Capecitabine interactions

Allopurinol: Avoid concomitant use of allopurinol with XELODA. (Capecitabine label, Drug interactions)

Co-administration of such combinations of a CYP2C9 inhibitor plus a strong or moderate CYP3A inhibitor with TRACLEER is not recommended. (Bosentan label, Drug interactions)

XELODA is contraindicated in patients with history of severe hypersensitivity reaction to fluorouracil or capecitabine [see Adverse Reactions (6.1) ] . (Capecitabine label, Contraindications)

In animal reproductive studies, administration of lapatinib to pregnant rats during the period of organogenesis and through lactation led to death of offspring within the first 4 days after birth at maternal exposures that were ≥ 3.3 times the human clinical exposure based on AUC following 1,250 mg dose of lapatinib plus capecitabine. (Lapatinib label, Warnings and precautions)

Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil. (Capecitabine label, Drug interactions)

Moderate dual CYP3A4 and CYP2C9 inhibitors (fluconazole, amiodarone) or use of combined CYP3A4 and CYP2C9 inhibitors may increase exposure to macitentan: avoid co-administration with OPSUMIT ( 7.3 , 12.3 ). (Macitentan label, Drug interactions)

WARNING: SERIOUS ADVERSE REACTIONS OR DEATH IN PATIENTS WITH COMPLETE DPD DEFICIENCY and INCREASED RISK OF BLEEDING WITH CONCOMITANT USE OF VITAMIN K ANTAGONISTS Increased risk of serious adverse reactions or death in patients with complete DPD deficiency • Test patients for genetic variants of DPYD prior to initiating XELODA unless immediate treatment is necessary. (Capecitabine label, Boxed warning)

WARNING: SERIOUS ADVERSE REACTIONS OR DEATH IN PATIENTS WITH COMPLETE DPD DEFICIENCY and INCREASED RISK OF BLEEDING WITH CONCOMITANT USE OF VITAMIN K ANTAGONISTS Increased risk of serious adverse reactions or death in patients with complete DPD deficiency • Test patients for genetic variants of DPYD prior to initiating XELODA unless immediate treatment is necessary. (Capecitabine label, Boxed warning)

WARNING: SERIOUS ADVERSE REACTIONS OR DEATH IN PATIENTS WITH COMPLETE DPD DEFICIENCY and INCREASED RISK OF BLEEDING WITH CONCOMITANT USE OF VITAMIN K ANTAGONISTS Increased risk of serious adverse reactions or death in patients with complete DPD deficiency • Test patients for genetic variants of DPYD prior to initiating XELODA unless immediate treatment is necessary. (Capecitabine label, Boxed warning)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for signs of renal toxicity when XELODA is used concomitantly with nephrotoxic drugs (e.g. platinum salts, irinotecan, methotrexate, intravenous bisphosphonates). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

HIV Protease inhibitor — Ritonavir (600 mg twice daily), a strong CYP3A4 inhibitor, which also inhibits CYP2C9, increased avanafil 50 mg single-dose C max and AUC equal to approximately 2-fold and 13-fold, and prolonged the half-life of avanafil to approximately 9 hours in healthy volunteers. (Avanafil label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Amiodarone Amiodarone and its metabolite desethyl amiodarone, inhibitors of CYP2C9, and P- glycoprotein increased concentrations of the S(-)-enantiomer of carvedilol by at least 2 fold [see Clinical Pharmacology (12.5) ]. (Carvedilol label, Drug interactions)

Co-administration of celecoxib with drugs that are known to inhibit CYP2C9 (e.g., fluconazole) may enhance the exposure and toxicity of celecoxib whereas co-administration with CYP2C9 inducers (e.g., rifampin) may lead to compromised efficacy of celecoxib. (Celecoxib label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Co-administration of diclofenac with CYP2C9 inhibitors (e.g. voriconazole) may enhance the exposure and toxicity of diclofenac whereas co- administration with CYP2C9 inducers (e.g. rifampin) may lead to compromised efficacy of diclofenac. (Diclofenac label, Drug interactions)

Co-administration of diclofenac with CYP2C9 inhibitors (e.g., voriconazole) may enhance the exposure and toxicity of diclofenac [see Clinical Pharmacology (12.3) ] whereas co-administration with CYP2C9 inducers (e.g., rifampin) may lead to compromised efficacy of diclofenac. (Diclofenac and misoprostol label, Drug interactions)

