Thalidomide

About Thalidomide

• Thalidomide received its first  U.S. Food and Drug Administration (FDA) approval in 1998 for treating erythema nodosum leprosum, a leprosy complication. Subsequently, in 2006, the FDA approved this drug, alongside dexamethasone, for managing newly diagnosed multiple myeloma.
• Thalidomide, in combination with dexamethasone, is prescribed for newly diagnosed multiple myeloma (MM) patients. Additionally, it’s indicated for treating the acute cutaneous symptoms of moderate to severe erythema nodosum leprosum (ENL). 
• However, it is not recommended as a standalone treatment for ENL if moderate to severe neuritis is present. Moreover, it serves as maintenance therapy to prevent and suppress the recurrence of cutaneous symptoms associated with ENL.
• Thalidomide’s mechanism of action involves immunosuppressive and anti-angiogenic effects mediated by modulation of inflammatory mediators like tumor necrosis factor-alpha (TNF-a) and IL-6. 
• It binds to cerebron, a component of the E3 ubiquitin ligase complex, leading to selective degradation of the transcription factors IKZF3 and IKZF1, crucial for the proliferation and survival of malignant myeloma cells. 
• Additionally, it inhibits basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), suggesting its potential anti-angiogenic application in cancer therapy.

Strength: 

Thalidomide capsule is available in strengths of  50 mg, 100 mg, 150 mg, and 200 mg. 

Recommended Dosage:

Multiple Myeloma

• The recommended dosage of Thalidomide for multiple myeloma, when used in combination with dexamethasone, is 200 mg once daily orally with water, preferably at bedtime and at least 1 hour after the evening meal, administered in 28-day treatment cycles. 
• The dosage of dexamethasone should be 40 mg daily orally on days 1-4, 9-12, and 17-20 of each 28-day cycle.

Erythema Nodosum Leprosum:

• For the treatment of cutaneous ENL, the recommended dosage is Thalidomide 100 mg/day to 300 mg/day orally, preferably at bedtime and at least 1 hour after the evening meal. 
• Patients under 50 kilograms should start at the lower end of the range, while consideration may be given to doses up to 400 mg/day for severe reactions or previous higher doses. 
• Corticosteroids can be used alongside this medicine for severe neuritis, with tapering as neuritis improves. Treatment should continue until symptoms subside, usually for at least 2 weeks, followed by tapering in Thalidomide 50 mg decrements every 2 to 4 weeks. 
• For those needing long-term maintenance, the minimum effective dose should be maintained, with tapering attempts every 3 to 6 months in 50 mg decrements every 2 to 4 weeks.

Important:

Intermittently suspend the dosing in the event of constipation, somnolence, or peripheral neuropathy, and deliberate on a dose reduction upon treatment resumption. Assess and potentially adjust the dosage in cases where patients develop adverse reactions. Permanently discontinue the medicine for instances of angioedema, anaphylaxis, Grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic manifestations.

Warnings & Precaution:

• Do not get pregnant while taking this medicine. Thalidomide carries a high risk of severe birth defects or embryo-fetal death if used during pregnancy, making it imperative for pregnant women or those who could become pregnant to avoid the drug. 
• Pregnancy must be ruled out before starting treatment, and effective contraception must be used thereafter.
• Thalidomide, when used with dexamethasone, significantly raises the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in multiple myeloma patients. Cases of ischemic heart disease, including myocardial infarction, and stroke have been reported in these patients. 
• Furthermore, adding pembrolizumab to dexamethasone and a thalidomide analog has led to increased mortality in multiple myeloma patients.
• Patients using this medicine should be aware of potential drowsiness and somnolence and advised to avoid situations where these effects could pose a risk. 
• Monitoring for signs of peripheral neuropathy is important, and the medicine should be discontinued if drug-induced peripheral neuropathy is detected. Patients should be instructed to sit upright for a few minutes before standing to prevent dizziness and orthostatic hypotension. 
• Neutropenia and thrombocytopenia may require dose adjustment or interruption, and HIV viral load should be monitored during treatment. 
• Monitoring for bradycardia and syncope is crucial, with dose adjustments or discontinuation as needed. 
• This medicine should be stopped for severe cutaneous reactions and seizures, and patients at risk of tumor lysis syndrome should be monitored with appropriate precautions. 
• Hypersensitivity reactions should also be monitored, with the discontinued for angioedema and anaphylaxis.

Common Thalidomide Side Effects:

• Fatigue
• Hypocalcemia
• Edema
• Constipation
• Neuropathy-sensory
• Dyspnea
• Muscle weakness
• Leukopenia
• Neutropenia
• Rash/desquamation
• Confusion
• Anorexia
• Nausea
• Anxiety/agitation
• Asthenia
• Tremor
• Fever
• Weight loss
• Thrombosis/embolism
• Neuropathy-motor
• Weight gain
• Dizziness
• Dry skin

Use in Specific Population

• Before starting the treatment, females of reproductive age should avoid pregnancy for four weeks and commit to using two reliable forms of contraception. 
• Two negative pregnancy tests are required before treatment initiation. 
• Males taking this medicine must use condoms during sexual activity and refrain from sperm donation. Blood donation is not permitted during treatment and for four weeks after discontinuation.
• Insufficient data on the drug’s presence in human milk and its effects on breastfed infants. Thalidomide is found in the milk of lactating rabbits. Women are advised against breastfeeding during the treatment due to potential risks to infants.
• Safety and efficacy have not been determined for pediatric patients under 12 years old with the medicine. 
• While no reports of physical or psychological dependence exist in users, like other tranquilizers/hypnotics, this medicine may lead to habituation to its sleep-inducing effects.

Storage and Handling 

• Each blister pack contains 28 capsules of Thalidomide in doses of 50 mg, 100 mg, 150 mg, or 200 mg.
• This medication should not be repackaged. 
• This medicine should be stored at temperatures between 20°C and 25°C (68°F and 77°F), with excursions permitted to 15°C-30°C (59°F-86°F).
• Keep the medicine away from pets and children.