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Some medicine may interfere with Capecitabine. These medicine include: Coumarin anticoagulants: Patients taking Coumarin-derivative anticoagulants concomitantly with Capecitabine should be monitored regularly for alterations in their coagulation parameters (PT or INR) and the anticoagulant dose adjusted accordingly.
Cytochrome P-450 2C9 substrates: Care should be exercised when Capecitabine is co-administered with these drugs.
Phenytoin: Patients taking Phenytoin concomitantly with Capecitabine should be regularly monitored for increased Phenytoin plasma concentrations.
Drug-food interaction: It is recommended that Capecitabine be administered with food. Administration with food decreases the rate of Capecitabine absorption.
Antacid: There was a small increase in plasma concentrations of Capecitabine and one metabolite (5'-DCFR); there was no effect on the 3 major metabolites (5'DFUR, 5-FU, FBAL).
Leucovorin (Folinic Acid): A combination study with Capecitabine and Folinic Acid indicated that Folinic Acid has no major effect on the pharmacokinetics of Capecitabine and its metabolites. However, Folinic Acid has an effect on the pharmacodynamics of Capecitabine and its toxicity may be enhanced by Leucovorin; the maximum tolerated dose (MTD) of Capecitabine alone using the intermittent regimen is 3000 mg/m2 per day whereas it is only 2000 mg/m2 per day when Capecitabine with Folinic Acid (30 mg orally bid).
Sorivudine and analogues: 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 occur 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.
Allopurinol: Interactions with Allopurinol have been observed for 5-FU; with possible decreased efficacy of 5-FU. Concomitant use of Allopurinol with Capecitabine should be avoided.
Interaction with cytochrome P-450: See interaction with Coumarin-derivative anti-coagulation.
Interferon alpha: The MTD of Capecitabine was 2000 mg/m2 per day when combined with interferon alpha-2a (3 MIU/m2 per day) compared to 3000 mg/m2 per day when Capecitabine was used alone.
Radiotherapy: The MTD of Capecitabine alone using the intermittent regimen is 30000 mg/m2 per day, whereas when combined with radiotherapy for rectal cancer, the MTD of Capecitabine is 2000 mg/m2 per day using either a continuous schedule or given daily Monday through Friday during 6-week course of radiotherapy.
