FDA Withdraws Approval of Generic Antidepressant

Pam Harrison


October 04, 2012

October 4, 2012 — The antidepressant Budeprion XL 300 mg, one of the generic formulations of extended-release bupropion hydrochloride, is not therapeutically equivalent to Wellbutrin XL 300 mg, the brand-name extended-release formulation, and will be removed from the market by the drug's manufacturers, according to an update from the US Food and Drug Administration (FDA).

Budeprion XL 300 mg is manufactured by Impax Laboratories and is marketed by Teva Pharmaceuticals USA.

The FDA has approved 5 generic versions of Wellbutrin XL 300 mg.

The Impax/Teva product, Budeprion XL 300 mg, was approved in December 2006.

"Each of these generics was approved based on bioequivalence studies comparing the 150 mg strength of the products to Wellbutrin XL 150 mg," the FDA states.

Studies were not done directly on the 300 mg strength of the drugs. Rather, results from the 150 mg bioequivalence studies were extrapolated to establish bioequivalence of the 300 mg product.

Between January 1 and June 30, 2007, the FDA received 85 postmarketing reports involving patients who switched from Wellbutrin XL 300 mg to Teva's extended-release formulation and who subsequently experienced an undesirable effect; 78 patients reported loss of antidepressant efficacy.

A number of patients also reported the new onset or worsening of side effects.

"More than half of the patients who switched back to Wellbutrin XL 300 mg reported improvement of depression and/or abatement of side effects," the FDA writes.

"Given the temporal relationships between the switch to the generic product and the recurrence of depression and/or onset of side effects, these patients and physicians attributed these effects to poor performance of the generic product."

The FDA asked Teva to compare its 300 mg extended-release formulation directly to the brand-name extended-release 300 mg formulation and to enroll patients who had reported loss of efficacy after they had switched from Wellbutrin XL 300 mg.

The company was unable to enroll enough patients who had reported lack of efficacy after the switch, and the study was abandoned in late 2011.

The FDA therefore sponsored its own bioequivalence study, in which it compared Budeprion XL 300 mg with Wellbutrin XL 300 mg in 24 healthy adults.

Results, available in August of this year, showed that Budeprion XL 300 mg tablets fail to release bupropion into the blood at the same rate and extent as Wellbutrin XL 300 mg, although no new safety signals were identified.

On the basis of the failed bioequivalence study, the FDA asked Impax Laboratories to voluntarily withdraw its application for the 300 mg strength of bupropion hydrochloride extended-release tablets.

At the FDA's request, Impax and Teva ceased product distribution as of September 28, 2012.

The FDA did not conduct bioequivalence studies of the other 4 generic versions of Wellbutrin XL 300 mg but has asked each of the other manufacturers to do so and to report results back to them no later than March, 2013.

The FDA is also revising its guidance to industry for how to conduct premarket bioequivalence studies in generic bupropion products.

Meanwhile, patients who are taking Budeprion XL 300 mg who have questions or concerns about the product should discuss the medication with a healthcare professional.