Class: Pyrimidine analog
- Tablets 150 mg
- Tablets 500 mg
Capecitabine is an oral systemic prodrug that is enzymatically converted to 5-fluorouracil (5-FU). Healthy and tumor cells metabolize 5-FU to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury by 2 different mechanisms. First, they inhibit the formation of thymidine triphosphate, which is essential for the synthesis of DNA. Second, nuclear transcriptional enzymes can mistakenly incorporate FUTP during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis.
T max is approximately 1.5 h for capecitabine and 2 h for 5-FU. Food decreased C max 60% and AUC 35% for capecitabine and decreased C max 4.3% and AUC 21% for 5-FU. Food delayed T max 1.5 h.
Less than 60% protein bound (approximately 35% bound to albumin).
Enzymatically metabolized to 5-FU (active) in tissues; also metabolized to inactive metabolites in the liver.
The t ½ is approximately 0.75 h (for capecitabine and 5-FU). Approximately 95.5% is excreted in urine (57% of the dose as inactive metabolite and 3% of the dose as unchanged drug); 2.6% is excreted in feces.
Special PopulationsRenal Function Impairment
In moderate to severe renal function impairment, there is increased exposure to inactive metabolites and a 25% increase in exposure to capecitabine.Hepatic Function Impairment
Capecitabine AUC and C max increased 60%; 5-FU was not affected.
Indications and Usage
Treatment of resistant metastatic breast cancer alone or in combination with docetaxel; colorectal cancer.
Adjuvant treatment of pancreatic cancer.
Hypersensitivity to 5-FU; severe renal function impairment (Ccr below 30 mL/min); dihydropyrimidine dehydrogenase deficiency (DPD).
Dosage and AdministrationAdults
PO 2,500 mg/m 2 /day in 2 divided doses, approximately 12 h apart, for 2 wk. After a 1-wk rest period, this 3-wk cycle is repeated. Round to the nearest dose that gives a whole tablet size rather than cutting tablets in half. Dosing adjustments are needed for toxicities. Once the capecitabine dose is reduced, it should not be increased. See manufacturer's recommendations.Renal Function Impairment
For moderate renal function impairment (30 to 50 mL/min), a dose reduction to 75% of the starting dose is recommended.
Administer each dose with water within 30 min after a meal.
Store at controlled room temperature (59° to 86°F).
May increase capecitabine levels.Cimetidine, metronidazole
May increase serum concentrations of fluorouracil and potentially increase toxicity.Fluorouracil
Drug interactions have been reported with fluorouracil, the principal active metabolite of capecitabine.Leucovorin
May enhance GI toxicity of fluorouracil.Levamisole
Risk of hepatotoxicity may be increased by coadministration with fluorouracil.Phenytoin
Levels may be elevated by capecitabine, increasing the risk of adverse reactions.Warfarin
May alter warfarin's effects, increasing the risk of bleeding.
Laboratory Test Interactions
None well documented.
Venous thrombosis (8%).
Paresthesia (21%); headache, peripheral sensory neuropathy (10%); dizziness (8%); insomnia (7%); taste disturbances (6%); depression, mood alteration (5%).
Hand-and-foot syndrome (54%); dermatitis (27%); nail disorder, skin discoloration (7%); alopecia (6%).
Eye irritation (15%); abnormal vision, pharyngeal disorder (5%); sore throat (2%); laryngitis (1%).
Diarrhea (55%); nausea (43%); abdominal pain (35%); vomiting (27%); decreased appetite (26%); stomatitis (25%); constipation (14%); GI motility disorder, oral discomfort (10%); dyspepsia, upper GI inflammatory disorders (8%); GI hemorrhage, ileus (6%).
Lymphopenia (94%); anemia (80%); thrombocytopenia (24%); neutropenia (26%); idiopathic thrombocytopenia purpura (1%).
Hyperbilirubinemia (48%); hepatic failure (postmarketing).
