Losartan: In clinical pharmacokinetic trials, no drug interactions of clinical significance have been identified with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital (see Alcohol, Barbiturates or Narcotics under Hydrochlorothiazide as follows), ketoconazole and erythromycin. Rifampin and fluconazole have been reported to reduce levels of active metabolite. The clinical consequences of these interactions have not been evaluated.
As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements or salt substitutes containing potassium, or other drugs that may increase serum potassium (e.g., trimethoprim-containing products) may lead to increases in serum potassium.
As with other drugs which affect the excretion of sodium, lithium excretion may be reduced. Therefore, serum lithium levels should be monitored carefully if lithium salts are to be co-administered with angiotensin II receptor antagonists.
Non-steroidal anti-inflammatory drugs (NSAIDs) including selective cyclooxygenase-2 (COX-2) inhibitors may reduce the effect of diuretics and other antihypertensive drugs. Therefore, the antihypertensive effect of angiotensin II receptor antagonists or ACE inhibitors may be attenuated by NSAIDs including selective COX-2 inhibitors.
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 cyclooxygenase-2 inhibitors, the co-administration of angiotensin II receptor antagonists or ACE inhibitors 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 in patients with compromised renal function.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) 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) as compared to monotherapy. Closely monitor blood pressure, renal function and electrolytes in patients on HYZAAR/HYZAAR PLUS/HYZAAR FORTE and other agents that affect the RAAS (see CONTRAINDICATIONS and PRECAUTIONS).
Hydrochlorothiazide: When given 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.
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 or glycyrrhizin (found in liquorice): Intensified electrolyte depletion, particularly hypokalemia.
Pressor amines (e.g., adrenaline): 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: Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity; concomitant use is not recommended. Refer to the package inserts for lithium preparations before use of such preparations.
Non-Steroidal Anti-inflammatory Drugs Including Cyclooxygenase-2 Inhibitors: The administration of a non-steroidal anti-inflammatory agent including a selective cyclooxygenase-2 inhibitor can reduce the diuretic, natriuretic and antihypertensive effects of diuretics (see Losartan as mentioned previously).
Drug/Laboratory Test Interactions: Because of their effects on calcium metabolism, thiazides may interfere with tests for parathyroid function (see PRECAUTIONS).