Proton Pump Inhibitors - CME Conferences
Proton Pump Inhibitors - CME Conferences
Proton Pump Inhibitors - CME Conferences
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6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Using Evidence-Based and Cost<br />
Effective Drug Therapy: Where do<br />
Generic Medications Fit?<br />
C. Wayne Weart Pharm. D., BCPS, FASHP,<br />
FAPhA<br />
Professor of Clinical Pharmacy and Outcome<br />
Sciences<br />
Professor of Family Medicine<br />
MUSC Campus SC College of Pharmacy<br />
1<br />
Faculty Disclosure<br />
• I am on the speakers bureau for Pfizer in the<br />
area of lipids and pain<br />
• I am a consultant for Merck in the area of<br />
outcomes research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Cost Consciousness in Patient Care — What Is<br />
Medical<br />
Education’s Responsibility?<br />
Molly Cooke, M.D.<br />
• “Value can be increased through costconscious<br />
diagnostic and management<br />
strategies and by the engineering of better<br />
and less wasteful processes of care.<br />
Evidence-based medicine and comparativeeffectiveness<br />
research help us understand<br />
the relative effectiveness of management<br />
strategies; appreciation of cost and metrics<br />
such as “number needed to treat” help us<br />
approach value.”<br />
– NEJM 2010, 362;14:1253<br />
3<br />
How Many Prescriptions Go Unfilled?<br />
• Oct. 26, 2011 Twenty four percent of patients<br />
given a new medication by their doctor did<br />
not fill the prescription in 2008, according to a<br />
new study by researchers at Harvard<br />
University, Brigham and Women's Hospital<br />
and CVS Caremark and published in the<br />
American Journal of Medicine (2011) 124,<br />
1081.e9-1081.e22<br />
4<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
AARP Rx Watchdog Report<br />
• Rx Price Watch Report August 2010<br />
– Trends in Retail Prices of Brand<br />
Name Prescription Drugs Widely<br />
Used by Medicare Beneficiaries 2005<br />
to 2009<br />
• By Stephen W. Schondelmeyer PRIME Institute,<br />
University of Minnesota<br />
• Leigh Purvis AARP Public Policy Institute<br />
5<br />
Average Annual % Change in Retail<br />
Prices for Widely Used Brand Name<br />
Prescription Medications<br />
AARP Rx Price Watch Report 8-2010 http://www.aarp.org/ppi<br />
6<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Average Annual % Change in Retail<br />
Prices for Widely Used Brand Name<br />
Prescription Medications<br />
AARP Rx Price Watch Report 8-2010 http://www.aarp.org/ppi<br />
7<br />
Generic Medication Use<br />
• In 2010 ~78% of all medications dispensed in<br />
the US were for generic medications<br />
• Recent Harris Poll (1/26/09)<br />
– Found that between Oct 2006 and Dec 2008 the<br />
proportion of adults who would choose generic<br />
drugs over branded drugs increased from 68% to<br />
81%<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
2010 Top 200 Generic Drugs by<br />
Total Prescriptions<br />
Rank Drug Total Rxs % Change from 2009<br />
• 1 Hydrocodone/APAP 122,806,850 2.1%<br />
• 2 Lisinopril 76,901,813 4.3%<br />
• 3 Simvastatin 76,771,821 4.9%<br />
• 4 Levothyroxine 68,222,152 8.2%<br />
• 5 Amoxicillin 51,083,822 -0.6%<br />
• 6 Amlodipine besylate 50,186,652 11.7%<br />
• 7 Azithromycin 48,756,188 -2.1%<br />
• 8 Alprazolam 46,201,182 3.9%<br />
• 9 Hydrochlorothiazide 45,838,017 -0.8%<br />
• 10 Omeprazole 44,795,175 15.4%<br />
– Drug Topics 2011 www.drugtopics.com<br />
2010 Top 200 Generic Drugs by<br />
Total Prescriptions<br />
Rank Drug Total Rxs % Change from 2009<br />
11 Metformin 41,932,689 4.7%<br />
• 12 Furosemide oral 36,583,895 -0.1%<br />
• 13 Metoprolol tartrate 34,707,807 -0.5%<br />
• 14 Atenolol 33,839,806 -11.0%<br />
• 15 Sertraline 33,409,838 8.9%<br />
• 16 Metoprolol succinate 32,224,000 12.0%<br />
• 17 Zolpidem tartrate 29,719,569 -2.8%<br />
• 18 Oxycodone/APAP 28,705,243 6.8%<br />
• 19 Citalopram HBR 27,993,635 9.4%<br />
• 20 Gabapentin 26,865,557 14.0%<br />
– Drug Topics 2011 www.drugtopics.com<br />
10<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
April 20, 2011 —A report from the IMS Institute<br />
for Healthcare Informatics<br />
• Continuing a major trend, IMS finds that 78%<br />
of the nearly 4 billion U.S. prescriptions<br />
written in 2010 were for generic drugs.<br />
• Commercial insurance helped pay for 63% of<br />
prescriptions, down from 66% five years ago.<br />
• Federal government spending through<br />
Medicare Part D covered 22% of prescriptions.<br />
Medicare Closing of the “Doughnut Hole”<br />
13<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Medicare Closing of the “Doughnut Hole”<br />
14<br />
Prescription Drug Prices Under Negotiation In<br />
Debt Talks.<br />
• 6/21/2011 a bipartisan bill HR2248 by Peter Welch D-Vt and<br />
Jo Ann Emerson R-Mo "requiring the government to negotiate<br />
lower prescription drug prices in Medicare" has been<br />
reintroduced. Supporters say this will save up to $156 billion<br />
over 10 years without cutting into benefits. The<br />
Pharmaceutical Research and Manufacturers of America,<br />
representing drug companies, said Medicare already has drug<br />
discounts. Currently HHS is not allowed to negotiate drug<br />
costs with manufacturers; the proposed bill would require<br />
negotiation. House Democrats have supported similar<br />
measures, saying the current program results in beneficiaries<br />
paying "higher prices than they should for prescription drugs.“<br />
– S44 is the companion bill in the Senate<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
April 20, 2011 —A report from the IMS Institute<br />
for Healthcare Informatics<br />
• For Americans covered by insurance,<br />
Medicare, or Medicaid, the average copayment<br />
for a prescription was $10.73 -- down<br />
