{"id":1097,"date":"2012-09-01T00:00:16","date_gmt":"2012-09-01T07:00:16","guid":{"rendered":"http:\/\/rhochistj.org\/RhoChiPost\/?p=1097"},"modified":"2014-02-17T22:24:43","modified_gmt":"2014-02-18T05:24:43","slug":"brand-vs-generic-every-prescriber-know","status":"publish","type":"post","link":"https:\/\/rhochistj.org\/RhoChiPost\/brand-vs-generic-every-prescriber-know\/","title":{"rendered":"Brand Vs. Generic: What Every Prescriber Should Know"},"content":{"rendered":"

By: Marina Yermolayeva, PharmD Candidate c\/o 2013<\/span><\/p>\n

–<\/p>\n

\u201cI\u2019m allergic to the generic; I need the brand name medication,\u201d is a common claim heard by many health care providers. \u00a0Managed care organizations get numerous calls from doctors and patients requesting prior authorizations to approve brand name medications whilst there are generic alternatives available on formulary. \u00a0Much-needed healthcare resources, time, and money can be saved by investing some effort to educate people about the differences (or lack thereof) between brand and generic drugs.<\/p>\n

Each medication available on the United States market today has been reviewed and approved by the U.S. Food and Drug Administration (FDA). \u00a0A company that has invented and synthesized a unique drug may designate this product with a \u201cbrand\u201d name, which is usually catchy and easier to pronounce than the official, chemical name for the active ingredient. \u00a0The company then may legally claim exclusive rights to manufacture this product for up to 17 years from the time of discovery, which is known as a patent.1<\/sup> \u00a0Once this patent expires, other companies are allowed to manufacture the product using the same active ingredient but different fillers, coloring, and packaging; these multi-source products are known as \u201cgenerics\u201d and go by their chemical names. \u00a0To differentiate between the two, brand names are usually capitalized and generic names are not.<\/p>\n

Generic products must meet stringent requirements set by the FDA. \u00a0The word \u201cgeneric\u201d is an adjective that refers to an entire class and is synonymous with \u201cgeneral.\u201d \u00a0It just means that the generic is not unique and has the same characteristics as another item, in this case, the brand name medication. \u00a0Under the 1984 Drug Price Competition and Patent Term Restoration Act, generic medications must show the same active ingredient, strength, quality, purity, and potency as the brand name dosage form for entry into the U.S. market.2,3<\/sup><\/p>\n

Therapeutic equivalence must be proven via several tests. \u00a0If the generic and brand products show the same concentration profiles in the blood after administration, they are considered to be bioequivalent, and therefore therapeutically equivalent. \u00a0Bioequivalence studies typically involve studying the pharmacokinetics of the brand and generic formulations in healthy adults (in-vivo) in a randomized, crossover study design.4<\/sup> \u00a0While bioequivalence studies typically call for only 18\u201425 healthy volunteers, brand-name clinical trials are required to test hundreds to thousands of people to demonstrate safety and efficacy because virtually nothing is known about the pioneer drug.3<\/sup> \u00a0Once safety and efficacy is established for a brand medication, bioequivalence studies are considered sufficient evidence to validate a generic drug. \u00a0In order to meet bioequivalence requirements, certain criteria need to be met. \u00a0The total extent of absorption (AUC, area under the curve), maximum serum concentrations (Cmax), and the times to Cmax (tmax) should be neither statistically nor clinically significantly different from the standard formulation (in this case the brand medication). 4<\/sup> The serum-concentration-versus-time curves for the two dosage forms should be identical.4<\/sup> \u00a0This data is published by the FDA in Approved Drug Products with Therapeutic Equivalence Evaluations<\/span> (known as \u201cthe List\u201d, or \u201cOrange Book\u201d, for short).5\u00a0 <\/sup>There are some exceptions to the in-vivo bioequivalence requirements. \u00a0Bioequivalence of intravenous (IV) or oral solution dosage forms are inferred; and, some older drug formulations for which no bioequivalence issues are anticipated are only required to submit in-vitro dissolution tests to the FDA.3 <\/sup><\/p>\n

