Etoricoxib Auxilto Drug Interactions

Pharmacodynamic interactions: Oral anticoagulants: Concurrent use of etoricoxib and warfarin may result in increased prothrombin time International Normalized Ratio (INR). 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 coadministration 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 of 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 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: 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 is used in combination.
Pharmacokinetic interactions: The effect of etoricoxib on the pharmacokinetics of other drugs: 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monitor blood lithium closely and adjust the lithium dosage while the combination is being taken and when the NSAID is withdrawn.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: Concurrent use of etoricoxib and methotrexate may result in increased methotrexate plasma concentrations and toxicity. Adequate monitoring for methotrexate-related toxicity is recommended when etoricoxib and methotrexate are administered concomitantly.
Oral contraceptives: Concurrent use of etoricoxib and ethinyl estradiol (oral contraceptives) may result in increased plasma concentration of ethinyl estradiol. 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 (HRT): Concurrent use of etoricoxib and conjugated estrogens or Hormone Replacement Therapy 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 oestrogen exposure might increase the risk of adverse events associated with HRT.
Prednisone/prednisolone: Etoricoxib did not have clinically important effects on the pharmacokinetics of prednisone/prednisolone.
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 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 not expected to inhibit cytochromes P450 (CYP) 1A2, 2C9, 2C19, 2D6, 2E1, or 3A4.
Effects of other drugs on the pharmacokinetics of etoricoxib: The main pathway of etoricoxib metabolism is dependent on CYP enzymes. CYP3A4 appears to contribute to the metabolism of etoricoxib in vivo. CYP2D6, CYP2C9, CYP1A2, and CYP2C19 also can catalyse the main metabolic pathway, but their quantitative roles have not been studied.
Ketoconazole: Ketoconazole, a potent inhibitor of CYP3A4, did not have any clinically important effect on the single-dose pharmacokinetics of 60 mg etoricoxib.
Voriconazole and Miconazole: Coadministration 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: Coadministration of etoricoxib with rifampicin, a potent inducer of CYP enzymes, produced a decrease in etoricoxib plasma concentrations. This interaction may result in recurrence of symptoms when etoricoxib is coadministered with rifampicin. While this information may suggest an increase in dose, doses of etoricoxib greater than those listed for each indication are not recommended.
Antacids: Antacids do not affect the pharmacokinetics of etoricoxib to a clinically relevant extent.