HealthDay News — The FDA is withdrawing Budeprion XL 300 mg from the market, after study results show the generic antidepressant is not therapeutically equivalent to brand-name Wellbutrin XL 150 mg.
Bupropion absorption for generic Budeprion XL 300 mg was 86% of that of the brand name product (90% CI: 77-96), and mean peak plasma concentrations was only 75% of that observed after administration of Wellbutrin XL 300 mg (90% CI: 65-87), results from direct comparative pharmacokinetic analyses indicate.
Current FDA guidelines specify that in order for two drug products to be deemed bioequivalent there must be significant agreement in pharmacokinetic parameters, “such that the entire 90% confidence interval associated with the generic-to-reference ratio of geometric means should fall within the bioequivalence limits of 80% to 125%.”
Maximum plasma concentration and area under the plasma concentration curve for Budeprion XL were less than 40% of those for Wellbutrin in certain patients. The time to peak drug concentration in the blood was shorter for Budeprion XL than for Wellbutrin XL — four hours compared with five hours, the agency found.
“We at the FDA are therefore changing our bioequivalence recommendations for extended-release bupropion products and have asked other manufacturers of 300-mg extended-release bupropion products to conduct additional bioequivalence studies,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, and colleagues reported in New England Journal of Medicine.
Other versions of extended-release bupropion hydrochloride are produced by Anchen, Actavis, Watson and Mylan.
The FDA initially approved Budeprion XL 300 mg in 2006 as a generic substitute for Wellbutrin XL 300 mg for patients with major depressive disorder based on extrapolated results from a bioequivalence study comparing 150 mg formulations of both medications. Initial studies were conducted using the lower doses due to concerns about a dose-related risk for seizures with Budeprion.
However, soon after the drug’s approval reports began surfacing about lack of efficacy or unwanted side effects in patients who switched from the brand-name drug to the generic version.
Delays in conducting a direct clinical comparison with the 300-mg product occurred after difficulty enrolling sufficient numbers of patients who met the entry criteria of lack of efficacy or unwanted side effects with Budeprion XL 300 mg.
“In retrospect, the conservative approach did not provide the right conclusions regarding therapeutic equivalence in a timely manner,” Woodcock and colleagues wrote.
However, the FDA said it was confident in the “overall reliability of the agency’s approval process for generic drugs, including the use of extrapolation, when scientifically appropriate.”
Failure to extrapolate in this case is likely due to “technical aspects of the Budeprion formulation,” the agency noted, adding that other generic 300-mg bupropion products do not use the same technology as Budeprion.