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Pharmacologic class: Synthetic glutamic acid derivative
Therapeutic class: Immunomodulator, angiogenesis inhibitor
Pregnancy risk category X
FDA Box Warning
When taken during pregnancy, drug may cause severe, life-threatening birth defects or fetal death. Never administer to women who are pregnant or could become pregnant during therapy. Because of its toxicity and to reduce risk of fetal exposure, drug is approved for marketing only under special Food and Drug Administration-approved restricted distribution program, called System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.TM). Only prescribers and pharmacists registered with program are allowed to prescribe and dispense drug. Also, patients must be advised of, agree to, and comply with program requirements.
Use of thalidomide in patients with multiple myeloma results in an increased risk of venous thromboembolic events (VTEs), such as deep venous thrombosis and pulmonary embolism. Risk increases significantly when thalidomide is used in combination with standard chemotherapeutic agents, including dexamethasone. In one controlled trial, rate of VTEs was 22.5% in patients receiving thalidomide in combination with dexamethasone compared to 4.9% in patients receiving dexamethasone alone (p = 0.002). Patients and physicians are advised to watch for signs and symptoms of thromboembolism. Instruct patients to seek medical care if they develop signs and symptoms, such as shortness of breath, chest pain, or arm or leg swelling. Consider thromboprophylaxis based on assessment of individual patient's underlying risk factors.
Suppresses excess levels of tumor necrosis factor-alpha in patients with erythema nodosum leprosum (ENL). Alters leukocyte migration by changing cell surface characteristics.
Capsules: 50 mg, 100 mg, 200 mg
Indications and dosages
➣ Cutaneous manifestations of moderate to severe ENL; to prevent and suppress recurrent ENL
Adults weighing 50 kg (110 lb) or more: 100 to 300 mg P.O. daily, or up to 400 mg P.O. daily, depending on disease severity or previous response. Continue therapy until symptoms of active reactions subside (usually after 2 weeks); then may taper in 50-mg decrements q 2 to 4 weeks.
Adults weighing less than 50 kg (110 lb): Initially, 100 mg P.O. daily, or up to 400 mg P.O. daily, depending on disease severity or previous response. Continue therapy until symptoms of active reactions subside (usually after 2 weeks); then may taper in 50-mg decrements q 2 to 4 weeks.
➣ Newly diagnosed multiple myeloma (MM)
Adults: 200 mg P.O. once daily, in combination with dexamethasone 40 mg/day P.O. on days 1 to 4, 9 to 12, and 17 to 20 every 28 days.
• Aphthous stomatitis
• Wasting syndrome associated with human immunodeficiency virus (HIV)
• Multiple myeloma
• Refractory Crohn's disease
• Hypersensitivity to drug or its components
Use cautiously in:
• neutropenia, bradycardia, peripheral neuropathy, hypotension, underlying malignancy, history of seizures or risk of seizures, risk of tumor lysis syndrome
• concurrent use of drugs that slow cardiac conduction, drugs that cause peripheral neuropathy (such as alcohol, amiodarone, bortezomib, cisplatin, disulfiram, docetaxel, metronidazole, paclitaxel, phenytoin, vincristine), and hormonal contraceptives
• concurrent use of opioids, antihistamines, antipsychotics, anti-anxiety agents, or other CNS depressants (avoid use)
• breastfeeding patients (use not recommended)
• children younger than age 12 (safety not established).
Follow all instructions provided by System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.TM) program, accessible at http://www.steps-info.com.
• Give with 8 oz of water just before bedtime, at least 1 hour after evening meal.
• Know that patients who need prolonged maintenance therapy to prevent cutaneous ENL recurrence and those who have flares during tapering should receive minimum effective dosage, with tapering attempted every 3 to 6 months. To taper, decrease dosage by 50 mg every 2 to 4 weeks.
