Capetero Drug Interactions

Interaction studies have only been performed in adults.
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 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. Since metabolism of R-warfarin was not affected, these results indicate that capecitabine down-regulates isozyme 2C9, but has no effect on isozymes 1A2 and 3A4. 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.
Cytochrome P450 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 conducted. 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 conducted, but the mechanism of interaction is presumed to be inhibition of the CYP2C9 isoenzyme system by capecitabine (see previously mentioned in Coumarin anticoagulants). Patients taking phenytoin concomitantly with Capecitabine should be regularly monitored for increased phenytoin plasma concentrations.
Drug-food interaction: In all 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. Administration with food decreases the rate of capecitabine absorption.
Antacid: The effect of an aluminium hydroxide and magnesium hydroxide-containing antacid on the pharmacokinetics of Capecitabine was investigated 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): 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: 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 was combined with folinic acid (30 mg orally bid).
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.
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.
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 3000 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 a 6-week course of radiotherapy.
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.