Celetor-200 Drug Interactions

Pharmacodynamic interactions: Anticoagulants: Anticoagulant activity should be monitored particularly in the first few days after initiating or changing the dose of celecoxib in patients receiving warfarin or other anticoagulants since these patients have an increased risk of bleeding complications. Therefore, patients receiving oral anticoagulants should be closely monitored for their prothrombin time INR, particularly in the first few days when therapy with celecoxib is initiated or the dose of celecoxib is changed. Bleeding events in association with increases in prothrombin time have been reported, predominantly in the elderly, in patients receiving celecoxib concurrently with warfarin, some of them fatal.
Anti-hypertensives: NSAIDs may reduce the effect of anti-hypertensive medicinal products including ACE-inhibitors, angiotensin II receptor antagonists, diuretics and beta-blockers. Inhibition of prostaglandins may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors and/or angiotensin II antagonists. As for NSAIDs, the risk of acute renal insufficiency, which is usually reversible, may be increased in some patients with compromised renal function (e.g. dehydrated patients, patients on diuretics, or elderly patients) when ACE inhibitors, angiotensin II receptor antagonists, and/or diuretics are combined with NSAIDs, including celecoxib. Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.
Ciclosporin and Tacrolimus: Coadministration of NSAIDs and ciclosporin or tacrolimus may increase the nephrotoxic effect of ciclosporin or tacrolimus, respectively. Renal function should be monitored when celecoxib and any of these drugs are combined.
Acetylsalicylic acid: Celecoxib can be used with low-dose acetylsalicylic acid but is not a substitute for acetylsalicylic acid for cardiovascular prophylaxis. In the submitted studies, as with other NSAIDs, an increased risk of gastrointestinal ulceration or other gastrointestinal complications compared to use of celecoxib alone was shown for concomitant administration of low-dose acetylsalicylic acid.
Pharmacokinetic interactions: Effects of celecoxib on other drugs: CYP2D6 Inhibition: Celecoxib is an inhibitor of CYP2D6. The plasma concentrations of drugs that are substrates of this enzyme may be increased when celecoxib is used concomitantly. Examples of drugs which are metabolized 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. Concomitant administration of celecoxib 200 mg twice daily resulted in 2.6-fold and 1.5-fold increases in plasma concentrations of dextromethorphan and metoprolol (CYP2D6 substrates), respectively. These increases are due to celecoxib CYP2D6 inhibition of the CYP2D6 substrate metabolism.
CYP2C19 Inhibition: In vitro studies have shown some potential for celecoxib to inhibit CYP2C19 catalysed metabolism. The clinical significance of this in vitro finding is unknown. Examples of drugs which are metabolized by CYP2C19 are diazepam, citalopram and imipramine.
Methotrexate: In patients with rheumatoid arthritis celecoxib had no statistically significant effect on the pharmacokinetics (plasma or renal clearance) of methotrexate (in rheumatologic doses). However, adequate monitoring for methotrexate-related toxicity should be considered when combining these two drugs.
Lithium: Patients on lithium treatment should be closely monitored when celecoxib is introduced or withdrawn due to increase in lithium plasma levels.
Oral contraceptives: Celecoxib had no clinically relevant effects on the pharmacokinetics of oral contraceptives (1 mg norethisterone /35 micrograms ethinylestradiol).
Glibenclamide/tolbutamide: Celecoxib does not affect the pharmacokinetics of tolbutamide (CYP2C9 substrate), or glibenclamide to a clinically relevant extent.
Effects of other drugs on celecoxib: CYP2C9 Poor Metabolizers: In individuals who are CYP2C9 poor metabolizers and demonstrate increased systemic exposure to celecoxib, concomitant treatment with CYP2C9 inhibitors such as fluconazole could result in further increases in celecoxib exposure. Such combinations should be avoided in known CYP2C9 poor metabolizers.
CYP2C9 Inhibitors and Inducers: Since celecoxib is predominantly metabolized by CYP2C9 it should be used at half the recommended dose in patients receiving fluconazole. Concomitant use of 200 mg single dose of celecoxib and 200 mg once daily of fluconazole, a potent CYP2C9 inhibitor, resulted in a mean increase in celecoxib Cmax of 60% and in AUC of 130%. Concomitant use of inducers of CYP2C9 such as rifampicin, carbamazepine and barbiturates may reduce plasma concentrations of celecoxib.
Ketoconazole and Fluconazole: Concomitant administration of fluconazole at 200mg once daily resulted in a two-fold increase in celecoxib plasma concentration. This increase is due to the inhibition of celecoxib metabolism via CYP450 2C9 by fluconazole. Celecoxib should be introduced at the lowest recommended dose in patients receiving the CYP2C9 inhibitor fluconazole.
Ketoconazole, a CYP3A4 inhibitor, showed no clinically relevant inhibition in the metabolism of celecoxib.