Thalidomide
FDA Drug Information • Also known as: Thalomid
- Brand Names
- Thalomid
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
⚠ Boxed Warning (Black Box)
WARNING: EMBRYO-FETAL TOXICITY AND VENOUS THROMBOEMBOLISM WARNING: EMBRYO-FETAL TOXICITY AND VENOUS THROMBOEMBOLISM See full prescribing information for complete boxed warning. EMBRYO -FETAL TOXICITY
If THALOMID is taken during pregnancy, it can cause severe birth defects or embryo-fetal death. THALOMID should never be used by females who are pregnant or who could be pregnant while taking the drug. Even a single dose [1 capsule (regardless of strength)] taken by a pregnant woman during her pregnancy can cause severe birth defects. Pregnancy must be excluded before start of treatment. Prevent pregnancy thereafter by the use of two reliable methods of contraception. ( 5.1 , 8.3 ) THALOMID is only available through a restricted distribution program, the THALOMID REMS ® program ( 5.2 ). VENOUS THROMBOEMBOLISM Significant increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with multiple myeloma receiving THALOMID with dexamethasone ( 5.3 ). EMBRYO-FETAL TOXICITY If THALOMID is taken during pregnancy, it can cause severe birth defects or embryo-fetal death. THALOMID should never be used by females who are pregnant or who could become pregnant while taking the drug. Even a single dose [1 capsule (regardless of strength)] taken by a pregnant woman during her pregnancy can cause severe birth defects. Because of this toxicity and in an effort to make the chance of embryo-fetal exposure to THALOMID as negligible as possible, THALOMID is approved for marketing only through a special restricted distribution program: THALOMID REMS program, approved by the Food and Drug Administration. Information about THALOMID and the THALOMID REMS program is available at www.thalomidrems.com or by calling the REMS Call Center at 1-888-423-5436. VENOUS THROMBOEMBOLISM The use of THALOMID in multiple myeloma results in an increased risk of venous thromboembolism, such as deep venous thrombosis and pulmonary embolism. This risk increases significantly when THALOMID is used in combination with standard chemotherapeutic agents including dexamethasone. In one controlled trial, the rate of venous thromboembolism was 22.5% in patients receiving THALOMID in combination with dexamethasone compared to 4.9% in patients receiving dexamethasone alone (p = 0.002). Patients and physicians are advised to be observant for the signs and symptoms of thromboembolism. Instruct patients to seek medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. Consider thromboprophylaxis based on an assessment of individual patients' underlying risk factors.Description
11 DESCRIPTION THALOMID, α-(N-phthalimido) glutarimide, is an immunomodulatory agent. The empirical formula for thalidomide is C 13 H 10 N 2 O 4 and the gram molecular weight is 258.2. The CAS number of thalidomide is 50-35-1. Chemical Structure of Thalidomide Note: ∙ = asymmetric carbon atom Thalidomide is an off-white to white, odorless, crystalline powder that is soluble at 25°C in dimethyl sulfoxide and sparingly soluble in water and ethanol. The glutarimide moiety contains a single asymmetric center and, therefore, may exist in either of two optically active forms designated S-(-) or R-(+). THALOMID is an equal mixture of the S-(-) and R-(+) forms and, therefore, has a net optical rotation of zero. THALOMID is available in 50 mg, 100 mg, 150 mg and 200 mg capsules for oral administration. Active ingredient: thalidomide. Inactive ingredients: pregelatinized starch and magnesium stearate. The 50 mg capsule shell contains gelatin, titanium dioxide, and black ink. The 100 mg capsule shell contains black iron oxide, yellow iron oxide, titanium dioxide, gelatin, and black ink. The 150 mg capsule shell contains FD&C blue #2, black iron oxide, yellow iron oxide, titanium dioxide, gelatin, and black and white ink. The 200 mg capsule shell contains FD&C blue #2, titanium dioxide, gelatin, and white ink. Chemical Structure
What Is Thalidomide Used For?
