Naprocap Drug Interactions

Anticoagulants: Altered coagulation parameters and/or bleeding in patients taking Capecitabine concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon. These events may occur within several days and up to several months after initiating Capecitabine therapy and, in a few cases, within 1 month after stopping Capecitabine. These events may occur in patients with and without liver metastases. In a drug interaction study with single-dose warfarin administration, there was a significant increase in the mean AUC of S-warfarin. This interaction is probably due to an inhibition of cytochrome P450 2C9 by capecitabine and/or its metabolites.
Phenytoin: The level of phenytoin should be carefully monitored in patients taking Capecitabine and phenytoin dose may need to be reduced. Post marketing reports indicate that some patients receiving Capecitabine and phenytoin had toxicity associated with elevated phenytoin levels. 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 by capecitabine and/or its metabolites.
Leucovorin: The concentration of 5-fluorouracil is increased and its toxicity may be enhanced by leucovorin. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil.
CYP2C9: Care should be exercised when Capecitabine is coadministered with CYP2C9 substrates.
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 folinic acid: 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. This interaction, which leads to increased fluoropyrimidine toxicity, is potentially fatal. Therefore, Capecitabine must not be administered concomitantly with sorivudine or its chemically related analogues, such as brivudine. There must be at least a 4 week waiting period between end of treatment with sorivudine or its chemically related analogues such as brivudine and start of Capecitabine therapy.
Antacids: The effect of an aluminum hydroxide and magnesium hydroxide-containing antacidon the pharmacokinetics of capecitabine is reported. There was a small increase in plasma concentrations of capecitabine and one metabolite (5'-DFCR); there was no effect on the 3major metabolites (5'-DFUR, 5-FU and FBAL).
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 Capacitabine was 2000 mg/m² per day when combined with interferon alpha-2a (3 MIU/m 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 occurred when Capecitabine was administered in combination with Oxaliplatin or in combination with Oxaliplatin and bevacizumab.
Bevacizumab: there was no clinically significant effect of bevacizumab on the pharmacokinetic parameters of Capecitabine or its metabolites in the presence of Oxaliplatin.