Article: Capecitabine

Capecitabine
Systematic (IUPAC) name
pentyl[1-(3,4-dihydroxy-5-methyl-tetrahydrofuran-2-yl)- 5-fluoro-2-oxo-1H-pyrimidin- 4-yl]aminomethanoate
Identifiers
CAS number	154361-50-9
ATC code	L01BC06
PubChem	60953
DrugBank	APRD00203
Chemical data
Formula	C15H22FN3O6
Mol. weight	359.35 g/mol
Pharmacokinetic data
Bioavailability	Extensive
Protein binding	< 60%
Metabolism	Tissue metabolism to fluorouracil (active metabolite); hepatic metabolism to inactive metabolites
Half life	0.75 hours
Excretion	Urine
Therapeutic considerations
Pregnancy cat.	D
Legal status
Routes	orally with water, within 30 minutes after a meal.

Capecitabine (brand name: Xeloda®) is an orally-administered chemotherapeutic agent used in the treatment of metastatic breast and colorectal cancers. It is enzymatically converted to fluorouracil in the body, where it inhibits DNA synthesis and slows growth of tumor tissue.

Indications

Capecitabine is FDA-approved for:

• Metastatic Colorectal Cancer - used as first-line monotherapy, if appropriate.
• Metastatic Breast Cancer - used in combination with docetaxel, after failure of anthracycline-based treatment. Also as monotherapy, if the patient has failed paclitaxel-based treatment, and if anthracycline-based treatment has either failed or cannot be continued for other reasons (i.e., the patient has already received the maximum lifetime dose of an anthracycline).

Dose

The usual starting dose is 2,500 mg/m2/day in two divided doses, 12 hours apart. One cycle includes two weeks of treatment followed by one week without treatment. Cycles can be repeated every three weeks.

Dose Adjustments

• For mild renal dysfunction (creatinine clearance 30-50 mL/min), it is recommended to reduce dose by 25%.
• For severe renal dysfunction (creatinine clearance <30 mL/min), treatment is not recommended.
• There is no recommendation for hepatic dysfunction.
• For elderly patients, lower doses may be required due to higher incidences of serious adverse reactions.

Side effects

Potential major adverse reactions include:

• Cardiovascular: EKG changes, myocardial infarction, angina (these may be more common in patients with pre-existing coronary artery disease)
• Dermatological: Hand-foot syndrome (numbness, tingling, pain, redness, or blistering of the palms of the hands and soles of the feet)
• Gastrointestinal: Diarrhea (sometimes severe), nausea, stomatitis
• Hematological: Neutropenia, anemia, thrombocytopenia
• Hepatic: Hyperbilirubinemia

Drug Interactions

• May interact with warfarin and increase bleeding risk.
• May inhibit cytochrome CYP2C9 enzyme, and therefore increase levels of substrates such as phenytoin and other substrates of CYP2C9.
• Much as fluorouracil, the concomitant use of leucovorin may increase both the efficacy and the toxicity of capecitabine.

Xeloda Logo

Formulation

Capecitabine (as brand-name Xeloda®) is available in light peach 150 mg tablets and peach 500 mg tablets.