According to the official FDA website, all generic manufacturing, packaging, and testing sites must pass the same quality standards as those of brand name drugs. \u00a0In fact, many generic drugs are made in the same manufacturing plants as brand name drug products.2<\/sup> \u00a0FDA inspectors evaluate each site to ascertain that Good Manufacturing Practice regulations are followed; samples of all drug products are randomly collected and sent to FDA laboratories for evaluation.3<\/sup> \u00a0Furthermore, the FDA imposes the same post-marketing surveillance tactics on generic products as it does on brands. \u00a0Programs such as MedWatch are in place for health care workers and patients to report adverse reactions. \u00a0These reports are investigated when necessary, and appropriate action is taken to ensure that only safe products are available on the U.S. market. \u00a0The FDA also encourages more extensive research to investigate which inactive ingredients are problematic among generics.2<\/sup><\/p>\n

If the regulations are not enough to convince health care professionals, there is published evidence of pharmacokinetic equivalence between brand and generic medications. \u00a0The FDA recently reviewed 2,070 human studies conducted between 1996 and 2007 to compare absorption of brand name and generic drugs by the human body.2<\/sup> \u00a0These studies were submitted to FDA to support approval of generics. \u00a0The average difference in absorption between the generic and brand name was 3.5 %.6<\/sup> \u00a0This amount is considered negligible and not expected to have clinical impact. \u00a0Even studies comparing batches of the same brand-name drug to itself, or to other brands, showed slight variability in absorption.\u00a0 The difference for the generic-to-brand comparison was about the same as the brand-to-brand comparison in this analysis. \u00a0The FDA permits very small variations in purity, size, strength, and other parameters for mass-produced brand and generic products.2<\/sup><\/p>\n

Clinical benefit was evaluated by a retrospective meta-analysis of cardiovascular brand and generic drug outcomes published in the Journal of American Medical association. \u00a0The authors pooled articles from peer-reviewed health care\u2013related journals between January 1984 and August 2008.7<\/sup> \u00a0In total, 47 articles [38 (81%) of which were randomized controlled trials (RCTs)], covering 9 subclasses of cardiovascular medications were identified and included in the analysis. \u00a0Clinical equivalence was found in RCTs of \u03b2-blockers (7\/7 RCTs), diuretics (10\/11 RCTs), calcium channel blockers (5\/7 RCTs), antiplatelet agents (3\/3 RCTs), statins (2\/2 RCTs), angiotensin-converting enzyme inhibitors (1\/1 RCT), and \u03b1-blockers (1\/1 RCT). \u00a0Furthermore, clinical equivalence was also detected among narrow therapeutic index drugs [1\/1 RCT of class 1 antiarrhythmic agents and 5\/5 RCTs of warfarin].7<\/sup> \u00a0The overall data (n = 837) did not indicate a statistically significant difference between the effect of brand and generic drugs. \u00a0Despite these findings, the same study found that more than half of published editorials [23 of 43 (53%)] published during the same time period recommended against generic drug substitution.7<\/sup><\/p>\n

In addition, allergies to medication warrant special attention and avoidance of the offending drug. \u00a0However, identifying the causative agent as well as the type of allergy is key to determining how to manage each patient. \u00a0If the main pharmaceutical ingredient is causing a life-threatening reaction (anaphylaxis, toxic skin reactions, etc.), all brand and generic products with that ingredient are contraindicated. \u00a0If, however, the patient is found to be allergic to an inactive excipient, he or she may benefit from a different pharmaceutical formulation with different fillers and dyes. \u00a0Each generic company will have their own combinations and ratios of excipients, so being allergic to one company\u2019s product does not warrant switching to a brand; instead, a different generic product from another manufacturer can be tried. \u00a0Health care practitioners should also differentiate between true allergies (immunologically mediated) and intolerances, or adverse reactions, to a drug product. \u00a0For example, if a patient has gastrointestinal upset or dyspepsia in response to a medication, these side effects can be managed (by taking the medication with food) rather than discontinuing or switching the medication.<\/p>\n

As for patients that claim their generic medication is \u201cnot working\u201d as well as the brand, there is no scientific evidence to support these claims based on the aforementioned FDA regulations and clinical studies. \u00a0Patients may extrapolate these theories from unfounded preconceived notions that generic drugs are inferior to brands. \u00a0If the patient is really not experiencing a clinical improvement, it is likely that the failure is due to the active ingredient and not the excipients. \u00a0Perhaps a different agent from the same therapeutic class should be tried, or even one from another class. \u00a0A patient may respond differently to certain drug characteristics unique to the active ingredient. \u00a0If the patient and doctor feel that the generic version of the medication is the underlying cause of treatment failure, a different generic manufacturer can be requested before resorting to a brand.<\/p>\n

