XELODA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XELODA (XELODA).
Prodrug of 5-fluorouracil (5-FU), inhibits thymidylate synthase, incorporates into RNA and DNA, leading to cell death.
| Metabolism | Activated by carboxylesterase, cytidine deaminase, and thymidine phosphorylase to 5-FU; 5-FU catabolized by dihydropyrimidine dehydrogenase (DPD); also metabolized by CYP2C9. |
| Excretion | Renal (95.5% as metabolites; 26.1% as parent drug and metabolites, primarily 5'-DFCR, 5'-DFUR, and FBAL); fecal (< 3%) |
| Half-life | Capecitabine: 0.65-0.85 h; 5'-DFCR: 0.9-1.1 h; 5'-DFUR: 0.75-1.0 h; 5-FU: 0.75-1.1 h. Terminal half-life of 5-FU is short, requiring continuous dosing for sustained exposure. |
| Protein binding | Capecitabine: approximately 10% (primarily to albumin); 5-FU: negligible binding (<10%). |
| Volume of Distribution | Capecitabine: Vd/F ~0.5-0.6 L/kg, indicating distribution into total body water; 5-FU: Vd ~0.5-0.8 L/kg, consistent with wide tissue distribution. |
| Bioavailability | Oral: capecitabine absolute bioavailability is approximately 100%. Food reduces rate and extent of absorption (Cmax decreased by 60%, AUC by 35%). |
| Onset of Action | Oral: Time to peak plasma concentration of capecitabine is 1.5-2 h; conversion to 5-FU occurs rapidly, with cytotoxic effects within hours of administration. |
| Duration of Action | Oral: Cytotoxic effects persist for several hours after peak; typical dosing (twice daily for 14 days, then 7-day rest) maintains prolonged exposure. |
| Action Class | Antimetabolites |
| Brand Substitutes | Capegard 500 Tablet, Distamine 500mg Tablet, Capecad 500mg Tablet, Cacit 500mg Tablet, Zenocite 500mg Tablet |
Capecitabine 1250 mg/m2 orally twice daily for 2 weeks followed by a 1-week rest period, administered as 3-week cycles.
| Dosage form | TABLET |
| Renal impairment | For CrCl 30-50 mL/min: reduce dose to 75% of standard; CrCl <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: insufficient data, use caution; Child-Pugh Class C: not recommended. |
| Pediatric use | Safety and efficacy not established; not recommended for pediatric use. |
| Geriatric use | No specific dose adjustment; monitor renal function and reduce dose for CrCl <50 mL/min as per renal adjustment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XELODA (XELODA).
| Breastfeeding | Excretion into breast milk unknown; M/P ratio not determined. Due to potential severe adverse reactions (immunosuppression, genotoxicity) in nursing infants, breastfeeding is contraindicated during therapy and for at least 2 weeks after last dose. |
| Teratogenic Risk | Capecitabine (Xeloda) is antimetabolite chemotherapy; contraindicated in pregnancy. First trimester: high risk of teratogenicity (malformations, embryolethality) based on animal studies (fluoropyrimidine class). Second/third trimester: fetal growth restriction, neurodevelopmental effects, prematurity, low birth weight. Pregnancy should be avoided. |
■ FDA Black Box Warning
Capecitabine may cause severe or fatal adverse reactions when taken with warfarin, including bleeding; monitor INR frequently. Capecitabine is contraindicated in patients with severe renal impairment (CrCl <30 mL/min). Capecitabine may cause severe diarrhea, sometimes with fatal outcome. Capecitabine may cause severe mucositis, hand-foot syndrome, and myelosuppression.
| Serious Effects |
Severe renal impairment (CrCl <30 mL/min), known hypersensitivity to capecitabine or 5-FU, DPD deficiency (relative), pregnancy, breastfeeding.
| Precautions | Severe diarrhea, hand-foot syndrome (palmar-plantar erythrodysesthesia), cardiotoxicity (angina, MI, arrhythmias), renal impairment dose adjustment, DPD deficiency (increased toxicity), bone marrow suppression, hyperbilirubinemia, ocular toxicity, and interaction with warfarin. |
Loading safety data…
| Fetal Monitoring | If unintentional exposure: confirm pregnancy, monitor fetal development via ultrasound, assess serial growth, amniotic fluid index, doppler studies. Maternal monitoring: CBC with differential, LFTs, renal function, bilirubin. Watch for dose-limiting toxicities: hand-foot syndrome, diarrhea, myelosuppression. |
| Fertility Effects | Capecitabine can impair fertility in humans based on animal data: ovarian failure, testicular atrophy. In premenopausal women, may cause amenorrhea, premature ovarian insufficiency. Men: potential oligospermia or azoospermia. Reversibility not guaranteed. Fertility preservation counseling advised. |