Celxib 200 Drug Interactions

General: Celecoxib metabolism is predominantly mediated via cytochrome P450 (CYP) 2C9 in the liver. Patients who are known or suspected to be poor CYP2C9 metabolizers based on previous history/experience with other CYP2C9 substrates should be administered Celecoxib with caution as they may have abnormally high plasma levels due to reduced metabolic clearance. Consider starting treatment at half the lowest recommended dose (see Dosage & Administration and Pharmacology: Pharmacokinetics: Metabolism under Actions).
Concomitant administration of Celecoxib with inhibitors of CYP2C9 can lead to increases in plasma concentrations of Celecoxib. Therefore, a dose reduction of Celecoxib may be necessary when Celecoxib is co-administered with CYP2C9 inhibitors. Concomitant administration of Celecoxib with inducers of CYP2C9, such as Rifampicin, Carbamazepine and Barbiturates can lead to decreases in plasma concentrations of Celecoxib. Therefore, a dose increase of Celecoxib may be necessary when Celecoxib is co-administered with CYP2C9 inducers.
Drug-specific: Interaction of Celecoxib with Warfarin or similar agents: See Use with Oral Anticoagulants under Precautions.
Lithium: Patients on Lithium treatment should be closely monitored when Celecoxib is introduced or withdrawn.
Aspirin: Celecoxib does not interfere with the anti-platelet effect of low-dose Aspirin (See Gastrointestinal (GI) Effects under Precautions). Because of its lack of platelet effects, Celecoxib is not a substitute for Aspirin in the prophylactic treatment of CV disease.
Antihypertensives including Angiotensin-converting enzyme inhibitors (ACEIs), Angiotensin II antagonists (also known as angiotensin receptor blockers, [ARBs]), diuretics and beta-blockers: Inhibition of prostaglandins may diminish the effect of antihypertensives including ACEIs and/or ARBs, diuretics and beta-blockers. This interaction should be given consideration in patients taking Celecoxib concomitantly with ACEIs and/or ARBs, diuretics and beta-blockers.
In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, angiotensin II antagonists or diuretics, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Therefore, the concomitant administration of these drugs should be done with caution.
Patients should be adequately hydrated and the clinical need to monitor the renal function should be assessed at the beginning of the concomitant treatment and periodically thereafter.
Cyclosporine: Because of their effect on renal prostaglandins, NSAIDs may increase the risk of nephrotoxicity with Cyclosporine.
Fluconazole and Ketoconazole: 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, may result in a mean increase in Celecoxib C_max of 60% and in AUC of 130%. Ketoconazole, a CYP3A4 inhibitor, shows no clinically relevant inhibition in the metabolism of Celecoxib.
Dextromethorphan and Metoprolol: Concomitant administration of Celecoxib 200 mg twice daily resulted in a 2.6-fold and a 1.5-fold increases in plasma concentrations of Dextromethorphan and Metoprolol (CYP2D6 substrates), respectively. These increases are due to Celecoxib inhibition to the CYP2D6 substrate metabolism via CYP2D6. Therefore, the dose of drugs as CYP2D6 substrate may need to be reduced when treatment with Celecoxib is initiated or increased when treatment with Celecoxib is terminated (see Use with Oral Anticoagulants under Precautions).
Diuretics: NSAIDs in some patients can reduce the natriuretic effect of Furosemide and Thiazides by inhibition of renal prostaglandin synthesis.
Methotrexate: No pharmacokinetic and clinically important interactions can be observed in Celecoxib and Methotrexate.
Oral contraceptives: Celecoxib have no clinically relevant effects on the pharmacokinetics of a prototype combination oral contraceptive (1 mg Norethindrone/0.035 mg Ethinyl estradiol).
Other drugs: No clinically important interactions can be observed with Celecoxib and antacids (Aluminum and Magnesium), Omeprazole, Glibenclamide (Glyburide), Phenytoin or Tolbutamide.