Generic Drugs

The upcoming issue of The Medical Letter includes a brief article on the FDA-forced withdrawal of a generic extended-release formulation of the antidepressant bupropion (Wellbutrin). Patients switched to the generic had complained for years that Teva’s Budeprion XL 300 mg was not as effective as and caused more side effects than the brand-name original Wellbutrin XL 300 mg (The Medical Letter 2008; 50:54). The FDA conducted pharmacokinetic studies in volunteers and found that, indeed, the generic 300-mg product did not release the drug into the blood at the same rate and to the same extent as the brand-name product.

Complaints about generic drugs are an old story, and we have written about them many times. The FDA does not require generic manufacturers to demonstrate that their candidate drug is as effective and safe as the original. They only need to show that their drug is bioequivalent: given to volunteers, it produces maximum serum concentrations and an area under the time/concentration curve (AUC) within 80-125% of those of the brand-name drug.

Brand-name manufacturers often complain that generic drugs are inferior, but convincing evidence is generally lacking (The Medical Letter 2009; 51:81). In one well-publicized attempt to demonstrate inferiority, the manufacturer of Synthroid, which dominated the market for levothyroxine, sponsored a study comparing their drug to several generics, and when the pharmacist who conducted the study found that they were equivalent to Synthroid, tried to keep her from publishing the results. She was courageous enough to publish them anyway (BJ Dong et al. JAMA 1997; 277:1205). Synthroid, of course, still dominates the market.

In randomized controlled trials of cardiovascular drugs, clinical outcomes with brand-name drugs were not any better than with generic drugs in 7 of 7 trials of beta blockers, 10 of 11 trials of diuretics, 5 of 7 trials of calcium channel blockers, and 5 of 5 trials of warfarin formulations. Patients who resist generic drugs may not know that many generics now are produced by large brand-name manufacturers, or that brand-name drugs are no less likely than generic drugs to be recalled for formulation problems.

For drugs that have a narrow therapeutic index, like warfarin or levothyroxine, there is something to be said for using the same manufacturer’s product consistently, and that can be difficult to manage with generics. In general, though, there is nothing wrong with taking generics, or with prescribing them. Now that Budeprion XL 300 is gone.

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Comments

  1. William Braden MD says:

    I use generics consistently. The major problem with them is that the chain pharmacies switch manufacturers, for what, to save a nickel? Then the patient who was getting green amitriptylines gets brown ones and has to be soothed; likely there are negative placebo effects too.

    • Jeffrey Lazar says:

      As Dr, Braden wrote, I, too, use generics consistently…both for myself and my patients. I fully agree with his comment. As a patient, however, I recently received some very poor advice from my Medicare Part D plan. They suggested I (as a patient) switch from Effient (prasugrel) to generic clopidogrel, as I could save some money. I content that they are incorrect in declaring them to be therapeutically equivalent, as there is a definite difference in their safety profiles, with clopidogrel being associated with a higher risk (and severity) of bleeding. I wonder how often this happens in “real life.”

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