Capecitabine Precautions: Essential Safety Measures
When taking capecitabine (Xeloda), patients must be monitored by a physician experienced in cancer chemotherapy as most adverse events require dose modifications rather than discontinuation. 1
Key Precautions
Hand-and-Foot Syndrome
- Hand-and-foot syndrome (palmar-plantar erythrodysesthesia) is the most common dose-limiting toxicity with capecitabine, occurring more frequently than with IV 5-FU 2
- Median time to onset is 79 days (range 11-360 days) 1
- Severity ranges from grade 1 (numbness, tingling, painless swelling) to grade 3 (moist desquamation, ulceration, severe pain) 1
- If grade 2-3 occurs, interrupt treatment until resolved or decreased to grade 1 1
- Following grade 3 hand-foot syndrome, subsequent doses should be decreased according to dose modification guidelines 1
Cardiotoxicity
- Monitor for myocardial infarction, angina, dysrhythmias, cardiac arrest, cardiac failure, and electrocardiographic changes 1
- Patients with prior history of coronary artery disease are at higher risk 1
Dihydropyrimidine Dehydrogenase (DPD) Deficiency
- Patients with DPD deficiency may experience unexpected, severe toxicity (stomatitis, diarrhea, neutropenia, neurotoxicity) 1
- Consider testing for DPD deficiency in patients with severe toxicity 1
Hepatic Dysfunction
- Carefully monitor patients with mild to moderate hepatic dysfunction due to liver metastases 1
- The effect of severe hepatic dysfunction on capecitabine disposition is unknown 1
Hyperbilirubinemia
- Grade 3-4 hyperbilirubinemia occurs in 19.1% of patients 1
- Higher risk in patients with hepatic metastases (22.8% vs 12.3% in those without) 1
- Monitor liver function tests regularly 1
Dosing and Administration
Standard Dosing
- Recommended dose: 1250 mg/m² twice daily (morning and evening) for 14 days followed by 7-day rest period, given as 3-week cycles 1
- Take within 30 minutes after a meal with water 1
Dose Modifications
- Toxicity management may require dose interruptions and adjustments 1
- Once dose is reduced, it should not be increased later 1
- For grade 2 events: interrupt until resolved to grade 0-1, then resume at 100% of original dose 1
- For grade 3 events: interrupt until resolved to grade 0-1, then resume at 75% of original dose 1
- For grade 4 events: discontinue permanently or interrupt until resolved to grade 0-1, then resume at 50% of original dose 1
Special Populations
- Renal impairment:
- Hepatic impairment:
Drug Interactions
- May increase serum phenytoin levels - monitor and adjust phenytoin dose as needed 1
- May increase INR in patients on warfarin - monitor coagulation parameters frequently 1
- Reduce dose of coumarin-derivative anticoagulants when administered concomitantly 1
Alternative Dosing Considerations
- North American patients may experience greater toxicity than European patients and may require lower starting doses (850-1000 mg/m² twice daily) 3
- Fixed-dose regimens (1500 mg twice daily for 7 days on/7 days off) have shown similar efficacy with less toxicity compared to body surface area-based dosing in some studies 4, 5
- Continuous fixed daily dosing (1500-2000 mg/day without cycling) has shown lower toxicity profiles in some patients 5
Patient Education
- Patients must be educated on proper administration and recognition of adverse events since capecitabine is taken in the outpatient setting 2
- Emphasize that temporary interruptions/dose modifications do not reduce overall efficacy but will help resolve side effects 2
- Instruct patients to report symptoms of hand-foot syndrome, diarrhea, or stomatitis promptly 1
Monitoring Recommendations
- Regular assessment for hand-foot syndrome, diarrhea, and stomatitis 1
- Monitor liver function tests for hyperbilirubinemia 1
- Cardiac monitoring in patients with history of coronary artery disease 1
- INR monitoring in patients on anticoagulants 1
By following these precautions, the safety profile of capecitabine can be optimized while maintaining therapeutic efficacy.