What are the side effects of Xeloda (capecitabine) and how are they managed?

Capecitabine (Xeloda) Side Effects and Management

The most common side effects of capecitabine include hand-foot syndrome (affecting up to 73% of patients), diarrhea, nausea, vomiting, stomatitis, abdominal pain, constipation, loss of appetite, and dehydration, with hand-foot syndrome being the most characteristic adverse effect requiring careful monitoring and management. 1, 2

Common Side Effects and Their Incidence

Dermatologic Effects

• Hand-foot syndrome (palmar-plantar erythrodysesthesia): Most characteristic side effect, affecting up to 73% of patients with 11% experiencing grade 3 events 1
• Skin rash, dry or itchy skin, and nail problems 2
• Hair loss (less common than with other chemotherapies) 2

Gastrointestinal Effects

• Diarrhea: One of the most frequent side effects (62.5% of patients) 3
• Nausea (82.7% of patients) and vomiting (54.8%) 3
• Stomatitis (mouth sores) 2
• Abdominal pain and constipation 2
• Loss of appetite 2

Hematologic Effects

• Thrombocytopenia (especially when combined with other agents) 1
• Lymphopenia and anemia 4

Other Effects

• Fatigue and weakness (54.8% of patients) 3
• Dizziness and headache 2
• Fever 2
• Taste problems 2

Management of Side Effects

Hand-Foot Syndrome

• For grade 1: Continue treatment with close monitoring 1
• For grade 2: Interrupt treatment until resolved to grade 0-1, then resume at same dose 2
• For grade 3: Interrupt treatment until resolved to grade 0-1, then resume at 75% of original dose 2
• For grade 4: Discontinue treatment unless physician considers it in patient's best interest to continue at 50% of original dose 2
• Supportive measures include topical emollients and creams; pyridoxine and COX-2 inhibitors show promise but need further study 5

Diarrhea

• For mild diarrhea: Loperamide 4 mg four times daily 6
• For persistent diarrhea (>1 week): Treat as grade 2 diarrhea 6
• For severe diarrhea: Loperamide every 2 hours; if no improvement after 24-48 hours, consider octreotide 100 μg three times daily 6
• For grade 3-4 diarrhea with neutropenia, fever, reduced oral intake, or other concerning symptoms: Immediate hospitalization may be required 6

Nausea and Vomiting

• Stop taking capecitabine and contact doctor if vomiting more than once in 24 hours 2
• For moderate emetogenic chemotherapy regimens: 5-HT-receptor antagonist (preferably palonosetron) + dexamethasone 8 mg on day 1, followed by dexamethasone 8 mg on days 2-3 6

Stomatitis

• Stop taking capecitabine and contact doctor if you have pain, redness, swelling or sores in your mouth 2
• Symptomatic treatment and dose interruption/reduction as needed 2

Dose Modifications

• Dose interruption or reduction is the most effective way to manage toxicities without compromising overall efficacy 7
• For most grade 2 toxicities: Interrupt treatment until resolved to grade 0-1, then resume at same dose 2
• For grade 3 toxicities: Interrupt treatment until resolved to grade 0-1, then resume at 75% of original dose 2
• For grade 4 toxicities: Discontinue treatment unless physician determines continuing at reduced dose is beneficial 2
• Patients over 65 years have higher risk of severe toxicity (34% grade 3 or higher) 1
• Patients with renal insufficiency require dose adjustment since elimination is primarily renal 1

Special Considerations

Drug Interactions

• May increase the effect of blood thinners such as warfarin, requiring more frequent monitoring of clotting times and possible dose adjustments 2
• May interact with phenytoin (Dilantin), requiring more frequent monitoring of phenytoin levels 2

High-Risk Populations

• Patients over 65 years have higher risk of severe toxicity 1
• Patients with renal insufficiency require dose adjustment 1
• Patients lacking the enzyme DPD (dihydropyrimidine dehydrogenase) should not take capecitabine 2

Patient Education and Monitoring

• Patients should be educated on proper administration: take within 30 minutes after meals, twice daily 2
• Patients should be instructed to report side effects promptly, especially diarrhea, vomiting, stomatitis, hand-foot syndrome, fever or infection 2
• Temporary interruptions or dose modifications do not reduce overall efficacy and will likely resolve side effects 7
• Patients should be monitored for toxicity, with dose adjustments made as necessary to accommodate individual tolerance 2

Common Pitfalls and Caveats

• Failure to recognize early signs of hand-foot syndrome can lead to progression to more severe grades requiring treatment interruption 5
• Delayed management of diarrhea can lead to dehydration and electrolyte imbalances 6
• Patients may not report side effects if not properly educated about their importance 7
• Capecitabine/5FU-induced enterocolitis is a rare but potentially serious complication that should be considered in patients with severe symptoms 6
• Patients with partial or complete DPD deficiency (3-5% of population) may experience potentially life-threatening toxicity 6