Thalidomide

Thalidomide, sold under the brand names Contergan and Thalomid among others, is an oral medication used to treat a number of cancers (e.g., multiple myeloma), graft-versus-host disease, and many skin disorders (e.g., complications of leprosy such as skin lesions). While thalidomide has been used in a number of HIV-associated conditions, such use is associated with increased levels of the virus.

Thalidomide
Clinical data
Pronunciation/θəˈlɪdəmd/
Trade namesContergan, Thalomid, others
Other namesα-Phthalimidoglutarimide
AHFS/Drugs.comMonograph
MedlinePlusa699032
License data
Pregnancy
category
  • AU: X (High risk)
Routes of
administration
By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability90%
Protein binding55% and 66% for the (R)-(+)- and (S)-(−)-enantiomers, respectively
MetabolismLiver (minimally via CYP2C19-mediated 5-hydroxylation; mostly via non-enzymatic hydrolysis at the four amide sites)
Elimination half-life5–7.5 hours (dose-dependent)
ExcretionUrine, feces and semen
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.029
Chemical and physical data
FormulaC13H10N2O4
Molar mass258.233 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • O=C1c2ccccc2C(=O)N1C3CCC(=O)NC3=O
  • InChI=1S/C13H10N2O4/c16-10-6-5-9(11(17)14-10)15-12(18)7-3-1-2-4-8(7)13(15)19/h1-4,9H,5-6H2,(H,14,16,17) Y
  • Key:UEJJHQNACJXSKW-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

Common side effects include sleepiness, rash, and dizziness. Severe side effects include tumor lysis syndrome, blood clots, and peripheral neuropathy. Thalidomide is a known human teratogen and carries an extremely high risk of severe, life-threatening birth defects if administered during pregnancy. Major human fetal abnormalities include skeletal deformities (e.g., amelia [absence of legs and/or arms], absence of bones, and phocomelia [malformation of the limbs]). A single dose of thalidomide, regardless of dosage, is enough to cause teratogenic effects.

Thalidomide was first marketed in 1957 in West Germany, where it was available over the counter. When first released, thalidomide was promoted for anxiety, trouble sleeping, "tension", and morning sickness. While it was initially thought to be safe in pregnancy, concerns regarding birth defects arose, resulting in its removal from the market in Europe in 1961. The total number of infants affected by thalidomide use during pregnancy is estimated at 10,000, of whom about 40% died around the time of birth. Those who survived had limb, eye, urinary tract, and heart problems. Its initial entry into the US market was prevented by Frances Kelsey, a reviewer at the FDA. The birth defects caused by thalidomide led to the development of greater drug regulation and monitoring in many countries.

It was approved in the United States in 1998 for use as a treatment for cancer. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication.

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