1 INDICATIONS AND USAGE
THALOMID in combination with dexamethasone is indicated for the treatment of patients with newly diagnosed multiple myeloma (MM). ( 1.1 ) THALOMID is indicated for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). THALOMID is not indicated as monotherapy for such ENL treatment in the presence of moderate to severe neuritis. THALOMID is also indicated as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence. ( 1.2 ) 1.1 Multiple Myeloma THALOMID in combination with dexamethasone is indicated for the treatment of patients with newly diagnosed multiple myeloma (MM) [see Clinical Studies (14.1) ] . 1.2 Erythema Nodosum Leprosum THALOMID is indicated for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). THALOMID is not indicated as monotherapy for such ENL treatment in the presence of moderate to severe neuritis. THALOMID is also indicated as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence [see Clinical Studies (14.2) ].Dosage and Administration
2 DOSAGE AND ADMINISTRATION
MM: 200 mg orally once daily. The recommended dose of dexamethasone is 40 mg/day on days 1-4, 9-12, and 17-20 every 28 days. ( 2.2 ) ENL: 100 to 300 mg/day for an episode of cutaneous ENL. Up to 400 mg/day for severe cutaneous ENL. ( 2.3 ) 2.1 Required Baseline Testing Drug prescribing to females of reproductive potential is contingent upon initial and continued negative results of pregnancy testing [see Warnings and Precautions (5.1 and 5.2) ] . THALOMID must only be administered in compliance with all of the terms outlined in the THALOMID REMS program. THALOMID may only be prescribed by prescribers certified with the THALOMID REMS program and may only be dispensed by pharmacists certified with the THALOMID REMS program. 2.2 Recommended Dosage for Multiple Myeloma The recommended dose of THALOMID 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. The dose of dexamethasone is 40 mg daily administered orally on days 1-4, 9-12, and 17-20 every 28 days. 2.3 Recommended Dosage for Erythema Nodosum Leprosum The recommended dose of THALOMID 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. Initiate dosing for patients weighing less than 50 kilograms at the low end of the dose range. Consider dosing in the higher dosage range 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. Consider concomitant use of corticosteroids 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. Continue dosing with THALOMID 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. Patients who have a documented history of requiring prolonged maintenance treatment to prevent the recurrence of cutaneous ENL 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. 2.4 Dosage Modifications for Adverse Reactions Interrupt THALOMID for constipation, somnolence, or peripheral neuropathy. Consider a reduced dose upon resumption of treatment. Consider dose reduction, delay, or discontinuation in patients who develop National Cancer Institute Common Toxicity Criteria (NCI CTC) Grade 3 or 4 adverse reactions and/or based on clinical judgment. Permanently discontinue THALOMID for angioedema, anaphylaxis, Grade 4 rash, skin exfoliation, bullae, or any other severe...Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described in detail in other labeling sections:
Teratogenicity [see Boxed Warning , Warnings and Precautions (5.1 , 5.2) , and Patient Counseling Information (17) ] Venous and Arterial Thromboembolism [see Boxed Warning , Warnings and Precautions (5.3) , and Patient Counseling Information (17) ] Increased Mortality in Patients with MM When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone [see Warnings and Precautions (5.4) ] Drowsiness and Somnolence [see Warnings and Precautions (5.5) ] Peripheral Neuropathy [see Warnings and Precautions (5.6) ] Dizziness and Orthostatic Hypotension [see Warnings and Precautions (5.7) ] Neutropenia [see Warnings and Precautions (5.8) ] Thrombocytopenia [see Warnings and Precautions (5.9) ] Increased HIV Viral Load [see Warnings and Precautions (5.10) ] Bradycardia [see Warnings and Precautions (5.11) ] Severe Cutaneous Reactions [see Warnings and Precautions (5.12) ] Seizures [see Warnings and Precautions (5.13) ] Tumor Lysis Syndrome [see Warnings and Precautions (5.14) ] Hypersensitivity [see Warnings and Precautions (5.16) ] MM: The most common adverse reactions (≥ 20%) are 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, and dry skin. ( 6.1 ) ENL: The most common adverse reactions (≥ 10%) are somnolence, rash, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS or embryo-fetal exposure: contact Bristol Myers Squibb at 1-800-721-5072 or 