Irbesartan: No significant drug-drug pharmacokinetic (or pharmacodynamic) interactions have been found in interaction studies with hydrochlorothiazide, digoxin, warfarin, and nifedipine.
In vitro studies show significant inhibition of the formation of oxidized irbesartan metabolites with the known cytochrome CYP 2C9 substrates/inhibitors sulphenazole, tolbutamide and nifedipine. However, in clinical studies the consequences of concomitant irbesartan on the pharmacodynamics of warfarin were negligible. Concomitant nifedipine or hydrochlorothiazide had no effect on irbesartan pharmacokinetics. Based on in vitro data, no interaction would be expected with drugs whose metabolism is dependent upon cytochrome P450 isozymes 1A1, 1A2, 2A6, 2B6, 2D6, 2E1, or 3A4.
In separate studies of patients receiving maintenance doses of warfarin, hydrochlorothiazide, or digoxin, irbesartan administration for 7 days had no effect on the pharmacodynamics of warfarin (prothrombin time) or the pharmacokinetics of digoxin. The pharmacokinetics of irbesartan were not affected by coadministration of nifedipine or hydrochlorothiazide.
Hydrochlorothiazide: When administered concurrently the following drugs may interact with thiazide diuretics: Alcohol, Barbiturates, Or Narcotics: potentiation of orthostatic hypotension may occur.
Antidiabetic Drugs (oral agents and insulin): dosage adjustment of the antidiabetic drug may be required.
Other Antihypertensive Drugs: additive effect or potentiation.
Cholestyramine And Colestipol Resins: absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively.
Corticosteroids, ACTH: intensified electrolyte depletion, particularly hypokalemia.
Pressor Amines (e.g., Norepinephrine): possible decreased response to pressor amines but not sufficient to preclude their use.
Skeletal Muscle Relaxants, Nondepolarizing (e.g., Tubocurarine): possible increased responsiveness to the muscle relaxant.
Lithium: should not generally be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparations with Irbezyd H.
Non-steroidal Anti-inflammatory Drugs: in some patients, the administration of a nonsteroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when Irbezyd H (irbesartan hydrochlorothiazide) Tablets and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.