Thalidomide (Thalomid) is a derivative of glutamic
acid that is chemically related to glutethimide. It exerts a number of
biological effects as an immunosuppressive, antiinflammatory, and
antiangiogenic agent, yet its mechanisms of action have not been fully
elucidated. Thalidomide potently inhibits production of tumor necrosis factor
(TNF) and interleukin (IL) 12, and its effect on these and other cytokines may
account for some of its clinical effects.
Its absorption from the
gastrointestinal tract is slow, with peak plasma levels being reached after 3
to 6 hours. It appears to undergo nonenzymatic hydrolysis in the plasma to a
large number of metabolites. The elimi-nation half-life is approximately 9
Thalidomide is approved for
use in the United States for the treatment of cutaneous manifestations of
erythema nodosum leprosum, a potentially life-threatening systemic vasculitis
that occurs in some pa-tients with leprosy. Although not approved for other in-dications,
thalidomide has also been shown to be very effective in the management of
Behçet’s disease, HIV-related mucosal ulceration (aphthosis), and select cases
of lupus erythematosus.
Thalidomide is a highly
teratogenic drug, characteris-tically causing phocomelia (aplasia of the
midportions of the limbs). Even a single dose may cause fetal malforma-tion.
Thalidomide should be prescribed to women of childbearing potential only when
no acceptable alterna-tive exists. Because it is not known whether thalidomide
is present in the ejaculate of males receiving the drug, male patients must use
a latex condom when engaging in sexual activity with women of childbearing
Other side effects of
thalidomide may include seda-tion (in fact, thalidomide was originally marketed
in Europe as a sleeping aid), constipation, and peripheral neuropathy, which
may be permanent.