a bit from 2009 due to increased use of generic<br />
drugs.<br />
• The average co-payment for branded drugs for<br />
which generic alternatives were available<br />
jumped 6% to $22.73.<br />
In 2010 the 10 drugs on which we<br />
spent the most were:<br />
1. Lipitor (atorvastatin)-- $7.2 billion (11-2011)<br />
2. Nexium (esomeprazole)-- $6.3 billion<br />
3. Plavix (clopidogrel) -- $6.1 billion (5-2012)<br />
4. Advair Diskus (salmeterol/fluticazone)-- $4.7 billion<br />
5. Abilify (aripiprazole)-- $4.6 billion<br />
6. Seroquel (quetiapine)-- $4.4 billion (3-2012)<br />
7. Singulair (montelukast)-- $4.1 billion (8-2012)<br />
8. Crestor (rosuvastatin)-- $3.8 billion<br />
9. Actos (pioglitazone)-- $3.5 billion (8-2012)<br />
10. Epogen (epoetin alfa)-- $3.3 billion<br />
2010 IMS report:<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Additional Opportunities for Generic<br />
Savings in 2011-2012<br />
• Levofloxacin – Levaquin 6-2011<br />
• Olanzapine – Zyprexa 10-2011<br />
• Atorvastatin/amlodipine – Caduet 11-2011<br />
• Escitalopram – Lexapro 2-2012<br />
• Ibandronate – Boniva 3-2012<br />
• Sildenafil – Viagra 3-2012<br />
• Irbesartan – Avapro 3-2012<br />
• Entanercept – Enbrel 8-2012<br />
• Valsartan – Diovan 9-2012<br />
• Valsartan/amlodipine – Exforge 9-2012<br />
• Ziprasidone – Geodon 9-2012<br />
• Candesartan – Atacand – 12-2012<br />
• Rizatriptan – Maxalt 12-2012<br />
April 20, 2011 —A report from the IMS<br />
Institute for Healthcare Informatics<br />
• The IMS reports that Americans spent $307<br />
billion on prescription drugs in 2010<br />
• Brands that lost their protection from generic<br />
competition led to $12.6 billion less spending in<br />
2010 than in 2009.<br />
• The price increase for drugs without generic<br />
competition led to $16.6 billion more spending in<br />
2010 than in 2009.<br />
• Drug companies offered $4.5 billion in rebates to<br />
assist patients with the high cost of brand name<br />
drugs for which there was no generic alternative.<br />
2010 IMS report:<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
April 20, 2011 —A report from the IMS Institute<br />
for Healthcare Informatics<br />
• Small molecule spending totaled $240<br />
billion,an increase of 0.5% as biologics grew<br />
by 6.6%, amounting to $67 billion.<br />
• Oral forms of medicines declined by 0.1%, but<br />
spending on injectables increased by 5.7%.<br />
FDA<br />
Regulation of Generic Drugs<br />
Office of Generic Drugs<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
FDA<br />
OGD Mission<br />
To ensure that safe and effective<br />
generic drugs are available to the<br />
American People.<br />
Center for Drug Evaluation and Research<br />
FDA<br />
Legislative History<br />
• 1906 Pure Food and Drug Act - establishes regulation of<br />
Food and Drugs.<br />
• 1938 Food, Drug and Cosmetic Act - introduced safety<br />
standards.<br />
• 1962 Kefauver-Harris Amendments to the FDA&C Act -<br />
tightened safety standards and introduced requirement that<br />
drugs must be effective.<br />
• 1984 Waxman-Hatch Act - created an abbreviated<br />
mechanism for approval of generic copies of all drugs<br />
approved approved after 1962, by stating that preclinical<br />
and clinical tests did not have to be repeated for generics.<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
FDA<br />
Hatch-Waxman Amendments<br />
to FFD&C Act - 1984<br />
• Considered one of the most successful pieces of<br />
legislation ever passed<br />
• Created the generic drug industry<br />
• Increased availability of generics<br />
• 1984 12% prescriptions were generic<br />
• 2000 44% prescriptions were generic - yet only<br />
8% of revenue<br />
for prescription drug<br />
• 2009 71% prescriptions were generic<br />
• 2010 78% prescriptions were generic<br />
• Compromise legislation to benefit both brand and<br />
generic firms<br />
Center for Drug Evaluation and Research<br />
FDA<br />
Hatch-Waxman Amendments<br />
to FFD&C Act - 1984<br />
• Allowed generic firms to rely on findings of<br />
safety and efficacy of innovator drug after<br />
expiration of patents and exclusivities (do not<br />
have to repeat expensive clinical and preclinical<br />
trials)<br />
• Allowed patent extensions and exclusivities to<br />
innovator firms<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Innovator Incentives (Patents)<br />
FDA<br />
• Prior to 1984, a patent would run for 17 years<br />
from issue date or 20 years from filing<br />
• W/H set to restore some incentive for<br />
innovation because pre-market approval<br />
requirements have increased<br />
• W/H may restore up to 5 years not to exceed<br />
14 years from the product’s approval date<br />
Center for Drug Evaluation and Research<br />
Innovator Incentives(cont.)<br />
FDA<br />
• URAA* (June 8, 1995) made all patents in<br />
force or filed as of this date have the longer<br />
term of 17 years from issuance or 20 years<br />
from filing<br />
• All patents filed after June 8, 1995 have an<br />
expiration date of 20 years from filing<br />
– *Uruguay Round Agreements Act<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Exclusivity Incentives<br />
FDA<br />
• NCE protection - 5 years<br />
• New salt or ester - 3 years<br />
• New use or dosage form - 3 years<br />
• Orphan drug status – 7 years<br />
Center for Drug Evaluation and Research<br />
Generic Incentives<br />
FDA<br />
• All approved products eligible for generic<br />
competition<br />
• Eliminated requirement for duplicative clinical<br />
trials<br />
• Created a regulatory process for faster<br />
approval of generic drugs<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
FDA<br />
Definition of a Generic Drug<br />
A drug product that is comparable to a<br />
brand/reference listed drug product in<br />
