this event and minimize the implication that the formulation change results in a lower and more acceptable seizure rate.
PRECAUTIONS
The
most significant changes I have made here are in the General Precautions
subsection. The sponsor has minimized
several of the adverse findings noted in this section: agitation and insomnia;
psychosis, etc., and appetite and weight changes. Again, the difficulty is that the SR data are based on a
generally lower dosage strategy than that used in the IR program. I have proposed modifications in this
section that illustrate more clearly the dose-relatedness for these findings
and their equal relevance for the IR and SR formulations.
ADVERSE
REACTIONS
The
general problem with this section was the same a in the earlier sections, a
failure to distinguish between the different doses of bupropion used in the IR
and SR programs. I have asked the sponsor
to redo this section, focusing on the 2 pertinent fixed doses used in the SR
program, i.e., 300 and 400 mg/day.
DOSAGE
AND ADMINISTRATION
I
have added back in the “General Dosing Considerations” statement that is in
current labeling, since I feel it is as relevant for the SR as for the IR. I have also modified dosing instructions to
clarify that 300 mg/day, and not 150 mg/day, is the initial target dose for
Wellbutrin.
3.0
CONCLUSIONS
AND RECOMMENDATIONS
Given
that the sponsor is now willing to recommend a dosing range for bupropion SR
that is comparable to the range currently recommended for bupropion IR, I think
we can consider this application approvable.
However, major work is still needed to develop labeling that will
adequately inform clinicians about the risks and benefits of this drug, and I
have proposed comments for a letter that emphasizes the discrepancy between the
labeling they have proposed and what is needed.
cc:
Orig
NDA 20-358
HFD-120/DivFile
HFd-120/TLaughren/PLeber/PAndreason/GDubitsky/PDavid
HFD-101/RTemple
DOC:
MEMBRPSR.AE1
4
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