PRACTICE RECOMMENDATIONS
• Do not authorize the pharmacy to switch patients from a brand-name antiepileptic drug to a generic without your approval. C
• Use caution when switching a patient to a generic modified-release formulation, which may not have the same pharmacokinetic profile as its brand-name counterpart. C
• Consult the FDA’s Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations, available at http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm for details on generic substitution. C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
Each year, Americans save an estimated $8 billion to $10 billion at retail pharmacies by purchasing generic drugs rather than brand-name medications, the US Food and Drug Administration (FDA) reports.1 The lower cost, of course, is the key advantage of generics. But the very reason for the cost savings—the fact that generic drugs do not have to undergo the large, expensive clinical trials that are required for approval of brand-name medications—gives rise to questions about the quality and safety of generics.
Are these concerns justified? Under what circumstances is it safe to prescribe generics, or to substitute a generic for a brand-name drug? Are brand-name drugs always better? To answer these questions, we conducted a thorough evidence review, which included numerous randomized controlled trials (RCTs) and case reports, as well as a single meta-analysis that assessed the benefits and risks of generics.
Generics: On the positive side
Safety and efficacy. Our literature search yielded little evidence that generic drugs are less safe or less effective than their brand-name equivalents. The meta-analysis, for example,2 included 47 studies (38 of 47 were RCTs) covering 9 subclasses of cardiovascular medications. In trials involving beta-blockers, diuretics, calcium channel blockers, antiplatelet agents, statins, angiotensin-converting enzyme inhibitors, and alpha-blockers, no evidence of superiority of brand-name drugs vs generics was found.2
Cost. Generic drugs typically cost 30% to 60% less than their brand-name counterparts,3 and widespread use of generics has the potential to reduce the price of other brand-name drugs by creating more competition.
Another plus: Patients taking generic drugs appear to be more willing to continue therapy than those taking brand-name medications.4 Lower co-pays are a key factor. In 1 recent study of patients with hypercholesterolemia or diabetes, those taking generics had greater adherence compared with patients receiving brand-name drugs.5
Quality. It is important to note that many generic medications are produced under the license of the manufacturer of the original brand-name product, with the lower-cost equivalent often introduced after the drug’s patent has expired. Even when different manufacturers produce the branded product and the generic, strict standards exist to guarantee the quality of generic drugs.
The journey to market—the similarities, the differences
Both brand-name and generic medications undergo similar new drug application (NDA) procedures. The manufacturers of both are required to submit detailed evidence of the chemistry, manufacturing, controls, labeling, and testing processes. From there, brand-name and generic products take divergent paths to market.
New nongeneric drugs must undergo rigorous animal and human studies, including large RCTs comparing the efficacy of the new product with that of a placebo and carefully tracking side effects. Bioavailability testing is required, as well. For generic drugs, the process is known as an abbreviated new drug application (ANDA), and bioequivalence studies are sufficient.1,6
The bioequivalence studies required for a new generic are based on pharmacokinetic parameters, most notably, the area under the plasma concentration curve (AUC)—a measure of overall drug exposure—and the maximal plasma concentration (Cmax). If AUC and Cmax are within an acceptance range (0.80–1.25 of the brand-name product parameters), the therapeutic equivalence of a generic drug is substantiated.7,8
Concerns about testing, formulation
Opponents of widespread use of generics point out that they are tested on only a few young, healthy individuals, compared with the large numbers of patients who participate in clinical trials of the original drug.
Bioequivalence
According to guidelines from the World Health Organization (WHO), 18 to 24 healthy adult volunteers are considered sufficient for a bioequivalence study.9 The number of participants may be greater, however, if absorption or clearance of the drug is highly variable. What’s more, the people who volunteer for generic drug studies cannot smoke or take concurrent medication. To exclude the possibility that food coadministration affects the generic medication being studied, the FDA further recommends bioequivalence testing of oral formulations on volunteers eating standardized meals.8 These criteria help minimize the magnitude of intersubject variability and reduce the possibility of bias—which could be caused by the disease process, concurrent conditions, or medication interaction, rather than by formulation differences.8