Increased bilirubin (20%); increased lymphocytes (13%); decreased calcium, decreased neutrophils, decreased neutrophils/granulocytes, increased ALT (2%); decreased Hgb, increased calcium (1%); decreased platelets (1%).
Dyspnea (14%); cough (7%); epistaxis (3%).
Fatigue/weakness (42%); pyrexia (18%); edema (15%); pain (12%); back pain (10%); myalgia (9%); arthralgia (8%); chest pain, pain in limb (6%); viral infections (5%).
Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking capecitabine concomitantly with coumarin-derivative anticoagulants. Increases in INR have occurred within several days to several months after initiating capecitabine and, in some cases, within 1 mo after stopping capecitabine. Risk factors include 60 yr of age and older and cancer diagnosis. Monitor INR or PT frequently; be prepared to adjust anticoagulant dose accordingly.
Category D .
Safety and efficacy not established.
Patients 80 yr of age and older may experience a greater incidence of grade 3 or 4 adverse reactions.
Patients with moderate renal function impairment at baseline require dosage modification. Carefully monitor patients with mild or moderate renal function impairment for adverse reactions.
Carefully monitor patients with mild to moderate hepatic function impairment caused by liver metastases.
Cardiotoxicity has been associated with fluorinated pyrimidine therapy.
Ensure women of childbearing potential use effective contraception before initiating therapy and for duration of treatment.
Capecitabine can induce diarrhea, sometimes severe. If grade 2, 3, or 4 diarrhea occurs, immediately interrupt administration until the diarrhea resolves or decreases in intensity to grade 1. Following grade 3 or 4 diarrhea, decrease subsequent doses of capecitabine. Monitor patient for development of diarrhea. Consider use of antidiarrheal therapy (eg, loperamide) and be prepared to administer fluid and electrolyte replacement if severe.
Rarely, unexpected, severe toxicity (eg, diarrhea, neurotoxicity, neutropenia, stomatitis) associated with 5-FU has been attributed to a deficiency of DPD activity.
If grade 2 or 3 hand-and-foot syndrome occurs, interrupt administration of capecitabine until the event resolves or decreases in intensity to grade 1. Following grade 3 hand-and-foot syndrome, decrease subsequent doses of capecitabine. Monitor patient for development of hand-and-foot syndrome (eg, discomfort of the hands and feet, numbness, redness, swelling), nausea, stomatitis, and vomiting. Inform health care provider if noted.
Grade 3 or 4 neutropenia, thrombocytopenia, or decreases in Hgb occur more frequently when capecitabine is used in combination with docetaxel.
If grade 2 to 4 elevations in bilirubin occur, immediately interrupt administration until the hyperbilirubinemia resolves or decreases in intensity to grade 1.
Bone marrow depression, diarrhea, GI irritation and bleeding, nausea, vomiting.
- Advise patient or caregiver to review patient information leaflet before starting therapy and with each refill.
- Review the following cyclic dosing schedule with patient or caregiver: twice daily for 2 wk, rest for 1 wk, then repeat cycle.
- Advise patient to take prescribed dose in the morning and evening with a glass of water and within 30 min after a meal.
- Advise patient or caregiver that if a dose is missed not to take the missed dose and not to double the next dose. Take the next dose at the regularly scheduled time.
- If patient is using a combination of different tablet strengths, ensure patient or caregiver can correctly identify the correct dose.
- Advise patient that medication may be used in combination with other chemotherapy agents to achieve max benefit possible.
- Advise patient to discontinue therapy and notify health care provider if any of the following occur: diarrhea with 4 to 6 stools/day or diarrhea at night, nausea or sores in the mouth that interfere with eating, vomiting 2 to 5 times within 24 h, redness, swelling, and pain of the hands or feet.
- Advise patient or caregiver that OTC antidiarrheals (eg, loperamide) can be used to treat mild diarrhea.
- Advise patient to report fever, chills, or other signs of an infection to health care provider immediately.
- Caution women of childbearing potential to avoid becoming pregnant while being treated.
Copyright © 2009 Wolters Kluwer Health.