Etrobax Drug Interactions

Warfarin: In subjects stabilized on chronic warfarin therapy, the administration of etoricoxib 120 mg daily was associated with an approximate 13% increase in prothrombin time International Normalized Ratio (INR). Standard monitoring of INR values should be conducted when therapy with etoricoxib is initiated or changed, particularly in the first few days, in patients receiving warfarin or similar agents.
Rifampin: Co-administration of etoricoxib with rifampin, a potent inducer of hepatic metabolism, produced a 65% decrease in etoricoxib plasma area under the curve (AUC). This interaction should be considered when etoricoxib is co-administered with rifampin.
Methotrexate: Two reported studies investigated the effects of etoricoxib 60, 90 or 120 mg administered once daily for seven days in patients receiving once-weekly methotrexate doses of 7.5 to 20 mg for rheumatoid arthritis. Etoricoxib at 60 and 90 mg had no effect on methotrexate plasma concentrations (as measured by AUC) or renal clearance. In one reported study, etoricoxib 120 mg had no effect on methotrexate plasma concentrations (as measured by AUC) or renal clearance. In the other reported study, etoricoxib 120 mg increased methotrexate plasma concentrations by 28% (as measured by AUC) and reduced renal clearance of methotrexate by 13%. Monitoring for methotrexate-related toxicity should be considered when etoricoxib at doses greater than 90 mg daily and methotrexate are administered concomitantly.
Diuretics, Angiotensin Converting Enzyme (ACE) Inhibitors and Angiotensin II Antagonists (AIIAs): Reports suggest that NSAIDs including selective COX-2 inhibitors may diminish the antihypertensive effect of diuretics; ACE inhibitors and AIIAs. This interaction should be given consideration in patients taking etoricoxib concomitantly with these products.
In some patients with compromised renal function (e.g., elderly patients or patients who are volume-depleted, including those on diuretic therapy) who are being treated with nonsteroidal anti-inflammatory drugs, including selective COX-2 inhibitors, the co-administration of ACE inhibitors or AIIAs may result in a further deterioration of renal function, including possible acute renal failure. These effects are usually reversible. 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.
Lithium: Reports suggest that non-selective NSAIDs and selective COX-2 inhibitors may increase plasma lithium levels. This interaction should be given consideration in patients taking etoricoxib concomitantly with lithium.
Aspirin: Etoricoxib can be used concomitantly with low-dose aspirin at doses for cardiovascular prophylaxis. At steady state, etoricoxib 120 mg once daily had no effect on the anti-platelet activity of low-dose aspirin (81 mg once daily). However, concomitant administration of low-dose aspirin with etoricoxib increase the rate of GI ulceration or other complications compared to use of etoricoxib alone. Concomitant administration of etoricoxib with doses of aspirin above those for cardiovascular prophylaxis or with other NSAIDs is not recommended (see PRECAUTIONS).
Cyclosporin and tacrolimus: Although this interaction has not been reported 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.
Oral Contraceptives: Etoricoxib 60 mg given concomitantly with an oral contraceptive containing 35 mcg ethinyl estradiol (EE) and 0.5 to 1 mg norethindrone for 21 days increased the steady state AUC_0-24hr of EE by 37%. Etoricoxib 120 mg given with the same oral contraceptive, either concomitantly or separated by 12 hours, increased the steady state AUC_0-24hr of EE by 50 to 60%. This increase in EE concentration should be considered when selecting an oral contraceptive for use with etoricoxib. An increase in EE exposure can increase the incidence of adverse events associated with oral contraceptives (e.g., venous thrombo-embolic events in women at risk).
Hormone Replacement Therapy: Administration of etoricoxib 120 mg with hormone replacement therapy consisting of conjugated estrogens (0.625 mg) for 28 days, increased the mean steady state AUC_0-24hr of unconjugated estrone (41%), equilin (76%), and 17-β-estradiol (22%). The effect of the recommended chronic doses of etoricoxib (30, 60 and 90 mg) has not been reported. The effects of etoricoxib 120 mg on the exposure (AUC_0-24hr) to these estrogenic components of conjugated estrogens were less than half of those observed when conjugated estrogens was administered alone and the dose was increased from 0.625 to 1.25 mg. The clinical significance of these increases is unknown, and higher doses of conjugated estrogens were not studied in combination with etoricoxib. These increases in estrogenic concentration should be taken into consideration when selecting post-menopausal hormone therapy for use with etoricoxib because the increase in oestrogen exposure might increase the risk of adverse events associated with HRT.
Prednisone/prednisolone: In reported drug-interaction studies, etoricoxib did not have clinically important effects on the pharmacokinetics of prednisone/prednisolone.
Digoxin: Etoricoxib 120 mg administered once daily for 10 days to healthy volunteers did not after the steady-state plasma AUC_0-24hr or renal elimination of digoxin. There was an increase in digoxin C_max (approximately 33%). This increase is not generally important for most patients. However, 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 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).
Ketoconazole: Ketoconazole, a potent inhibitor of CYP3A4, dosed at 400 mg once a day for 11 days to healthy volunteers did not have any clinically important effect on the single-dose pharmacokinetics of 60 mg etoricoxib (43% increase in AUC).
Antacids: do not have clinically important effects on the pharmacokinetics of etoricoxib.