Thalidomide Oral capsule

Teratogenic Effects
• Known human teratogen; extremely high risk of severe, life-threatening birth defects if administered during pregnancy. Single dose (regardless of dosage strength) can cause teratogenic effects.
• Major human fetal abnormalities include skeletal deformities (e.g., amelia [absence of legs and/or arms], absence of bones, phocomelia [short legs and/or arms], bone hypoplasia); external ear deformities (e.g., anotia, microtia or micro pinna, small or absent auditory canals); facial palsy; ocular abnormalities (e.g., anophthalmos and microphthalmos); congenital heart defects; renal and urinary tract malformations; genital malformations; and GI tract malformations.
• Mortality rate at or shortly after birth in neonates with thalidomide-induced abnormalities about 40%.

Teratogenicity Precautions
• Contraindicated in pregnant women; use in females of childbearing potential only when alternative therapies considered inappropriate.
• Pregnancy must be excluded by negative pregnancy test (sensitivity to detect human serum chorionic gonadotropin [HCG] concentrations of 50 million IU/mL) ≤24 hours before treatment initiation. Repeat pregnancy tests throughout therapy (i.e., once weekly during first month, then monthly or every 2 weeks in women with regular or irregular menstrual cycles, respectively).
• Pregnancy must be prevented (even in females with a history of infertility) by simultaneous use of 2 forms of reliable contraception for ≥4 weeks prior to, throughout, and for 4 weeks after completion of therapy. (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Mandatory contraception not required for females who have undergone hysterectomy, are postmenopausal and have had no menses for ≥24 consecutive months, or practice continuous abstinence from heterosexual contact.
• Sexually mature males (including successfully vasectomized men) must completely avoid unprotected sexual contact with women of childbearing potential (i.e., use latex condom throughout and for ≥4 weeks after thalidomide therapy) because thalidomide distributes into semen.
• Provide pregnancy tests and counseling if a patient misses her period or has abnormalities in menstrual bleeding.
• If pregnancy occurs, immediately discontinue treatment. Refer patient to obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to FDA MedWatch Program at 1-800-FDA-1088 and to manufacturer at 1-888-423-5436.

Restricted Distribution Program
• Available only through restricted distribution program, the System for Thalidomide Education and Prescribing Safety (STEPS), designed to help ensure that fetal exposure does not occur. (See Restricted Distribution under Dosage and Administration.)
• Limits access to thalidomide to prescribing clinicians, pharmacies, and patients who are registered in program and mandates compliance with registration, education, and safety requirements.
• Registered prescribing clinicians must understand risks of teratogenicity if used during pregnancy and must not provide a prescription until a documented negative pregnancy test available.
• Patient or parent/legal guardian (for minors 12–18 years of age) must be capable of understanding and complying with patient registration, education, patient survey, and safety requirements, including mandatory contraceptive measures and pregnancy testing.
• Provide oral and written warnings of risk of possible contraceptive failure, hazards of using drug during pregnancy, exposing fetus to drug, and presence of drug in semen.
• Patient or parent/legal guardian must provide written acknowledgment of understanding of these warnings and need for mandatory contraceptive measures.

Venous Thromboembolism
• Increased risk of venous thromboembolism (e.g., DVT, pulmonary embolism) in patients with multiple myeloma, especially when used in combination with chemotherapy, including dexamethasone.
• Monitor for signs and symptoms of thromboembolism.
• In selected patients, anticoagulation or aspirin may be beneficial.

REMS:

FDA approved a REMS for thalidomide to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of thalidomide and consists of the following: medication guide, elements to assure safe use, and implementation system. See the FDA REMS page ([Web]) or the ASHP REMS Resource Center ([Web]).