CNS: drowsiness, dizziness, vertigo, sedation, tremor, asthenia, peripheral neuropathy, fatigue, confusion, anorexia, anxiety, agitation (with MM use), headache, seizures
CV: bradycardia, orthostatic hypotension, peripheral edema, deep vein thrombosis (with MM use)
EENT: rhinitis, sinusitis, pharyngitis
GI: nausea, constipation, diarrhea, abdominal pain, oral moniliasis
GU: erectile dysfunction
Hematologic: leukopenia, neutropenia
Musculoskeletal: muscle weakness (with MM use), back pain
Respiratory: dyspnea, pulmonary embolus (with MM use)
Skin: dry skin, desquamation (with MM use), exfoliative, purpuric, bullous, or maculopapular rash; pruritus; fungal dermatitis; nail disorder; photosensitivity; toxic epidermal necrolysis, Stevens-Johnson syndrome
Other: weight gain or loss (with MM use), fever, tooth pain, chills, accidental injury, hypersensitivity reactions, increased HIV viral load, severe birth defects, fetal death, tumor lysis syndrome
Drug-drug. Barbiturates, chlorpromazine, reserpine, sedative-hypnotics, and other CNS depressants: increased sedation
Cardiovascular agents (such as alpha-and beta-adrenergic blockers, beta blockers, calcium channel blockers, digoxin), neuromuscular blockers (succinylcholine), lithium, noncardiovascular agents such as H2 blockers (cimetidine, famotidine), tricyclic antidepressants: increased risk of bradycardia
Drugs linked to peripheral neuropathy: increased risk of peripheral neuropathy
Hormonal contraceptives: increased risk of thromboembolic disease
Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, lipids, liver function tests: increased values
Calcium, hemoglobin, neutrophils, white blood cells: decreased values
Drug-food. High-fat meal: interference with drug absorption
Drug-behaviors. Alcohol use: increased sedation, increased risk of peripheral neuropathy
Monitor for signs and symptoms of hypersensitivity reaction. If rash occurs, discontinue drug and contact prescriber immediately. Don't restart drug if Stevens-Johnson syndrome, toxic epidermal necrolysis, or exfoliative, purpuric, or bullous rash occurs.
Watch for and report signs and symptoms of peripheral neuropathy. If symptoms develop, discontinue drug immediately. Usually, treatment with thalidomide should only be reinitiated if the neuropathy returns to baseline status.
• Assess CBC with white cell differential.
• Carefully monitor patient's reproductive status.
Monitor patients at risk for tumor lysis syndrome (such as those with high tumor burden before treatment) and take appropriate precautions.
Closely monitor patients with history of seizures or who are at risk for seizures for clinical changes that could precipitate acute seizure activity.
Observe patients (particularly patients being treated for MM) for signs and symptoms of thromboembolism.
• Monitor patients for bradycardia and possible syncope; dosage reduction or drug discontinuation may be required.
• Be aware that patients treated for MM who develop such adverse reactions as constipation or somnolence may benefit from temporarily discontinuing drug or continuing drug at lower dosage.
• Measure viral load after first and third months of treatment and every 3 months thereafter.
• Instruct patient to take with 8 oz of water just before bedtime, at least 1 hour after dinner.
Tell patient to immediately report signs and symptoms of peripheral neuropathy, tumor lysis syndrome, seizures, thromboembolism, bradycardia, or hypersensitivity reaction, especially rash.
• Teach patient about risks of fetal exposure to drug. Carefully review relevant portions of S.T.E.P.S.TM program with patient.
• Instruct female of childbearing age to use two highly effective birth control methods simultaneously, from 1 month before first thalidomide dose until 1 month after last dose.
• Explain mandatory pregnancy testing schedule to female patient, and stress importance of compliance.
Advise female patient to contact prescriber immediately if she suspects she's pregnant.
• Caution female patient not to breastfeed.
• Instruct male patient to use latex condoms during every sexual encounter.
• Tell patient that dizziness and orthostatic hypotension may occur. Advise patient to remain upright for a few minutes before standing up from a lying position.
• Tell patient to avoid alcohol and drugs that may cause drowsiness during drug therapy.
• Advise patient not to donate blood or sperm while taking this drug and for 4 weeks after stopping drug.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and behaviors mentioned above.
Mechanisms of teratogenicity The most plausible mechanism is thalidomide’s binding to and inactivation of the protein cerebron, which is critical in limb formation. Thalidomide has undergone a renaissance of interest and is in clinical trials for a wide array of conditions, due to its inhibition of TNF-alpha production, cytokine modulation and antiangiogenesis