Accutane (isotretinoin) is a medication for severe acne created by Hoffmann-LaRoche Inc. (Roche). The drug, approved by the U.S. Food and Drug Administration (FDA) in 1982, proved to be a miracle for some, offering blemish-free skin to those who had given up after trying many other treatments.
The drug works for severe (cystic) acne, providing long-lasting and sometimes complete reduction of acne for 80 percent of patients. However, clear skin may be accompanied by serious side effects like Crohn’s disease, birth defects and suicide.
Following numerous reports of adverse events – and after doctors noted potential dangers with the drug and the FDA issued a black-box warning, Roche recalled Accutane in 2009. Generic brands of the medication — Amnesteen, Claravis and Sotret — are still available.
Uses of Accutane
Accutane is part of a class of medications called retinoids and originally was marketed as a chemotherapy drug. It is known for its ability to treat acne that has not responded to antibiotics. The medication is a derivative of vitamin A and works by controlling the oil in the sebaceous glands. The acne it treats consists of nodules with a diameter or 5 mm or greater. Having this type of acne can be socially debilitating, so the potential of a cure can be life-changing.
Undergoing Accutane treatment is a commitment of time and energy. It can take months to be effective, and patients often must deal with side effects like dry eyes and headaches. In addition, acne may worsen during the beginning stages of treatment before it starts to clear up.
Doses of Accutane range from 0.5 to 1.0 mg/kg body weight per day, with a cumulative dose of greater than 100 to 120 mg/kg. Accutane comes in capsules of 10, 20 and 40 mg, and should be taken with food. Most patients take the medication for 15 to 20 weeks, and may repeat the treatment course if acne returns. Due to the risk of serious birth defects, women of child-bearing age must commit to programs aimed at preventing pregnancies during treatment.
Doctor Warnings and a Recall
The first prescriptions of Accutane were written in 1982, and a year later came the first report of a baby born with malformations after Accutane was taken during pregnancy. In 1983, there were two “Dear Doctor letters” — special communications the FDA requires drug manufacturers to send out if the drug label is not complete in covering the extent and severity of side effects — sent out, alerting physicians of the possibility of birth defects. From 1984 to 1988, seven more of the letters went out.
The FDA was not alone in noting the dangers of Accutane. Dr. Frank Yoder, one of the scientists involved in the discovery of Accutane, wrote a letter to the Journal of American Medicine in 1983, informing the public of the possibility that Roche was not clear in alerting users of the toxicity associated with Accutane.
That same year, a nonprofit health advocacy group, the Public Citizen, petitioned the FDA to add warnings of birth defects to Accutane labels. The FDA took action in 1985, when a black-box warning, indicating that Accutane can cause fetal deformities and possibly fetal death, was added to the medication.
By 1988, a pregnancy prevention program had been put into place, with the goal of decreasing the number of woman getting pregnant while taking the drug. The program was eventually effective in decreasing the percentage of woman getting pregnant while taking the drug, from 4 women per every 1,000 a year to less than 2 for every 1,000. However the number of prescriptions given out also increased, keeping the number of affected pregnant women taking Accutane high.
Other countries had even stricter rules about Accutane use by women of childbearing age. For example, in Britain, prior to receiving the medication, women were required to agree to have an abortion if they became pregnant during treatment.
The Centers for Disease Control (CDC) played a role in affirming the danger of Accutane by publishing information on the fetal toxicity of the drug, conducting a study of Accutane-exposed pregnancies to raise awareness, and sending a letter to the FDA in 1998 recommending that the drug not be sold due to these dangers. Also, the CDC division of Birth Defects and Developmental Disabilities received reports of infant death following maternal exposure to Accutane.
In June 2009, as the number of adverse events reported to the FDA and lawsuits from patients continued to grow, Roche finally recalled Accutane. The company claimed the decision was not related to safety concerns but was an economic decision based on generic brands of the medication taking over the market. Accutane also was recalled in 11 other countries.
Milder Side Effects of Accutane
Most people experience some measure of common side effects with Accutane use and should not be concerned unless these conditions worsen or become extremely painful. With more serious side effects, however, a doctor should be consulted immediately.
Common side effects include:
- Diminished night vision
- Increased bone injuries due to thickened or weakened bones
- Increased reaction to UV exposure
- Red, cracked or sore lips
- Changes in nails
- Peeling skin
- Unusual hair growth or loss
- Bleeding or swollen gums
- Voice changes
- Slow healing of cuts or sores
- Cold symptoms
- Dry skin and eyes
- Muscle aches
Birth Defects Related to Accutane
The FDA gave Accutane a pregnancy rating of X, which means it should not be taken during pregnancy because there is evidence of fetal abnormalities when it is used during pregnancy. The FDA reported that infants whose mothers took Accutane were born with both internal and external abnormalities such as cleft palate, missing ears, facial dysmophism and central nervous system malformations.