dosage form, strength, route of administration,<br />
quality and performance characteristics,<br />
and intended use.<br />
Center for Drug Evaluation and Research<br />
FDA<br />
NDA vs. ANDA Review Process<br />
Brand Name Drug<br />
NDA Requirements<br />
Generic Drug<br />
ANDA Requirements<br />
1. Chemistry 1. Chemistry<br />
2. Manufacturing 2. Manufacturing<br />
3. Controls 3. Controls<br />
4. Labeling 4. Labeling<br />
5. Testing 5. Testing<br />
6. Animal Studies<br />
7. Clinical Studies 6. Bioequivalence<br />
8. Bioavailability<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Therapeutic Equivalence of<br />
Generic Drugs: FDA Requirements<br />
• Pharmacologically equivalent<br />
– Contains same amount of active drug<br />
– Meets USP standard for purity, strength, quality<br />
• Bioequivalent (mean AUC values are typically<br />
within 3-4% of each other)<br />
• Adequate labeling<br />
• Manufactured in compliance with GMP<br />
32<br />
Bioequivalence of Drugs:<br />
FDA Accepted Parameters<br />
• Single dose of reference drug and test drug given to<br />
24 to 36 healthy adults in a crossover design.<br />
Bioequivalence accepted when the 90% confidence<br />
interval of the ratios<br />
– AUC<br />
– C max<br />
– T max<br />
• Fall between 0.8 and 1.25 (log-transformed data)<br />
• The generic manufacturer’s main challenge has been<br />
to make a generic that was absorbed as poorly as the<br />
brand (IE phenytoin delayed – Dilantin)<br />
Meyer MC. J Clin Psychiatry 2001;62(suppl 5):4-9<br />
33<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
35<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
FDA<br />
What are the<br />
Generic Drug Requirements?<br />
• Same active ingredient(s)<br />
• Same route of administration<br />
• Same dosage form<br />
• Same strength<br />
• Same conditions of use<br />
• Compared to reference listed drug<br />
(RLD) - (brand name product)<br />
Center for Drug Evaluation and Research<br />
FDA<br />
FDA Requirements for Generic<br />
Ophthalmics<br />
According to Dr Wiley Chambers Acting<br />
Director of the Division of Anti-Infective and<br />
Ophthalmology Products at the FDA, there<br />
are two potential paths to market for<br />
generic ophthalmic solutions approved after<br />
1992.<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
FDA<br />
FDA Requirements for Generic<br />
Ophthalmics<br />
The first path involves a waiver of clinical trials if the<br />
generic ophthalmic solution has the same active and<br />
inactive ingredients in the same concentrations as the<br />
original. “If it does not have the same active and<br />
inactive ingredients in the same concentrations, then it<br />
would have to demonstrate bioequivalence in a clinical<br />
study,” says Dr. Chambers. “For ophthalmic drug<br />
products where the innovator (the original proprietary<br />
drug) was approved prior to 1992, there are cases<br />
where the inactive ingredients are not the same as the<br />
innovator.<br />
Center for Drug Evaluation and Research<br />
FDA<br />
FDA Requirements for Generic<br />
Ophthalmics<br />
According to IMS Health, latanoprost-<br />
Xalatan had U.S. sales of about $711<br />
million in 2010. Cost is the most obvious<br />
allure generics have, especially for<br />
pharmacy benefit managers. In fact, many<br />
pharmacy benefit formularies have<br />
dropped Xalatan this year in favor of the<br />
generic solution.<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
FDA Requirements for Generic<br />
Ophthalmics<br />
• The following companies that offer generic latanoprost in<br />
the same formula as Xalatan include:<br />
– Brand Xalatan by Pfizer - $81.85 AWC/2.5ml 0.005% soln<br />
– Bausch + Lomb - $13.43 AWC/2.5ml 0.005% soln<br />
– Falcon Pharmaceuticals Ltd., an affiliate of Alcon Laboratories,<br />
Inc. (owned by Novartis) - $10.00 AWC/2.5ml 0.005% soln<br />
– Apotex Corp. - $53.12 AWC/2.5ml 0.005% soln<br />
– Greenstone LLC (owned by Pfizer) - $13.38 AWC/2.5ml 0.005%<br />
soln<br />
– Mylan – $6.90 AWC/2.5ml 0.005% soln<br />
– Note that all of the above have FDA Therapeutic Equivalent<br />
Codes of AT and are considered by the FDA therapeutically<br />
equivalent<br />
FDA Orange Book for Solutions<br />
• All solutions and DESI drug products containing the<br />
same active ingredient in the same topical dosage<br />
form for which a waiver of in vivo bioequivalence has<br />
been granted and for which chemistry and<br />
manufacturing processes are adequate to<br />
demonstrate bioequivalence, are considered<br />
therapeutically equivalent and coded AT.<br />
Pharmaceutically equivalent topical products that<br />
raise questions of bioequivalence, including all post-<br />
1962 non-solution topical drug products, are coded<br />
AB when supported by adequate bioequivalence<br />
data, and BT in the absence of such data.<br />
41<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
FDA<br />
When can a Generic Drug<br />
be Marketed?<br />
•After patent & exclusivity protection<br />
ends, or<br />
•patent owner waives its rights, or<br />
•patent challenge is won, and<br />
•FDA requirements are met<br />
Center for Drug Evaluation and Research<br />
FDA<br />
APPROVED<br />
DRUG PRODUCTS<br />
WITH<br />
THERAPEUTIC EQUIVALENCE EVALUATIONS<br />
31st EDITION<br />
THE PRODUCTS IN THIS LIST HAVE BEEN APPROVED UNDER<br />
SECTION 505 OF THE FEDERAL FOOD, DRUG, AND<br />
COSMETIC ACT.<br />
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES<br />
PUBLIC HEALTH SERVICE<br />
FOOD AND DRUG ADMINISTRATION<br />
CENTER FOR DRUG EVALUATION AND RESEARCH<br />
OFFICE OF MANAGEMENT<br />
DIVISION OF DATABASE MANAGEMENT<br />
2011<br />
Electronic Orange Book - http://www.fda.gov/cder/ob/<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
How Did the<br />
“Orange Book” Get it’s Nickname?<br />