Monitor for increased dronabinol-related adverse reactions when dronabinol oral solution is co-administered with inhibitors of CYP2C9 (e.g., amiodarone, fluconazole) and inhibitors of CYP3A4 enzymes (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, erythromycin, grapefruit juice). (Dronabinol label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Effect of TRIKAFTA on Other Drugs CYP2C9 Substrates Ivacaftor may inhibit CYP2C9; therefore, monitoring of the international normalized ratio (INR) during concomitant use of TRIKAFTA with warfarin is recommended. (Elexacaftor, tezacaftor, and ivacaftor label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Leucovorin The concentration of fluorouracil is increased and its toxicity may be enhanced by leucovorin, folic acid, or folate analog products. (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

…Antiepileptic drugs Ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate Azoles Fluconazole, ketoconazole, itraconazole, miconazole, voriconazole Antineoplastic agents Capecitabine, fluorouracil Antidepressants Fluoxetine, fluvoxamine, sertraline Gastric acid reducing agents H 2 antagonists (cimetidine), omeprazole Sulfonamides Sulfamethizole, sulfaphenazole,… (Fosphenytoin label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for signs of renal toxicity when XELODA is used concomitantly with nephrotoxic drugs (e.g. platinum salts, irinotecan, methotrexate, intravenous bisphosphonates). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for signs of renal toxicity when XELODA is used concomitantly with nephrotoxic drugs (e.g. platinum salts, irinotecan, methotrexate, intravenous bisphosphonates). (Capecitabine label, Drug interactions)

Strong CYP3A4 or CYP2C9 Inhibitors Patients with renal or hepatic impairment who are taking strong inhibitors of CYP3A4 and CYP2C9 may have a significant increase in exposure to VIMPAT. (Lacosamide label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Thus concomitant usage of CYP2C9 inhibitors (such as amiodarone, fluconazole, and sulphaphenazole) may lead to abnormally high plasma levels of meloxicam due to reduced metabolic clearance [ see Use in Specific Populations ( 8.8 ); and Clinical Pharmacology ( 12.3 , 12.5 ) ]. (Meloxicam label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for signs of renal toxicity when XELODA is used concomitantly with nephrotoxic drugs (e.g. platinum salts, irinotecan, methotrexate, intravenous bisphosphonates). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for signs of renal toxicity when XELODA is used concomitantly with nephrotoxic drugs (e.g. platinum salts, irinotecan, methotrexate, intravenous bisphosphonates). (Capecitabine label, Drug interactions)

Vitamin K antagonists: Monitor INR more frequently and dose adjust oral vitamin K antagonist as appropriate Phenytoin : Closely monitor phenytoin levels in patients taking XELODA concomitantly with phenytoin and adjust the phenytoin dose as appropriate. (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Fluconazole (strong CYP2C9 inhibitor): Increases systemic exposure of ramelteon; administer with caution. (Ramelteon label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for signs of renal toxicity when XELODA is used concomitantly with nephrotoxic drugs (e.g. platinum salts, irinotecan, methotrexate, intravenous bisphosphonates). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Rosuvastatin plasma levels can be significantly increased with concomitant administration of inhibitors of CYP2C9 and transporters. (Rosuvastatin label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). (Capecitabine label, Drug interactions)

CYP2C9: Concomitant use with CYP2C9 inhibitors can decrease torsemide clearance. (Torsemide label, Drug interactions)

Zafirlukast exposure is likely to be increased by other moderate and strong CYP2C9 inhibitors. (Zafirlukast label, Precautions)

Closely monitor for signs of renal toxicity when XELODA is used concomitantly with nephrotoxic drugs (e.g. platinum salts, irinotecan, methotrexate, intravenous bisphosphonates). (Capecitabine label, Drug interactions)

However, at high concentrations in vitro , clopidogrel inhibits CYP2C9. (Clopidogrel label, Drug interactions)

In the 251 patients with metastatic breast cancer who received XELODA with docetaxel, 68% had grade 3 or 4 neutropenia, 2.8% had grade 3 or 4 thrombocytopenia, and 10% had grade 3 or 4 anemia. (Capecitabine label, Warnings and precautions)

Fluconazole is an inhibitor of CYP2C9 and CYP3A enzymes. (Terbinafine label, Drug interactions)

Toremifene is a weak inhibitor of CYP2C9. (Toremifene label, Drug interactions)

The interaction is a consequence of blocking hepatic metabolism of vardenafil by ritonavir, a HIV protease inhibitor and a highly strong CYP3A4 inhibitor, which also inhibits CYP2C9. (Vardenafil label, Drug interactions)

CYP2C9 Venlafaxine did not inhibit CYP2C9 in vitro . (Venlafaxine label, Drug interactions)