Cozaar - Warnings & Precautions

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Losartan potassium has been shown to produce adverse effects in rat fetuses and neonates, including decreased body weight, delayed physical and behavioral development, mortality and renal toxicity. With the exception of neonatal weight gain (which was affected at doses as low as 10 mg/ kg/ day), doses associated with these effects exceeded 25 mg/ kg/ day (approximately three times the maximum recommended human dose of 100 mg on a mg/ m 2 basis). These findings are attributed to drug exposure in late gestation and during lactation. Significant levels of losartan and its active metabolite were shown to be present in rat fetal plasma during late gestation and in rat milk.

Hypotension — Volume-Depleted Patients

In patients who are intravascularly volume-depleted (e. g., those treated with diuretics), symptomatic hypotension may occur after initiation of therapy with COZAAR. These conditions should be corrected prior to administration of COZAAR, or a lower starting dose should be used (see DOSAGE AND ADMINISTRATION).

PRECAUTIONS

General Hypersensitivity

Angioedema. See ADVERSE REACTIONS, Post-Marketing Experience.

Impaired Hepatic Function

Based on pharmacokinetic data which demonstrate significantly increased plasma concentrations of losartan in cirrhotic patients, a lower dose should be considered for patients with impaired liver function (see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY, Pharmacokinetics).

Impaired Renal Function

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function have been reported in susceptible individuals treated with COZAAR; in some patients, these changes in renal function were reversible upon discontinuation of therapy. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e. g., patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors has been associated with oliguria and/ or progressive azotemia and (rarely) with acute renal failure and/ or death. Similar outcomes have been reported with COZAAR.