Dosing and uses of Xeloda (capecitabine)
Adult dosage forms and strengths
tablet
- 150mg
- 500mg
Duke Stage C Colon Cancer
Adjuvant therapy
1,250 mg/m² PO BID x 2 weeks, followed by 1-week rest period, given as 3-week cycles for a total of 8 cycles (24 weeks)
Colorectal Cancer
Metastatic disease
1250 mg/m² BID for 2 weeks q21 days
Breast Cancer
Metastatic, resistant to paclitaxel, anthracyclines
Monotherapy: 1250 mg/m² BID for 2 weeks q3Weeks
Combo therapy with Docetaxel: 1250 m² PO BID for 2 weeks q3Weeks plus docetaxel 75 mg/m² 1 hour IV infusion q3Weeks
Administration
Swallow with water within 30 min after a meaL
Dosage may need to be individualized to optimize patient management
Dose Modifications
Renal impairment
- CrCl 30-50 mL/min: Reduce dose by 25%
- CrCl <30 mL/min: Contraindicated
Pediatric dosage forms and strengths
Safety & efficacy not established
Xeloda (capecitabine) adverse (side) effects
Varies with carcinoma type
10%
Diarrhea
Nausea
Anemia
Lymphopenia
Hand and foot syndrome
Edema
Fatigue
Fever
Headache
Pain
Paresthesia
Alopecia
Dermatitis
Abdominal pain
Anorexia
Appetite decreased
Constipation
Dyspepsia
Stomatitis
Vomiting
Neutropenia
Thrombocytopenia
Dyspnea
Bilirubin increased
Eye irritation
1-10%
Chest pain
Dermatitis
Pruritus
Rash
Dizziness
Headache
Weakness
Dehydration
Dry mouth
Dyspepsia
Taste disturbance
Back pain
Postmarketing reports
Toxic leukoencephalopathy
Warnings
Black box warnings
Capecitabine may increase the anticoagulant effects of warfarin increasing the INR several days up to several months after initiating capecitabine or within one month after stopping the therapy. Risk factors include >60 years of age and cancer. Monitor closely
Contraindications
Hypersensitivity to capecitabine or fluorouracil (5-FU)
Severe renal impairment (CrCl <30 mL/min)
Cautions
May result in bleeding, death; monitor anticoagulant response (e.g., INR) and adjust anticoagulant dose accordingly
Diarrhea may be severe; interrupt capecitabine treatment immediately until diarrhea resolves or decreases to grade 1; recommend standard antidiarrheal treatments
May cause cardiomyopathy and acute decreases in LVEF
Increased risk of severe or fatal adverse reactions in patients with low or absent dihydropyrimidine dehydrogenase (DPD) activity; withhold or permanently discontinue capecitabine in patients with evidence of acute early-onset or unusually severe toxicity, which may indicate near complete or total absence of DPD activity; no capecitabine dose has been proven safe in patients with absent DPD activity
Interrupt capecitabine treatment until dehydration is corrected; potential risk of acute renal failure secondary to dehydration; monitor and correct dehydration
Can cause fetal harm; advise women of the potential risk to the fetus
Severe mucocutaneous reactions, Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), reported; discontinue therapy in patients who experience a severe mucocutaneous reaction during treatment; capecitabine may induce hand-and-foot syndrome; interrupt capecitabine treatment until hand-and-foot syndrome event resolves or decreases in intensity
If hypervilirubinemia occurs, interrupt therapy immediately until it resolves or decreases in intensity
Do not treat patients with neutrophil counts <1.5 x 10^9;/L or thrombocyte counts <100 x 10^9;/L; if grade 3-4 neutropenia or thrombocytopenia occurs, stop therapy until condition resolves
Pregnancy and lactation
Pregnancy category: d
Lactation: excretion in milk unknown/not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Xeloda (capecitabine)
Half-life: 0.75 hr
Peak Plasma Time: 1.5 hr
Protein Bound: <60%
Metabolism: hepatic
Metabolites: 5'-DFUr
Excretion: urine (95%)
Dialyzable: yes
Pharmacogenomics
Dihydropyrimidine dehydrogenase (DPD), an enzyme encoded by the DPYD gene, is the rate-limiting step in pyrimidine catabolism and deactivates >80% of 5FU standard doses and the 5FU prodrug capecitabine
Contraindicated in patients with DPD deficiency; causes severe toxicity with conventional doses (ie, grade III/IV toxicity and potentially fatal neutropenia, mucositis, and diarrhea)
Because true DPD deficiency is rare and because the clinical implications of partial deficiency are still unclear, screening for mutations prior to initiating therapy is not warranted
Genetic testing laboratories
- The following companies currently offer testing for DPYD*2A mutations
- EntroGen (https://www.entrogen.com)
- Myriad (https://www.myriadtests.com)
- LabCorp (https://www.labcorp.com)
- Molecular Diagnostics Laboratories (https://www.mdl-labs.com)
Mechanism of action
Converted to 5-FU by thymidine phosphorylase in neoplastic tissue