The lower price of generics only adds to the suspicion of their inferiority among patients, since a higher price is generally associated with greater benefit or safety. \u00a0In fact, while the original brand-name manufacturer spent millions of dollars on research, discovery, synthesis, and approval of the medication, the generic manufacturer skips these costs and must only ascertain that their drug is bioequivalent and comparable to the brand-name product for market approval. \u00a0This is the reason that generic companies are able to charge less for the same active medication and still make up their cost and accrue profit. \u00a0On average, the cost of a generic drug is 80\u201485 % lower than its brand counterpart.2<\/sup><\/p>\n

Finally, reluctance to use a generic product may result in therapy interruption. \u00a0Patients are often left without any medication in the time it takes to acquire authorization from a third party payer for a non-formulary brand name drug. \u00a0It is a time consuming process to get the prescription to the pharmacy, alert the doctor of an authorization block, have the doctor call the insurance plan and explain the situation, and ultimately allow the pharmacy to activate the authorization and dispense the drug. \u00a0This may take up to a few days, and the patient may not receive any medication in the meantime, not wanting to pay for it out of pocket. \u00a0If only the misconceptions about generic medications could be exposed and eradicated, this could be avoided.<\/p>\n

In the majority of cases, substituting drugs within the same therapeutic class is reasonable and safe; the only exceptions are narrow therapeutic index drugs and antibiotics. \u00a0For example, some of the most popular formulary-exception and prior authorization requests are for brand-name proton pump inhibitors (PPIs). \u00a0There are currently six brand-name medications (Protonix\u00ae [pantoprazole], Nexium\u00ae [esomeprazole], Aciphex\u00ae [rabeprazole], Prevacid\u00ae [lansoprazole], Dexilant\u00ae [dexlansoprazole], Prilosec\u00ae [omeprazole]) and three generic medications (pantoprazole, omeprazole, lansoprazole) on the U.S. market. \u00a0These agents have the same mechanism of action and similar pharmacokinetic properties and side effect profiles. \u00a0Few head-to-head clinical trials have been executed comparing the effectiveness among these agents; therefore, it is difficult to judge which one will optimally benefit an individual patient. \u00a0If the patient\u2019s formulary does not cover a drug prescribed by a clinician, it may be permissible to substitute not only with a generic product, but with any other PPI. \u00a0Clinical outcomes are expected to be the same among these agents, as long as adequate dosing is achieved and the patient is not subjected to undue interruptions in treatment.<\/p>\n

In some clinical cases, it is preferred to use brand-name products or be consistent with the generic manufacturer of one\u2019s medication. \u00a0Drugs with narrow therapeutic indices, such as Dilantin\u00ae (phenytoin), Lanoxin\u00ae (digoxin), Synthroid\u00ae (levothyroxine), and Coumadin\u00ae (warfarin) should not be substituted.1<\/sup> \u00a0Patients stabilized on one company\u2019s formulation should remain on it for adequate therapeutic control.<\/p>\n

As healthcare costs continue to skyrocket, managed care organizations are scrambling to cut down costs. \u00a0One cost-saving method is to substitute brand medications with their generic equivalents on formularies whenever possible. \u00a0In 2010 alone, the use of FDA-approved generics saved $158 billion, an average of $3 billion every week.3<\/sup> \u00a0Patients still benefit from the active ingredients, with significant decreases in insurance and co-payment costs. \u00a0Health care practitioners should take the time to educate patients on the concept of brand and generic medication to help develop an affordable, individualized, consistent therapy plan acceptable and beneficial to the patient.<\/p>\n

