Romark IVA - Digital PDF interaction 10.13

When diarrhea persists more than 14 days…

…which pathogens do you suspect?

ALINIA ® is the only FDA-approved product for the treatment of diarrhea caused by both

Cryptosporidium parvum and Giardia lamblia in patients 1 year of age and older*

*Indications

ALINIA ® for Oral Suspension (patients 1 year of age and older) and ALINIA Tablets (patients 12 years and older) are indicated for the treatment of diarrhea caused by

Giardia lamblia or Cryptosporidium parvum.

Limitations of Use: ALINIA for Oral Suspension and ALINIA Tablets have not been shown to be effective for the treatment of diarrhea caused by Cryptosporidium parvum

in HIV-infected or immunodeficient patients.

Important Safety Information

• ALINIA Tablets and ALINIA for Oral Suspension are contraindicated in patients with a prior hypersensitivity

to nitazoxanide or any other ingredient in the formulations.

• The most common adverse reactions in ≥2% of patients were abdominal pain, headache, chromaturia and nausea.

• Tizoxanide (the active metabolite of nitazoxanide) is highly bound to plasma protein (>99.9%). Therefore, monitor for adverse reactions when administering nitazoxanide

concurrently with other highly plasma protein-bound drugs with narrow therapeutic indices, as competition for binding sites may occur (e.g., warfarin).

• ALINIA tablets and ALINIA for Oral Suspension should be taken with food.

• Safety and efficacy of ALINIA for Oral Suspension in pediatric patients less than one year of age has not been studied.

*Please read the Full Prescribing Information.

To report suspected adverse reactions, contact Romark at 1-813-282-8544 or FDA at 1-800-FDA-1088 or

www.fda.gov/medwatch.

IDSA Guidelines

2

Per 2017 Infectious Disease Society of America (IDSA) guidelines, for patients with

diarrhea that persists ≥ 14 days, consider parasitic pathogens 1

Clinical presentation of chronic diarrhea may be associated with the following pathogens 1 :

Cryptosporidium spp., Giardia lamblia, Cyclospora caytanensis † , Cystoisospora belli † , and Entamoeba histolytica †

†

Nitazoxanide is not indicated for diarrhea caused by these parasites

Considerations when evaluating patients

with infectious diarrhea 1

• International Travel

• Immunocompromised Hosts

• Foodborne/Waterborne Vectors

• Animal Exposure (Zoonoses)

• Antimicrobial Association

• Certain Sexual Practices

• Long-Term Care Facilities

• Child Care Facilities

• Healthcare Associated

*Indications

ALINIA ® for Oral Suspension (patients 1 year of age and older) and ALINIA Tablets (patients 12 years and older)

are indicated for the treatment of diarrhea caused by Giardia lamblia or Cryptosporidium parvum.

Limitations of Use: ALINIA for Oral Suspension and ALINIA Tablets have not been shown to be effective for the

treatment of diarrhea caused by Cryptosporidium parvum in HIV-infected or immunodeficient patients.




AGA Clinical Guidelines

3

In 2019 guidelines, the American Gastroenterology Association (AGA) strongly

recommends: patients with chronic diarrhea should be tested for Giardia 2

Summary of Recommendations on the Laboratory Evaluation of Functional Diarrhea

and Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) † in Adults 2

Statement

recommendation

Recommendation 1: In patients presenting with chronic diarrhea, the AGA suggests the use of either fecal

calprotectin or fecal lactoferrin to screen for IBD

Recommendation 2: In patients presenting with chronic diarrhea, the AGA suggests against the use of ESR or CRP

to screen for IBD

Strength of

recommendation

Conditional

Conditional

Quality of evidence

Low

Low

Recommendation 3: In patients presenting with chronic diarrhea, the AGA recommends testing for Giardia Strong High

Recommendation 4: In patients presenting with chronic diarrhea with no travel history to or recent immigration

from high-risk areas, the AGA suggests against testing stools for ova and parasites (other than Giardia)

Recommendation 5: In patients presenting with chronic diarrhea, the AGA recommends testing for celiac disease

with IgA-tTG and a second test to detect celiac disease in the setting of IgA deficiency

Conditional

Strong

Low

Moderate

Recommendation 6: In patients presenting with chronic diarrhea, the AGA suggests testing for bile acid diarrhea Conditional Low

Recommendation 7: In patients presenting with chronic diarrhea, the AGA makes no recommendation for the use

of currently available serologic tests for diagnosis of IBS

†

Nitazoxanide is not indicated for diarrhea caused by IBD, IBS, or IBS-D

None

Knowledge gap

*Indications








Patient Journey: CDC Study

4

In a recent publication of U.S. insurance claims of 3,000 patients with giardiasis evaluating

diagnosis and treatment practices, it was observed that patient care can be improved 3

