Bioequivalence and Therapeutic Equivalence of Generic and Brand Bupropion in Adults With Major Depression: A Randomized Clinical Trial

Abstract

Controversy persists about bupropion XL 300 mg generic equivalence to brand product. A prospective, randomized, double-blinded crossover in 70 adults with major depression in stable remission taking any bupropion XL 300 mg tested bioequivalence and therapeutic equivalence of available XL 300 mg products. After a 4-week lead-in on patients' existing bupropion, four 6-week phases evaluated brand and three generics. Patients were uninformed of switching. Drug overencapsulation ensured blinding. There were no differences between any generic and brand, or between generics, in peak plasma concentration (Cmax ) and area under the plasma concentration-time curve over the 24-hour dosing interval (AUC0-24 ) for racemic bupropion or major metabolites. All generics met formal bioequivalence criteria for bupropion and metabolites. There were no differences between generics and brand, or between generics, in depression symptoms or side effects, assessed by every 3-week in-person interview and daily smartphone-based self-report. There were no differences in patients' perceptions of bupropion products. Results show three bupropion XL 300 mg generic products are both bioequivalent and not therapeutically different from brand drug and each other.

Conflict of interest statement

Conflict of Interest: The authors declared no competing interests for this work.

© 2018 The Authors Clinical Pharmacology & Therapeutics © 2018 American Society for Clinical Pharmacology and Therapeutics.

Figures

Figure 1.

CONSORT diagram

Figure 2.

Bioequivalence of brand and generic bupropion. Shown are steady-state plasma concentrations of bupropion and major metabolites in subjects with major depressive disorder receiving bupropion XL 300mg brand (marketed by Valeant) and generic (marketed by Par, Watson, and Mylan). Results are shown as the mean ± standard deviation. Standard deviations are shown for the Valeant data and others are omitted for clarity. The standard deviations for the other drug products were of the same magnitude as those for Valeant.

Figure 3.

Steady-state plasma concentrations of bupropion and major metabolites in the patient who suffered a major depression relapse. The subject withdrew in the middle of the third crossover session, while taking the Watson generic (after first PAR and then Valeant (brand) products in the first two sessions). The pharmacokinetic profile of the Watson generic resembles that of the PAR generic and Valeant (brand) products.

Figure 4.

Therapeutic comparison of brand and generic bupropion. Results are MADRS depression scores from (A) clinic visits and (B) cell phone assessments, and ASEC side effect data from (C) clinic visits and (D) cell phone assessments. Box plots represent the median (solid horizontal line), mean (diamond), 25th and 75th percentile (box boundaries), 10th and 90th percentiles (whiskers), and individual outliers.