Thalidomide
THALOMID
What it isThe original immunomodulatory drug (IMiD), used for multiple myeloma and erythema nodosum leprosum.
Why this oneIts resurrection is the story: the teratogen that caused the limb-defect catastrophe proved to work in myeloma and leprosy reactions, founding the class that led to lenalidomide.
What limits itIt demands a locked-down pregnancy-prevention REMS, causes cumulative peripheral neuropathy and sedation, and adds venous thromboembolism risk requiring prophylaxis.
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Multiple myeloma (with dexamethasone, 28-day cycles) | Adults | 200 mg QHS | 200 mg QHS | |
| Erythema nodosum leprosum, cutaneous episode | Adults (<50 kg: start low end) | 100–300 mg QHS | Continue until active reaction subsides (usually ≥2 wk), then taper | 400 mg/day (severe ENL; QHS or divided) |
Renal Undefined
Hepatic Undefined
MM: dexamethasone 40 mg PO days 1–4, 9–12, 17–20 of each 28-day cycle
Instructions
- Take with water, preferably at bedtime and ≥1 hr after the evening meal
- ENL taper: 50 mg decrements q2–4wk once reaction subsides; if on maintenance, attempt taper q3–6mo
- THALOMID REMS required: 2 negative pregnancy tests before start, then weekly x1 month, then monthly (q2wk if irregular cycles); 2 reliable contraception methods from 4 wk before through 4 wk after therapy; males use latex/synthetic condom and must not donate sperm; no blood donation during and 4 wk after
- Interrupt for constipation, somnolence, or peripheral neuropathy; consider reduced dose on resumption
- Permanently discontinue for angioedema, anaphylaxis, Grade 4 rash, skin exfoliation, or bullae
Contraindications
- Pregnancy — powerful human teratogen; ~40% infant mortality at or shortly after birth; discontinue immediately if pregnancy occurs
Cautions
- Venous and arterial thromboembolism (DVT/PE; ischemic heart disease incl. MI; stroke) — consider thromboprophylaxis
- Increased mortality when PD-1/PD-L1 blocker (pembrolizumab) added to thalidomide analogue + dexamethasone in MM
- Drowsiness/somnolence — avoid hazardous tasks; additive with other sedating drugs
- Peripheral neuropathy — common, may be irreversible; discontinue if symptoms occur
- Dizziness and orthostatic hypotension — sit upright before standing
- Neutropenia and thrombocytopenia — may need dose interruption/reduction
- Increased HIV viral load — measure during treatment
- Bradycardia — possible syncope; may need dose reduction/discontinuation
- Severe cutaneous reactions — discontinue for severe reactions
- Seizures — monitor patients with seizure history/risk factors
- Tumor lysis syndrome — monitor high tumor burden
Adverse reactions
- MM (≥20%): fatigue, hypocalcemia, edema, constipation, sensory neuropathy, dyspnea, muscle weakness, leukopenia/neutropenia, rash/desquamation, confusion, anorexia, nausea, anxiety/agitation, tremor, fever, weight change, thrombosis/embolism, motor neuropathy, dizziness, dry skin
- ENL (≥10%): somnolence, rash, headache
- DVT 13% and PE 7% (Grade 3/4) with dex in Study 2
Pregnancy Contraindicated — human teratogen; severe birth defects (amelia, phocomelia) or fetal death even after a single dose; REMS + pregnancy exposure registry
Lactation Advise women not to breastfeed during treatment
⚠ BOXED WARNINGS
- Embryo-fetal toxicity (REMS)
- Venous thromboembolism
Classes and tags
Clinical profile
Mechanism of action: Thalidomide ballicule
