Xeltabine Drug Interactions

Coumarin-derivative anticoagulants: Patients taking coumarin-derivative anticoagulants concomitantly with Capecitabine (Xeltabine) should be monitored regularly for alterations in their coagulation parameters (PT or INR) and the anti-coagulant dose adjusted accordingly. Altered coagulation parameters and/or bleeding have been reported in patients taking Capecitabine (Xeltabine) concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon. These reactions occurred within several days and up to several months after initiating Capecitabine (Xeltabine) therapy and, in a few cases, within one month after stopping Capecitabine (Xeltabine). In a clinical pharmacokinetic interaction study, after a single 20 mg dose of warfarin, Capecitabine (Xeltabine) 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 (Xeltabine) down-regulates isozyme 2C9, but has no effect on isozymes 1A2 and 3A4.
Antacid: The effect of an aluminum hydroxide and magnesium hydroxide-containing antacid on the pharmacokinetics of Capecitabine (Xeltabine) was investigated. There was a small increase in plasma concentrations of Capecitabine (Xeltabine) and one metabolite (5'-DFCR); there was no effect on the 3 major metabolites (5'-DFUR, 5-FU and FBAL).
Allopurinol: Interactions with allopurinol have been observed for 5-FU. Concomitant use of allopurinol with Capecitabine (Xeltabine) should be avoided.
Paclitaxel: Phase I studies with cancer patients evaluating the effect of Capecitabine (Xeltabine) on the pharmacokinetics of paclitaxel and vice versa showed no effect by Capecitabine (Xeltabine) on the pharmacokinetics of paclitaxel (C_max, AUC) and no significant effect by paclitaxel on the pharmacokinetics clinically.
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 (Xeltabine) 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 (Xeltabine) therapy.
Phenytoin: Increased phenytoin plasma concentrations resulting in symptoms of phenytoin intoxication in single cases have been reported during concomitant use of Capecitabine (Xeltabine) with phenytoin. Patients taking phenytoin concomitantly with Capecitabine (Xeltabine) should be regularly monitored for increased phenytoin plasma concentrations.
Plasma proteins: Capecitabine (Xeltabine) has low plasma protein binding rate (54%). Therefore interaction resulting from replacement procedure to drug with high plasma protein binding rate is not in concern.
Cytochrome P-450: See Coumarin-derivative anticoagulation for interaction isoenzyme 1A2, 2C9 and 3A4 on previous text.
Interferon alpha: The maximum tolerated dose (MTD) of Capecitabine (Xeltabine) 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 (Xeltabine) was used alone.
Radiotherapy: The maximum tolerated dose (MTD) of Capecitabine (Xeltabine) alone using the intermittent regimen is 3000 mg/m² per day, whereas, when combined with radiotherapy for rectal cancer, the maximum tolerated dose (MTD) of Capecitabine (Xeltabine) is 2000 mg/m² per day (using either a continuous schedule or given daily Monday through Friday during a 6-week course of radiotherapy).
Folinic acid: A combination study with Capecitabine (Xeltabine) and folinic acid indicated that folinic acid has no major effect on the pharmacokinetics of Capecitabine (Xeltabine) and its metabolites. However, folinic acid has an effect on the pharmacodynamics of Capecitabine (Xeltabine) and its toxicity may be enhanced by folinic acid: the maximum tolerated dose (MTD) of Capecitabine (Xeltabine) alone using the intermittent regimen is 3000 mg/m² per day whereas it is only 2000 mg/m² per day when Capecitabine (Xeltabine) was combined with folinic acid (30 mg orally twice daily).
Taking a tegafur, gimeracil, oteracil potassium complex combined with Capecitabine (Xeltabine) or taking the complex within seven days after interruption of Capecitabine (Xeltabine) administration is contraindicated. Blood fluorouracil contents increased remarkably due to gimeracil inhibiting metabolism of fluorouracil cause gastrointestinal disorder like severe blood disorder, diarrhea or stomatitis etc.
Oxaliplatin: No clinically significant differences in exposure to Capecitabine (Xeltabine) or its metabolites, free platinum or total platinum occurred when Capecitabine (Xeltabine) was administered in combination with oxaliplatin or in combination with oxaliplatin and bevacizumab.