Pharmacodynamic interactions: Oral anticoagulants: Coadministration with BIOCOXIB 90 MG and 120 MG Film Coated Tablet may increase the risk of anticoagulant-induced bleeding (eg. GI bleeding). Therefore, patients receiving oral anticoagulants should be closely monitored for their prothrombin time INR, particularly in the first few days when therapy with etoricoxib is initiated or the dose of etoricoxib is changed.
Diuretics, ACE inhibitors and Angiotensin II Antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclooxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. These interactions should be considered in patients taking etoricoxib concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.
Acetylsalicylic Acid: Etoricoxib can be used concomitantly with acetylsalicylic acid at doses used for cardiovascular prophylaxis (low-dose acetylsalicylic acid). However, concomitant administration of low-dose acetylsalicylic acid with etoricoxib may result in an increased rate of GI ulceration or other complications compared to the use of etoricoxib alone. Concomitant administration of etoricoxib with doses of acetylsalicylic acid above those for cardiovascular prophylaxis or with other NSAIDs is not recommended.
Cyclosporin and tacrolimus: Although this interaction has not been studied with etoricoxib, coadministration of cyclosporin or tacrolimus with any NSAID may increase the nephrotoxic effect of cyclosporin or tacrolimus. Renal function should be monitored when etoricoxib and either of these drugs are used in combination.
Pharmacokinetic interactions: Lithium: NSAIDs decrease lithium renal excretion and therefore increase lithium plasma levels. If necessary, monitor blood lithium closely and adjust the lithium dosage while the combination is being taken and when the NSAID is withdrawn.
Methotrexate: Concomitant administration with BIOCOXIB 90 MG and 120 MG Film Coated Tablet may increase the risk of methotrexate toxicity (eg. stomatitis, bone marrow suppression, nephrotoxicity). Adequate monitoring for methotrexate-related toxicity is recommended when etoricoxib and methotrexate are administered concomitantly.
Oral contraceptives: Concurrent use of ethinyl estradiol (EE)/norethindrone and etoricoxib may result in increased ethinyl estradiol exposure. Use caution with the concomitant use of etoricoxib with oral contraceptives containing ethinyl estradiol as etoricoxib may increase ethinyl estradiol plasma concentrations. Consider the increased risk for adverse effects (eg, venous thromboembolic events) with higher ethinyl estradiol exposure in at-risk patients when selecting an oral contraceptive to be used concurrently with etoricoxib.
Hormone Replacement Therapy (HRT): Concurrent use of conjugated estrogens and etoricoxib may result in increased conjugated estrogen exposure. These increases in estrogenic concentration should be taken into consideration when selecting post-menopausal hormone therapy for use with etoricoxib because the increase in estrogen exposure might increase the risk of adverse events associated with HRT.
Prednisone/prednisolone: Concurrent use of corticosteroids and NSAIDs may result in increased risk of gastrointestinal ulcer or bleeding. If coadministration is necessary, monitor for signs of bleeding.
Digoxin: Concurrent use of digoxin and NSAIDs may result in increased serum concentration of digoxin; prolonged half-life of digoxin. Patients at high risk of digoxin toxicity should be monitored for this when etoricoxib and digoxin are administered concomitantly.
Effect of etoricoxib on drugs metabolised by sulfotransferases: Etoricoxib is an inhibitor of human sulfotransferase activity, particularly SULT1E1, and has been shown to increase the serum concentrations of ethinyl estradiol. While knowledge about the effects of multiple sulfotransferases is presently limited and the clinical consequences for many drugs are still being examined, it may be prudent to exercise care when administering etoricoxib concurrently with other drugs primarily metabolised by human sulfotransferases (e.g., oral salbutamol and minoxidil).
Effect of etoricoxib on drugs metabolised by CYP isoenzymes: Etoricoxib is metabolized primarily by the cytochrome P450 (CYP) 3A4 isoenzyme. However, it appears to have limited inhibitory effects on CYP3A4.
Effects of other drugs on the pharmacokinetics of etoricoxib: The main pathway of etoricoxib metabolism is dependent on CYP enzymes, extensively via CYP3A4 (in vitro data suggest that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 may also play a role in metabolism).
Voriconazole and Miconazole: Co-administration of either oral voriconazole or topical miconazole oral gel, strong CYP3A4 inhibitors, with etoricoxib caused a slight increase in exposure to etoricoxib, but is not considered to be clinically meaningful based on published data.
Rifampicin: Concurrent administration of etoricoxib and rifampin may cause reduced etoricoxib blood concentrations. This interaction may result in the recurrence of symptoms when etoricoxib is co-administered with rifampicin. While this information may require etoricoxib dose increases beyond current recommendations for each indication, and therefore is not recommended.
Antacids and Ketoconazole: Antacids and ketoconazole (a potent inhibitor of CYP3A4) did not have clinically important effects on the pharmacokinetics of BIOCOXIB.