By Thomas P. Fuller, ScD, CIH

Almost everyone knows the story of “thalidomide babies”: the drug used widely in the early 1960’s to reduce the affects of morning sickness in pregnant women. Without adequate safety testing, the drug was marketed as a sedative, hypnotic and anti-inflammatory agent in nearly 50 countries between 1957 and 1961. In the end, somewhere between 5,850¹ and 10,000² infants with multiple, severe physical deformities were born worldwide as a result of maternal exposure to thalidomide.

Fortunately, through the obstinacy of a Food and Drug Administration reviewer, Frances Oldham Kelsey, the German company selling the product all over the world never got the product approved in the U.S.³ By the end of 1961, when thalidomide had been identified as the causative agent and was banned worldwide, only 17 American children were born with deformities.

For the next 30 years the thalidomide story had a great impact on the advent of modern regulatory authority over potential developmental toxicants. But it really never stopped being investigated for clinical use. In 1998 thalidomide was approved by the FDA to treat leprosy. It has also recently been approved for use in studies and treating multiple myeloma, AIDS, Behchet disease, lupus, Sjogren syndrome, rheumatoid arthritis, inflammatory bowel disease and macular degeneration.⁴

At this time, thalidomide may be dispensed only by licensed pharmacists who are registered in 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 surveys.

Thalidomide is rated as a Pregnancy Category X drug, meaning that the risk to the unborn fetus clearly outweigh any possible benefit to the pregnant mother. A single dose of 50 mg may cause birth defects.⁵ With the Category X pregnancy rating, both male and female nurses should wear gloves and use standard hand-washing techniques when directly handling thalidomide capsules.

The teratogenic potential from inhalation, skin contact or eye exposures to thalidomide dust is well known. Therefore, it is not recommended that Thalidomide capsules or suspensions be crushed or mixed without well thought out protocols, training and protective equipment. As a safety precaution, all health care professionals, care givers and patients should avoid direct contact with the powder contents of thalidomide capsules. Thalidomide should only be used following well thought-out and practiced protocols by knowledgeable and well-trained staff.

The exact target organs and metabolic route of thalidomide is not known in humans, but it seems that much of it tends to undergo non-enzymatic hydrolysis in plasma to multiple products. The mean half-life of elimination ranges from approximately five to seven hours following a single dose. 0.7 percent is released in the urine as unchanged drug.⁶

Thalidomide has been detected in the semen of some men treated with oral thalidomide.⁷
No data are currently available regarding the presence of thalidomide in other body fluids of treated patients. As with all patients, all health workers exposed to patient’s body fluids should practice universal precautions.

The need to closely follow precautions and monitor worker exposures when working with thalidomide patients and administering medications cannot be over emphasized. Small accidental or chronic exposures to a pregnant worker could be catastrophic. In lieu of more information about metabolic pathways and processes the most extreme care should be taken at all times. Both male and female workers should be well informed of potential risks, particularly those practicing unprotected sex or attempting to conceive.

References
1. Klaassen, Curtis, Casarett & Doull’s Toxicology The Basic Science of Poisons, McGraw-Hill, NY, 5th Edition (1996).
2. http://en.wikipedia.org/wiki/Thalidomide
3. www.fda.gov/fdac/features/1997/679_thal.html
4. http://cerhr.niehs.nih.gov/common/thalidomide.html
5. Celgene, Material Safety Data Sheet, CAS 50-35-1, Sept. 21, 2006.
6. Celgene, Thalomid ® (thalidomide) Capsules, product literature, electronic correspondence to T. Fuller, September 2006.
7. Teo S, Harden JL, Burke AB, Noormohamed FH, Youle M, Johnson MA, Peters BS, Stirling DI, Thomas SD. “Thalidomide is distributed into human semen after oral dosing,” Drug Metabolism and Disposition (2001); 29(10):1355-7.