Multiple Myeloma (MM): Thalidomide, in combination with dexamethasone, is indicated for the treatment of patients with newly diagnosed multiple myeloma.

Erythema Nodosum Leprosum (ENL): Thalidomide is indicated for the acute management of moderate to severe cutaneous manifestations of erythema nodosum leprosum. It is also used as maintenance therapy to prevent and control recurrence of these skin manifestations.

Thalidomide exerts its cellular effects through binding to cereblon, which is a component of the cullin-RING E3 ubiquitin ligase complex. It has immunomodulatory, anti-inflammatory, and anti-angiogenic properties. Studies suggest that its immunological effects are associated with suppression of excessive production of tumor necrosis factor-alpha (TNF-α) and downregulation of certain cell surface adhesion molecules involved in leukocyte migration. Additionally, thalidomide may reduce macrophage activity in prostaglandin synthesis and regulate the production of interleukin-10 and interleukin-12 by peripheral blood mononuclear cells. In patients with multiple myeloma, thalidomide therapy has been shown to increase circulating natural killer (NK) cells and elevate plasma levels of interleukin-2 and interferon-gamma. Its anti-angiogenic effect may involve inhibition of endothelial cell proliferation, thereby reducing the formation of new blood vessels.

Multiple Myeloma: The recommended dose of thalidomide in combination with dexamethasone is 200 mg once daily (in 28-day treatment cycles) orally with water, preferably at bedtime and at least 1 hour after the evening meal.

Erythema Nodosum Leprosum: The recommended dose of thalidomide for an episode of cutaneous ENL is 100 to 300 mg/day once daily orally with water, preferably at bedtime and at least 1 hour after the evening meal.

Dosing for patients weighing less than 50 kilograms should be initiated at the low end of the dose range.

Higher dosage range should be considered for patients with a severe cutaneous ENL reaction, or in those who have previously required higher doses to control the reaction (possibly up to 400 mg/day) once daily at bedtime or in divided doses with water, at least 1 hour after meals. Concomitant use of corticosteroids should be considered in patients with moderate to severe neuritis associated with a severe ENL reaction. Steroid usage can be tapered and discontinued when the neuritis has ameliorated.

Higher dosage of Thalidomide should be continued until signs and symptoms of active reaction have subsided, usually a period of at least 2 weeks. Patients may then be tapered off medication in 50 mg decrements every 2 to 4 weeks.

Opioids, Antihistamines, Antipsychotics, Anti-anxiety agents, or other CNS depressants (including alcohol): Concurrent use with thalidomide may produce additive sedative effects and should be avoided.

Drugs causing bradycardia: Medicines that slow cardiac conduction, when used with thalidomide, may increase the risk of bradycardia and should be used cautiously.

Drugs affecting hormonal contraceptives: Co-administration of HIV protease inhibitors, griseofulvin, modafinil, penicillins, rifampin, rifabutin, phenytoin, carbamazepine, or herbal products such as St. John’s Wort may reduce the effectiveness of hormonal contraceptives for up to one month after discontinuation. Females using these drugs must use two reliable contraceptive methods while taking thalidomide.

Drugs causing peripheral neuropathy: Concurrent use with agents such as bortezomib, amiodarone, cisplatin, docetaxel, paclitaxel, vincristine, disulfiram, phenytoin, metronidazole, or alcohol may increase the risk of neuropathy and should be used with caution.

Therapies increasing thromboembolism risk: Erythropoietic agents or estrogen-containing therapies may increase thromboembolic risk and should be used cautiously in patients receiving thalidomide with dexamethasone.

Thalidomide is contraindicated in pregnant females due to the risk of fetal harm. It is also contraindicated in patients with known hypersensitivity to thalidomide or its components.