• When the first print edition of Approved Drug Products with<br />
Therapeutic Equivalence Evaluations was being prepared October<br />
1980, staff members in the Office of Generic Drugs had to choose a<br />
color for the cover. The project manager suggested, "It's almost<br />
Halloween. How about orange?"<br />
“Orange Book”<br />
FDA<br />
• All FDA approved drug products listed<br />
(NDA’s, OTC’s & ANDA’s)<br />
• Therapeutic equivalence codes<br />
–“A” = Substitutable<br />
–“B” = Inequivalent, NOT substitutable<br />
• Expiration dates: patent and exclusivity<br />
• Reference Listed Drugs/brand drugs identified by<br />
FDA for generic companies to compare their<br />
proposed products with<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
FDA Ratings<br />
FDA<br />
• “A” rated drugs are considered bioequivalent to the brand<br />
name original.<br />
– They either have been demonstrated to be so by human<br />
bioavailability study (“AB”) or considered inherently<br />
unlikely to have bioavailability problems (“AA”)<br />
– Other “A” designations (AN, AO, AP, AT) refer to nonoral<br />
formulations considered bioequivalent by the FDA<br />
– Only “A” rated products are interchangeable with their<br />
brand name equivalents by the FDA<br />
Center for Drug Evaluation and Research<br />
Levothyroxine Ratings<br />
FDA<br />
• UNITHROID (STEVENS J)<br />
– 0.025MG AB1<br />
• LEVOTHYROXINE SODIUM (MYLAN)<br />
– 0.025MG AB1<br />
• LEVOXYL (KING PHARMS)<br />
– 0.025MG AB1<br />
• SYNTHROID (ABBOTT)<br />
– 0.025MG AB1<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Levothyroxine Ratings<br />
FDA<br />
• SYNTHROID (ABBOTT)<br />
– 0.025MG AB2<br />
• LEVOTHYROXINE SODIUM (MYLAN)<br />
– 0.025MG AB2<br />
• LEVO-T (ALARA PHARM)<br />
– 0.025MG AB2<br />
• UNITHROID (STEVENS J)<br />
– 0.025MG AB2<br />
• LEVOTHYROXINE SODIUM (GENPHARM)<br />
– 0.025MG AB2<br />
Center for Drug Evaluation and Research<br />
Levothyroxine Ratings<br />
FDA<br />
• LEVOXYL (KING PHARMS)<br />
– 0.025MG AB3<br />
• LEVO-T (ALARA PHARM)<br />
– 0.025MG AB3<br />
• UNITHROID (STEVENS J)<br />
– 0.025MG AB3<br />
• LEVOTHYROXINE SODIUM (MYLAN)<br />
– 0.025MG AB3<br />
• LEVOTHYROXINE SODIUM (GENPHARM)<br />
– 0.025MG AB3<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Levothyroxine Ratings<br />
FDA<br />
• LEVOTHROID (LLOYD)<br />
– 0.025MG AB4<br />
• LEVOTHYROXINE SODIUM (MYLAN)<br />
– 0.025MG AB4<br />
Therapeutic equivalence has been established between products<br />
that have the same AB+number TE code according to the FDA<br />
Center for Drug Evaluation and Research<br />
FDA<br />
Additional FDA Approved Mediactions<br />
with AB sub classifications<br />
• Norethindrone<br />
– Nor-QD (AB1) vs. Micronor (AB2)<br />
• Diltiazem<br />
– (AB1 thru AB4)<br />
• Nifedipine<br />
– Adalat CC (AB1) vs. Procardia XL (AB2)<br />
• Transdermal Nitroglycerin<br />
– Nitro Dur and Minitran (AB1)<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
FDA Ratings<br />
FDA<br />
• “B” rated drugs have not been demonstrated to<br />
be bioequivalent by an in-vivo test.<br />
– These drugs are generally older drugs that were<br />
approved by the FDA on the basis of chemistry,<br />
manufacturing controls and in-vitro dissolution<br />
tests.<br />
– Less than 3% of marketed generic drugs have a<br />
“B” rating<br />
Center for Drug Evaluation and Research<br />
FDA Ratings<br />
FDA<br />
No well documented therapeutic differences<br />
between brand name originals and FDAapproved<br />
generics have been reported<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
FDA<br />
FDA Data on Generics<br />
• FDA recently evaluated 2,070 human studies conducted between<br />
1996 and 2007. These studies compared the absorption of brand<br />
name and generic drugs into a person’s body. These studies were<br />
submitted to FDA to support approval of generics. The average<br />
difference in absorption into the body between the generic and the<br />
brand name was 3.5 percent. Some generics were absorbed slightly<br />
more, some slightly less. This amount of difference would be<br />
expected and acceptable, whether for one batch of brand name drug<br />
tested against another batch of the same brand, or for a generic<br />
tested against a brand name drug. In fact, there have been studies in<br />
which brand name drugs were compared with themselves as well as<br />
with a generic. As a rule, the difference for the generic-to-brand<br />
comparison was about the same as the brand-to-brand comparison.<br />
– Davit et al. Comparing generic and innovator drugs: a review of 12<br />
years of bioequivalence data from the United States Food and Drug<br />
Administration. Ann Pharmacother. 2009;43(10):1583-97.<br />
Center for Drug Evaluation and Research<br />
FDA<br />
FDA Data on Generics<br />
• FDA requires generic drugs to have the same<br />
quality and performance as brand name drugs.<br />
• Research shows that generics work just as well as<br />
brand<br />
FDA<br />
name<br />
Facts<br />
drugs.<br />
about Generic Drugs<br />
– A study evaluated the results of 38 published clinical<br />
trials that compared cardiovascular generic drugs to<br />
their brand name counterparts. There was no evidence<br />
that brand name heart drugs worked any better than<br />
generic heart drugs<br />
• Kesselheim et al. Clinical equivalence of generic and brand<br />
name drugs used in cardiovascular disease: a systematic<br />
review and meta-analysis. JAMA. 2008;300(21)2514-2526<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
FDA<br />
FDA Facts about Generic Drugs<br />
• When it comes to price, there is a big difference<br />
between generic and brand name drugs. On<br />
average, the cost of a generic drug is 80 to 85<br />
percent lower than the brand name product. (an<br />
