What is thalidomide (generic name) used for and what are its potential side effects, particularly in women of childbearing age?

Thalidomide: Clinical Uses and Critical Safety Considerations

Thalidomide is a potent immunomodulatory agent with established efficacy in multiple myeloma and erythema nodosum leprosum, but its use is severely restricted due to devastating teratogenicity causing limb malformations and other birth defects, along with significant risks of peripheral neuropathy and venous thromboembolism. 1

Primary Approved Indications

Thalidomide has FDA approval for:

• Multiple myeloma (in combination with dexamethasone) 1
• Erythema nodosum leprosum (ENL) - a complication of leprosy 2

The drug exerts therapeutic effects through modulation of tumor necrosis factor-alpha (TNF-α), immunomodulatory properties, and anti-angiogenic activity 2, 3

Investigational Uses with Evidence

Refractory Crohn's Disease (Pediatric)

The Journal of Crohn's and Colitis guidelines describe thalidomide as a potential option for highly selected pediatric patients who have failed anti-TNF therapy 4:

• Clinical remission achieved in 46.4% vs 11.5% placebo in a controlled trial (1.5-2.5 mg/kg/day for 8 weeks) 4
• Open-label studies showed 63-75% remission rates in refractory cases 4
• Dosing: Start 50 mg daily in adolescents (2 mg/kg in younger children), increase based on response 4
• Reserved only for patients who cannot tolerate or lost response to biologics 4

Idiopathic Pulmonary Fibrosis (IPF) with Chronic Cough

The CHEST guidelines evaluated thalidomide for refractory cough in IPF 4:

• Significant improvement in cough quality of life (11.37-point decrease, P<0.001) and cough severity (31.2 mm VAS decrease, P<0.001) 4
• Dosing: 50 mg daily, escalating to 100 mg if no improvement after 2 weeks 4
• The recommendation failed to pass guideline approval (only 67% panel agreement vs 80% required) due to concerns about side effects and limited evidence 4

Critical Safety Profile

Teratogenicity - Absolute Contraindication in Pregnancy

Thalidomide is one of the most potent human teratogens known, causing severe birth defects including 5, 1:

• Phocomelia (shortened limbs) and amelia (absent limbs)
• Cardiac defects (interventricular septal defects)
• Facial abnormalities (absent external ear canals, eye malformations)
• Internal organ malformations (urinary, gastrointestinal, genital tracts)
• Mortality in approximately 40% of affected infants 1

Critical period: Days 20-36 after conception during limb development 5

Mandatory REMS Program Requirements

Due to teratogenic risk, thalidomide is only available through restricted distribution 1:

For women of childbearing potential:

• Two negative pregnancy tests before starting (10-14 days apart, second within 24 hours of first dose) 1
• Pregnancy testing weekly for first month, then monthly (or every 2 weeks if irregular cycles) 1
• Two forms of contraception starting 4 weeks before therapy, during treatment, and continuing 4 weeks after discontinuation 1
• Absolute abstinence from heterosexual intercourse is the only alternative 1

For male patients:

• Must use latex/synthetic condom during any sexual contact with women of reproductive potential 1
• Contraception required during therapy and for 4 weeks after discontinuation 1
• Cannot donate sperm 1

All patients:

• Cannot donate blood during treatment and for 4 weeks after 1

Peripheral Neuropathy

Occurs in 25-42% of pediatric patients and 10.4% of adults (Grade 3-4) 4, 6:

• May be irreversible, especially with high cumulative doses 6, 7
• Presents as tingling, paresthesia, numbness 6

Monitoring protocol 4, 6, 7:

• Baseline neurological examination with vibration sensitivity testing before initiation
• Repeat examination every 6 months during therapy
• Immediate discontinuation if neuropathy develops

Venous Thromboembolism (VTE)

Grade 3-4 VTE occurs in 15.3% when combined with dexamethasone 6:

• Risk ranges 17-28% when combined with chemotherapy or corticosteroids 7

Mandatory prophylaxis 6:

• The National Comprehensive Cancer Network requires prophylactic anticoagulation when thalidomide is combined with dexamethasone 6
• Low-molecular-weight heparin is superior to warfarin or aspirin 6
• Initiate anticoagulation immediately when starting therapy 6

Contraindications to anticoagulation 7:

• Active uncontrollable bleeding
• Cerebrovascular hemorrhage
• Severe peptic ulceration
• Bacterial endocarditis

Other Common Adverse Effects

Most frequent (77% of patients experience side effects) 4:

• Constipation (managed with docusate sodium) 4
• Dizziness
• Malaise
• Somnolence 2

Clinical Decision Algorithm

Use thalidomide ONLY when:

1. Patient has failed standard therapies (anti-TNF agents in Crohn's disease, antitussives in IPF)
2. Pregnancy is absolutely excluded (women) or prevented (mandatory contraception)
3. Baseline neurological examination is normal
4. VTE prophylaxis can be safely administered (if using with dexamethasone/chemotherapy)
5. Patient enrolled in REMS program with documented counseling

Avoid thalidomide in:

• Any woman who cannot comply with strict contraception requirements 1
• Patients with pre-existing peripheral neuropathy 7
• Recent cardiovascular events (within 6-12 months) 7
• Contraindications to anticoagulation when combination therapy planned 7

Common Pitfalls

• Underestimating teratogenic risk: Even a single dose during the critical 20-36 day window can cause severe malformations 5
• Inadequate contraception counseling: Male patients often not informed that drug is present in semen 1
• Missing early neuropathy: Symptoms may be subtle initially but can become irreversible 6, 7
• Omitting VTE prophylaxis: Mandatory when combined with dexamethasone or chemotherapy 6
• Prescribing outside REMS program: Illegal and exposes patients to unmonitored risks 1