What is the history of thalidomide?
Thalidomide was first prescribed in the late 1950s in Europe to treat anxiety, insomnia and, in pregnant women, morning sickness. It also was marketed in numerous other countries, including Japan, Australia and Canada. It was withdrawn from the market in the early 1960s when doctors learned that it caused devastating birth defects. About 10,000 children around the world were born with major malformations because their mothers had taken the drug during early pregnancy (2).
The worldwide thalidomide tragedy changed the way drugs are developed, tested and regulated in the United States, significantly broadening FDA authority (3). Dr. Kelsey often is credited with sealing the FDA's reputation as the world's premier authority on food and drug safety.
What birth defects does thalidomide cause?
In 1961, doctors in Germany, Australia and Great Britain noted a significant increase in the number of babies born with severely malformed or missing arms and legs. These birth defects were traced to the use of thalidomide during early pregnancy.
Mothers who had taken the drug in early pregnancy, when their babies' arms and legs were beginning to form, delivered babies with a variety of limb defects. The most well-known defect, a severe shortening of the arms or legs with flipper-like hands or feet, is called phocomelia. Affected babies almost always had defects on both sides and often had both the arms and legs malformed. In especially severe cases, the babies had complete absence of limbs. The drug also caused malformations of the eyes and ears, heart, genitals, kidneys, and digestive tract (including the lips and mouth) (2, 4).
Thalidomide was recognized as one of the most powerful human teratogens (drugs or other agents that cause abnormal development in the embryo or fetus). Taking even a single dose of thalidomide during early pregnancy may cause major birth defects (5). Women who cannot avoid the chance of pregnancy must not take thalidomide.
What disorder is thalidomide approved to treat?
The FDA gave approval for thalidomide to be marketed for the treatment of erythema nodosum leprosum (ENL), a complication of leprosy (1). This disfiguring skin disorder affects about 6,500 persons in the United States (6).
Now that the drug has been approved for ENL, physicians can prescribe it for people with other conditions. Because thalidomide may become available to women capable of having children, they need to be warned about the serious risks of birth defects.
What other disorders might be treated with thalidomide?
Thalidomide is being used experimentally to treat a number of serious disorders.
One disorder for which thalidomide is showing promise is multiple myeloma, a bone marrow cancer (2, 4). It also appears effective for treating severe ulcers of the mouth and throat in individuals with AIDS, and ulcers of the mouth and genitals in individuals with Behcet disease. These ulcerous sores are large, deep and painful. The mouth ulcers can prove debilitating and may lead to malnutrition because they interfere with eating. Studies also suggest that thalidomide may improve weight gain in AIDS and cancer patients suffering from a severe weight loss, called wasting (2, 4).
The effectiveness of thalidomide treatment also is being studied in rheumatoid arthritis, lupus erythematosus, Sjogren syndrome and inflammatory bowel disease (Crohn's disease). The drug is being investigated as a treatment for a number of cancers including Kaposi's sarcoma (seen mainly in AIDS patients) and kidney and brain cancers (2, 4).
What other risks does thalidomide pose?
Thalidomide can cause severe nerve damage (peripheral neuropathy) that may not be reversible after a patient stops taking the drug. Symptoms include a burning sensation, or numbness or tingling in the arms, hands, legs or feet (5). Other side effects may include drowsiness and reduced ability to think clearly. Thalidomide can interfere with the ability to drive a car or operate machinery.
What safeguards are in place to prevent use of thalidomide in pregnancy?
Because of thalidomide's danger to a developing baby, the FDA requires special safeguards never before imposed on any drug. To prevent fetal exposure to thalidomide, the drug's manufacturer has developed the System for Thalidomide Education and Prescribing Safety (STEPS) program (1). Only physicians who are registered in the program may prescribe thalidomide to patients, and those patients—both male and female—must comply with mandatory contraceptive measures, patient registration and patient surveys.
Only certain licensed pharmacists can dispense thalidomide. They must be registered in the STEPS program and educated to understand the risk of severe birth defects when thalidomide is used during pregnancy.
In addition, female patients' prescriptions cannot be filled without a physician's written report of a negative pregnancy test that has been conducted within 24 hours of starting thalidomide therapy. Pregnancy testing is required weekly during the first four weeks of thalidomide use, then every 28 days thereafter in women with regular cycles, or every two weeks if cycles are irregular. Prescriptions are only for a four-week supply. A female patient must abstain from sexual contact or use at least one highly effective method of birth control and one additional method at the same time for at least four weeks before receiving thalidomide, and she must continue their use until four weeks after the last thalidomide dose (1, 5).
All patients must participate in a mandatory registry that provides follow-up to detect any adverse effects of using thalidomide. This follow-up helps identify areas in which safeguards need to be improved, if problems occur.
The FDA reminds female patients that no method of birth control is completely reliable, except for having no sexual contact at all (abstinence). Women being treated with thalidomide should refrain from any other activities that could result in pregnancy, such as assisted fertilization methods. Women taking thalidomide should not breastfeed or donate blood (5).
A male must abstain from sexual contact or use a latex condom during sexual contact with a woman who could get pregnant while he is taking thalidomide and for four weeks afterward, because thalidomide may be present in his semen. Males taking thalidomide should not donate sperm or blood (5).
Patients on thalidomide should never share or give the drug to others (5).
What research is being done on thalidomide?
Scientists continue to develop chemical compounds that may have thalidomide's benefits without its risk of birth defects and nerve damage. Some of these compounds may be ready for clinical testing soon (2).
For more information
Read the fact sheet provided by the Organization of Teratology Information Services.
References
1. Food and Drug Administration. FDA approves thalidomide for Hansen's disease side effect, imposes unprecedented restrictions on distribution. FDA Talk Paper, July 16, 1998.
2. Franks, M.E., et al. Review: Thalidomide. The Lancet, volume 363, May 29, 2004, pages 1802-1811.
3. Bren, L. Frances Oldham Kelsey: FDA medical reviewer leaves her mark on history. FDA Consumer Magazine, March-April 2001.
4. Perri, A.J., and Hsu, S. A review of thalidomide's history and current dermatologic applications. Dermatology Online Journal, volume 9, number 5, 2003.
5. Food and Drug Administration. Thalomid consumer information, accessed 4/1/05.
6. National Hansen's Disease Programs, Health Resources Services Administration. Frequently asked questions, accessed 4/4/05.
June 2005 (R 4-07)