average of ~ $3 billion every week in savings)<br />
• Cheaper does not mean lower quality<br />
• FDA monitors adverse events reports for generic<br />
drugs<br />
• FDA is actively engaged in making all regulated<br />
products – including generic drugs – safer.<br />
– FDA website 4-2-2012 update<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
American Academy of Neurology<br />
Consensus Statement<br />
“ Nonequivalence can have very serious<br />
effects. Decreased serum drug<br />
concentrations can cause breakthrough<br />
seizures, and increased concentrations<br />
can lead to toxicity……The overall cost<br />
to society of breakthrough seizures or<br />
drug toxicity may outweigh any<br />
economic incentive for mandating<br />
generic substitution”<br />
Neurology 1990;40:1647-1651<br />
FDA<br />
FDA Estimate of Savings<br />
Center for Drug Evaluation and Research<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Lipid Lowering Therapy<br />
• The current and anticipated updated NCEP-ATP-<br />
IV guidelines recommend using a full dose of an<br />
evidence based high potency statin which has<br />
been demonstrated to reduce clinical CV events<br />
before adding a second lipid altering agent<br />
• Are we treating to reduce events or just to achieve<br />
goal lipid levels?<br />
• LDL is primary goal (< 70mg% or < 100mg%)<br />
• Non-HDL is secondary goal (30 mg% above LDL<br />
goal)<br />
• New AHA/ACC triglyceride goals (optimal<br />
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Comparison of Dose Dependent LDL Lowering<br />
Effects of Statins and Cost per Month<br />
Statin Daily Dose Average LDL Reduction Cost/Month** Generic<br />
Fluvastatin (Lescol)<br />
20mg 22% $117.59<br />
40mg 25% $109.19<br />
80mgXL 36% $145.99<br />
Simvastatin (Zocor) Best Buy<br />
5mg 26% $77.30 ($17.99)<br />
10mg 30% $93.99 ($19.99)<br />
20mg 38% $173.99 ($27.99)<br />
40mg 41% $173.99 ($27.99)<br />
80mg 47% $178.99 ($35.99)<br />
Cost is per 30 day supply from Drugstore.com 3-2012<br />
Comparison of Dose Dependent LDL Lowering<br />
Effects of Statins and Cost per Month<br />
Statin Daily Dose Average LDL Reduction Cost/Month Generic<br />
Atorvastatin (Lipitor) (scheduled to go genric Nov 2011)<br />
10mg 39% $113.70 $92.00<br />
20mg 43% $162.30 $120.00<br />
40mg 50% $162.30 $120.00<br />
80mg 60% $162.30 $120.00<br />
Rosuvastatin (Crestor)<br />
5mg 28% $154.99<br />
10mg 46% $154.99<br />
20mg 52% $155.98<br />
40mg 55% $156.99<br />
Cost is per 30 day supply from Drugstore.com 3-2012<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
<strong>Proton</strong> <strong>Pump</strong> <strong>Inhibitors</strong><br />
AGA Technical Review 2008<br />
• Ample evidence that PPIs are more effective<br />
than H2RAs in patients with esophageal GERD<br />
syndromes<br />
• Data supporting PPI doses higher than<br />
standard are minimal<br />
• There is no evidence that adding a nocturnal<br />
dose of an H2RA to twice daily PPI therapy<br />
improves long-term efficacy<br />
• Gastroenterology 2008;135:1392-1413<br />
<strong>Proton</strong> <strong>Pump</strong> <strong>Inhibitors</strong><br />
• A Cochrane review of 134 treatment trials in 36,978<br />
patients with esophagitis, concluded that PPIs exhibit a<br />
better healing effect and faster symptom relief then<br />
H2RAs which in turn are better than placebo<br />
• concluded that there is no major difference in<br />
efficacy among the currently available PPIs<br />
(esomeprazole, lansoprazole, omeprazole,<br />
pantoprazole, rabeprazole)<br />
• the gain achieved by doubling the standard dose of<br />
PPI therapy is modest.<br />
• Cochrane Database Syst Rev 2007;2:CD003244<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Esomeprazole Vs. Lansoprazole<br />
Treatment of Erosive<br />
Esophagitis at 8 weeks<br />
Number<br />
% Healed<br />
(intent to treat)<br />
Esomeprazole 40 mg 2624 92.6%<br />
Lansoprazole 30 mg 2617 88.8%<br />
(E 40 Vs L 30 ARR 3.8%, NNT-27)<br />
Am J Gastroenterol 2002; 97: 575-583<br />
Consumer Reports Best Buy Drugs January<br />
2007<br />
• “Taking effectiveness, safety, and cost into account, we<br />
have chosen over-the-counter Prilosec OTC (omeprazole)<br />
20mg as the Consumer Reports Best Buy Drug if you need<br />
a PPI.”<br />
• A comparison table from the Drug Effectiveness Review<br />
Project -Oregon Health Sciences University may be<br />
accessed at the link :<br />
www.ohsu.edu/ohsuedu/research/policycenter/DERP/about/finalproducts.cfm<br />
• Mc Donagh and Carson, Drug Class Review on <strong>Proton</strong> <strong>Pump</strong><br />
<strong>Inhibitors</strong>, Final Report, July 2006<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
<strong>Proton</strong> <strong>Pump</strong> <strong>Inhibitors</strong><br />
• The most important recommendation<br />
with any PPI is to take it 30-60<br />
minutes prior to a significant meal!<br />
• “Seventy percent of primary care physicians<br />
and 20% of gastroenterologists prescribe PPIs<br />
sub optimally, either at bedtime or unrelated to<br />
food intake, this is the most common cause of<br />
PPI failure.”<br />
• Gastroenterology 2008; 134: 1842-1860<br />
PPI’s Benefits vs. Risk?<br />
• Potential risks include:<br />
• Community and hospital acquired pneumonia<br />
• Risk of nosocomial C. difficile infection<br />
• Risk of fractures including hip fracture<br />
• Risk of B12, calcium and magnesium<br />
deficiencies<br />
• Risk of acid rebound<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
<strong>Proton</strong> <strong>Pump</strong> <strong>Inhibitors</strong><br />
• Omeprazole Generic<br />
Prilosec<br />
• 20mg caps $33.32/30 $195.99/30<br />
• 40mg caps $195.00/30 $291.00/30<br />
• Omeprazole OTC Generic Prilosec OTC<br />
• 20.6mg tabs $21.99/42 $24.99/42<br />
• Lansoprazole Generic Prevacid<br />
