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US FDA Advisory Committee Meetings Held to Discuss Isotretinoin, Safety Issues and a New Accutane Formulation

Stuart Maddin, MD, FRCPC
Division of Dermatology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

There is no drug that has provided as much therapeutic benefit for 12 million acne patients as this retinoid has done in the past 18 years following its introduction. However, it is a retinoid and, therefore, a teratogen. In spite of the elaborate pregnancy prevention program put in place by Hoffman-LaRoche, as well as a tracking program monitored by the Slone Epidemiology Unit in Boston Massachusetts, there are patients taking isotretinoin who still get pregnant. More recently, adverse psychiatric events have surfaced in patients who have taken isotretinoin (Accutane).

Such adverse events triggered these meetings called by the US FDA. On September 18th and 19th a joint meeting of the Dermatologic and Ophthalmic Drug/Pharmaceutical Science Advisory Committees met to discuss three issues with regard to isotretinoin (Accutane):

  • risk management regarding pregnancy and isotretinoin use
  • possible link with psychiatric events
  • a new formulation (Accutane NF) for which an NDA was submitted by Hoffman-LaRoche in October 1999.

Day 1

On the first day of meetings, risk management options to prevent pregnancy in patients taking Accutane were explored by the Committee. Discussions included Roche’s revised US Pregnancy Prevention Program (Targeted PPP or T-PPP). The Committee recommended that a risk management program for pregnancy prevention should consist of Roche’s T-PPP, a mandatory physician and patient enrollment, as well as establishing a linkage between the pharmacy that dispenses an Accutane prescription and confirmation of negative pregnancy test results for the patient.

Day 2

The second day of meetings focused on risk management options for psychiatric events and Accutane NF, Roche’s new formulation.

In light of the lack of clear linkage between depressive illness and Accutane, an opinion expressed by several FDA Committee members, the Committee defeated a motion to expand the registry to include all patients, and to include questions about psychiatric illness in the registry’s informed consent database. Currently, the registry only includes women in their childbearing years. But, the committee did recommend that Roche and NIH fund additional research in this area including a basic science study on retinoids and retinoid receptors in the adolescent and adult brain, prospective controlled studies, etc.

The Committee supported the new formulation because the dosage is less than the current formulation, and there is a reduced variability of drug absorption when taken with or without food. However, they noted that there could be possible consequences associated with the simultaneous availability of the two formulations for both patients and prescribers. Roche stated that it will be launching Accutane NF in very different packaging than the original formulation and will be providing additional information on the new formulation to prescribers.

Conclusion

By the end of the meetings, the Dermatologic and Ophthalmic Drug/Pharmaceutical Science Advisory Committees supported the new formulation (Accutane NF). The Committee agreeed that there was at present no causal link between psychiatric events and Accutane. In spite of this, they recommended additional research with regard to possible psychiatric connections to Accutane, as well as the establishment of a registry to track women who are in their childbearing years taking Accutane. Challenges await Hoffman-LaRoche and the US FDA in establishing such a registry. It will be interesting to follow their progress.


In this issue:

  1. Perspectives on Isotretinoin and the Canadian Consensus Guidelines on Treatment of Acne
  2. US FDA Advisory Committee Meetings Held to Discuss Isotretinoin, Safety Issues and a New Accutane Formulation
  3. Update on Drugs and Drug News - Number 2 2000