Joint Meeting of the
Dermatologic and Ophthalmic Drugs Advisory Committee (DODAC)
Drug Safety and Risk Management Advisory Committee (DSaRM)
ACS Conference Room,
1. Based on the information from the clinical studies conducted for tazarotene capsules, is there an adequate demonstration of effectiveness for moderate to severe psoriasis? Is there an adequate demonstration of efficacy for “very severe” psoriasis?
2. Has the safety profile for this product been adequately assessed?
A) Please provide discussion of the clinical and preclinical safety data, including comments on bone and liver abnormalities, hyperlipidemia, and teratogenicity.
B) Please discuss any potential issues, regarding long term safety of oral tazarotene with repeated use.
3. Given the safety and efficacy information, does the Committee find a favorable balance of risks and benefits which would support approval of this product?
4. Allergan has submitted a risk minimization proposal to the NDA that is similar to the isotretinoin SMART program. In addition, they have described in their package to the advisory committee a registry program that appears to be similar to the emerging isotretinoin risk minimization program. Both programs exempt males and females not of childbearing potential from many program requirements, including refill restrictions.
A) Please comment on which teratogenic risk management program is preferred for tazarotene?
B) Please comment on the advantages and disadvantages of having teratogenicity program requirements applied solely for Female Child Bearing Potential.
C) Are the scientific and clinical uncertainties surrounding semen levels of tazarotenic acid a factor to be considered in tazarotene risk minimization?
5.) How can FDA best address the potential clinical relevance of high tazarotenic acid levels in semen? Options might include:
A) further delineation of the potential risks (via consultation with teratogenicity experts, additional preclinical studies, etc.)
B) informing clinicians and patients of the finding and its uncertain clinical relevance
C) recommending precautions (such as the use of condoms) pending characterization of the potential risk
Please comment on whether further risk assessment should be done and whether any cautionary language or recommendations should be made while additional risk assessment is pending.
6.) What additional studies are needed? Are these studies needed before or after approval of the product?