Multiple Myeloma (MM): Thalidomide, when used 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. Additionally, it is used as maintenance therapy to prevent and control recurrence of ENL skin lesions.

Thalidomide exerts its effects primarily through binding to cereblon, a component of the cullin-ring E3 ubiquitin ligase complex. It exhibits immunomodulatory, anti-inflammatory, and antiangiogenic properties. Preclinical and clinical studies suggest that thalidomide’s immunologic actions may involve suppression of excessive tumor necrosis factor-alpha (TNF-α) production and downregulation of certain cell surface adhesion molecules critical for leukocyte migration. Additional effects may include inhibition of macrophage-mediated prostaglandin synthesis and modulation of interleukin-10 (IL-10) and interleukin-12 (IL-12) production by peripheral blood mononuclear cells.

In patients with multiple myeloma, thalidomide treatment is associated with increased numbers of circulating natural killer (NK) cells and elevated plasma levels of interleukin-2 (IL-2) and interferon-gamma (IFN-γ). Its antiangiogenic activity may involve inhibition of endothelial cell proliferation and other processes essential for new blood vessel formation.

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.

CNS Depressants (Opioids, Antihistamines, Antipsychotics, Anti-anxiety Agents, Alcohol): Concurrent use of thalidomide with opioids, antihistamines, antipsychotics, anti-anxiety agents, or other central nervous system (CNS) depressants may lead to additive sedation and should be avoided.

Drugs Causing Bradycardia: Thalidomide combined with medications that slow cardiac conduction may produce an additive bradycardic effect and should be used with caution.

Drugs Affecting Hormonal Contraceptives: Medications such as HIV-protease inhibitors, griseofulvin, modafinil, penicillins, rifampin, rifabutin, phenytoin, carbamazepine, and certain herbal supplements (e.g., St. John’s Wort) can reduce the effectiveness of hormonal contraceptives for up to one month after discontinuation. Women requiring these drugs must use two additional effective or highly effective contraceptive methods while taking thalidomide.

Drugs Causing Peripheral Neuropathy: Concurrent use of drugs associated with peripheral neuropathy—such as bortezomib, amiodarone, cisplatin, docetaxel, paclitaxel, vincristine, disulfiram, phenytoin, metronidazole, or alcohol—may result in additive neuropathic effects and should be used with caution.

Therapies Increasing Risk of Thromboembolism: Agents that increase thromboembolic risk, including erythropoietic drugs or estrogen-containing therapies, should be used with caution in multiple myeloma patients receiving thalidomide in combination with dexamethasone.

Thalidomide is strictly contraindicated in pregnant women, as it can cause severe fetal harm. It is also contraindicated in patients with a known hypersensitivity to thalidomide or any of its components.

The most commonly reported adverse reactions include fatigue, hypocalcemia, edema, constipation, sensory neuropathy, dyspnea, muscle weakness, leukopenia, neutropenia, rash or desquamation, confusion, anorexia, nausea, anxiety or agitation, tremor, fever, weight changes (loss or gain), thrombosis or embolism, motor neuropathy, dizziness, and dry skin.

Pregnancy: Thalidomide is contraindicated during pregnancy due to its known risk of causing severe embryo-fetal harm. If thalidomide is used during pregnancy, or if a patient becomes pregnant while on therapy, the patient must be informed of the potential fetal risk. Treatment should be immediately discontinued if pregnancy occurs.

Lactation: There is no information on the presence of thalidomide in human breast milk or its effects on the breastfed child or milk production. Because many drugs are excreted in human milk and thalidomide can cause serious adverse reactions in a nursing infant, women should not breastfeed while receiving thalidomide.

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 conducted 10–14 days prior, and the second test within 24 hours before initiation. During therapy and dose interruptions, weekly testing is recommended for the first 4 weeks, then every 4 weeks for women with regular menstrual cycles. For irregular cycles, testing should be done every 2 weeks.

Contraception (Females): Females of reproductive potential must either abstain continuously from heterosexual intercourse or use two reliable methods of contraception simultaneously. Contraception must begin at least 4 weeks before starting thalidomide, continue during treatment and any dose interruptions, and persist for 4 weeks after discontinuation.

Contraception (Males): Thalidomide is present in semen. Males must use a latex or synthetic condom during any sexual contact with females of reproductive potential while on therapy, during dose interruptions, and for up to 28 days after stopping thalidomide.

Embryo-Fetal Toxicity: Thalidomide is a potent human teratogen capable of causing severe, life-threatening birth defects, even after a single dose. Approximately 40% of affected infants may die at or shortly after birth. Females of reproductive potential may only be treated with thalidomide when no satisfactory alternatives exist, and strict measures to prevent pregnancy must be followed. There is no specific data on reproductive risks from cutaneous contact or inhalation, so females of reproductive potential should avoid direct contact with thalidomide capsules. If contact occurs with broken capsules or powder, wash the exposed area thoroughly with soap and water. Healthcare providers and caregivers exposed to patient body fluids should also wash exposed areas. Gloves and other protective measures should be used to minimize cutaneous exposure.

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

Venous and Arterial Thromboembolism: Thalidomide use in multiple myeloma patients increases the risk of venous thromboembolism, including deep vein thrombosis and pulmonary embolism. This risk is higher when thalidomide is combined with standard chemotherapeutic agents such as dexamethasone. Thromboprophylaxis should be considered based on individual patient risk factors, and both patients and physicians should monitor for signs and symptoms of thromboembolism.

Thrombocytopenia: Thalidomide may cause thrombocytopenia, including severe (Grade 3 or 4) cases. Blood counts, including platelet counts, should be monitored regularly. Dose reduction, delay, or discontinuation may be necessary. Patients should be observed for bleeding signs, such as petechiae, epistaxis, or gastrointestinal bleeding, especially when taking concomitant medications that increase bleeding risk.

Drowsiness and Somnolence: Thalidomide frequently causes drowsiness and somnolence. Patients should avoid activities requiring alertness, such as driving or operating machinery, and should not take other sedating medications without medical advice. Dose adjustments may be required if drowsiness is significant.

Peripheral Neuropathy: Thalidomide can cause peripheral neuropathy, which may be permanent. This adverse effect is common (>10%) and may be severe. Neuropathy usually develops with chronic use over several months but can occur even with short-term use. Medications known to cause neuropathy should be used cautiously in patients receiving thalidomide.

Dizziness and Orthostatic Hypotension: Thalidomide may cause dizziness and orthostatic hypotension. Patients should rise slowly from a recumbent position to minimize the risk of falls or injury.

Neutropenia: Thalidomide may reduce white blood cell counts, including neutrophils. Treatment should not be initiated if the absolute neutrophil count (ANC) is below 750/mm³. White blood cell counts and differentials should be monitored regularly, particularly in patients at higher risk, such as HIV-positive individuals. If ANC drops below 750/mm³ during therapy, thalidomide use should be re-evaluated and may need to be withheld if neutropenia persists.

Pediatric Use: The safety and effectiveness of thalidomide in pediatric patients under 12 years of age have not been established.

Geriatric Use: Patients over 65 years of age may experience higher rates of adverse events compared to younger patients, including atrial fibrillation, constipation, fatigue, nausea, hypokalemia, deep vein thrombosis, hyperglycemia, and pulmonary embolism.

Immunosuppressant

Store in a cool, dry place at temperatures below 30°C. Protect from light and keep out of reach of children.