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 International Normalized Ratio (INR) prothrombin time. 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 7 days in patients receiving once-weekly methotrexate doses of 7.5-20 mg for rheumatoid arthritis. Arcoxia at 60 mg 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 >90 mg daily and methotrexate are administered concomitantly.
Diuretics, Angiotension 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.
Lithium: Reports suggest that nonselective 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. However, concomitant administration of low-dose aspirin with Arcoxia results in an increased rate of GI ulceration or other complications compared to use of Arcoxia alone. At steady-state, etoricoxib 120 mg once daily had no effect on the antiplatelet activity of low-dose aspirin (81 mg once daily). (See Precautions).
Oral Contraceptives: Arcoxia 60 mg given concomitantly with an oral contraceptive containing 35 mcg ethinyl estradiol (EE) and 0.5-1 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 concomitantly or separated by 12 hrs, increased the steady-state AUC_0-24hr of EE by 50-60%. 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 (eg, venous thromboembolic 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 mg 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 0.625-1.25 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 postmenopausal hormone therapy for use with Arcoxia.
Others: 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.