In fact, among Accutane-exposed pregnancies, 42 percent of infants suffer from birth defects.
Because of the high risk of miscarriage and deformities, the FDA worked with Roche to create programs to ensure that Accutane users were not and would not become pregnant. The first program was put into place in 2002 and was called SMART (System to Manage Accutane Related Teratogenicity). SMART required qualification stickers on prescriptions, signed consent forms, patient education videos and information guides. In addition, doctors and pharmacists were required to read literature on the risks.
In 2006, a stricter system was put in place, called the i-PLEDGE program. The computer-based system required registration by pharmacies, doctors and patients. Within the system, negative pregnancy tests from approved labs were periodically required before medication was dispensed, prescriptions only covered 30 days at a time, and users were required to utilize two types of birth control.
According to a 2007 study funded by the Canadian Institutes of Health Research and published in the British Journal of Clinical Pharmacology, the rate of elective abortions for patients who got pregnant during Accutane use was 84 percent. This rate was based on 90 women, out of 8,609, who became pregnant while taking Accutane. Of the remaining pregnant women, three had spontaneous abortions, two had delivery trauma that resulted in neonatal death, and nine infants survived. One of the nine was born with face and neck abnormalities.
Inflammatory Bowel Disease
Women of child-bearing age are not the only ones who have suffered after taking Accutane. Adults of all ages, as well as teenagers, have had their lives interrupted with other serious side effects, including inflammatory bowel disease and suicidal behavior.
Roche maintains that it was not aware of side effects relating to inflammatory bowel disease, however, early animal trials of Accutane by Roche showed evidence of gastrointestinal bleeding in dogs. Another early study by Roche of 523 patients found that 21 percent experienced gastrointestinal disorders.
Since Accutane’s release, many patients have sued after developing gastrointestinal conditions, mainly consisting of inflammatory bowel diseases that come in two forms. One is ulcerative colitis, associated with inflammation of the digestive tract and ulcers in the large intestine and rectum. The other is Crohn’s disease, which may develop anywhere in the intestinal tract and can cause fistulas and bowel obstructions. Both conditions can be devastating, causing patients to suffer for years from symptoms like vomiting, rectal bleeding and diarrhea. In addition, patients may require surgery to remove parts of the bowel.
Psychiatric problems have also been linked to Accutane use. From 1982 to May 2000, the FDA received hundreds of reports linking isotretinoin use to depression, including 37 suicides, 110 hospitalizations for depression or suicidal behavior, and 284 cases of non-hospitalized depression. Roche responded to the reports of depression and suicide in 1998 by adding a warning to the medication’s label stating that Accutane could cause psychiatric disorders.
According to a study in the book Drug Injury: Liability, Analysis and Prevention, Drs. Donald Marks and Tzarina Middlekoop found that the number of formal adverse reaction reports, from national and international health agencies, of suicide and suicidal behavior associated with Accutane use reached 500, making it the fourth highest number of adverse reactions in the United States prior to 2005. The mechanism of action that makes Accutane cause psychiatric events is not fully understood, nor has a link between depression and Accutane been proven. However, the high number of reports of depression in people without a psychiatric history suggests there is a link.
Kamie Kendall, a New Jersey Accutane user who was diagnosed with ulcerative colitis, won a verdict of $10.5 million in 2008. Two years later, another bowel disease verdict for Accutane was decided in Atlantic City, N.J., when Andrew McCarrell – who required five surgeries and the removal of his colon—received $25.16 million from Roche.
In 2012, also in Atlantic City, two more claimants who developed bowel disease, Kathleen Rossitto and Riley Wilkinson, received $9 million each for damages. These are just a few of the 7,000-plus lawsuits that have been filed against Roche over the debilitating side effects of Accutane.
While some claimants receive millions — for damages and medical expenses — the numbers do not compare to the company’s revenue from selling the dangerous drug. For example, annual Accutane sales at their peak, in 2000, were up to $759.4 million.
Lawsuits against Roche are not limited to bowel disease. They also come from patients and families of patients who have experienced side effects such as birth defects, depression and suicide attempts. Because warnings were added slowly between the time Accutane was released in 1982 and the time it was recalled in 2009, some cases hinge on the dates that the medication was prescribed, when health concerns were diagnosed, and when warnings were publicized.