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Capecitabine

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Capecitabine, Xeloda

  • See Also
  1. Chemotherapy
  2. Antimetabolite Chemotherapy
  • Indications
  1. Adjuvant Chemotherapy (FDA approved)
    1. Colorectal Cancer (including metastatic cancer)
    2. Metastatic Breast Cancer
  2. Off-Label Use (non-FDA approved)
    1. Gastrointestinal Cancer (Gastric Cancer, Esophageal Cancer, Pancreatic Cancer, Hepatobiliary cancer, anal cancer)
    2. Gynecologic Cancer (Ovarian Cancer, Fallopian tube cancer, peritoneal cancer)
    3. Neuroendocrine Tumors
  • Contraindications
  1. Creatinine Clearance <30 ml/min
  • Mechanism
  1. Antimetabolite Chemotherapy (Antineoplastic Agent)
  2. Fluoropyrimidine Carbamate, acts as a prodrug
    1. Selectively activated by tumor cells to 5-Fluorouracil (5-FU)
  3. 5-Fluorouracil (5-FU) is further metabolized by normal cells and tumor cells to 2 active agents
    1. 5-fluoro-2-deoxyuridine monophosphate (FdUMP)
      1. Decreases thymidine synthesis
      2. Inhibits DNA synthesis and cell division
    2. 5-fluorouridine triphosphate (FUTP)
      1. Competes with Uridine Triphosphate for incorporation into RNA
      2. Inhibits RNA and Protein synthesis
  • Dosing
  1. See other references for disease specific dosing protocols
  • Adverse Effects
  1. Cardiovascular (cardiac toxicity, esp in Overdose)
    1. Arrhythmia
    2. Cardiomyopathy
    3. Myocardial Infarction
  2. Endo
    1. Impaired future fertility
  3. Gastrointestinal
    1. Mucositis
    2. Severe Diarrhea
    3. Hyperbilirubinemia
    4. Typhlitis (RLQ Pain in neutropenic patients)
  4. Hematologic
    1. Myelosuppression (peaks at 1 week after dose)
      1. Neutropenia
      2. Anemia
      3. Leukopenia
  5. Neuro
    1. Headache
    2. Palmar-Plantar erythrodysesthesia (sensory Neuropathy)
    3. Encephalopathy
  6. Skin
    1. Acral swelling and erythema (hand and foot syndrome)
    2. Alopecia
  • Pharmacokinetics
  1. Oral Bioavailability: 40 to 60%
  2. Peak serum concentration: 2 hours
  3. Catabolized by dihydropyrimidine dehydrogenase (DPD) into inactive metabolite
    1. Variable metabolism in DPD deficiency
  4. Inactive metabolite excreted in the urine
  • Safety
  1. Avoid in Pregnancy (any trimester)
    1. Use reliable Contraception
  2. Avoid in Lactation
  3. Monitoring
    1. Complete Blood Count
  • Drug Interactions
  1. Capecitabine increases level of other drugs
    1. Phenytoin (Dilantin)
    2. Warfarin
      1. Raises INR
  2. Antacids
    1. Increase Capecitabine levels
  3. Allopurinol
    1. Avoid with Capecitabine
  1. Evaluation
    1. Complete Blood Count (repeated several days after dose)
    2. Comprehensive metabolic panel
    3. Consider serum Troponin
    4. Electrocardiogram (EKG)
  2. Acute ingestion
    1. Consider Activated Charcoal
      1. Indicated if <1 hour after ingestion and intact mentation
    2. Consider Uridine Triacetate 10 g
      1. Indicated in severe toxicity or acute Overdose >2 g
  3. Other supportive measures
    1. Intravenous Fluids
    2. Granulocyte colony stimulation factors if significant myelosuppression
  4. Disposition
    1. Patients with mild gastrointestinal symptoms after therapeutic dose may be discharged
    2. Observe patients with severe symptoms or intentional Overdose
  • Resources
  1. Capecitabine Tablet (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a1de8bba-3b1d-4c9d-ab8a-32d2c05e67c8
  • References
  1. Tomaszewski (2024) Crit Dec Emerg Med 38(2): 34