THALIDOMIDE
Clinical safety rating
avoidContraindicated (not allowed)
Immunomodulatory and antiangiogenic action: TNF-alpha inhibitor, alters adhesion molecule expression, inhibits angiogenesis via VEGF/FGF inhibition, modulates T-cell co-stimulation and NF-κB activity.
| Metabolism | Primarily non-enzymatic hydrolysis in plasma; minor CYP2C19-mediated hydroxylation. |
| Excretion | Thalidomide is primarily eliminated by nonenzymatic hydrolysis in plasma and tissues; renal excretion accounts for <1% of unchanged drug; metabolites are excreted renally (~90%) and fecally (~10%). |
| Half-life | Terminal elimination half-life is approximately 5-7 hours in healthy adults, but may be prolonged to 7-10 hours in patients with renal impairment or advanced age. |
| Protein binding | Approximately 55-65% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 1.2 L/kg (range 0.8-1.5 L/kg), indicating extensive distribution into body tissues. |
| Bioavailability | Oral bioavailability is approximately 90-100% (absolute bioavailability). |
| Onset of Action | Oral: Onset of action for immunomodulatory effects is typically 2-4 weeks; for sedation, onset is 30-60 minutes. |
| Duration of Action | Oral: Duration of immunomodulatory effects persists for several hours to days; sedative effects last 4-6 hours. |
| Molecular Weight | 258.23 |
100 mg orally once daily, preferably at bedtime to minimize sedation; maximum dose 400 mg daily for multiple myeloma or erythema nodosum leprosum.
| Dosage form | CAPSULE |
| Renal impairment | No dosage adjustment required for renal impairment. Thalidomide is minimally renally excreted; however, use with caution in severe renal impairment (CrCl <30 mL/min) due to limited data. |
| Liver impairment | Child-Pugh Class A: 100 mg daily. Child-Pugh Class B: Reduce to 50 mg daily or 100 mg every other day. Child-Pugh Class C: Not recommended due to lack of safety data. |
| Pediatric use | Not approved for use in children; safety and efficacy not established. In investigational settings, 2-5 mg/kg/day orally divided every 12 hours, with a maximum of 100 mg/day. |
| Geriatric use | No specific dose adjustment, but start at low end of dosing range (50-100 mg daily) due to increased risk of sedation, constipation, and peripheral neuropathy. Monitor renal function, though no dose adjustment required. |
| 1st trimester | Absolute contraindication due to severe teratogenic effects; high risk of fetal malformations including limb defects, congenital heart disease, and other anomalies. Use is strictly prohibited during the first trimester. |
| 2nd trimester | Absolute contraindication; continued risk of teratogenicity and potential for fetal harm. Avoid use throughout second trimester. |
| 3rd trimester | Absolute contraindication; potential for fetal harm persists. Avoid use during third trimester unless no alternative and under strict risk-benefit assessment. |
Clinical note
CNS depressants may enhance sedative effects Is a known human teratogen and requires strict pregnancy prevention program.
| Placental transfer | Thalidomide crosses the placenta readily, as evidenced by its potent teratogenicity. Studies in humans and animals confirm placental transfer, with fetal concentrations reaching maternal levels. |
| Breastfeeding | Thalidomide is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants, including sedation and peripheral neuropathy, breastfeeding is not recommended during thalidomide therapy. Women should discontinue breastfeeding or avoid thalidomide. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Thalidomide is contraindicated in pregnancy. First trimester exposure causes severe limb defects (phocomelia, amelia), ear anomalies, ocular defects, and cardiac malformations in up to 50% of exposed fetuses. Second and third trimester exposure risks fetal growth restriction and neurodevelopmental effects. No safe trimester exists. |
| Fetal Monitoring | For women of childbearing potential, mandatory negative pregnancy test within 24 hours before starting therapy, weekly during first month, then every 2-4 weeks thereafter. Fetal monitoring via ultrasound if exposure occurs. In men, sperm donation prohibited and condom use required during and for 4 weeks after therapy. |
| Fertility Effects | Thalidomide does not appear to impair fertility in males or females based on animal studies; however, human data are limited. Sperm abnormalities (decreased motility) reported in some male patients. |
■ FDA Black Box Warning
THALIDOMIDE IS CONTRAINDICATED IN PREGNANCY (CATEGORY X). Severe birth defects (phocomelia, other fetal anomalies) and fetal death. Must not be used by women who are pregnant or may become pregnant. Also contraindicated in sexually active women of childbearing potential unless using two reliable forms of contraception. Male patients must use latex condom during sexual contact with pregnant or childbearing-potential women. [See REMS program]
| Common Effects | leprosy |
| Serious Effects |
Pregnancy or potential pregnancy in women of childbearing age without strict contraception (at least two effective methods, including one highly effective method, for 4 weeks before, during, and 4 weeks after therapy)Women of childbearing potential who are not using effective contraceptionMen who are not using condoms during sexual contact with a pregnant woman or a woman of childbearing potential not using contraceptionBreastfeedingHypersensitivity to thalidomide or any of its componentsConcurrent use with certain drugs (e.g., those that cause peripheral neuropathy, such as other neurotoxic agents, should be avoided if possible)
| Precautions | Thromboembolism (DVT/PE) - increased risk with concurrent dexamethasone. Severe peripheral neuropathy (monitor for paresthesias). Neutropenia, thrombocytopenia. Dizziness, somnolence. Hypersensitivity reactions (angioedema, Stevens-Johnson syndrome). Bradycardia, syncope. Increased LFTs. Seizures. Amyloid deposition. Angioedema. Increases risk of hepatotoxicity. Use in renal/hepatic impairment with caution. |
| Food/Dietary | Avoid grapefruit juice (may increase exposure). No specific food restrictions otherwise. |
| Clinical Pearls | Strict REMS program required due to teratogenicity; screen for pregnancy before and during therapy. Monitor for thromboembolism, neuropathy, and bradycardia. Dose reduction needed in renal impairment. Can cause tumor lysis syndrome in multiple myeloma. |
| Patient Advice | Never use during pregnancy – can cause severe birth defects. · Women must use two reliable contraceptives and undergo monthly pregnancy tests. · Men must use condoms during sexual activity with a pregnant woman or a woman who could become pregnant. · Avoid blood donation while on therapy and for 4 weeks after stopping. · Report numbness, tingling, drowsiness, or rash immediately. |
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