What are the contraindications for thalidomide (Thalidomide)?

Thalidomide Contraindications

Thalidomide is absolutely contraindicated in pregnancy due to its severe teratogenic effects, causing life-threatening birth defects in up to 40% of exposed fetuses, and requires mandatory enrollment in a restricted distribution program (REMS) with strict contraception and pregnancy testing requirements. 1

Absolute Contraindications

Pregnancy

• Thalidomide causes severe and life-threatening birth defects including phocomelia (absent or shortened limbs), amelia (complete absence of limbs), facial abnormalities, cardiac defects, and mortality in approximately 40% of affected infants. 1
• The drug is contraindicated during pregnancy and for females of reproductive potential who cannot comply with mandatory contraception requirements. 1
• Fetal exposure must be reported immediately to FDA MedWatch (1-800-FDA-1088) and the REMS Call Center (1-888-423-5436). 1

Inability to Comply with REMS Program Requirements

• Patients who cannot participate in the mandatory POMALYST/Thalidomide REMS program are contraindicated from receiving thalidomide. 1
• This includes patients unable to use two forms of reliable contraception, undergo mandatory pregnancy testing, or comply with restricted distribution requirements. 1

Mandatory Risk Mitigation Requirements (Not Contraindications, But Essential)

For Females of Reproductive Potential

• Two negative pregnancy tests required before initiation: first within 10-14 days, second within 24 hours of prescribing. 1
• Weekly pregnancy testing during the first month, then monthly with regular cycles or every 2 weeks with irregular cycles. 1
• Mandatory use of two reliable contraception methods beginning 4 weeks before therapy, during treatment, during dose interruptions, and for 4 weeks after discontinuation. 1
• Absolute abstinence from heterosexual intercourse is the only alternative to dual contraception. 1

For Males

• Males must use latex or synthetic condoms during any sexual contact with females of reproductive potential while taking thalidomide and for 4 weeks after discontinuation, even after vasectomy. 1
• Pomalidomide (thalidomide analogue) is present in semen of treated patients. 1
• Males cannot donate sperm during treatment and for 4 weeks after discontinuation. 1

For All Patients

• Blood donation is prohibited during treatment and for 4 weeks following discontinuation to prevent transfusion to pregnant females. 1

Relative Contraindications and High-Risk Situations

Active or High Bleeding Risk

• Thalidomide should not be used as monotherapy for VTE prophylaxis in patients with active bleeding or high bleeding risk. 2
• Anticoagulation (required with thalidomide/dexamethasone combinations) is relatively contraindicated in active uncontrollable bleeding, cerebrovascular hemorrhage, severe peptic ulceration, and bacterial endocarditis. 2

Recent Cardiovascular Events

• While not an absolute contraindication, thalidomide should be used with extreme caution or avoided in patients with cardiovascular events in the preceding 6-12 months due to thromboembolism risk. 2
• The risk of venous thromboembolism ranges from 17-28% when thalidomide is combined with dexamethasone or chemotherapy. 2

Pre-existing Peripheral Neuropathy

• Peripheral neuropathy may be irreversible, especially after high cumulative doses, occurring in 25-42% of pediatric patients in clinical studies. 2
• The Annals of the Rheumatic Diseases guideline states that the toxicity profile of thalidomide, particularly severe birth defects and potentially irreversible peripheral neuropathies, outweighs therapeutic benefit in many conditions. 2
• Baseline neurological assessment with vibration sensitivity testing is mandatory before initiation, with 6-monthly monitoring thereafter. 2, 3

Clinical Context and Pitfalls

Common Prescribing Errors to Avoid

• Never prescribe thalidomide without confirming REMS enrollment for prescriber, pharmacy, and patient. 1
• Do not assume vasectomy eliminates the need for condom use in males—condoms are still mandatory. 1
• The 100-mg dose historically used as a sleep aid was found equivalent to placebo for hypnotic effects while maintaining full teratogenic risk. 4

Drug Interactions Requiring Caution

• Strong CYP1A2 inhibitors (ciprofloxacin, fluvoxamine) increase thalidomide exposure by 125% and should be avoided or require dose reduction. 1

Mandatory Prophylactic Anticoagulation

• Low-molecular-weight heparin is superior to warfarin or aspirin for DVT prophylaxis and should be initiated immediately when starting thalidomide with dexamethasone. 3
• Grade 3-4 venous thromboembolism occurs in 15.3% of patients receiving thalidomide/dexamethasone without adequate prophylaxis. 3