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Agents Increasing Serum Potassium: Coadministration of losartan with other drugs that raise serum potassium levels may result in hyperkalemia.
Lithium: Increases in serum lithium concentrations have been reported with concomitant use of angiotensin II receptor antagonists (including losartan) or thiazide diuretics (including hydrochlorothiazide).
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) including selective COX-2 Inhibitors: In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs including selective COX-2 inhibitors, with losartan and hydrochlorothiazide may result in deterioration of renal function, including possible acute renal failure. These effects are reversible. Co-administration of NSAIDs including COX-2 inhibitors can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing, and thiazide diuretics. NSAIDs including COX-2 inhibitors may also attenuate antihypertensive effect of losartan.
ACE Inhibitors and Aliskiren: Dual blockade of renin-angiotensin system (RAS) with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.
Do not co-administer aliskiren with Losartan Potassium + Hydrochlorothiazide in patients with diabetes and in patients with renal impairment (GFR <60 mL/min).
Antidiabetic drugs: Dosage adjustment of the antidiabetic drug may be required.
Cholestyramine and Colestipol resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Hydrochlorothiazide should be administered at least 4 hours before or 4 to 6 hours after the administration of the resin.
Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur when co-administered with hydrochlorothiazide.
Other antihypertensive drugs: Additive effect or potentiation.
Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine): Possible increased responsiveness to muscle relaxant if administered with hydrochlorothiazide.
Corticosteroids, ACTH, or glycyrrhizin (found in liquorice): Concomitant use with hydrochlorothiazide may intensify electrolyte depletion, particularly hypokalemia.
Pressor amines (e.g., norepinephrine): Co-administration of hydrochlorothiazide can cause possible decreased response to pressor amines but not sufficient to preclude their use.