Missteps in diagnosis or treatment

Only 18% of patients had a Giardia-specific test followed

by an antiparasitic medication effective against giardiasis 3

27% of patients received a systemic antibiotic ineffective

against Giardia 3

Of 1,000 surveyed pediatricians, approximately 10% said

they would suspect parasites in patients with persistent

diarrhea lasting more than 1 – 2 weeks 4

50% of patients had 3 or more visits to the clinic during

the study window 3

Chronic or persistent disease

22% of patients (n = 657) waited >30 days from their first GI

symptom visit to their first visit with a giardiasis diagnosis 3

Nearly 40% of patients (n=1,192) endured symptoms or

waited for a diagnosis for more than 1-month 3

Following acute infection, giardiasis might also lead to

long-term chronic disease, including IBS 3,5 †

Awareness of parasitic infections can enhance

selection of appropriate treatments and potentially

alleviate the patient’s symptoms earlier

†

Nitazoxanide is not indicated for diarrhea caused by IBS

*Indications








About Giardiasis

5

In the U.S., Giardia is the most common intestinal parasitic infection 6,7

Causes an estimated 1.2 million episodes of

illness annually with the highest incidence

among children aged 1-9 years 3,6,7

Although giardiasis is frequently reported

among travelers returning from endemic

areas, only 7-8% of U.S. giardiasis cases

are travel-associated 3,6,8

Following acute infection, giardiasis may

also lead to long-term chronic disease,

including irritable bowel syndrome (IBS) 3,5 †

Data indicates that in the U.S. there is often a

delayed diagnosis for Giardia 3

When Giardia is diagnosed, over ¼ of those patients

are prescribed a systemic antibiotic ineffective

against giardiasis

Most cases of giardiasis are not accurately

diagnosed. Additionally, many are not properly

treated with the right medications 3,6,7

†

Nitazoxanide is not indicated for diarrhea caused by IBS

*Indications








About Cryptosporidiosis (Crypto)

6

Cryptosporidiosis is a highly underdiagnosed parasitic illness 6,9

Responsible for 89% of all infectious cases

of recreational water disease 9 99% of cases in the U.S. go undiagnosed 6

- Commonly missed by a variety of diagnostic

tests, including ova & parasite (O&P) 10

- In two controlled clinical trials, oocysts were

undetected in 27% to 46% of symptomatic

patients known to have Crypto 11,12

Crypto is protected by an outer shell that

makes it tolerant to chlorine and able

to live outside the body for long periods

of time 9

There’s only one FDA-approved

medication for treating diarrhea caused by

Cryptosporidium parvum

*Indications








ALINIA ® Tablets Clinical Study Design † †

Study design for OS in pediatric patients can be found on page 10 of this presentation7

In clinical trials, patients were enrolled with diarrhea and with

or without enteric symptoms, including 13 :

• Diarrhea

• Nausea

• Fever

• Loss of appetite

• Abdominal pain/cramps

• Vomiting

• Bloating

• Gas

ALINIA demonstrated efficacy against diarrhea with a “well”

clinical response defined as 13 :

• No symptoms, no watery stools and no more than two soft stools with no

hematochezia within the past 24 hours, or

• No symptoms and no unformed stools within the past 48 hours

*Indications

ALINIA ® for Oral Suspension (patients 1 year of age and older) and ALINIA Tablets (patients 12 years and older) are indicated for the treatment of diarrhea caused by

Giardia lamblia or Cryptosporidium parvum.

Limitations of Use: ALINIA for Oral Suspension and ALINIA Tablets have not been shown to be effective for the treatment of diarrhea caused by Cryptosporidium parvum

in HIV-infected or immunodeficient patients.




• The most common adverse reactions in ≥2% of patients were abdominal pain, headache, chromaturia and nausea.

• Tizoxanide (the active metabolite of nitazoxanide) is highly bound to plasma protein (>99.9%). Therefore, monitor for adverse reactions when administering nitazoxanide

concurrently with other highly plasma protein-bound drugs with narrow therapeutic indices, as competition for binding sites may occur (e.g., warfarin).

• ALINIA tablets and ALINIA for Oral Suspension should be taken with food.

• Safety and efficacy of ALINIA for Oral Suspension in pediatric patients less than one year of age has not been studied.

*Please read the Full Prescribing Information.

To report suspected adverse reactions, contact Romark at 1-813-282-8544 or FDA at 1-800-FDA-1088 or

www.fda.gov/medwatch.

