Coxicare Drug Interactions

General: Etoricoxib is an inhibitor of human sulfotransferase activity, particularly SULT1E1 and has been shown to increase the serum concentrations of ethinyl oestradiol (see INTERACTIONS, Oral Contraceptives as follows).
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 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.
Aspirin: Etoricoxib can be used concomitantly with low-dose aspirin at doses for cardiovascular prophylaxis. At steady state, etoricoxib 120mg once daily had no effect on the anti-platelet activity of low-dose aspirin (81mg once daily), as assessed by ex vivo platelet aggregation and serum TXB2 generation in clotting blood. However, concomitant administration of low-dose aspirin with etoricoxib increases the rate of GI ulceration or other complications, compared to use of etoricoxib alone.
Digoxin: Etoricoxib 120mg once daily for 10 days did not alter the steady state plasma AUC0-24hr or renal elimination of digoxin. Therefore, digoxin and etoricoxib may be co-administered without dose adjustment.
Frusemide: Clinical studies have shown that NSAIDs can reduce the natriuretic effect of frusemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis.
Ketoconazole: Ketoconazole, a potent inhibitor of CYP3A4, dosed at 400mg once a day increased the AUC of etoricoxib by 43%. The clinical significance of this increase is not known.
Lithium: NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. Thus, when etoricoxib and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.
Methotrexate: Two studies investigated the effects of etoricoxib 60, 90 or 120mg administered once daily for seven days in patients receiving once-weekly methotrexate doses of 7.5 to 20mg for rheumatoid arthritis. etoricoxib at 60 and 90mg had no effect on methotrexate plasma concentrations (as measured by AUC) or renal clearance. In one study, etoricoxib 120mg had no effect on methotrexate plasma concentrations (as measured by AUC) or renal clearance. In the other study, etoricoxib 120mg increased methotrexate plasma concentrations by 28% (as measured by AUC) and reduced renal clearance of methotrexate by 13%. In these two studies, at 24 hours post-dose, a similar proportion of patients treated with methotrexate alone (approximately 93%) and subsequently treated with methotrexate co-administered with etoricoxib 120mg (approximately 82%) had methotrexate plasma concentrations below the measurable limit (5ng/mL). Standard monitoring for methotrexate-related toxicity should be considered when etoricoxib at doses greater than 90mg daily and methotrexate are administered concomitantly.
Oral Contraceptives: Etoricoxib 60mg given concomitantly with an oral contraceptive containing 35mcg ethinyl estradiol (EE) and 0.5 to 1mg norethindrone for 21 days increased the steady state AUC0-24hr of EE by 37%. Etoricoxib 120mg given with the same oral contraceptive, concomitantly or separated by 12 hours, increased the steady state AUC0-24hr 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 thromboembolic events in women at risk).
Hormone Replacement Therapy: Administration of etoricoxib 120mg with hormone replacement therapy consisting of conjugated oestrogens (0.625mg PREMARIN) for 28 days, increased the mean steady state AUC0-24hr of unconjugated estrone (41%), equilin (76%), and 17-β-oestradiol (22%). The effects of etoricoxib 120mg on the exposure (AUC0-24) to these oestrogenic components of PREMARIN were less than half of those observed when PREMARIN was administered alone and the dose was increased from 0.625 to 1.25mg. The clinical significance of these increases is unknown, and higher doses of PREMARIN were not studied in combination with etoricoxib. These increases in oestrogenic concentration should be taken into consideration when selecting post-menopausal hormone replacement therapy for use with etoricoxib.
Prednisone/prednisolone: Etoricoxib did not have any clinically important effect on the pharmacokinetics of prednisolone or prednisone.
Rifampicin: Co-administration of etoricoxib with rifampicin, a potent inducer of hepatic metabolism, 600mg daily, produced a 65% decrease in etoricoxib plasma AUC. This interaction should be taken into consideration when etoricoxib is co-administered with rifampicin.
Warfarin: Anticoagulant activity should be monitored, particularly in the first few days after initiating or changing etoricoxib therapy in patients receiving warfarin or similar agents, since these patients are at an increased risk of bleeding complications. In a multiple dose study in healthy subjects receiving both warfarin and etoricoxib 120mg, the steady state prothrombin time (measured as INR) was increased by approximately 13%.