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Author: Admin | 2025-04-28
Drug interactions have been found in studies of losartan potassium with hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital.However, rifampin has been shown to decrease the AUC of losartan and its active metabolite by 30% and 40%, respectively. Fluconazole, an inhibitor of cytochromeP450 2C9, decreased the AUC of the active metabolite by approximately 40%, but increased the AUC of losartan by approximately 70% following multiple doses.Conversion of losartan to its active metabolite after intravenous administration is not affected by ketoconazole, an inhibitor of P450 3A4. The AUC of active metabolitefollowing oral losartan was not affected by erythromycin, an inhibitor of P450 3A4, but the AUC of losartan was increased by 30%.The pharmacodynamic consequences of concomitant use of losartan and inhibitors of P450 2C9 have not been examined. Subjects who do not metabolize losartan toactive metabolite have been shown to have a specific, rare defect in cytochrome P450 2C9. These data suggest that the conversion of losartan to its active metabolite ismediated primarily by P450 2C9 and not P450 3A4.Clinical StudiesHypertensionAdult HypertensionThe antihypertensive effects of COZAAR were demonstrated principally in 4 placebo-controlled, 6- to 12-week trials of dosages from 10 to 150 mg per day in patientswith baseline diastolic blood pressures of 95-115. The studies allowed comparisons of two doses (50-100 mg/day) as once-daily or twice-daily regimens, comparisonsof peak and trough effects, and comparisons of response by gender, age, and race. Three additional studies examined the antihypertensive effects of losartan andhydrochlorothiazide in combination.The 4 studies of losartan monotherapy included a total of 1075 patients randomized to several doses of losartan and 334 to placebo. The 10- and 25-mg doses producedsome effect at peak (6 hours after dosing) but small and inconsistent trough (24 hour) responses. Doses of 50, 100 and 150 mg once daily gave statistically significantsystolic/diastolic mean decreases in blood pressure, compared to placebo in the range of 5.5-10.5/3.5-7.5 mmHg, with the 150-mg dose giving no greater effect than 50-100 mg. Twice-daily dosing at 50-100 mg/day gave consistently larger trough responses than once-daily dosing at the same total dose. Peak (6 hour) effects wereuniformly, but moderately, larger than trough effects, with the trough-to-peak ratio for systolic and diastolic responses 50-95% and 60-90%, respectively.Addition of a low dose of hydrochlorothiazide (12.5 mg) to losartan 50 mg once daily resulted in placebo-adjusted blood pressure reductions of 15.5/9.2 mmHg.Analysis of age, gender, and race subgroups of patients showed that men and women, and patients over and under 65, had generally similar responses. COZAAR waseffective in reducing blood pressure regardless of race, although the effect was somewhat less in Black patients (usually a low-renin population).Pediatric HypertensionThe antihypertensive effect of losartan was studied in one trial enrolling 177 hypertensive pediatric patients aged 6 to 16 years old. Children who weighed DOSAGE AND ADMINISTRATION] . The majority of the children had hypertension associated with renal and urogenital disease.The sitting diastolic blood pressure (SiDBP) on entry into the study was higher than the 95th percentile level for the patient's age, gender, and height. At the end of threeweeks, losartan
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