Few drugs can be considered real breakthroughs, but Accutane was one of those few. When it hit the market in 1982 it was hailed as the first drug that could really cure severe acne, with a success rate of 85 percent within five months. Accutane was meant for people with cystic acne, a lot more than just pimples. It leaves permanent scars. It also leaves emotional scars, and can lead to depression and social isolation.
The maker of Accutane was the big pharma company Hoffman-La Roche (Roche). Because the promise for this drug was so high, the U.S. Food and Drug Administration (FDA) rushed it through approval as a top priority drug. What happened next is a story of what can happen when a new drug is rushed into the market. Accutane proved to be very effective at treating acne. It also proved to be extremely effective at causing severe birth defects.
Accutane is one of the most dangerous drugs a pregnant woman can take. The only comparable drug is thalidomide. Severe birth defects will occur in about 25 percent of pregnancies. Even one dose can cause defects of the ears, eyes, face, skull, heart, or brain. Forty percent of pregnancies will result in miscarriage. Children born without birth defects may develop severe learning disabilities. These may be even more common than birth defects. Women who become pregnant on Accutane may be advised to abort their pregnancy.
Isotretinoin is a derivative of vitamin A. In the 1960s, researchers in Switzerland were using this drug to treat skin cancer. They discovered it could cure acne, but they knew that vitamin A caused birth defects in animals. When the drug did not prove successful for skin cancer, research was discontinued. This was during the time of the thalidomide tragedy. The thought of exposing women to another drug that could cause birth defects was too scary.
Roche Takes That Chance
In 1975, researchers were testing isotretinoin for Roche as a treatment for a severe but rare skin disease, when they rediscovered the cure for acne. In 1976, they reported their findings in the British medical journal Lancet. Roche gave the drug a brand name, Accutane, and started clinical trials for acne.
These researchers knew about the possible danger of birth defects. They did not include women of child-bearing age in most of their studies. When they did, they ruled out pregnancy with a pregnancy test. When they presented their impressive results to the FDA, they suggested the drug be marketed as category C. This means the drug is known to cause birth defects in animals, but has not been tested in humans.
The FDA was more cautious and move the drug to category X, meaning not safe for pregnant women, but neither the FDA or Roche put mandatory restrictions on the drug. Women who were enrolled in the clinical studies had to take pregnancy tests and use birth control to avoid pregnancy. These precautions were not mandatory for women in the U.S. population when the drug was released.
European countries had the same information as the FDA, but they decided to place mandatory limitations. In Switzerland, doctors had to register with the government to prescribe Accutane. In the UK, only hospitals could dispense it. Sweden refused to approve Accutane. Spain kept a registry of every woman who was prescribed the drug.
Accutane is one of the most dangerous drugs a pregnant woman can take. The only comparable drug is thalidomide. Severe birth defects will occur in about 25 percent of pregnancies. Even one dose can cause defects of the ears, eyes, face, skull, heart, or brain. Forty percent of pregnancies will result in miscarriage.
Early Success and Disaster
During the first six months of marketing Accutane in the United States, doctors wrote over 200,000 prescriptions. It did not take long for severe birth defects to show up. In the first 18 months, after 400,000 patients had taken Accutane, there were over 20 major birth defects reported. The FDA and Roche strengthened their warning about birth defects. The FDA placed a boxed warning on the label, but prescriptions did not go down. In 1988, it was estimated that between 900 and 1,300 “Accutane babies” had been born. Many other pregnancies were aborted or lost to miscarriage.
Roche announced a new Pregnancy Prevention Program. It required anyone who could become pregnant to have counseling and sign an informed consent before treatment. Although this program did reduce pregnancies on the drug, Roche was fighting and settling a number of expensive lawsuits through most of the 1990s.
In 2005, the FDA started its current pregnancy prevention program called iPledge. The prevention strategies were mandatory. They continue to this day and include registration of patients, doctors, and pharmacies. There must be a signed consent form, two forms of birth control, and a pregnancy test before, during, and after treatment.
In 2009, due to the high cost of personal-injury lawsuits, Roche withdrew Accutane from the U.S. market. They still market it in Europe under a different brand name. Isotretinoin has survived because it is still the best treatment for severe acne. Many people have benefited. Generic versions of isotretinoin are available in the U.S. under the brand names Amnesteem, Claravis, and Sotret. However, you should never take these medications if there is any chance you may become pregnant. In this situation, the risk far outweighs the benefit.