With oral dosing, the onset of diuresis occurs within 1 hour and the peak effect occurs during the first or second hour and diuresis lasts about 6 to 8 hours. In healthy subjects given single doses, the dose-response relationship for sodium excretion is linear over the dose range of 2.5 mg to 20 mg. The increase in potassium excretion is negligible after a single dose of up to 10 mg and only slight (5 mEq to 15 mEq) after a single dose of 20 mg.

Congestive Heart Failure  
DEMADEX has been studied in controlled trials in patients with New York Heart Association Class II to Class IV congestive heart failure. Patients who received 10 mg to 20 mg of daily DEMADEX in these studies achieved significantly greater reductions in weight and edema than did patients who received placebo.

Nonanuric Renal Failure  
In single-dose studies in patients with nonanuric renal failure, high doses of DEMADEX (20 mg to 200 mg) caused marked increases in water and sodium excretion. In patients with nonanuric renal failure, severe enough to require hemodialysis, chronic treatment with up to 200 mg of daily DEMADEX has not been shown to change steady-state fluid retention. When patients in a study of acute renal failure received total daily doses of 520 mg to 1200 mg of DEMADEX, 19% experienced seizures. Ninety-six patients were treated in this study; 6/32 treated with torsemide experienced seizures, 6/32 treated with comparably high doses of furosemide experienced seizures, and 1/32 treated with placebo experienced a seizure.

Hepatic Cirrhosis  
When given with aldosterone antagonists, DEMADEX also caused increases in sodium and fluid excretion in patients with edema or ascites due to hepatic cirrhosis. Urinary sodium excretion rate relative to the urinary excretion rate of DEMADEX is less in cirrhotic patients than in healthy subjects (possibly because of the hyperaldosteronism and resultant sodium retention that are characteristic of portal hypertension and ascites). However, because of the increased renal clearance of DEMADEX in patients with hepatic cirrhosis, these factors tend to balance each other, and the result is an overall natriuretic response that is similar to that seen in healthy subjects. Chronic use of any diuretic in hepatic disease has not been studied in adequate and well-controlled trials.

Essential Hypertension  
In patients with essential hypertension, DEMADEX has been shown in controlled studies to lower blood pressure when administered once a day at doses of 5 mg to 10 mg. The antihypertensive effect is near maximal after 4 to 6 weeks of treatment, but it may continue to increase for up to 12 weeks. Systolic and diastolic supine and standing blood pressures are all reduced. There is no significant orthostatic effect, and there is only a minimal peak-trough difference in blood pressure reduction.

The antihypertensive effects of DEMADEX are, like those of other diuretics, on the average greater in black patients (a low-renin population) than in nonblack patients.

When DEMADEX is first administered, daily urinary sodium excretion increases for at least a week. With chronic administration, however, daily sodium loss comes into balance with dietary sodium intake. If the administration of DEMADEX is suddenly stopped, blood pressure returns to pretreatment levels over several days, without overshoot.

DEMADEX has been administered together with β-adrenergic blocking agents, ACE inhibitors, and calcium-channel blockers. Adverse drug interactions have not been observed, and special dosage adjustment has not been necessary.