One of the most important drugs used in Dermatology today is Isotretinoin, also known as Accutane, for severe acne. It is the only medication capable of curing the most severe forms of scarring cystic acne.
Accutane is the brand name used by Roche, which discovered and developed the drug. It is derived from vitamin A acid (trans-retinoic acid) and was approved by the FDA more than 20 years ago.
Unfortunately, isotretinoin has many potential side effects. Most of them are minor and easily tolerated such as dry lips, dry eyes, muscle and joint pains, and abdominal pain. It has even been suggested that there is an association between taking isotretinoin and developing inflammatory bowel disease or depression although cause and effect has not been proven conclusively.
An example of litigation regarding Accutane is that Roche Holding AG was ordered to pay 18 million dollars on June 29, 2012 to two former users who blamed the drug for their
inflammatory bowel disease. The New Jersey jury found that Roche failed to properly warn patients of the risk. According to Bloomberg.com , Roche has now lost nine out of 13 lawsuits of this type that have gone to trial since 2007. Some of the verdicts have been overturned by appeals courts.
In a new study in the February 2013 issue of JAMA Dermatology, the authors compared 2159 cases of inflammatory bowel disease (IBD), equally divided between ulcerative colitis and Crohn’s disease, to 43,180 controls. Only 10 cases (0.46%) and 191 controls (0.44%) were exposed to isotretinoin. This study also adjusted for severe acne, use of tetracycline antibiotics and oral contraceptives, which have all been considered to be risk factors for the development of IBD. The authors concluded that isotretinoin use does not increase the risk of developing IBD and that the drug should not be withheld from patients because of this unproven concern or fear of liability.
Another large retrospective population-based study of all residents of British Columbia aged 12-29 years included 47,000 patients treated with isotretinoin over a 12-year period. After adjusting for prior tetracycline use and comparing isotretinoin to topical acne treatment and no treatment, it appeared that having the diagnosis of acne may be a risk factor for developing IBD.
The most serious side effect is that isotretinoin causes birth defects in children born to women who get pregnant while taking it. This was known before FDA approval, and the warning was prominently displayed on each individual capsule package.
In spite of the warnings, pregnancies occurred which resulted in either serious birth defects or abortions, both spontaneous and voluntary, which were followed by costly lawsuits. Roche eventually stopped manufacturing isotretinoin due to the liability, but it is still distributed by generic pharmaceutical companies. The FDA attempted to reduce fetal exposure to isotretinoin by instituting a strict program of registering prescribers, pharmacists, and patients taking the drug. They are required to have multiple pregnancy tests (females) and other blood tests before and during treatment. Male patients must also be registered. Isotretinoin is metabolized rapidly and is not stored in the body, therefore, it is safe to get pregnant three months after stopping the drug.
Although I still believe that isotretinoin is as close as we get to a miracle drug for acne, I decided to opt out of the FDA’s “iPledge” program because of the incredible time commitment on the telephone or computer enrolling all patients including men who of course can’t get pregnant. Therefore, while I have not prescribed isotretinoin since 2006, I have always made sure that there is a provider in my group practice who could prescribe it for one of my patients who needed it.
Here’s the sorry punch line: In spite of heavy regulation and restrictions, mandatory repeated office visits and laboratory tests, the iPledge program has failed to reduce the number of fetal exposures per year to isotretinoin, which remains unacceptably high at about 120.
On July 16,2012, partly in response to no decrease in fetal exposure to isotretinoin, the FDA instituted a new iPledge non-compliance policy for prescribers who receive complaints. Penalties range from re-education and corrective action to permanent expulsion from the program for repeat offenders.
Further, in August 2012, the sponsors of iPledge released a “lessons learned” document with recommendations on how to prevent exposure of pregnant women to isotretinoin:
1. Never take leftover medications. This caused 33 fetal exposures during 6 years.
2. Dispose of medication after the treatment course is completed.
3. Obtain screening and confirmatory negative pregnancy tests prior to taking the first dose of isotretinoin.