Arcoxia Drug Interactions

Warfarin: In subjects stabilized on chronic warfarin therapy, the administration of ARCOXIA 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 ARCOXIA is initiated or changed, particularly in the first few days, in patients receiving warfarin or similar agents.
Rifampin: Co-administration of ARCOXIA 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 ARCOXIA is co-administered with rifampin.
Methotrexate: Two studies investigated the effects of ARCOXIA 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. ARCOXIA at 60 and 90 mg had no effect on methotrexate plasma concentrations (as measured by AUC) or renal clearance. In one study, ARCOXIA 120 mg had no effect on methotrexate plasma concentrations (as measured by AUC) or renal clearance. In the other study, ARCOXIA 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 ARCOXIA 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 ARCOXIA 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 non-steroidal 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.
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 ARCOXIA concomitantly with lithium.
Aspirin: ARCOXIA 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 ARCOXIA increases the rate of GI ulceration or other complications compared to use of ARCOXIA alone (see PRECAUTIONS).
Oral Contraceptives: ARCOXIA 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%. ARCOXIA 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 appropriate oral contraceptive for use with ARCOXIA. 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 ARCOXIA 120 mg with hormone replacement therapy consisting of conjugated estrogens (0.625 mg PREMARIN) 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 ARCOXIA (60 and 90 mg) has not been studied. The effects of ARCOXIA 120 mg on the exposure (AUC_0-24hr) to these estrogenic components of PREMARIN were less than half of those observed when PREMARIN 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 PREMARIN were not studied in combination with ARCOXIA. These increases in estrogenic concentration should be taken into consideration when selecting post-menopausal hormone therapy for use with ARCOXIA.
Other: In drug-interaction studies, ARCOXIA did not have clinically important effects on the pharmacokinetics of prednisone/prednisolone or digoxin.
Antacids and ketoconazole (a potent inhibitor of CYP3A4) did not have clinically important effects on the pharmacokinetics of ARCOXIA.