Antidepressant: According to an investigation, generic medication works differently than an original preparation
A study reveals differences in the effects of an antidepressant between the original drug and a generic drug. Generic Budeprion XL does not have a therapeutic equivalent in the 300 milligram dosage to the original product Wellbutrin XL 300 milligram, reports the specialist magazine "The New England Journal of Medicine", citing a recent study by the American drug approval agency FDA (Food and Drug Administration). The study results raise the question of how the effects of generics should be determined in the future.
Antidepressants based on the active ingredient bupropion hydrochloride are originally offered under the name Wellbutrin, but can also be purchased as generics in the USA under the name Budeprion. The generic is significantly 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 found considerable differences in effects. This sensational result of the study fundamentally questions the previous practice in the approval of generics.
Generic with significant side effects Already in the first year after approval of the generic, the side effects in numerous patients who switched from the original drug to Budeprion XL 300 mg had caught the attention of the authorities and the media. The approval process was then examined again. As is usual with other generics, the 300 milligram dose was not explicitly checked for approval, but the approval body was based on the results of a bioequivalence study for Budeprion XL 150 mg and Wellbutrin XL 150 mg, which was subsequently used for the 300 milligram products were extrapolated. The FDA's new investigation now enables "direct comparative pharmacokinetic analysis of 300 mg products," reports the New England Journal of Medicine.
Generic and original drug not therapeutically equivalent In the current bioequivalence study, the FDA found significant differences between the single doses of the generic drug Budeprion XL 300 mg (manufactured by Impax Laboratories; sold by Teva Pharmaceuticals) and the single doses of the original drug Wellbutrin XL 300 mg (manufacturer Biovail). The generic drug could therefore not be considered therapeutically equivalent to the branded product. For example, the uptake rate of the generic drug only reached 77 to 96 percent of the uptake rate of the original product. The average plasma concentration reached only 75 percent of the concentration for the original drug, reports the FDA. Over the metabolization period, the values would have only reached 40 percent of those of the original product. In addition, the time to reach the maximum active substance concentration in the blood was different. Overall, the FDA comes to the conclusion that the previous procedure for the approval of generics urgently needs to be adjusted in order to avoid misinterpretation comparable to Budeprion XL 300 mg in the future. Additional bioequivalence studies have now been requested from the other manufacturers of generic products containing the active ingredient bupropion hydrochloride, the experts at the Center for Drug Evaluation and Research added.
Simplified approval regulations for generics Generics offer enormous potential for reducing costs in the healthcare system. In the case of older medications whose patent protection has expired, generics can provide patients with significantly cheaper care. In order to facilitate the introduction of the corresponding generics, these are subject to easier approval regulations in the USA and Europe, in which no further clinical trials are necessary, but only the bioequivalence has to be demonstrated. This means that the generics must, for example, achieve an active ingredient intake and active ingredient concentration in the blood corresponding to the original product over a certain period of time. As a rule, individual proofs are not required for all doses, but the results are extrapolated from the bioequivalence studies with low doses for higher doses. However, this procedure has significant weaknesses, as the current FDA study shows. An adjustment of the admission regulations seems urgently necessary here. This also applies to the European pharmaceutical market, although antidepressants based on the active ingredient bupropion hydrochloride are currently only available as original medication in the EU. The preparations are mainly used to treat depression, but also to quit smoking. (fp)
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