Rancelex Capsules 200 mg Drug Interactions

General: Celecoxib metabolism is predominantly mediated via cytochrome P450 (CYP) 2C9 in the liver. Co-administration of celecoxib with drugs that are known to inhibit CYP2C9 should be done with caution. Significant interactions may occur when celecoxib is administered together with drugs that inhibit CYP2C9.
Celecoxib is an inhibitor of CYP2D6. Therefore, there is a potential for an in vivo drug interaction with drugs that are metabolized by CYP2D6. During celecoxib treatment, the plasma concentrations of the CYP2D6 substrate dextromethorphan have been reported to be increased by 136%. The plasma concentrations of drugs that are substrates of this enzyme may be increased when celecoxib is used concomitantly. Examples of drugs which are metabolised by CYP2D6 are antidepressants (tricyclics and SSRIs), neuroleptics, anti-arrhythmic drugs, etc. The dose of individually dose-titrated CYP2D6 substrates may need to be reduced when treatment with celecoxib is initiated or increased if treatment with celecoxib is terminated.
Warfarin: Anticoagulant activity should be monitored, particularly in the first few days, after initiating or changing celecoxib therapy in patients receiving warfarin or similar agents, since these patients are at an increased risk of bleeding complications. The effect of celecoxib on the anticoagulant effect of warfarin has been reported in healthy subjects receiving daily 2-5 mg doses of warfarin. In these subjects, celecoxib did not alter the anticoagulant effect of warfarin as determined by prothrombin time. However, serious bleeding events, some of which were fatal, have been reported, predominantly in the elderly, in association with increases in prothrombin time in patients receiving celecoxib concurrently with warfarin.
Lithium: The mean steady-state lithium plasma levels have been reported to increase approximately 17% in subjects receiving lithium 450 mg twice daily with celecoxib 200 mg twice daily as compared to subjects receiving lithium alone. Patients on lithium treatment should be closely monitored when celecoxib is introduced or withdrawn.
Aspirin: Celecoxib can be used with low-dose aspirin. However, concomitant administration of aspirin with celecoxib increases the rate of GI ulceration or other complications, compared to use of celecoxib alone (see Precautions). Because of its lack of platelet effects, celecoxib is not a substitute for aspirin for cardiovascular prophylaxis (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
ACE-inhibitors and Angiotensin II Antagonists: Reports suggest that NSAIDs may diminish the antihypertensive effect of Angiotensin Converting Enzyme (ACE) inhibitors and angiotensin II antagonists. This interaction should be given consideration in patients taking celecoxib concomitantly with ACE inhibitors and angiotensin II antagonists (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Fluconazole: A two-fold increase in celecoxib plasma concentration has been reported after concomitant administration of fluconazole 200 mg once daily due to the inhibition of celecoxib metabolism via P450 2C9 by fluconazole (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions). Celecoxib should be introduced at the lowest recommended dose in patients receiving fluconazole.
Furosemide: NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis.
Methotrexate: Celecoxib has been reported to have no effect on the pharmacokinetics of methotrexate in rheumatoid arthritis patients (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Concomitant NSAID Use: The concomitant use of celecoxib with any dose of non-aspirin NSAID should be avoided due to the potential for increased risk of adverse reactions.