Thalamia

Approved Indications:

• Multiple Myeloma (MM): In combination with dexamethasone for newly diagnosed MM patients.
• Erythema Nodosum Leprosum (ENL): For treatment and suppression of cutaneous manifestations of moderate to severe ENL.
• HIV-associated Wasting Syndrome: Off-label for cachexia and weight loss.
• Myelodysplastic Syndromes (MDS): Off-label in certain anemic patients with low/intermediate risk.
• Crohn’s Disease: Off-label for refractory or fistulizing disease.
• Lupus Erythematosus (Discoid or Systemic): Off-label use for severe or resistant cases.
• Graft-Versus-Host Disease (GVHD): Off-label for chronic GVHD after hematopoietic stem cell transplantation.
• Kaposi Sarcoma (HIV-associated): Off-label as an antiangiogenic agent.

Route: Oral administration, with or without food.

Multiple Myeloma:

• Adults: 200 mg once daily at bedtime (to reduce somnolence). Dose may be adjusted in combination therapy.

Erythema Nodosum Leprosum (ENL):

• Acute Treatment: 100–300 mg/day in divided doses.
• Maintenance/Suppression: 50–200 mg once daily at bedtime.

HIV Wasting, MDS, Crohn’s Disease (Off-label):

• Starting dose typically ranges from 50–100 mg daily. Titrate based on response and tolerance.

Pediatric Use:

• Safety and efficacy have not been established.

Elderly Patients:

• Use cautiously due to increased risk of adverse effects (especially sedation, thromboembolism).

Renal Impairment:

• No specific dose adjustment, but monitor closely.

Hepatic Impairment:

• No established dose modifications; use cautiously.

Additional Instructions:

• Bedtime dosing is recommended to minimize sedative effects.
• Swallow whole; do not crush or chew.

Thalidomide acts through multiple mechanisms. It has immunomodulatory, anti-inflammatory, and anti-angiogenic effects. Thalidomide inhibits tumor necrosis factor-alpha (TNF-α) production, modulates T-cell activity, and reduces leukocyte migration. It also inhibits vascular endothelial growth factor (VEGF)-induced angiogenesis. These combined actions make it effective in malignancies, autoimmune diseases, and inflammatory dermatoses.

• Absorption: Oral bioavailability is approximately 90%. Peak plasma levels reached within 2–6 hours.
• Distribution: Widely distributed; protein binding ~55%.
• Metabolism: Not significantly metabolized by CYP450 enzymes. Undergoes non-enzymatic hydrolysis in plasma.
• Half-life: Approx. 5–7 hours.
• Excretion: Mainly through renal route as unchanged drug and metabolites.
• Special Populations: No significant difference in pharmacokinetics between healthy and renally impaired subjects.

• Pregnancy: Contraindicated. Thalidomide is a known human teratogen causing severe birth defects (phocomelia, limb deformities, internal organ malformations). It is classified under FDA Pregnancy Category X.
• Lactation: Unknown whether excreted in human milk. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy.
• Contraceptive Guidance: Mandatory dual contraception for females of reproductive potential. Men must use condoms due to presence in semen.

• Primary Class: Immunomodulatory Agent (IMiD)
• Subclasses:
• Angiogenesis Inhibitor
• TNF-α Inhibitor
• Anti-inflammatory/Antineoplastic Agent

• Known hypersensitivity to thalidomide or any component of the formulation
• Pregnancy or potential for pregnancy without strict contraceptive compliance
• Women of reproductive potential who are not enrolled in a REMS (Risk Evaluation and Mitigation Strategy) program
• Patients unable to comply with required safety guidelines

• Teratogenicity: Black box warning. Extreme risk of fetal malformations.
• Thromboembolism: Increased risk of DVT and PE, especially when combined with dexamethasone or chemotherapy.
• Peripheral Neuropathy: Common and may be irreversible; monitor for signs of numbness or tingling.
• Sedation/Dizziness: May impair mental alertness; caution when operating machinery.
• Bradycardia and Hypotension: Monitor cardiac function in high-risk individuals.
• Neutropenia and Thrombocytopenia: Monitor complete blood counts regularly.
• Tumor Lysis Syndrome: Reported in MM patients with high tumor burden.

Common:

• Neurological: Somnolence, dizziness, peripheral neuropathy
• GI: Constipation, nausea
• General: Fatigue, rash

Hematologic:

• Neutropenia, thrombocytopenia, anemia

Serious/Rare:

• Deep vein thrombosis, pulmonary embolism
• Stevens-Johnson syndrome, toxic epidermal necrolysis
• Seizures (rare)
• Hepatotoxicity
• Bradycardia

Timing & Severity:

• Peripheral neuropathy may develop after prolonged use (>6 months)
• Thromboembolic events more common in first 3–6 months

• CYP450 Interaction: Minimal CYP metabolism; low risk of enzyme-mediated drug interactions.
• Drugs Increasing Sedation: Alcohol, benzodiazepines, opioids may enhance sedative effects.
• Estrogen-containing Contraceptives: Increases thromboembolic risk.
• Dexamethasone & Chemotherapy: Potentiates risk of VTE; prophylactic anticoagulation advised.
• Immunosuppressants (e.g., cyclosporine): Additive risk of immunosuppression.

• REMS Program Requirements: Updated protocols mandate strict enrollment, monthly pregnancy testing, and counseling for both males and females of reproductive potential.
• Multiple Myeloma Guidelines: Continued inclusion in front-line and maintenance regimens; shifting toward newer IMiDs (e.g., lenalidomide) in some settings.
• Anti-thrombotic Guidelines: Stronger recommendation for prophylactic anticoagulation in MM patients receiving thalidomide-based therapy.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Humidity/Light: Store in original blister pack to protect from moisture and light.
• Handling Precautions: Avoid direct contact with broken capsules. Use gloves if capsule content is exposed.
• Disposal: Dispose of unused medication per hazardous drug guidelines; do not flush.