Common adverse reactions include fatigue, hypocalcemia, edema, constipation, sensory neuropathy, dyspnea, muscle weakness, leukopenia, neutropenia, rash or skin peeling, confusion, anorexia, nausea, anxiety or agitation, tremor, fever, weight loss, thrombosis or embolism, motor neuropathy, weight gain, dizziness, and dry skin.

Pregnancy: Thalidomide can cause severe fetal harm based on its mechanism and available human and animal data. It is strictly contraindicated during pregnancy. If pregnancy occurs during treatment, the drug should be discontinued immediately and the patient should be informed of the risk.

Lactation: It is unknown whether thalidomide is excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, breastfeeding should be avoided during treatment.

Females and Males of Reproductive Potential

Pregnancy testing: Females of reproductive potential must have two negative pregnancy tests before starting thalidomide. The first test should be done within 10–14 days prior, and the second within 24 hours before starting treatment. During therapy, pregnancy testing should be done weekly for the first 4 weeks, then every 4 weeks for regular cycles or every 2 weeks for irregular cycles.

Contraception: Females must either abstain from sexual intercourse or use two reliable contraceptive methods. Contraception should begin 4 weeks before therapy, continue during treatment, during interruptions, and for 4 weeks after stopping therapy.

Males: Thalidomide is present in semen. Therefore, males must use a latex or synthetic condom during sexual contact with females of reproductive potential while on treatment, during interruptions, and for 28 days after discontinuation.

Embryo-Fetal Toxicity: Thalidomide is a potent human teratogen that can cause severe, life-threatening birth defects even after a single dose. Approximately 40% of affected infants may die at or shortly after birth. When no suitable alternative therapy is available, females of reproductive potential may be treated with thalidomide only with strict pregnancy prevention measures. There are no specific data regarding risks from skin contact or inhalation; however, females should avoid handling thalidomide capsules. If contact occurs with broken capsules or powder, the affected area should be washed thoroughly with soap and water. Healthcare providers exposed to patient body fluids should also wash the area and use protective measures such as gloves.

Blood Donation: Patients must not donate blood during treatment and for at least 4 weeks after stopping thalidomide.

Venous and Arterial Thromboembolism: Thalidomide increases the risk of thromboembolic events such as deep vein thrombosis and pulmonary embolism, particularly when combined with agents like dexamethasone. Thromboprophylaxis should be considered based on individual risk. Patients should be monitored for signs and symptoms of thrombosis.

Thrombocytopenia: Cases of thrombocytopenia, including severe (Grade 3–4), have been reported. Platelet counts should be monitored regularly. Dose adjustment, interruption, or discontinuation may be required. Patients should be observed for bleeding symptoms such as petechiae, nosebleeds, or gastrointestinal bleeding.

Drowsiness and Somnolence: Thalidomide commonly causes drowsiness. Patients should avoid activities requiring alertness, such as driving or operating machinery, and should not take other sedative medications without medical advice. Dose reduction may be necessary.

Peripheral Neuropathy: Thalidomide can cause potentially irreversible nerve damage. Peripheral neuropathy is common and may occur after long-term use, though it can also occur with short-term therapy. Concomitant use of other neurotoxic drugs should be approached with caution.

Dizziness and Orthostatic Hypotension: Patients may experience dizziness and low blood pressure upon standing. They should be advised to rise slowly from sitting or lying positions.

Neutropenia: Reduced white blood cell counts, including neutropenia, have been reported. Treatment should not begin if ANC is <750/mm³. Blood counts should be monitored regularly. If neutropenia develops or persists, treatment adjustment or discontinuation should be considered.

Pediatric Use: Safety and effectiveness in children under 12 years of age have not been established.

Geriatric Use: Patients over 65 years of age have shown higher rates of adverse effects such as atrial fibrillation, constipation, fatigue, nausea, hypokalemia, deep vein thrombosis, hyperglycemia, and pulmonary embolism compared to younger patients.

Immunosuppressant

Store below 30°C in a cool, dry place. Protect from light. Keep out of reach of children.