ALINIA ® OS Head-to-Head Data

8

ALINIA efficacy vs. metronidazole in pediatric patients with Giardia lamblia 13 :

ALINIA for Oral Suspension (OS), 100 mg/5 mL

Clinical Response Rates a (% “Well”)

Nitazoxanide (3 days treatment) 90% (43/48)

95%

}

Per Protocol b CI Diff

Metronidazole (5 days treatment) 83% (39/47)

-8%, 21%

0% 20% 40% 60% 80% 100%

Randomized, controlled study of 110 pediatric patients treated with ALINIA for Oral Suspension a

a

ALINIA for Oral Suspension 100 mg BID (24-47 months) and 200 mg BID (ages 4-11 years) x 3 days, was compared to metronidazole 125 mg BID (ages

2-5 years) and 250 mg BID (ages 6-11 years) x 5 days; clinical response evaluated 7-10 days after treatment initiation

b

Per protocol analysis includes only patients who took all of their medication and completed the study. Seven patients in each treatment group missed at

least 1 dose of medication and 1 in the metronidazole treatment group was lost to follow-up

*Indications








ALINIA ® Tablets Efficacy

9

ALINIA Tablets, 500 mg, demonstrated efficacy against diarrhea caused by

Cryptosporidium parvum and Giardia lamblia 13

Pathogen and

Study Number

Clinical Response Rate (% “Well”)

Alinia Tablets (n)

Placebo Control (n)

Cryptosporidium 1 96% (28) 41% (27)

Cryptosporidium 2 71% (21) 43% (21)

Giardia 1 85% (54) 44% (27)

Giardia 2 100% (8) 30% (10)

*Indications








ALINIA ® for Oral Suspension (OS) Study Design & Efficacy Data

10

In clinical trials, pediatric patients were enrolled with diarrhea

and with or without enteric symptoms, including 13 :

• Abdominal distention

• Colic

• Nausea

• Left/right iliac fossa tenderness

• Vomiting

ALINIA demonstrated efficacy against diarrhea with a “well”

clinical response defined as 13 :

• No symptoms, no watery stools and no more than two soft stools with no

hematochezia within the past 24 hours, or

• No symptoms and no unformed stools within the past 48 hours


demonstrated efficacy in pediatric patients

with Cryptosporidium parvum 13

Population

Outpatient study

(3 days treatment) age 1-11 years

Clinical Response Rates

Alinia for OS (n) † Placebo Control (n)

88% (24) 38% (24)

†

Clinical response rates statistically significantly higher compared to placebo

*Indications








ALINIA ® OS Head-to-Head Data

11

ALINIA efficacy vs. metronidazole in pediatric patients with Giardia lamblia 13 :


Clinical Response Rates a (% “Well”)

Nitazoxanide (3 days treatment) 90% (43/48)

95%

}

Per Protocol b CI Diff

Metronidazole (5 days treatment) 83% (39/47)

-8%, 21%

0% 20% 40% 60% 80% 100%

Randomized, controlled study of 110 pediatric patients treated with ALINIA for Oral Suspension a

a

ALINIA for Oral Suspension 100 mg BID (24-47 months) and 200 mg BID (ages 4-11 years) x 3 days, was compared to metronidazole 125 mg BID (ages

2-5 years) and 250 mg BID (ages 6-11 years) x 5 days; clinical response evaluated 7-10 days after treatment initiation

b

Per protocol analysis includes only patients who took all of their medication and completed the study. Seven patients in each treatment group missed at

least 1 dose of medication and 1 in the metronidazole treatment group was lost to follow-up

*Indications








How & Where ALINIA ® Works 12

How ALINIA works

• ALINIA is the first in class and only FDA-approved thiazolide

• The antiprotozoal activity of ALINIA is believed to be due to interference with

PFOR enzyme-dependent electron transfer reaction, which is essential to

anaerobic energy metabolism. This may not be the only pathway by which

nitazoxanide exhibits antiprotozoal activity 13

• Nitazoxanide is absorbed through the intestine and rapidly converted to the

active metabolite, tizoxanide, circulating in the blood 13

Where ALINIA works

• Approximately 2⁄3 of the oral dose of nitazoxanide is excreted in the feces

and 1⁄3 in the urine 13

• ALINIA treats diarrhea caused by an intracellular pathogen (Cryptosporidium

parvum) and a lumenal anaerobic pathogen (Giardia lamblia) 13

*Indications








ALINIA ® Safety Profile

13

Most Common Adverse Reactions

≥2% of Patients †

Abdominal pain

Headache

Chromaturia

Nausea

†

In pooled controlled clinical trials involving 536 HIV-uninfected subjects treated with ALINIA tablets or ALINIA for oral suspension 14

• Adverse events similar to placebo in clinical trials using the recommended dose 14

