THALIDOMIDE
Overview
In the 1960s the drug thalidomide was used by some pregnant women in Europe and Canada to treat morning sickness. Women who took the drug in early pregnancy gave birth to children with severe birth defects such as missing or shortened limbs. Shortly after the birth defects were observed, thalidomide was banned worldwide. It has recently been discovered that thalidomide is effective in treating symptoms of diseases such as leprosy and possibly AIDS. The state of California has identified thalidomide as a developmental hazard, which means there is proof that it may harm unborn children. However, thalidomide was approved in 1998 by the U.S. Food and Drug Administration (FDA) to treat leprosy. In order to avoid tragic birth defects, the FDA has established several restrictions. Doctors prescribing and pharmacists dispensing thalidomide are required to participate in a program sponsored by the drug's manufacturer, and patients must also be educated about the drug's effects. Female patients must be tested for pregnancy before and while taking the drug and must use two forms of birth control if sexually active. Men taking thalidomide must also practice birth control because it is not known if thalidomide can produce defects in the children they conceive. Donating of blood or semen and breast feeding are prohibited while taking the drug.
History of birth defects
In Europe and Canada during the early 1960s, thalidomide was prescribed to treat morning sickness in pregnant women. At that time, it was not approved in the United States because Dr. Frances Kelsey from the Food and Drug Administration (FDA) stated there was insufficient proof of the drug’s safety in humans. Thalidomide was soon banned worldwide when it was discovered that it caused tragic birth defects. According to the March of Dimes (MOD, November 1998), "More than 10,000 children around the world were born with major malformations, many missing arms and legs, because their mothers had taken the drug during early pregnancy. Mothers who had taken the drug when arms and legs were beginning to form had babies with a widely varying but recognizable pattern of limb deformities. The most well-known pattern, absence of most of the arm with the hands extending flipper-like from the shoulders, is called phocomelia. Another frequent arm malformation called radial aplasia was absence of the thumb and the adjoining bone in the lower arm. Similar limb malformations occurred in the lower extremities. The affected babies almost always had both sides affected and often had both the arms and the legs malformed. In addition to the limbs, the drug caused malformations of the eyes and ears, heart, genitals, kidneys, digestive tract (including the lips and mouth), and nervous system. Thalidomide was recognized as a powerful human teratogen (a drug or other agent that causes abnormal development in the embryo or fetus). Taking even a single dose of thalidomide during early pregnancy may cause major birth defects."
New Therapeutic Uses
In 1998 the Food and Drug Administration (FDA) approved thalidomide for use in treating leprosy symptoms (FDA Talk Paper: July 16, 1998). Studies are also being conducted to determine the effectiveness of thalidomide in treating symptoms associated with AIDS, Behchet disease, lupus, Sjogren syndrome, rheumatoid arthritis, inflammatory bowel disease, macular degeneration, and some cancers (MOD, November 1998).
Government regulation and safeguards
The California Environmental Protection Agency (Cal/EPA) has added thalidomide to its Proposition 65 list of developmental toxins. This means there is evidence that the compounds can be harmful to unborn children (Cal/EPA Proposition 65 List).
The Food and Drug Administration (FDA) approved thalidomide for treatment of leprosy symptoms in 1998 (FDA Talk Paper: July 16, 1998). The approval was based upon the establishment of strict safeguards to prevent the occurrence of birth defects. The March of Dimes has summarized the FDA restrictions and the following information comes from their web site (MOD, November 1998):
To prevent fetal exposure to thalidomide, the drug’s manufacturer has developed the System for Thalidomide Education and Prescribing Safety (STEPS) program. Only physicians who are registered may prescribe thalidomide to patients and those patients—both male and female—must comply with mandatory contraceptive measures, patient registration and patient surveys.
Thalidomide may be dispensed only by licensed pharmacists who are registered in the S.T.E.P.S. program and have been educated to understand the risk of severe birth defects if thalidomide is used during pregnancy.
Thalidomide was banned in the early 1960s after it was found to cause deformed limbs in the children of women who took it early in pregnancy. The drug is now being investigated for use in treating AIDS, tuberculosis, and other illnesses.
Researchers have found that thalidomide can inhibit the growth of HIV in test tubes. Thalidomide works in lab experiments against HIV by suppressing a natural substance produced in the body. The substance is called tumor necrosis factor (TNF), also known as cachectin. TNF is released by white cells during infection and helps fight invading organisms.
In some people with HIV infection, the production of TNF is high. High TNF levels are associated with more rapid progression to AIDS and with the development of HIV related central nervous system disease. Excessive production of TNF over a period of time may lead to weight loss and/or interfere with the ability of the immune system to deal with infections.
In a small trial, treatment with thalidomide was found to help with severe weight loss in people with AIDS. Researchers concluded that thalidomide had a beneficial effect on the symptoms of wasting syndrome but did not improve T4 cell counts or reduce HIV replication in this study.
Trials have also shown that thalidomide can treat mouth ulcers very effectively in people with HIV. The technical name for this condition is aphthous ulcers. Other studies for HIV and related conditions are ongoing.
Side effects of thalidomide include: sleepiness, drowsiness, constipation, skin rash, severe headaches, stomach aches, peripheral neuropathy (numbness and pain in your arms, hands, legs and feet) dizziness and nausea, giddiness or nervousness at higher doses, shivering and buzzing in the ears, depression or mood-swings, a general sense of illness and severe birth defects if taken even once during pregnancy.
The drug company that makes thalidomide is Celgene. Their brand is called Thalidomid. Thalidomid is now approved for the treatment of a condition associated with leprosy. For more information Celgene can be reached at (800) 890-4619 x3905.
Thalidomide, which was developed in the 1950s to prevent nausea during pregnancy but was found to produce fetal limb abnormalities, has been found to inhibit replication of the AIDS virus and to heal canker sores in patients with AIDS and other conditions. Thalidomide is used for treatment some symptoms of Hansen's disease, or leprosy.