Clinical Pharmacology and Biopharmaceutics Review
|
NDA: |
21-515 |
|
Brand
Name: |
Wellbutrin
XL |
|
Generic
Name: |
Bupropion
HCl |
|
Type
of Dosage Form: |
Extended
Release Tablet |
|
Strengths: |
150
mg, 300 mg |
|
Indications: |
Major
Depressive Disorder |
|
Type
of Submission: |
New/3S |
|
Sponsor: |
GlaxoSmithKline |
|
Submission
Date: |
August 26, 2002 April
15, 2003 December 18, 2002 April
17, 2003 January 24, 2003 February 11, 2003 |
|
OCPB
Division: |
DPE-I |
|
OND
Division: |
Division of Neuropharmacological Drug Products
HFD-120 |
|
OCPB
Reviewer: |
Sally Usdin Yasuda, MS, PharmD |
|
OCPB
Team Leader: |
Ramana Uppoor, PhD |
1
Executive Summary
This
NDA review evaluates in vivo and in vitro data regarding WELLBUTRIN
XL (extended release) tablets (50 mg and 300 mg) to be indicated for major
depressive disorder. The to-be-marketed
tablets were used in the pharmacokinetic studies. This NDA is entirely based on bioequivalence studies. Clinical studies were not conducted on these
tablets.
·
Bioequivalence
was demonstrated for bupropion metabolites between the highest strength
WELLBUTRIN XL tablet (300 mg) and the approved immediate release product
WELLBUTRIN given as 100 mg three times daily.
Although bioequivalence could not be demonstrated for the parent
compound (for Cmin only: Cmax and AUC met bioequivalence
criteria), consideration should be given to the active metabolites, since they
are responsible for more than 90% of the exposure following administration of
bupropion. Therefore it is reasonable
to suggest that the two products were comparable in exposure.
It should be noted that although comparable exposure
was demonstrated, there are differences in the shapes of the curves for
bupropion in the WELLBUTRIN XL formulation compared with immediate release
formulation. The clinical relevance of
these differences cannot be predicted based on the pharmacokinetics. However, the comparable exposure and the
role of the metabolites in the exposure and pharmacologic activity support the
approval of the WELLBUTRIN XL formulation. Of note, for WELLBUTRIN SR, although there were also
differences in the shapes of the plasma concentration curves compared to WELLBUTRIN
IR, a clinical trial demonstrated efficacy of WELLBUTRIN SR in
maintaining antidepressant response.
1
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