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Leber:
Wellbutrin SR approvable |
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that allows 225 mg of the SR to be administered twice daily.
Accordingly,
although Wellbutrin SR may reasonably be deemed effective at the doses being
recommended (300 to 400 mg a day) it will fail, logically, to provide the
intended antidepressant effect to the proportion of the depressed population
that would fail to respond to 400 mg a day of the IR, but would respond to
doses of the latter in the range of 400 to 450 mg a day.
One
obvious solution to the problem would have been to require the firm to make a
225 mg formulation, but the Office did not wish to impose this solution.
Safety and Labeling
Dr.
Laughren recommends that Wellbutrin SR not be approved under the labeling
proposed by the sponsor in its 9/22/95 resubmission of the NDA. As he explains in detail in his February 8,
1996 memorandum to the NDA file, the firm’s proposed labeling makes the product
appear ‘safer’ than we actually know it to be under the conditions of use that
are proposed in the labeling drafted by the Division (i.e., Dr. Laughren)2.
Discussion:
The
representations made in the Wellbutrin SR NDA imply that the SR is superior to
the currently marketed IR formulation.
Basically, the firm asks the agency 1) to compare observations, made at
different times, by different investigators, in different populations, under
very different sets of conditions of use (formulation, regimen and daily dose)
and, the, 2) to conclude that any differences in outcome associated with the
use of the SR product are attributable to its superior to the IR. Clearly, this is
2 Presumably a reflection of
the firm’s intent to promote the drug for use at the lower end of the dosing
interval (300 mg a day). The problem is
that this dose is probably ineffective for a substantial proportion of the
population, a conclusion supported by the firm’s inability to document the
efficacy of Wellbutrin SR under this dosing in clinical trials.
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