Update: Bupropion Hydrochloride Extended-Release 300 mg Bioequivalence Studies
FDA’s update on this issue is an activity that is funded under FDA’s user fee program in the Center for Drug Evaluation and Research (CDER). Some FDA activities that do not rely on annual appropriations are continuing during the government shutdown.
[10-10-2013] FDA is providing an update on its request for studies to assess the bioequivalence of marketed bupropion hydrochloride (HCl) extended-release (ER) 300 mg tablets. We have completed our review of the studies from all four manufacturers of bupropion HCl ER 300 mg products currently on the market: Actavis, Inc.,* Mylan Inc., Par Pharmaceutical (formerly Anchen Pharmaceuticals), and Watson.*
Data submitted by Actavis, Inc., Mylan Inc., and Par Pharmaceutical confirmed that their generic bupropion HCl ER 300 mg tablet products are therapeutically equivalent to the reference-listed drug, Wellbutrin XL 300 mg. Patients can have confidence that these generics will have the same clinical effect and safety as the brand name drug.
Based on data submitted by Watson, FDA has determined that that company’s generic bupropion HCl ER 300 mg tablet product is not therapeutically equivalent to Wellbutrin XL 300 mg. Watson has agreed to voluntarily withdraw this product from the distribution chain. Also, FDA has changed the Therapeutic Equivalence Code for the Watson product from AB (therapeutically equivalent) to BX (data are insufficient to determine therapeutic equivalence) in the Orange Book. FDA does not anticipate a drug shortage.
We recommend that patients taking the Watson product continue taking their medication and contact their health care professional or pharmacist to address any concerns.
*Note that Actavis and Watson recently merged.
FDA Update: Budeprion XL 300 mg Not Therapeutically Equivalent to Wellbutrin XL 300 mg
[10-3-2012] The U.S. Food and Drug Administration (FDA) has reviewed new data that indicate Budeprion XL 300 mg (bupropion hydrochloride extended-release tablets), manufactured by Impax Laboratories, Inc., and marketed by Teva Pharmaceuticals USA, Inc., is not therapeutically equivalent to Wellbutrin XL 300 mg. FDA has changed the therapeutic equivalence rating for this product in the Agency’s Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) from AB to BX, signifying that Budeprion XL 300 mg fails to demonstrate therapeutic equivalence to Wellbutrin XL 300 mg. Impax has requested that the Agency withdraw approval of budeprion XL 300 mg extended-release tablets. Impax and Teva have stopped shipping the product and are issuing detailed information to their customers. This announcement relates only to Budeprion XL 300 mg manufactured by Impax and marketed by Teva. It does not affect the Impax/Teva Budeprion 150 mg product or generic bupropion products made by other manufacturers.
FDA has approved five generic versions of Wellbutrin XL 300 mg. Each of these generics was approved based on bioequivalence studies comparing the 150 mg strength of the products to Wellbutrin XL 150 mg. Studies were not performed directly on the 300 mg strength of the products. Rather, the bioequivalence studies were performed using the 150 mg strength, and the results were extrapolated to establish bioequivalence of the 300 mg product. This methodology was based on FDA’s guidance at the time the products were approved. FDA has determined that this approach is no longer appropriate to establish bioequivalence of 300 mg bupropion hydrochloride extended-release tablets to Wellbutrin XL 300 mg, and the Agency is revising its guidance to industry for how to conduct premarket bioequivalence studies in generic bupropion products.
The Impax/Teva product, Budeprion XL 300 mg, was approved in December 2006. Soon after, FDA began to receive reports that patients who were switched from Wellbutrin XL 300 mg to its generic counterparts were experiencing reduced efficacy. FDA analyzed those reports and concluded that the complaints appeared to be linked to the Impax/Teva product. FDA therefore asked Impax/Teva to conduct a study directly on its 300 mg extended-release product to compare its bioequivalence to Wellbutrin XL 300 mg. FDA asked that the study include patients who had reported lack of efficacy after switching from Wellbutrin XL 300 mg to Budeprion XL 300 mg. Impax/Teva began the study, but terminated it in late 2011, reporting that, despite efforts to enroll patients, Impax/Teva was unable to recruit a significant number of affected patients to generate the necessary data.
In 2010, in light of the public health interest in obtaining bioequivalence data, FDA decided to sponsor a bioequivalence study comparing Budeprion XL 300 mg to Wellbutrin XL 300 mg. This study was conducted in 24 healthy adult volunteers and was designed to measure both the rate and the extent of release of bupropion into the blood. The results of this study became available in August 2012, and show that Budeprion XL 300 mg tablets fail to release bupropion into the blood at the same rate and to the same extent as Wellbutrin XL 300 mg.
FDA has not identified any new safety information associated with Budeprion XL 300 mg; however, in some patients, the drug may not provide the desired efficacy (beneficial effect).
FDA did not conduct bioequivalence studies of the other four generic versions of Wellbutrin XL 300 mg. FDA did, however, recently ask each of the other manufacturers – Anchen, Actavis, Watson, and Mylan – to conduct their own studies to assess the bioequivalence of their 300 mg extended-release bupropion tablets to Wellbutrin XL 300 mg. FDA has asked these companies to submit the data from those studies no later than March 2013. FDA believes the study results may be unique to the Impax/Teva version of 300 mg bupropion hydrochloride. FDA does not currently have data indicating that the other four generic products are not bioequivalent to Wellbutrin XL 300 mg. The Agency will review the data from the additional bioequivalence studies when the data are received, and will provide additional updates at that time.
Budeprion XL 300 mg tablets manufactured by Impax and marketed by Teva are not therapeutically equivalent to Wellbutrin XL 300 mg and will be removed from the market by Impax/Teva. FDA’s actions with respect to Budeprion XL 300 mg reflect FDA’s ongoing role in monitoring drugs on the market to ensure their continued safety and efficacy. The role of patients and health care professionals in sharing their experiences with generic versions of Wellbutrin XL 300 mg contributed to further studies, which led to this action. FDA remains firmly committed to its science-based responsibilities and to making sure that generic drugs are safe and effective. This commitment is reflected in the results of the FDA-sponsored bioequivalence study described above.
Patients taking Budeprion XL 300 mg as a substitute for Wellbutrin XL 300 mg should talk with their health care professionals if they have questions about taking this medication.