• Less than 1% of patients discontinued in clinical trials due to adverse events 14

• No significant inhibitory effect on cytochrome P450 enzymes 13

*Indications








ALINIA ® Dosing

14

ALINIA Tablets dosing and administration

For patients 12 years and older:

1 tablet (500 mg) po BID x 3 days with food

+

+

+

ALINIA OS dosing and administration

For patients 1 year and older:

1

2

dose

times per day

Age Dosage Duration

1-3 years

5 mL of ALINIA for Oral Suspension (100 mg nitazoxanide) BID with food

3

day course of treatment -

taken with food

4-11 years

≥12 years



3 Days

*Indications








ALINIA ® Patient Savings

15

With the ALINIA co-pay program, your eligible commercially insured patients may pay

as little as $10 per prescription †

• ALINIA is covered by most managed care plans

• Your commercially insured patients can use the ALINIA co-pay card, or if they do not have one,

an e-Voucher may be available

• E-Vouchers are applied automatically for eligible patients at eVoucherRx TM pharmacies

Visit eVoucherRx.RelayHealth.com/storelookup

to find a local participating store

Maximum benefit up to $300 for ALINIA Tablets †

Maximum benefit up to $75 for ALINIA for Oral Suspension †

†

Terms and conditions apply. Get more information here

You can also eScribe to one of ALINIA national pharmacy

partners for fast and discreet home delivery:

• Foundation Care Pharmacy: Earth City, MO (NCPDP Provider ID: 26355)

• PantherRx: Pittsburgh, PA 15275 (NPI: 1316213531)

*Indications








References

16

1. Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America Clinical Practices Guidelines for the Diagnosis and Management of Infectious Diarrhea.

Clin Infect Dis 2017;65(12):e45-e80.

2. Smalley W, Falck-Ytter C, Carrasco-Labra A, Wani S, Lytvyn L, Falck-Ytter Y. AGA Clinical Practice Guidelines on the Laboratory Evaluation of Functional Diarrhea and

Diarrhea-Predominant Irritable Bowel Syndrome in Adults (IBS-D). Gastroenterology 2019;157(3):851-854.

3. Beer KD, Collier SA, Du F, Gargano JW. Giardiasis Diagnosis and Treatment Practices Among Commercially Insured Persons in the United States. Clin Infect Dis

2017;64(9):1244-1250.

4. Attias E, Czinn SJ, Harro C, Munoz FM, Sockolow RE, Black JT. Emerging Issues in Managing Pediatric Parasitic Infections: An Assessment of Clinical and Epidemiological

Knowledge of Giardiasis and Cryptosporidiosis. Pediatr Therapeutics 2015;5(3):1-7.

5. Litleskare S, Rortveit G, Eide GE, Hanevik K, Langeland N, Wensaas K-A. Prevalence of Irritable Bowel Syndrome and Chronic Fatigue 10 Years After Giardia Infection.

Clin Gastroenterol H 2018;16(7): 1064-1072.e4.

6. Scallan E, Hoekstra RM, Angulo FJ, et al. Foodborne illness acquired in the United States—major pathogens. Emerg Infect Dis 2011;17:7–15.

7. Painter JE, Gargano JW, Collier SA, Yoder JS; Centers for Disease Control and Prevention. Giardiasis surveillance—United States, 2011–2012. MMWR Morb Mortal Wkly

Rep Suppl 2015; 64(3):15–25.

8. Chute CG, Smith RP, Baron JA. Risk factors for endemic giardiasis. Am J Public Health. 1987;77:585–7.

9. Hlavsa MC, Cikesh BL, Roberts VA, et al. Outbreaks Associated with Treated Recreational Water — United States, 2000–2014. MMWR Morb Mortal Wkly Rep

2018;67:547–551.

10. Painter JE, Hlavsa MC, Collier SA, et al. Cryptosporidiosis Surveillance, 2011-2012. MMWR Morb Mortal Wkly Rep Suppl 2015;64(3):1-13.

11. Okhuysen PC, et al. Infectivity of a Cryptosporidium parvum Isolate of Cervine Origin for Healthy Adults and Interferon-y Knockout Mice. J Infect Dis. 2002;185:1320-9.

12. Okhuysen PC, et al. Virulence of Three Distinct Cryptosporidium parvum Isolates for Healthy Adults. J Infect Dis. 1999;180:1275-81

13. ALINIA (nitazoxanide) Prescribing Information. June 2019.

14. Romark L.C., data on file.

Alinia is a registered trademark of Romark, L.C. Intended only for Healthcare Professionals of the United States of America. ©2020, Romark L.C. RM-AL-094-01V1 R10.20

*Indications








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