I sotretinoin must feel like a wounded prizefighter taking body blows and struggling to stay on his feet. This “champion” acne medication, that has literally changed the lives of thousands of acne sufferers, has come under fire again and again, despite industry and physician efforts to regulate its use.

No one questions the severe consequences for women who become pregnant while taking the medication. Approximately 25% of babies born to mothers taking the drug have serious birth defects, and 50% are mentally disabled.1

Despite efforts to the contrary, from 1982 to 2000, 162 babies were reportedly born with birth defects attributable to isotretinoin.2

Past Programs
The first effort to prevent pregnancy (Pregnancy Prevention Program or PPP) in women taking isotretinoin was developed in 1988 by the FDA.

Because of perceived inadequate participation in this program, another FDA committee met in 2000. The result — the System to Manage Accutane Related Teratogenicity (S.M.A.R.T.) was launched in the spring of 2002 by Accutane’s manufacturer, Roche, and the FDA. That year, 61 documented pregnancies still occurred on isotretinoin.3

We now have the newest regulatory effort, the risk minimization action plan (RiskMAP). RiskMAP is the work of a February 2004 FDA committee, and it is tentatively slated to take effect this July.4

Details are still undergoing finalization. The new program will link prescribers, patients and pharmacies through a single centralized registry. The goal is to confirm that an appropriately timed pregnancy test is negative prior to authorizing the prescriptions to female patients who can become pregnant, and that informed consent, counseling and patient education have occurred. Positive pregnancy test results will not be communicated to the patient via the registry; the patient will learn this from her healthcare provider.

The program’s details are not yet clearly delineated, so potential prescribers should monitor the FDA’s Web site (www.fda.gov) or take other measures to be kept abreast of the progress.

Déjà vu?
If this newest risk management program, RiskMAP, sounds familiar, it should. Celgene,
the makers of thalidomide (Thalomid) and creators of System for Thalidomide Education and Prescribing Safety (S.T.E.P.S), which regulates thalidomide, is the owner of the business process patents on components that are essential elements of RiskMAP. However, Celgene won’t handle or dispense isotretinoin in any way.4

What Will Be the fate of Isotretinoin?
Does this program mean the death of isotretinoin as doctors and patients shrink away from tedious regulatory procedure? For years, and even more vociferously lately, select officials have called for the ban of the medication. Curt D. Furberg, M.D., Ph.D., Professor, Department of Public Health Sciences at Wake Forest University (and advisor to the FDA), in testimony to the FDA stated: “Simply put, I believe that isotretinoin is not safe and cannot be used in a safe manner.”5

Moreover, Dr. Sidney Wolfe, Director of Public Citizen’s Health Research Group, exclaims that the situation “is one of the two worst epidemics of preventable serious birth defects ever seen in the United States. It is time to end it.”6

Furthermore, the purported, yet unsubstantiated, link between isotre-tinoin and depression has dogged the medication via high-profile news stories, despite a lack of scientific evidence. I’ve even heard leading dermatologists claim that photodynamic therapy, laser treatments and the fear of litigation are driving them away from prescribing isotretinoin as much as they had previously done.

One birth defect is too many, and no one wants abortions to increase. However, is isotretinoin being unfairly singled out simply because its therapeutic target is acne, a disease that does not threaten life or limb? Such thinking is naïve, especially to dermatologists who have seen the dramatic results isotretinoin produces, and seen patients experience elevations in mood, increased confidence and overall dramatic improvement in quality of life when a patient’s severe acne clears.

Because acne is primarily a disease of adolescents and teenagers, those who often have fragile emotional states, the psychological effects of acne can be devastating. As far as physical sequelae are concerned, the scarring can last a lifetime. The notion that current treatments can replace isotretinoin is not supported by evidence. No other therapy attains anywhere near the 80% to 85% clearance rates seen in severe acne patients.

Despite such negativity, the RiskMAP program may save isotretinoin. Granted, fewer dermatologists may prescribe it after RiskMAP is implemented, but such a vigorous program (that has been successful for thalidomide) may avoid a ban — the worst of all outcomes.

Serious Blow
Most dermatologists would probably agree that losing isotretinoin would deal a serious blow to our ability to manage severe acne, thus providing a great disservice to our patients for whom acne can be devastating.