• 15mg caps $99.99/30 $195.00/30<br />
• 30mg caps $99.99/30 $183.25/30<br />
• Lansoprazole OTC Prevacid 24<br />
• 15mg caps $26.99/42<br />
Drugstore.com 3-2012<br />
<strong>Proton</strong> <strong>Pump</strong> <strong>Inhibitors</strong><br />
• Pantoprazole Generic <strong>Proton</strong>ix<br />
• 20mg tabs $15.99/30 $186.38/30<br />
• 40mg tabs $15.99/30 $190.00/30<br />
• Esomeprasole<br />
Nexium<br />
• 20mg caps $200.99/30<br />
• 40mg caps $189.99/30<br />
• Dexlansoprazole<br />
Dexilant<br />
• 30 and 60mg caps $149.99/30<br />
• Rabeprazole<br />
Aciphex<br />
• 20mg tabs $249.99/30<br />
Drugstore.com 3-2012<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Hypnotics<br />
• Identify the underlying problem with a good sleep<br />
history<br />
• Treat the underlying problem not just the symptom<br />
of insomnia<br />
• Diabetes<br />
• GERD<br />
• Heart failure<br />
• Depression<br />
• Pain<br />
• BPH<br />
Benzodiazepine Receptor Agonists<br />
Drug Onset (min) T1/2 (hr) Dose (mg) Cost/30 doses<br />
Sonata 10-20 1.0 5-20 $150.98 (10mg)<br />
zaleplon<br />
$34.99 (10mg)<br />
Ambien 10-20 1.5-2.4 5-10 $209.98 (10mg)<br />
Ambien CR 10-20 6.25-12.5 $193.99 (both)<br />
zolpidem<br />
$17.99 (10mg)<br />
Lunesta 10-30 5-6 1-3 $230.00(all)<br />
Rozerem 20-45 1-2.6 8 $170.08<br />
Triazolam 10-20 1.5-5 0.125-0.25 $17.99 (all)<br />
Restoril 45-60 8-20 7.5-30 $345.99 (all)<br />
Temazepam 45-60 8-20 7.5-30 $12.99 (15 & 30mg)<br />
Flurazepam 15-30 36-120 15-30 $12.99 (all)<br />
Drugstore.com 4-2012<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Blood Pressure Goals<br />
• Most important goal is to control the BP!<br />
• If at all possible use evidence-based medications<br />
and doses that have been demonstrated to reduce<br />
events in selected patients with hypertension<br />
(compelling indications – ACEI with diabetes, renal<br />
disease, post MI, HF, etc.)<br />
• Watch for the new JNC-8 guidelines which will<br />
incorporate weighted evidence in 2012?<br />
ACE <strong>Inhibitors</strong><br />
• Lisinopril Generic Best Buy Zestril<br />
• 5 mg tabs $14.89/30 5mg $50.99/30<br />
• 10mg tabs $13.99/30 10 mg $55.11/30<br />
• 20mg tabs $14.99/30 20mg $57.99/30<br />
• 30mg tabs $20.99/30 30mg $71.99/30<br />
• 40mg tabs $17.99/30 40mg $73.99/30<br />
• Lisinopril/HCTZ Generic<br />
Zestoretic<br />
• 10/12.5mg $23.99/30 10/12.5mg $56.78/30<br />
• 20/12.5mg $21.99/30 20/12.5mg $60.05/30<br />
• 20/25mg $21.99/30 20/25mg $59.99/30<br />
• Drugstore.com 4/2012<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
ACE <strong>Inhibitors</strong><br />
• Ramipril Generic<br />
Altace<br />
• 2.5mg caps $49.99/30 2.5mg $77.99/30<br />
• 5mg caps $52.99/30 5mg $81.99/30<br />
• 10mg caps $62.99/30 10mg $90.99/30<br />
• Quinapril Generic<br />
Accupril<br />
• 5mg tabs $23.99/30 5mg $69.27/30<br />
• 10mg tabs $19.99/30 10mg $62.99/30<br />
• 20mg tabs $26.97/30 20mg $67.99/30<br />
• 40mg tabs $21.99/30 40mg $66.99/30<br />
• Drugstore.com 4-2012<br />
ACE <strong>Inhibitors</strong><br />
• Benazepril Generic<br />
Lotensin<br />
• 5mg tabs $24.33/30 $62.80/30<br />
• 10mg tabs $25.99/30 $67.99/30<br />
• 20mg tabs $25.99/30 $64.99/30<br />
• 40mg tabs $25.99/30 $67.99/30<br />
• Benazepril/HCTZ Generic<br />
Lotensin HCT<br />
• 10/12.5mg tabs $22.99/30 $62.99/30<br />
• 20/12.5mg tabs $26.99/30 $65.99/30<br />
• 20/25mg tabs $26.99/30 $63.99/30<br />
• Drugstore.com 4-2012<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Angiotensin Receptor Blockers (ARB’s)<br />
• Losartan Generic<br />
Cozaar<br />
• 25mg tabs $50.10/30 $64.99/30<br />
• 50mg tabs $67.88/30 $86.86/30<br />
• 100mg tabs $83.49/30 $118.32/30<br />
• Losartan/HCTZ Generic<br />
Hyzaar<br />
• 50/12.5mg tabs $75.05/30 $96.05/30<br />
• 100/12.5mg tabs $102.23/30 $130.66/30<br />
• 100/25mg tabs $102.23/30 $130.84/30<br />
• AWP 2012<br />
Angiotensin Receptor Blockers (ARB’s)<br />
• Valsartan (Diovan) generic 9/2012<br />
• 40mg tabs $89.99/30<br />
• 80mg tabs $100.99/30<br />
• 160mg tabs $111.99/30<br />
• 320mg tabs $136.99/30<br />
• Candesartan (Atacand) generic 12/2012<br />
• 4mg tabs $84.99/30<br />
• 8mg tabs $83.99/30<br />
• 16mg tabs $85.99/30<br />
• 32mg tabs $111.99/30<br />
• Drugstore.com 4-2012<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Angiotensin Receptor Blockers (ARB’s)<br />
• Telmisartan (Micardis) each tab wrapped in foil<br />
(hydroscopic)<br />
• 20mg tabs $123.99/30<br />
• 40mg tabs $123.99/30<br />
• 80mg tabs $122.99/30<br />
• Olmesartan (Benicar)<br />
• 5mg tabs $78.99/30<br />
• 20mg tabs $95.99/30<br />
• 40mg tabs $134.99/30<br />
• Drugstore.com 4-2012<br />
Angiotensin Receptor Blockers (ARB’s)<br />
• Irbesartan (Avapro) generic 3/2012<br />
• 75mg tabs $95.91/30<br />
• 150mg tabs $98.99/30<br />
• 300mg tabs $119.99/30<br />
• Eprosartan (Teveten)<br />
• 400mg tabs $90.00/30<br />
• 600mg tabs $119.99/30<br />
• Azilsartan (Edarbi)<br />
• 40 mg tabs $85.99/30<br />
• 80 mg tabs $89.99/30<br />
• Drugstore.com 4-2012<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Direct Renin Inhibitor<br />
• Aliskiren (Tekturna)<br />
• 150mg tabs $97.92/30<br />
• 300mg tabs $123.00/30<br />
• Aliskiren/HCTZ (Tekturna HCT)<br />
• 300/25 tabs $123.41/30<br />
• Aliskiren/Valsartan (Valturna) AVOID in patients<br />
with DM<br />
• 150/160 tabs $95.99/30<br />
• 300/320 tabs $117.99/30<br />
• Drugstore.com 4-2012<br />
Amlodipine<br />
• Amlodipine Generic Best Buy! Norvasc<br />
• 2.5mg tabs $21.97/100 $245.51/100<br />
• 5mg tabs $25.54/100 $259.07/100<br />
• 10mg tabs $26.66/100 $333.29/100<br />
• Benazepril/Amlodipine Generic Lotrel<br />
• 2.5/10mg caps $69.99/30 $123.99/30<br />
• 5/10mg caps $76.99/30 $127.99/30<br />
• 5/20mg caps $69.99/30 $117.93/30<br />
• 5/40mg caps $115.99/30 $145.97/30<br />
• 10/20mg caps $89.99/30 $158.99/30<br />
