Thalidomide: a remarkable comeback

The thalidomide product is a racemic mixture of the L- and D-enantiomeric forms of a synthetic glutamic acid derivative that contains a phthalimide ring and a glutarimide ring. Initially marketed as a sedative, it was withdrawn from the world market after it was found to be associated with severe birth defects. Recently, the compound has generated renewed interest because of its immunomodulatory and anti-angiogenic properties. The nature of its immunologic effects is under active investigation. It is orally bioavailable and can be administered in once daily dosing. Its primary route of metabolism is spontaneous hydrolysis. In controlled clinical trials, thalidomide has proven effective in the treatment of erythema nodosum leprosum, oral and oesophageal aphthous ulceration associated with advanced HIV infection and oral ulceration associated with Behcet's syndrome. Promising results have been obtained in preliminary studies of other immunologic and neoplastic disorders, but controlled clinical studies are still lacking for these entities. Adverse effects include teratogenicity peripheral neuropathy and sedation. In the US, thalidomide can be prescribed only through a restricted drug distribution program.