1-888-423-5436, respectively, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Most patients taking THALOMID can be expected to experience adverse reactions. Adverse Reactions in Multiple Myeloma Controlled Clinical Trials The safety analyses were conducted in two controlled clinical studies (Study 1 and Study 2). The safety analysis in Study 1 was conducted on 204 patients who received treatment. Table 1 lists the most common adverse reactions (≥ 10%). The most frequently reported adverse reactions were fatigue, hypocalcemia, edema, constipation, sensory neuropathy, dyspnea, muscle weakness, leukopenia, neutropenia, rash/desquamation, confusion, anorexia, nausea, anxiety/agitation, tremor, fever, weight loss, thrombosis/embolism, neuropathy-motor, weight gain, dizziness, and dry skin. Twenty-three percent of patients (47/204) discontinued due to adverse reactions; 30% (31/102) from the THALOMID/dexamethasone arm and 16% (16/102) from the dexamethasone alone arm. Table 1: Adverse Reactions Reported in ≥10% of Patients in the THALOMID/Dexamethasone Arm (Study 1 - Safety Population; N=204) Body System Adverse Reaction Thal + Dex* (N=102) Dex Alone* (N=102) All Grades n (%) Grade 3/4 n (%) All Grades n (%) Grade 3/4 n (%) * Treatment-emergent adverse reactions reported in ≥10% of patients in THALOMID/dexamethasone arm and with a ≥1% difference in the THALOMID/dexamethasone arm compared to the dexamethasone alone arm. Metabolic/Laboratory 97 (95) 33 (32) 96 (94) 30 (29) Hypocalcemia 73 (72) 11 (11) 60 (59) 5 (5) Neurology 92 (90) 30 (29) 76 (74) 18 (18) Neuropathy-sensory 55 (54) 4 (4) 28 (28) 1 (1) Confusion 29 (28) 9 (9) 12 (12) 3 (3) Anxiety/agitation 26 (26) 1 (1) 14 (14) 3 (3) Tremor 26 (26) 1 (1) 6 (6) 0 (0) Neuropathy-motor 22 (22) 8 (8) 16 (16) 5 (5) Dizziness/ lightheadedness 20 (20) 1 (1) 14 (14) 0 (0) Depressed level of consciousness 16 (16) 3 (3) 3 (3) 3 (3) Constitutional Symptoms 91 (89) 19...Drug Interactions
7 DRUG INTERACTIONS
Use caution if other drugs which have sedative and hypnotic properties, slow cardiac conduction and/or cause peripheral neuropathy must be used. ( 7.1 , 7.2 , 7.3 ) It is not known whether concomitant use of hormonal contraceptives further increases the risk of thromboembolism with THALOMID. ( 5.15 , 7.4 ) Patients taking concomitant therapies such as erythropoietin stimulating agents or estrogen containing therapies may have an increased risk of thromboembolism. ( 7.7 ) 7.1 Opioids, Antihistamines, Antipsychotics, Anti-anxiety Agents, or Other CNS Depressants (Including Alcohol) The use of opioids, antihistamines, antipsychotics, anti-anxiety agents, or other CNS depressants concomitantly with THALOMID may cause an additive sedative effect and should be avoided. 7.2 Drugs which Cause Bradycardia The use of drugs which slow cardiac conduction concomitantly with THALOMID may cause an additive bradycardic effect and should be used with caution. Cardiovascular medications which may cause bradycardia include calcium channel blockers, beta blockers, alpha/beta-adrenergic blockers, and digoxin. Non-cardiac drugs that may cause bradycardia include H2 blockers (e.g., famotidine, cimetidine), lithium, tricyclic antidepressants and neuromuscular blockers (succinylcholine). In 16 healthy men, the pharmacokinetic profile of a single 0.5 mg digoxin dose was similar with and without the coadministration of THALOMID 200 mg/day at steady state levels. The single dose of digoxin had no effect on the pharmacokinetic profile of THALOMID. The safety of long-term concomitant use of THALOMID and digoxin has not been evaluated. 7.3 Drugs which Cause Peripheral Neuropathy The use of drugs which cause peripheral neuropathy (e.g., bortezomib, amiodarone, cisplatin, docetaxel, paclitaxel, vincristine, disulfiram, phenytoin, metronidazole, alcohol) can cause an additive effect and should be used with caution. 7.4 Hormonal Contraceptives Hormonal contraceptives increase the risk of thromboembolism. It is not known whether concomitant use of hormonal contraceptives further increases the risk of thromboembolism with THALOMID. In 10 healthy women, the pharmacokinetic profiles of norethindrone and ethinyl estradiol following administration of a single dose containing 1.0 mg of norethindrone acetate and 75 mcg of ethinyl estradiol were studied. The results were similar with and without coadministration of THALOMID 200 mg/day to steady-state levels. 7.5 Warfarin In 13 healthy men, the pharmacokinetic profile and international normalized ratio (INR) of prothrombin time for warfarin, following a single oral dose of 25 mg, were similar with and without the coadministration of THALOMID 200 mg/day at steady-state levels. The single dose of warfarin had no effect on the pharmacokinetic profile of thalidomide. 7.6 Drugs that Interfere with Hormonal Contraceptives Concomitant use of HIV-protease inhibitors, griseofulvin, modafinil, penicillins, rifampin,...Contraindications
