Caxeta Drug Interactions

Coumarin anticoagulants: Altered coagulation parameters and/or bleeding have been reported in patients taking capecitabine concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon. These events occurred within several days and up to several months after initiating capecitabine therapy and, in a few cases, within one month after stopping capecitabine. In a reported clinical interaction study, after a single 20 mg dose of warfarin, capecitabine treatment increased the AUC of S warfarin by 57% with a 91% increase in INR value. These results suggest an interaction, probably due to an inhibition of the cytochrome P450 2C9 isoenzyme system by capecitabine. Patients taking coumarin-derivative anticoagulants concomitantly with capecitabine should be monitored regularly for alterations in their coagulation parameters (PT or INR) and the anti-coagulant dose adjusted accordingly (see PRECAUTIONS).
Cytochrome P-450 2C9 substrates: No formal drug-drug interaction studies with capecitabine and other drugs known to be metabolized by the cytochrome P450 2C9 isoenzyme have been reported. Care should be exercised when capecitabine is co-administered with these drugs.
Phenytoin: Increased phenytoin plasma concentrations have been reported during concomitant use of capecitabine with phenytoin. Formal drug-drug interaction studies with phenytoin have not been reported, but the mechanism of interaction is presumed to be inhibition of the CYP 2C9 isoenzyme system by capecitabine. Patients taking phenytoin concomitantly with capecitabine should be regularly monitored for increased phenytoin plasma concentrations.
Drug-food interaction: In all reported clinical trials, patients were instructed to take capecitabine within 30 minutes after a meal. Since current safety and efficacy data are based upon administration with food, it is recommended that capecitabine be administered with food.
Antacid: The effect of an aluminium hydroxide and magnesium hydroxide containing antacid on the pharmacokinetics of capecitabine was reported in cancer patients. There was a small increase in plasma concentrations of capecitabine and one metabolite (5'-DFCR), there was no effect on the 3 major metabolites (5'-DFUR, 5-FU and FBAL).
Leucovorin (folinic acid): The effect of leucovorin on the pharmacokinetics of capecitabine was reported in cancer patients. Leucovorin has no effect on the pharmacokinetics of capecitabine and its metabolites. However, leucovorin has an effect on the pharmacodynamics of capecitabine and its toxicity may be enhanced by leucovorin.
Sorivudine and analogues: A clinically significant drug-drug interaction between sorivudine and 5-FU, resulting from the inhibition of dihydropyrimidine dehydrogenase by sorivudine, has been described in the literature. This interaction, which leads to increased fluoropyrimidine toxicity, is potentially fatal. Therefore, capecitabine should not be administered concomitantly with sorivudine or its chemically related analogues, such as brivudine (see CONTRAINDICATIONS). There must be at least a 4-week waiting period between the end of treatment with sorivudine or its chemically related analogues, such as brivudine and start of capecitabine therapy.
Oxaliplatin: No clinically significant differences in exposure to capecitabine or its metabolites, free platinum or total platinum occurred when capecitabine and oxaliplatin were administered in combination, with or without bevacizumab.
Bevacizumab: There was no clinically significant effect of bevacizumab on the pharmacokinetic parameters of capecitabine or its metabolites.