Indications
Pharmacology
- Prodrug of Fluorouracil: hydrolyzed in the liver to form fluorouracil, which is the active compound (see 5-Fluorouracil, 5-Fluorouracil)
- 5-Fluorouracil is a Fluorinated Pyrimidine Antimetabolite Which Inhibits Thymidylate Synthetase: blocks the methylation of deoxyuridylic acid to thymidylic acid, interfering with DNA synthesis (and to a lesser extent, RNA synthesis)
- 5-Fluorouracil appears to be phase-specific for the G1 and S phases of the cell cycle
Metabolism
- Hepatic: to inactive metabolites 5′-deoxy-5-fluorocytidine and 5′-deoxy-5-fluorouridine
- Tissue: enzymatically metabolized to fluorouracil –> this is then metabolized to the active metabolites, 5-fluoxyuridine monophosphate (F-UMP) and 5-5-fluoro-2′-deoxyuridine-5′-O-monophosphate (F-dUMP)
- Elimination Half-Life: 0.75 hr
Administration
Dose Adjustment
- Hepatic
- Mild-Moderate Impairment: no dose adjustment necessary
- Severe Impairment: has not been studied
- Renal
- CrCl >51 mL/min: no dose adjustment necessary
- CrCl 30-50 mL/min: administer 75% of usual dose
- CrCl <30 mL/min: use is contraindicated
Drug Interactions
- Coumadin (see Coumadin, Coumadin): capecitabine may increased effects of coumadin
- Effects may continue for up to 1 mo after capecitabine discontinuation
- May occur in patients with/without liver metastases
Adverse Effects
Cardiovascular Adverse Effects
Cardiotoxicity
Dermatologic Adverse Effects
- Epidemiology
- Incidence: 54-60% of cases (however, grade at least 3 occurs in only 11-17% of cases)
- Median Onset: 79 days
- Clinical
- Desquamation/Blistering
- Dysesthesia/Parasthesias
- Erythema
- Numbness
- Painless/Painful Edema
- Severe Pain
Dermatitis
- Epidemiology: occurs in 27-37% of cases
- Epidemiology: fatal cases have been reported
Gastrointestinal Adverse Effects
- Epidemiology: may occur
- Clinical
- Elevated Alkaline Phosphatase
- Hyperbilirubinemia
- Transaminitis
- Epidemiology: has been reported
- Epidemiology: occurs in 34-43% of cases
Necrotizing Enterocolitis/Typhlitis (see Typhlitis, Typhlitis)
- Epidemiology: has been reported
Hematologic Adverse Effects
Myelosuppression
Rheumatologic Adverse Effects
- Epidemiology: occurs in <15% of cases
Other Adverse Effects
- Epidemiology: occurs in 7-18% of cases
References
- Ileitis secondary to oral capecitabine treatment? Case Rep Med. 2012;2012:154981 [MEDLINE]