4 CONTRAINDICATIONS
Pregnancy ( Boxed Warning , 4.1 , 5.1 , 5.2 , 8.1 , 17 ) Demonstrated hypersensitivity to the drug or its components ( 4.2 , 5.16 , 6.2 ) 4.1 Pregnancy THALOMID is contraindicated in females who are pregnant. THALOMID can cause fetal harm when administered to a pregnant female [see Boxed Warning , Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . THALOMID is a powerful human teratogen, inducing a high frequency of severe and life-threatening birth defects, even after a single dose [see Boxed Warning ] . Mortality at or shortly after birth has been reported in about 40% of infants. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus. If pregnancy occurs during THALOMID treatment, the drug should be discontinued immediately. 4.2 Hypersensitivity THALOMID is contraindicated in patients who have demonstrated hypersensitivity to the drug or its components [see Warnings and Precautions (5.16) ].Pregnancy and Breastfeeding
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to THALOMID during pregnancy as well as female partners of male patients who are exposed to THALOMID. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to THALOMID to the FDA via the MedWatch program at 1-800-FDA-1088 and to the REMS Call Center at 1-888-423-5436. Risk Summary Based on the mechanism of action [see Clinical Pharmacology (12.1) ] , human and animal data (see Data ) , THALOMID can cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy [see Boxed Warning , Contraindications (4.1) , and Warnings and Precautions (5.1) ] . THALOMID is a human teratogen, inducing a high frequency of severe and life-threatening birth defects such as amelia (absence of limbs), phocomelia (short limbs), hypoplasticity of the bones, absence of bones, external ear abnormalities (including anotia, micropinna, small or absent external auditory canals), facial palsy, eye abnormalities (anophthalmos, microphthalmos), and congenital heart defects. Alimentary tract, urinary tract, and genital malformations have also been documented and mortality at or shortly after birth has been reported in about 40% of infants. Even a single dose taken by a pregnant woman can cause birth defects. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus. If pregnancy does occur during treatment, immediately discontinue the drug. Under these conditions, refer the patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to THALOMID to the FDA via the MedWatch program at 1-800-FDA-1088 and also the REMS Call Center at 1-888-423-5436. Thalidomide crossed the placenta...
Overdosage
10 OVERDOSAGE There is no specific antidote for a THALOMID overdose. In the event of an overdose, the patient's vital signs should be monitored and appropriate supportive care given to maintain blood pressure and respiratory status.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING (THIS PRODUCT IS ONLY SUPPLIED TO PHARMACIES CERTIFIED IN THE THALOMID REMS PROGRAM - See BOXED WARNING ) 16.1 How Supplied 50 mg capsules [white opaque], imprinted "BMS/50 mg" with a "Do Not Get Pregnant" logo. Individual blister packs of 1 capsule (NDC 59572-205-17). Individual blister packs of 28 capsules (NDC 59572-205-14). 100 mg capsules [tan], imprinted "BMS/100 mg" with a "Do Not Get Pregnant" logo. Individual blister packs of 28 capsules (NDC 59572-210-15). 150 mg capsules [tan and blue], imprinted "BMS/150 mg" with a "Do Not Get Pregnant" logo. Individual blister packs of 28 capsules (NDC 59572-215-13). 200 mg capsules [blue], imprinted "BMS/200 mg" with a "Do Not Get Pregnant" logo. Individual blister packs of 28 capsules (NDC 59572-220-16). 16.2 Storage This drug must not be repackaged. Store at 20°C- 25°C (68°F -77°F); excursions permitted to 15-30º C (59-86º F). [See USP Controlled Room Temperature]. Protect from light. 16.3 Handling and Disposal Care should be exercised in handling of THALOMID. THALOMID capsules should not be opened or crushed. If powder from THALOMID contacts the skin, wash the skin immediately and thoroughly with soap and water. If THALOMID contacts the mucous membranes, flush thoroughly with water. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on the subject have been published 1 . Rx only and only able to be prescribed and dispensed under the terms of the THALOMID REMS Restricted Distribution Program.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.