Antidepressant generic other than original

Antidepressant: Generic acts according to an investigation unlike an original drug

11/12/2012

A study reveals an antidepressant effect differences between the original drug and a generic drug. The generics Budeprion XL in the 300 milligram dose therapeutically not equivalent to the original preparation Wellbutrin XL 300 milligrams, reports the journal „The New England Journal of Medicine“ citing a recent investigation by the US Food and Drug Administration (FDA). The study results raise the question of how the effect of generic drugs should be determined in the future.

Antidepressants based on the active ingredient bupropion hydrochloride are offered as an original under the name Wellbutrin, but can also be obtained in the US as generic drugs under the name Budeprion. The generic is much cheaper and should actually have the same effect as the original. However, in a bioequivalence study of single doses of the different preparations, the FDA has now found significant differences in efficacy. This sensational study result fundamentally calls into question the current practice in the approval of generics.

Generic with significant side effects
Already in the first year after the approval of the generic drug, the side effects in numerous patients who had changed from the original drug to Budeprion XL 300 mg had attracted the attention of the authorities and the media. The approval procedure was then re-examined. As with other generic drugs, the 300 mg dose was not explicitly tested for approval, but the Admissions Office followed the results of a bioequivalence study for Budeprion XL 150 mg and Wellbutrin XL 150 mg, which were subsequently used for the 300 mg products were extrapolated. The new FDA investigation now allows one „direct comparative pharmacokinetic analyzes of the 300 mg products“, reports that „New England Journal of Medicine“.

Generic and original drug not therapeutically equivalent
In the current bioequivalence study, the FDA found clear differences between the single doses of the generic Budeprion XL 300 mg (manufactured by Impax Laboratories, distributed by Teva Pharmaceuticals) and the single doses of the original drug Wellbutrin XL 300 mg (manufactured by Biovail). Accordingly, the generic drug can not be considered therapeutically equivalent to the branded product. For example, the take-up rate of the generic drug only reached 77 to 96 percent of the intake rate of the original drug. The average plasma concentration reached only 75 percent of the original drug's concentration, reports the FDA. Over the metabolization period, the values ​​would have reached as much as 40 percent of that of the original preparation. In addition, the duration was different until reaching the maximum drug concentration in the blood. Overall, the FDA comes to the conclusion that the current approach to the approval of generic drugs must be urgently adjusted to avoid similar misjudgment as Budeprion XL 300 mg in the future. Additional bioequivalence studies have now been requested from the other manufacturers of generic products containing bupropion hydrochloride, added the experts from the Center for Drug Evaluation and Research..

Facilitated approval requirements for generics
Generics offer enormous potential for cost reduction in healthcare. In older drugs, whose patent protection has expired, can be achieved by the generics significantly cheaper care of patients. In order to facilitate the introduction of generic drugs, these are easier to approve in the United States and Europe, which do not require re-testing, but only require bioequivalence. This means that, for example, generics must achieve a drug uptake and drug concentration in the blood that will match the original product over a period of time. In general, individual proofs are not required for all doses, but the results are extrapolated from the low dose bioequivalence studies for higher doses. However, this procedure has considerable weaknesses, as the current FDA study shows. Here an adjustment of the registration regulations seems urgently necessary. This also applies to the European pharmaceutical market, although in the EU antidepressants based on the active substance bupropion hydrochloride are currently only available as original drugs. The preparations are mainly used for the treatment of depression, but also for smoking cessation. (Fp)

Image: Eva-Maria Rossmann