September 28, 2011

Thalidomide, now recognized as the cause of an epidemic of infant malformations, was originally a tranquilizer developed by Ciba, a Swiss pharmaceutical company in 1953. It was one of many chemical compounds discovered in the post-World War II decade. After briefly testing thalidomide, ciba abandoned the product because the company observed no marketable pharmacological effects.

In 1954, the German company Chemie Gruenthal acquired thalidomide and marketed it as an anticonvul-sant for epileptics. Again, it had no efficacy. They began trials for its use as an antihistamine, which also failed. The trials, however, demonstrated that the drug was well tolerated and was effective as a sedative and sleep aid. Gruenthal also found that it was particularly effective for pregnant women suffering from morning sickness.

In 1957, Gruenthal began marketing thalidomide in Germany for nausea and morning sickness. The drug quickly became the “drug of choice” to help pregnant women with severe morning sickness. It was advertised as a nontoxic medication, with no side effects, and completely safe for pregnant women. All of these claims were untrue. A major side effect associated with long-term use is peripheral neurosis, an often irreversible numbing of the hands and feet. Most insidious were the teratogenic effects (ability to cause birth defects), which were undiscovered because the drug was not tested on pregnant animals.

The first baby suffering from complications due to thalidomide was born on Christmas Day, 1956, a few months prior to the marketing release in Germany. It would be roughly 4- years until Dr. McBride, an obstetrician in Sydney, Australia, would first publicly report a connection between thalidomide and birth defects. No action was taken to remove the product from shelves in Germany until 1961, when these results were confirmed by Dr. Lenz in Germany. Prior to that time, as many as 20,000 children were born from mothers who took thalidomide. Thousands more were stillborn or miscarried.

Thalidomide actually has a limited window of ter-atogenic activity (activity causing malformations), which consists of a 15-day period during the first trimester of pregnancy. Common malformations that may result from its use during this period include deafness, blindness, cleft palate, malformed organs, no arms, no legs, no fingers, and even flippers growing from the shoulders.

Sadly, thalidomide babies are still being born in Third World countries due to the availability of the drug on the black market. Today, there are approximately 5,000 thalidomide survivors worldwide.

Thalidomide was never approved in the United States for morning sickness, mostly due to the efforts of a young physician, Frances Kelsey, who was then serving as an investigator for the U.S. Food and Drug Administration (FDA). Dr. Kelsey was given the thalido-mide approval as an “easy start” for her career. The agency thought that since the drug was already approved in almost every European country, it would be an uncomplicated process. Fortunately for many would-be U.S. thalidomide consumers, Kelsey was a physician-pharmacologist with a profound interest in fetal development. She refused to approve the drug until the fetal interactions of the drug were shown to be safe. She fought a several-year battle against drug approval with the Richardson-Merrell corporation (the U.S. Gruenthal licensee) until it was shown in the global community that the drug was dangerous to fetal development, and the application was terminated.
The thalidomide crisis and subsequent infant malformation epidemic provided the motivation to establish more stringent drug testing and approval procedures worldwide. In the United States, the Food, Drug and Cosmetic Act (FDCA) has required FDA approval for new drugs since 1938, but it was not until 1962, after the thalidomide crisis, that the FDCA was amended to require new drug sponsors to demonstrate the safety and effectiveness of their products prior to receiving FDA approval.

In recent years, thalidomide has experienced a comeback. In addition to being an effective sedative, thalidomide gas been found to be helpful in modulating the immune system (an immunomodulatory drug). The FDA first approved its use in 1998 for the treatment of lesions associated with leprosy. Researchers are also examining its usefulness for the treatment of breast, prostate, and brain cancer, macular degeneration (an overgrowth of new blood vessels in the eye covering the retina), and HIV.

The FDA still recognizes thalidomide as a very dangerous drug and has imposed unprecedented regulatory controls on its distribution. The regulations promote a zero tolerance policy for thalidomide exposure during pregnancy. The System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.) program is a comprehensive information package for prescribers and patients. It requires a 100% patient registry and requires that heterosexual women who have sex while taking the medication must use at least two forms of birth control. Additionally, heterosexual men must use condoms because thalidomide is present and can be transmitted in semen.

Despite its tainted history and potentially dangerous consequences, thalidomide is a true story of a pharmaceutical comeback. While in the past it caused harm and heartache, scientists are now using the once-negative aspects of the drug as the basis of possible cures for some of our most dangerous and elusive diseases.

See Also: Pregnancy


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