Source: FDA, National Drug Code (US) Revision Year: 2020
The mechanism of the antihypertensive effect of thiazides is unknown. DIURIL (chlorothiazide) does not usually affect normal blood pressure.
DIURIL (chlorothiazide) affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage all thiazides are approximately equal in their diuretic efficacy.
DIURIL (chlorothiazide) increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.
After oral use diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours. Following intravenous use of Sodium DIURIL, onset of the diuretic action occurs in 15 minutes and the maximal action in 30 minutes.
DIURIL is not metabolized but is eliminated rapidly by the kidney; 96 percent of an intravenous dose is excreted unchanged in the urine within 23 hours. The plasma half-life of chlorothiazide is 45 to 120 minutes. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
Carcinogenicity studies have not been conducted with chlorothiazide.
Chlorothiazide was not mutagenic in vitro in the Ames microbial mutagen test (using a maximum concentration of 5 mg/plate and Salmonella typhimurium strains TA98 and TA100) and was not mutagenic and did not induce mitotic nondisjunction in diploid-strains of Aspergillus nidulans.
Chlorothiazide had no adverse effects on fertility in female rats at doses up to 60 mg/kg/day and no adverse effects on fertility in male rats at doses up to 40 mg/kg/day. These doses are 1.5 and 1.0 times** the recommended maximum human dose, respectively, when compared on a body weight basis.
** Calculations based on a human body weight of 50 kg
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