THALOMID
Clinical safety rating
cautionComprehensive clinical and safety monograph for THALOMID (THALOMID).
Thalidomide is an immunomodulatory agent with antiangiogenic and anti-inflammatory properties. Its exact mechanism is not fully understood, but it inhibits tumor necrosis factor-alpha (TNF-α) production, modulates cytokine activity, and suppresses angiogenesis by inhibiting basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF).
| Metabolism | Thalidomide is primarily metabolized by spontaneous hydrolysis in plasma and tissues, not by cytochrome P450 enzymes. Minor metabolism involves hydroxylation and conjugation. |
| Excretion | Primarily renal: >80% of absorbed dose excreted unchanged in urine. Minor fecal elimination (<15%). No significant biliary excretion. |
| Half-life | Mean terminal elimination half-life is approximately 5-7 hours in healthy adults; may be prolonged to 12-18 hours in patients with hepatic impairment due to decreased metabolism. |
| Protein binding | Approximately 55-66% bound to serum albumin. |
| Volume of Distribution | Apparent Vd is 0.7-1.2 L/kg, suggesting distribution into total body water with some tissue binding. |
| Bioavailability | Oral bioavailability is >90% with minimal first-pass metabolism. |
| Onset of Action | Oral: 1-2 hours for initial immunomodulatory effects; clinical response in erythema nodosum leprosum typically within 24-48 hours. |
| Duration of Action | Duration of immunomodulatory effects persists for 4-6 hours post-peak; however, once-daily dosing maintains therapeutic levels due to sustained effects on cytokine modulation. |
| Molecular Weight | 258.23 |
200 mg orally once daily, taken with water preferably at bedtime to reduce sedation; dose may be titrated up to 400 mg daily based on tolerability.
| Dosage form | CAPSULE |
| Renal impairment | For GFR 30-60 mL/min: reduce dose by 50%; for GFR <30 mL/min or dialysis: administer 100 mg once daily; for severe renal impairment, consider alternative therapy. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B or C: use with caution, consider dose reduction; limited data for severe hepatic impairment. |
| Pediatric use | Not recommended for use in children <18 years due to lack of safety and efficacy data; in clinical trials for specific conditions (e.g., recurrent brain tumors), doses of 3-6 mg/kg/day have been used, but not approved. |
| Geriatric use | Start at lower end of dosing range (e.g., 100 mg daily) due to increased sensitivity to sedation and thromboembolic risk; monitor renal function as elderly often have decreased GFR. |
| 1st trimester | Contraindicated due to high risk of severe birth defects (phocomelia, other limb defects, congenital heart defects). Pregnancy category X. |
| 2nd trimester | Contraindicated; continued risk of teratogenicity throughout pregnancy. |
| 3rd trimester | Contraindicated; risk of fetal harm persists. |
Clinical note
Comprehensive clinical and safety monograph for THALOMID (THALOMID).
| Placental transfer | Extensive placental transfer documented; teratogenic effects are well-established. |
| Breastfeeding | Excreted in human milk; potential for serious adverse reactions in nursing infants. Breastfeeding is not recommended during therapy. |
| Lactation Rating | L5 |
| Teratogenic Risk | Thalidomide is a known human teratogen. In the first trimester, exposure is associated with a high risk of severe birth defects including limb reduction defects, congenital heart disease, and anotia. No safe gestational trimester exists; contraindicated in pregnancy. |
| Fetal Monitoring | Pregnancy test prior to therapy, weekly during first month, then monthly; effective contraception mandatory; monitor for signs of thrombosis; fetal ultrasound if accidental exposure. |
| Fertility Effects | May impair spermatogenesis in males; reversible upon discontinuation. Females should avoid pregnancy due to teratogenicity. |
■ FDA Black Box Warning
THALOMID is contraindicated in pregnancy due to severe life-threatening birth defects. It must never be used by females who are pregnant or could become pregnant. If thalidomide is used during pregnancy, it can cause severe birth defects or death of the fetus. Additionally, females of reproductive potential must use two effective forms of contraception or abstain from heterosexual intercourse for at least 4 weeks before starting therapy, during therapy, and for 4 weeks after discontinuing therapy.
| Serious Effects |
PregnancyFemales of childbearing potential unless using highly effective contraception and meeting strict program requirementsMales with partner of childbearing potential unless using condoms or vasectomyHypersensitivity to thalidomide or any component
| Precautions | Venous thromboembolic events (VTE) – increased risk, especially when combined with dexamethasone, Fetal exposure – requires patient enrollment in the THALOMID REMS program, Hypersensitivity reactions – including rash, Stevens-Johnson syndrome, Peripheral neuropathy – may be irreversible, monitor for symptoms, Somnolence and dizziness – may impair ability to drive or operate machinery, Syncope and bradycardia – may occur, especially in elderly, Hepatotoxicity – monitor liver function tests, Hematologic toxicity – neutropenia and thrombocytopenia, Seizures – use with caution in patients with history of seizures |
| Food/Dietary | Take with water on an empty stomach (at least 1 hour before or 2 hours after meals). Avoid grapefruit juice, alcohol, and high-fat meals as they may alter absorption and increase risk of side effects. |
| Clinical Pearls | Thalomid (thalidomide) is a potent teratogen requiring strict pregnancy prevention. It has immunomodulatory, anti-inflammatory, and anti-angiogenic properties. Used primarily for erythema nodosum leprosum (ENL) and multiple myeloma. Monitor for thromboembolic events, peripheral neuropathy, and bradycardia. Dose adjustment needed for hepatic impairment. Ensure patient enrollment in THALOMID REMS program. |
| Patient Advice | Thalidomide can cause severe birth defects; use two forms of contraception during treatment and for 4 weeks after stopping. · Do not take during pregnancy or if planning to become pregnant; male patients must use condoms during sexual activity. · Report any numbness, tingling, or pain in hands/feet immediately. · Seek emergency care for signs of blood clots: chest pain, shortness of breath, leg swelling, or vision changes. · Avoid alcohol and grapefruit juice as they may increase side effects. · Do not donate blood or sperm while on therapy and for 4 weeks after discontinuation. |
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