• 10/40mg caps $115.99 $175.00/30<br />
• Drugstore.com 4-2012<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Evidence Based Diuretics<br />
• Chlorthalidone Generic<br />
• 25mg tabs $11.97/100 (FUL $5.10/100) AWP<br />
• 50mg tabs $12.97/100 (FUL $5.50/100)<br />
• Indapamide Generic Lozol<br />
• 1.25mg tabs $15.99/90 (FUL $10.35/100) $122.21/100<br />
• 2.5mg tabs $19.97/90 (FUL $11.25/100)<br />
• Spironolactone Generic Aldactone<br />
• 25mg tabs $33.30/100 (FUL $30.00/100) $113.30/100<br />
• 50mg tabs $52.19/100 $195.52/100<br />
• Eplerenone Generic Inspra<br />
• 25mg tabs $275.99/90 $424.73/90<br />
• 50mg tabs $275.99/90 $425.09/90<br />
• Drugstore.com 4-2012<br />
Evidence Based Beta Blockers in HF<br />
• Metoprolol succinate (Toprol XL) MERIT-HF<br />
• 25 mg tabs $46.99/30 Brand $29.99/30 generic<br />
• 50 mg tabs $44.99/30 Brand $33.99/30 generic<br />
• 100 mg tabs $60.99/30 Brand $44.99/30 generic<br />
• 200 mg tabs $98.99/30 Brand $65.33/30 generic<br />
• Carvedilol (Coreg) COMET/COPERNICUS<br />
• 3.125 mg tabs $138.99/60 Brand $34.99/60 generic<br />
• 6.25 mg tabs $150.96/60 Brand $29.98/60<br />
• 12.5 mg tabs $149.00/60 Brand $31.98/60 generic<br />
• 25 mg tabs $157.99/60 Brand $31.99/60 generic<br />
• Drugstore.com 4-2012<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Evidence Based Beta Blockers in HF<br />
• Coreg CR (Not evidence based!) QD no generic<br />
• 10 mg caps (3.125 BID equivalent) $141.99/30<br />
• 20 mg caps (6.25 BID equivalent) $141.99/30<br />
• 40 mg caps (12.5 mg BID equivalent) $141.99/30<br />
• 80 mg caps (25 mg BID equivalent) $143.99/30<br />
• Bisoprolol fumarate(Zebeta) Not FDA approved but<br />
evidence-based CIBIS-II<br />
• 5 mg tabs $35.99/30 Brand $114.43/30<br />
• 10 mg tabs $37.99/30 Brand $114.43/30<br />
• Drugstore.com 4-2012<br />
ADA/EASD Consensus Algorithm for the Initiation<br />
and Adjustment of Therapy<br />
Diabetes Care 2009; 32:193–203<br />
a - Sulfonylureas other than glybenclamide (glyburide) or<br />
chlorpropamide.<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Avoid Use of Glyburide?<br />
In-hospital mortality in patients on sulfonylureas before admission (n = 459) according to the type of<br />
sulfonylureas and stratified by specific subgroups (J Clin Endocrinol Metab, November 2010, 95(11):4993–5002)<br />
UK Prospective Diabetes Study<br />
Glucose Interventional Trial<br />
Dietary<br />
Run-in<br />
744<br />
Diet failure<br />
FPG >15 mmol/l<br />
Randomisation<br />
1977-1991<br />
2,729<br />
Intensive<br />
with sulfonylurea/insulin<br />
Trial end<br />
1997<br />
Intensive<br />
P<br />
5,102<br />
Newly-diagnosed<br />
type 2 diabetes<br />
4209<br />
1,138 (411 overweight)<br />
Conventional<br />
with diet<br />
Conventional<br />
P<br />
149<br />
Diet satisfactory<br />
FPG
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Any Diabetes Related Endpoint (%) at 10<br />
years<br />
• Diet + Metformin 28.7%<br />
• Diet + Sulf/Insulin 36.8%<br />
• Diet only 38.9%<br />
• RRR 26.2% with diet + metformin vs. diet alone<br />
• ARR 10.2%<br />
• NNT 10<br />
All Cause Mortality (%) at 10 years<br />
• Diet + Metformin 14.6%<br />
• Diet + Sulf/Insulin 20%<br />
• Diet alone 21.7%<br />
• RRR 32.7% with metformin + diet vs. diet alone<br />
• ARR 7.1%<br />
• NNT 14<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Myocardial Infarction (%)<br />
at 10 years<br />
• Diet + Metformin 11.4%<br />
• Diet + Sulf/Insulin 14.6%<br />
• Diet alone 17.8%<br />
• RRR 36% with diet + metformin vs, diet alone<br />
• ARR 6.4%<br />
• NNT 16<br />
Stroke (%) at 10 years<br />
• Diet + Metformin 3.5%<br />
• Diet + Sulf/Insulin 6.3%<br />
• Diet alone 5.6%<br />
• RRR 44.4% with diet + metformin vs, diet +<br />
sulf/insulin<br />
• ARR 2.8%<br />
• NNT 36<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Long-term Effects of Metformin on Metabolism<br />
and Microvascular and Macrovascular Disease<br />
in Patients With Type 2 Diabetes Mellitus Treated with<br />
Insulin Arch Intern Med. 2009;169(6):616-625<br />
•390 patients treated with insulin in the<br />
outpatient clinics of 3 hospitals in a<br />
randomized, placebo-controlled trial with a<br />
follow-up period of 4.3 years. Either<br />
metformin hydrochloride, 850 mg, or placebo<br />
(1-3 times daily) was added to insulin therapy.<br />
•The primary end point was an aggregate of<br />
microvascular and macrovascular morbidity<br />
and mortality. The secondary end points were<br />
microvascular and macrovascular morbidity<br />
and mortality independently.<br />
“Hyperinsulinemia the Outcome of its<br />
Metabolic Effects (HOME)”<br />
Long-term Effects of Metformin on Metabolism<br />
and Microvascular and Macrovascular Disease<br />
in Patients With Type 2 Diabetes Mellitus Treated with<br />
Insulin Arch Intern Med. 2009;169(6):616-625<br />
Results:<br />
• Metformin treatment prevented weight gain (mean weight gain, −3.07 kg<br />
[range, −3.85 to −2.28 kg]; P.001),<br />
• Improved glycemic control (mean reduction in HbA1c level, 0.4%<br />
percentage point [95% CI, 0.55-0.25]; P.001), despite the aim of similar<br />
glycemic control in both groups,<br />
• Reduced insulin requirements (mean reduction, 19.63 IU/d [95% CI,<br />
24.91-14.36 IU/d]; P.001).<br />
• Metformin was not associated with an improvement in the primary end<br />
point.<br />
• It was, however, associated with an improvement in the secondary,<br />
macrovascular end point (hazard ratio, 0.61 (95% CI, 0.40-0.94; P=.02),<br />
which was partly explained by the difference in weight.<br />
• The number needed to treat to prevent 1 macrovascular end point was<br />
16.1 (95% CI, 9.2-66.6).<br />
• These sustained beneficial effects support the policy to continue<br />
metformin treatment after the introduction of insulin in any patient with<br />
