Capecitabine

🔴 Red Flag (Important) Information — Capecitabine (Xeloda)

• Severe diarrhoea and dehydration:

  • Common dose-limiting toxicity; may be life-threatening.

  • Stop treatment immediately for grade ≥2 diarrhoea or dehydration and rehydrate aggressively.

• Hand–Foot Syndrome (Palmar–Plantar Erythrodysaesthesia):

  • Common and may be dose-limiting.

  • Interrupt therapy for grade ≥2; resume at reduced dose once improved.

• Cardiotoxicity:

  • Risk of angina, arrhythmia, myocardial infarction, or heart failure.

  • Use with caution in patients with cardiac history or on cardiotoxic drugs.

• Dihydropyrimidine Dehydrogenase (DPD) deficiency:

  • Contraindicated in known complete DPD deficiency (can cause fatal toxicity).

  • Consider DPD testing before initiation.

• Severe renal impairment:

  • Contraindicated if CrCl <30 mL/min.

  • Dose reduction required if CrCl 30–50 mL/min.

• Drug interactions:

  • Warfarin: ↑ INR and bleeding risk — monitor INR frequently.

  • Phenytoin: ↑ plasma concentration — monitor levels.

  • Leucovorin (folinic acid): ↑ toxicity risk.

• Pregnancy:

  • Contraindicated; teratogenic.

  • Use contraception during and 6 months after treatment.

🔹 1. Basic Information

Generic name: Capecitabine
Brand name: Xeloda
Drug class: Oral fluoropyrimidine (prodrug of 5-fluorouracil)
Formulation: Film-coated oral tablets
Strengths: 150 mg, 500 mg
Mechanism of Action:
Converted in tumour tissue to 5-fluorouracil (5-FU) via thymidine phosphorylase → interferes with DNA synthesis → tumour cell death.

🔹 2. Indications

• Colorectal cancer:

  • Adjuvant treatment of stage III (Dukes’ C) colon cancer.

  • First-line treatment of metastatic colorectal cancer.

• Breast cancer:

  • In combination with docetaxel after failure of anthracycline-based therapy.

  • Monotherapy in patients resistant to both paclitaxel and anthracyclines.

  • Adjuvant chemotherapy in HER2-negative breast cancer (ideal in TNBC), following initial neo-adjuvant chemotherapy, surgery, and with the patient having residual disease (See Create-X Trial) 

• Gastric cancer:

  • In combination regimens for advanced or metastatic disease.

🔹 3. Dosing & Administration

Monotherapy:

• 1250 mg/m² twice daily (morning and evening) for 14 days, followed by 7 days rest → 21-day cycle.

Combination therapy:

• 800–1000 mg/m² twice daily for 14 days every 21-day cycle (dose adjusted to regimen).

Administration:

• Oral; take within 30 minutes after a meal.

• Swallow tablets whole with water.

• Dose calculation based on body surface area (BSA).

Renal impairment:

• CrCl 30–50 mL/min → reduce starting dose by 25%.

• CrCl <30 mL/min → contraindicated.

Hepatic impairment:

• Mild–moderate → use with caution.

• Severe → avoid.

🔹 4. Dose Modifications

• Haematological toxicity (neutropenia, thrombocytopenia):

  • Withhold until recovery to ≤Grade 1.

• Non-haematological toxicity (e.g. diarrhoea, mucositis, PPE, hyperbilirubinaemia):

  • Grade 2 → Interrupt until recovery, resume at 75% dose.

  • Grade 3 → Interrupt until recovery, resume at 50% dose.

  • Grade 4 → Permanently discontinue.

🔹 5. Co-medications

• Often combined with oxaliplatin, cisplatin, or docetaxel in combination regimens.

• Avoid concomitant use with sorivudine or brivudine (fatal interaction via DPD inhibition).

• Caution with warfarin, phenytoin, folinic acid, and allopurinol (reduces efficacy).

🔹 6. Contraindications

• Hypersensitivity to capecitabine, 5-FU, or excipients.

• Severe renal impairment (CrCl <30 mL/min).

• Known DPD enzyme deficiency.

• Pregnancy or breastfeeding.

• Co-administration with brivudine, sorivudine, or analogues.

🔹 7. Monitoring Requirements

• Baseline and ongoing:

  • FBC (neutrophils, platelets).

  • Renal and hepatic function.

  • INR (if on warfarin).

  • Cardiac monitoring if prior cardiac disease.

• At each visit:

  • Diarrhoea, mucositis, hand–foot syndrome, dehydration.

🔹 8. Side Effects & Management

🔹 9. Use in Special Populations

• Renal impairment: Dose adjust or avoid if CrCl <30 mL/min.

• Hepatic impairment: Caution in mild–moderate; avoid in severe.

• Elderly: Increased sensitivity to toxicity; close monitoring.

• Pregnancy/Lactation: Contraindicated.

• DPD deficiency: Contraindicated (risk of fatal toxicity).

🔹 10. Duration of Use / When to Stop the Drug

Continue until:

• Planned cycle completion or

• Disease progression or unacceptable toxicity.

Permanently discontinue if:

• Grade 4 or recurrent grade ≥3 toxicity.

• Life-threatening diarrhoea, mucositis, or myelosuppression.

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2024/11/pi_capecitabine.pdf