SOURCES:<\/span><\/b><\/p>\n

    \n
  1. Maniscalco-Feichtl M, Whalen KL. Chapter 14. Community\/Ambulatory Care. In: Kier KL, Nemire RE, eds. Pharmacy Student Survival Guide<\/i>. 2nd ed. New York: McGraw-Hill; 2009. <http:\/\/www.accesspharmacy.com\/content.aspx?aID=5258983>.<\/a> Accessed June 26, 2012.<\/li>\n
  2. \u201cFacts about Generic Drugs.\u201d U.S. Food and Drug Administration. 2012 Jun 6. <http:\/\/www.fda.gov\/drugs\/resourcesforyou\/consumers\/buyingusingmedicinesafely\/understandinggenericdrugs\/ucm167991.htm>.<\/a> Accessed June 27, 2012.<\/li>\n
  3. Nightingale SL, Morrison JC. \u201cGeneric Drugs and the Prescribing Physician.\u201d JAMA.<\/i> 1987 Sept 4, 258(9):1200-4. <http:\/\/jama.jamanetwork.com\/data\/Journals\/JAMA\/8962\/jama_258_9_039.pdf>.<\/a> Accessed June 27, 2012.<\/li>\n
  4. Bauer LA. Chapter 8. Clinical Pharmacokinetics and Pharmacodynamics. In: Talbert RL, DiPiro JT, Matzke GR, Posey LM, Wells BG, Yee GC, eds. Pharmacotherapy: A Pathophysiologic Approach<\/i>. 8th ed. New York: McGraw-Hill; 2011. <http:\/\/www.accesspharmacy.com\/content.aspx?aID=7966654>.<\/a> Accessed June 26, 2012.<\/li>\n
  5. \u201cOrange Book Preface.\u201d U.S. Food and Drug Administration. 2012 Feb 3. <http:\/\/www.fda.gov\/drugs\/developmentapprovalprocess\/ucm079068.htm<\/a>>. Accessed August 30, 2012.<\/li>\n
  6. Davit BM, Nwakama PE, et al. \u201cComparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration.\u201d Ann Pharmacother<\/i>. 2009 Oct; 43(10):1583-97. http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19776300>.<\/a> Accessed June 27, 2012.<\/li>\n
  7. Kesselheim AS, Misono AS, et al. \u201cClinical equivalence of generic and brand name drugs used in cardiovascular disease: a systematic review and meta-analysis.\u201d JAMA<\/i>. 2008; 300(21): 2514\u201426. <http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2713758\/>.<\/a> Accessed June 27, 2012.<\/li>\n
  8. \u00a0\u201cGenerics have the same quality as brand name drugs.\u201d Image. U.S. Food and Drug Administration. 2012 Jun 6. <http:\/\/www.fda.gov\/ucm\/groups\/fdagov-public\/documents\/image\/ucm298661.png>.<\/a> Accessed June 27, 2012.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    By: Marina Yermolayeva, PharmD Candidate c\/o 2013 – \u201cI\u2019m allergic to the generic; I need the brand name medication,\u201d is a common claim heard by many health care providers. \u00a0Managed care organizations get numerous calls from doctors and patients requesting prior authorizations to approve brand name medications whilst there are generic alternatives available on formulary.…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7,4,8],"tags":[1822,1825,343,2245,98,22,197,61,1823,1160,15,13,2229,2227,1436,2232,35,314,1647,1044,20,376,1646,93,96,1273,14,340,363,1621,968,1625,657,328,1644,19,2230,11,42,330,31,220,1679,187,1818,350,578,33,21,1145,1161,16,623,153,44],"class_list":["post-1097","post","type-post","status-publish","format-standard","hentry","category-clinical","category-featured","category-advice-opinions","tag-against","tag-agents","tag-and","tag-approval","tag-august","tag-blood","tag-book","tag-calcium","tag-chemical","tag-control","tag-disease","tag-drug","tag-drugs","tag-ebola-virus-disease","tag-esomeprazole","tag-fda","tag-food","tag-for","tag-formulation","tag-generic","tag-health","tag-human","tag-intravenous","tag-january","tag-june","tag-levothyroxine","tag-medication","tag-met","tag-of","tag-omeprazole","tag-one","tag-or","tag-oral","tag-original","tag-pantoprazole","tag-patient","tag-pharmaceutical","tag-pharmacy","tag-public","tag-rabeprazole","tag-research","tag-review","tag-short","tag-side","tag-skin","tag-solution","tag-strength","tag-student","tag-study","tag-test","tag-therapy","tag-treatment","tag-type","tag-upset","tag-warfarin"],"views":1400,"_links":{"self":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/1097","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/comments?post=1097"}],"version-history":[{"count":0,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/1097\/revisions"}],"wp:attachment":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/media?parent=1097"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/categories?post=1097"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/tags?post=1097"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}