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Author: Admin | 2025-04-28
Of hydrochlorothiazide decreased by 45 and 85% in patients with mild and moderate renal impairment, respectively. Use the usual regimens of therapy with losartan potassium and hydrochlorothiazide as long as the patient’s creatinine clearance is greater than 30 mL/min. Safety and effectiveness of losartan potassium and hydrochlorothiazide in patients with severe renal impairment (creatinine clearance less than 30 mL/min) have not been established [see Use in Specific Populations (8.8)]. Drug Interactions Losartan Potassium No clinically significant 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 cytochrome P450 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 metabolite following 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 to active 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 is mediated primarily by P450 2C9 and not P450 3A4. 13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityLosartan Potassium-Hydrochlorothiazide No carcinogenicity studies have been conducted with the losartan potassium-hydrochlorothiazide combination. Losartan potassium and hydrochlorothiazide when tested at a weight ratio of 4:1, was negative in the Ames microbial mutagenesis assay and the V-79 Chinese hamster lung cell mutagenesis assay. In addition, there was
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