Thalidomide Dosage

Usual Adult Dose for Leprosy - Erythema Nodosum Leprosum

Cutaneous erythema nodosum leprosum (ENL):
Initial dose: 100 to 300 mg orally once a day with water, preferably at bedtime and at least 1 hour after the evening meal; patients less than 50 kg should be started at the low end of the dose range

Severe cutaneous ENL reaction or patients previously requiring higher doses to control the reaction:
Initial dose: Up to 400 mg/day orally once a day at bedtime or in divided doses with water, at least 1 hour after meals

In general, dosing should continue until active reaction subsides (usually at least 2 weeks), then tapered in 50 mg decrements every 2 to 4 weeks.

Patients with a history of requiring prolonged maintenance to prevent recurrence or who flare during tapering should be maintained on the minimum dose necessary to control the reaction. Tapering off medication should be attempted every 3 to 6 months, in decrements of 50 mg every 2 to 4 weeks.

Usual Adult Dose for Multiple Myeloma

200 mg orally once a day with water, preferably at bedtime and at least 1 hour after the evening meal

Thalidomide is administered in combination with dexamethasone in 28-day treatment cycles. The dexamethasone dose is 40 mg orally daily, administered on days 1 through 4, 9 through 12, and 17 through 20, every 28 days.

Usual Pediatric Dose for Leprosy - Erythema Nodosum Leprosum

Cutaneous erythema nodosum leprosum (ENL):
12 years or older:
Initial dose: 100 to 300 mg orally once a day with water, preferably at bedtime and at least 1 hour after the evening meal; patients less than 50 kg should be started at the low end of the dose range

Severe cutaneous ENL reaction or patients previously requiring higher doses to control the reaction:
Initial dose: Up to 400 mg/day orally once a day at bedtime or in divided doses with water, at least 1 hour after meals

In general, dosing should continue until active reaction subsides (usually at least 2 weeks), then tapered in 50 mg decrements every 2 to 4 weeks.

Patients with a history of requiring prolonged maintenance to prevent recurrence or who flare during tapering should be maintained on the minimum dose necessary to control the reaction. Tapering off medication should be attempted every 3 to 6 months, in decrements of 50 mg every 2 to 4 weeks.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

In patients with moderate to severe neuritis associated with a severe ENL reaction, corticosteroids may be started concomitantly with thalidomide. Steroid usage can be tapered and discontinued when the neuritis has ameliorated.

Multiple myeloma patients who develop side effects such as constipation, oversedation, or peripheral neuropathy may benefit by either temporarily discontinuing the drug or continuing at a lower dose. With the decrease of these side effects, the drug may be started at a lower dose or at the previous dose based on clinical judgment.

Precautions

Thalidomide can cause severe birth defects or death to an unborn baby. Because of these teratogenic effects, thalidomide is restricted to use by the FDA through a regulatory program known as S.T.E.P.S.(R), or "System for Thalidomide Education and Prescribing Safety". In this program, only physicians and pharmacists who are registered as participants can prescribe and dispense the drug according to strict guidelines. Each patient must comply with all S.T.E.P.S.(R) program guidelines, and fulfill all requirements of the program to be eligible to receive the drug each month. Blood donations and sperm donations are not allowed while taking the drug.

Thalidomide is contraindicated in female patients who are pregnant or may become pregnant. Even a single 50 mg capsule taken by a pregnant woman during her pregnancy can cause severe birth defects. When there is no alternative treatment, women of childbearing age may be treated with the drug if precautions are taken to prevent pregnancy. Contraceptive precautions should be followed 4 weeks prior to initiation of, during, and for 4 weeks after discontinuation of thalidomide therapy. If pregnancy occurs during thalidomide treatment, the drug must be discontinued immediately and the patient should be referred to an obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling.

Patients with neoplastic and various inflammatory conditions being treated with thalidomide may have an increased incidence of pulmonary embolism, deep vein thrombophlebitis, thrombophlebitis, or thrombosis. Patients should be monitored for signs and symptoms of thromboembolism and should seek medical care if symptoms develop. Preliminary data suggest that patients who are appropriate candidates may benefit from concurrent prophylactic anticoagulation or aspirin treatment.

Thalidomide can cause irreversible peripheral neuropathy. Patients receiving thalidomide should be evaluated each month during the first 3 months of therapy and frequently thereafter for detection of early signs of peripheral neuropathy. Electrophysiological testing at baseline and then every 6 months to detect asymptomatic neuropathy may be appropriate. If neuropathy symptoms develop, withdrawal of thalidomide should be considered to prevent further nerve damage. Thalidomide should only be restarted following resolution of symptoms. Drugs that have been associated with neuropathy should be used with caution in patients receiving thalidomide.

Thalidomide can cause decreased white blood cell counts, including neutropenia. Treatment should not be initiated in patients whose absolute neutrophil count (ANC) is below 750/mm3. White blood cell count and differential should be monitored frequently in patients at risk for neutropenia, such as those with HIV infection. If ANC falls below 750/mm3 during treatment, the need for continued therapy should be reevaluated. Withdrawal of the drug should be considered if neutropenia persists.

Hypersensitivity has been reported with thalidomide. Therapy interruption may be needed if severe. If the reaction recurs when the drug is restarted, thalidomide should be discontinued.

Serious dermatologic reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis), which may be fatal, have been reported. Thalidomide should be discontinued if skin rash develops and resumed only after appropriated clinical evaluation. Thalidomide should not be restarted if the rash is exfoliative, purpuric, or bullous or if Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected.

Seizures (including grand mal convulsions) have been reported during postmarketing experience. Patients with a history of seizures or other risk factors for seizure development should be monitored closely during thalidomide therapy for clinical changes that could precipitate acute seizure activity.

In a study of HIV-seropositive patients, plasma HIV RNA levels were found to increase during thalidomide therapy. It is recommended that viral loads be measured after the first and third months of treatment and every 3 months thereafter.

Safety and efficacy have not been established in pediatric patients less than 12 years of age.

Dialysis

Renally-impaired patients on dialysis: No adjustment recommended.

Other Comments

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for thalidomide. It includes a Medication Guide, elements to assure safe use, and an implementation system. Additional information is available at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm.

Drug prescribing to women of childbearing potential should be contingent upon initial and continued confirmed negative results of pregnancy testing.

Thalidomide causes drowsiness and somnolence. Performance of tasks that require concentration and mechanical dexterity such as operation of machinery and driving should be avoided.

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