Losartan

Additional information

Pharmacokinetics and dosing

In a pharmacokinetic study, single oral and intravenous doses of losartan produced plasma concentrations of losartan that were two-fold higher in hypertensive women than in hypertensive men, due to reduced systemic clearance in women. However, plasma concentrations of the active metabolite of losartan, E 3174 (ten times more effective than the parent compound), were similar in men and women [1-4].

Even though some pharmacokinetic sex differences of losartan have been described, the clinical relevance of these has not been shown and therefore no dosage adjustment based on patient’s sex has been considered necessary [3].

Effects

A review evaluating clinical experience with losartan from worldwide, double-blind, controlled studies, confirm that the antihypertensive effect of losartan is similar in women and men [1, 3-6].

The large randomized, triple-blind LIFE study (4230 men, 4963 women), conducted by the pharmaceutical company, compared losartan with atenolol in patients, aged 55-80 years, with hypertension and left ventricular hypertrophy [7, 8]. Blood pressure lowering effect of losartan (50 mg daily) was similar in men and women. Only women had a significant reduction in the primary composite end point (cardiovascular mortality, stroke, and myocardial infarction), regardless of treatment with losartan or atenolol. When analyzing the endpoints separately, women on losartan had significant reduction in stroke and total mortality [7-9].

A prospective, randomized trial (4230 men, 4963 women) reported that women had less regression of electrocardiographic (ECG) left ventricular hypertrophy than men during losartan therapy. Regression of ECG left ventricular hypertrophy is associated with improved prognosis. These findings suggest that women may derive less prognostic benefit [10]. In the original LIFE-study [7], a change of the definition of LVH on ECG in women during the study was therefore necessary.

The randomized, double-blind, placebo-controlled RENAAL trial (956 men, 557 women) evaluated losartan 50-100 mg once daily in addition to conventional hypertensive treatment in patients with type 2 diabetes and advanced renal disease. The primary endpoint (a composite of doubling of serum creatinine, end-stage renal disease, or death) was similarly reduced in men and women (HR 0.90 vs. 0.80) [9, 11].

Adverse effects

Reviews and meta-analysis consisting of several double-blind trials, have reported that the overall incidence of adverse clinical events in losartan-treated patients were similar in men and women [5, 6]. In the LIFE study, women had more adverse events than men, regardless of treatment with losartan or atenolol. However, serious adverse events (i.e. events causing hospitalization, prolongation of hospitalization, or death) did not differ between men and women (36.3% vs. 38.3%) [8].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).