead to serious consequences. Concomitant 

tacrolimus use may increase tacrolimus whole blood concentrations. 

Please see adjacent brief summary of prescribing information for KAPIDEX.

BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION 

KAPIDEX (dexlansoprazole) delayed release capsules 


KAPIDEX is indicated for: 

 

 

 

 


 

 

[see Adverse Reactions] 


Gastric Malignancy 

 

 


Clinical Trials Experience 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 2: Incidence of Treatment-Emergent Adverse 

Reactions in Controlled Studies 

Adverse Reaction 

Placebo 

(N=896) 

% 

KAPIDEX 

30 mg 

(N=455) 

% 

KAPIDEX 

60 mg 

(N=2218) 

% 

KAPIDEX 

Total 

(N=2621) 

% 

Lansoprazole 

30 mg 

(N=1363) 

% 

 

 

 

 

 

Tract Infection 

 

 

 

 

 

 

 

 

Blood and Lymphatic System Disorders: Cardiac 

Disorders: 

Ear and Labyrinth Disorders: 

Endocrine Disorders: Eye Disorders: 

Gastrointestinal Disorders: 

 

 

 

 

 

 

 

 

General Disorders and Administration Site Conditions: 

 

Hepatobiliary Disorders: 

Immune System Disorders: 

Infections and Infestations: 

 

Injury, Poisoning and Procedural Complications: 

Laboratory Investigations: ALP 

 

 

 

Metabolism and Nutrition 

Disorders: Musculoskeletal 

and Connective Tissue Disorders: 

Nervous System Disorders: 

 

Psychiatric Disorders: 

Renal and 

Urinary Disorders: Reproductive System and 

Breast Disorders: 

disorder; Respiratory, Thoracic and Mediastinal Disorders: 

 

Skin and Subcutaneous Tissue Disorders: 

Vascular Disorders: 

 

 

 

 

 

 

 

 

 

 

 

 

 


Drugs with pH-Dependent Absorption Pharmacokinetics 

 

 

 

 

 

 

 

 

 

Warfarin 

 

 

 

 

 

 

 

Tacrolimus 

 

 

 


Pregnancy 

Teratogenic Effects 

 

 

 

 

 

 

 

 

 

 

 

 

 

Nursing Mothers 

 

 

 

 

[see Carcinogenesis, Mutagenesis, Impairment of Fertility] 

 

 

Pediatric Use

Geriatric Use 

 

 

 

 

 

 

Renal Impairment 

 

 

 

 

 

Hepatic Impairment 

 

 

 

 

 

OVERDOSAGE 

 

 

 

 

 


Pharmacodynamics 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

[see Nonclinical Toxicology ] 

 

 

c 

 

 

c 

NONCLINICAL TOXICOLOGY 

Carcinogenesis, Mutagenesis, Impairment of Fertility 

 

 

 

 

 

 

 

[see Clinical Pharmacology]. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PATIENT COUNSELING INFORMATION 

[see FDA-Approved Patient Labeling in the full prescribing information] 

Information for Patients 

 

 

 

 

 

 

 

 

 

 

 

 

Takeda Pharmaceuticals America, Inc. 

 

 

 

 

 

 

 

 

 

 

 

KAPIDEX and Dual Delayed Release are trademarks of Takeda Pharmaceuticals North America, Inc., 

and are used under license by Takeda Pharmaceuticals America, Inc. 

Reference: 1. KAPIDEX (dexlansoprazole) package insert, Takeda Pharmaceuticals America, Inc. 

©2009 Takeda Pharmaceuticals North America, Inc. 

LPD-00827 10/09 Printed in U.S.A.

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