DM2, unless contraindicated.<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Risk of fatal and nonfatal lactic acidosis with<br />
metformin use in type 2 diabetes mellitus<br />
The Cochrane Library 2010, Issue 4<br />
• Main results:<br />
– Pooled data from 347 comparative trials and cohort studies<br />
revealed no cases of fatal or nonfatal lactic acidosis in 70,490<br />
patient years of metformin use or in 55,451 patients-years in<br />
the non-metformin group. Using Poisson statistics the upper<br />
limit for the true incidence of lactic acidosis per 100,000<br />
patient-years was 4.3 cases in the metformin group and 5.4<br />
cases in the non-metformin group.<br />
– There was no difference in lactate levels, either as mean<br />
treatment levels or as a net change from baseline, for<br />
metformin compared to non-metformin therapies.<br />
• Authors’ conclusions:<br />
– “There is no evidence from prospective comparative trials or<br />
from observational cohort studies that metformin is associated<br />
with an increased risk of lactic acidosis, or with increased<br />
levels of lactate, compared to other anti-hyperglycemic<br />
treatments.”<br />
Proposed Recommendations for Use of<br />
Metformin Based on e-GFR<br />
Diabetes Care 2011;34:1435<br />
eGFR (ml/min per 1.73m2)<br />
Action<br />
>60 No renal contraindication to metformin<br />
>45 Continue use<br />
Increase monitoring of renal function (every 3–6<br />
months)<br />
30 Prescribe metformin with caution<br />
Use lower dose (e.g., 50%, or half-maximal dose)<br />
Closely monitor renal function (every 3-6 months)<br />
Do not start new patients on metformin<br />
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Metformin<br />
• Metformin HCl Immediate release tabs<br />
• 500 mg $12.99/60 Glucophage $69.99/60<br />
• 850 mg $61.99/60 Glucophage $113.29/60<br />
• 1000 mg $31.97/60 Glucophage $141.08/60<br />
• Metformin Extended release tabs<br />
• 500 mg $18.00/60 Glucophage XR $69.99/60<br />
Glumetza $233.40/60<br />
• 750 mg $65.98/60 Glucophage XR $107.98/60<br />
• 1000 mg $169.62/60 Glumetza $515.98/60<br />
• Drugstore.com 4-2012<br />
Sulfonylureas<br />
• Glipizide Immediate release<br />
• 5 mg $13.45/60 Glucotrol $43.99/30<br />
• 10 mg $13,00/60 Glucotrol $81.89/60<br />
• Glipizide XL (Extended release)<br />
• 10 mg $23.99/30 Glucotrol XL $48.99/30<br />
• Glimepiride<br />
• 2 mg $13.99/30 Amaryl $39.99/30<br />
• 4 mg $14.99/30 Amaryl $63.99/30<br />
• Glyburide AVOID!<br />
• 5mg $18.99/30 Micronase $41.99/30<br />
Diabeta $45.75/30<br />
Drugstore.com 4-2012<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Insulins<br />
• Regular Insulin (10cc vial)<br />
• Humalin R $73.99 Novolin R $75.99<br />
• ReliOn (Humalin R) $23.67 Walmart<br />
• NPH Insulin (10cc vial)<br />
• Humalin N $73.99 Novolin N $75.99<br />
• ReliOn (Humalin N) $23.67 Walmart<br />
• 70/30 NPH/Regular Insulin (10cc vial)<br />
• Humalin 70/30 $73.99<br />
• Novolin 70/30 $75.99<br />
3 cc pen $135.99/3 pens<br />
• ReliOn (Humalin 70/30) $23.67 Walmart<br />
• Drugstore.com 4-2012<br />
Insulins<br />
• Insulin glargine - Lantus<br />
• 10cc vial $124.99/vial<br />
• SoloStar pen (3cc) $234.99/5 pens<br />
• Insulin detimir – Levemir<br />
• 10cc vial $136.00/vial<br />
• FlexPen (3cc) $242.99/5 pens<br />
• Drugstore.com 4-2012<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Insulins<br />
• Insulin lispro – Humalog<br />
• 10 cc vial $137.98/vial<br />
• Kwik Pen (3cc) $268.99/5 pens<br />
• Insulin aspart – Novolog<br />
• 10cc vial $140.70/vial<br />
• FlexPen (3cc) $268.99/5 pens<br />
• Insulin glulisine – Apidra<br />
• SoloStar (3cc) $218.28/5 pens<br />
• Drugstore.com 4-2012<br />
Insulins<br />
• Insulin lispro/NPH – Humalog Mix<br />
• 50/50 Kwik Pen (3cc) $271.00/5 pens<br />
• 75/25 Kwik Pen (3cc) $281.43/5 pens<br />
• Insulin aspart/NPH – Novolog Mix<br />
• 70/30 FlexPen (3cc) $258.98/5 pens<br />
• Drugstore.com 4-2012<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
Pioglitazone - Actos<br />
• Actos 15 mg tabs $193.48/30<br />
• Actos 30 mg tabs $289.98/30<br />
• Actos 45 mg tabs $310.00/30<br />
• ActosPlus Met XR 30/1000 mg tabs $309.99/30<br />
• Drugstore.com 4-2012<br />
GLP-1 Agonists<br />
• Exenatide – Byetta<br />
• 5mcg/0.02ml Solution 1.2ml Pen $350.28/pen AWP<br />
• 10mcg/0.04ml Solution 2.4ml Pen $350.28/pen<br />
• Extenatide extended release – Bydureon<br />
• 2mg/vial in cartons of 4 doses (28 day supply)<br />
• $325.99 Drugstore.com 4-2012<br />
• Liraglutide – Victoza<br />
• 18 mg/3 mL Pen in box of 2 pens $312.07 AWP<br />
• 18 mg/3 mL Pen in box of 3 pens $468.11 AWP<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
DPP-4 <strong>Inhibitors</strong><br />
• Sitagliptin – Januvia<br />
• 25 mg tabs $243.60/30 AWP<br />
• 50 mg tabs $243.60/30 AWP<br />
• 100mg tabs $243.60/30 AWP<br />
• Sitagliptin + metformin IR – Janumet (BID)<br />
• 50/500 mg tabs $243.60/60 AWP<br />
• 50/1000 mg tabs $243.60/60 AWP<br />
• Sitagliptin + metformin XR – Janumet XR<br />
• 50/500 mg tabs<br />
• 50/1000 mg tabs<br />
• 100/1000 mg tabs<br />
DPP-4 <strong>Inhibitors</strong><br />
• Saxagliptin – Onglyza<br />
• 2.5 mg tabs $243.58/30 AWP<br />
• 5 mg tabs $243.58/30 AWP<br />
• Saxagliptin + metformin XR – Kombiglyze XR<br />
• 2.5/1000 mg tabs $243.58/30 AWP<br />
• 5/500 mg tabs $243.58/30 AWP<br />
• 5/1000 mg tabs $243.58/30 AWP<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx
6 th Annual Primary Care Spring Conference Thursday, April 12, 2012<br />
DPP-4 <strong>Inhibitors</strong><br />
• Linagliptin – Tradjenta<br />
• 5 mg tabs $241.00/ 30 Drugstore.com 4-2012<br />
• Linagliptin + metformin IR – Jentaduento (BID)<br />
• 2.5/500 mg tabs<br />
• 2.5/850 mg tabs<br />
• 2.5/1000 mg tabs<br />
Wayne Weart, Pharm D<br />
Cost Effective Rx