5 WARNINGS AND PRECAUTIONS

5.1 Hypotension and Worsening Renal Function

Excessive diuresis may cause potentially symptomatic dehydration, blood volume reduction and hypotension and worsening renal function, including acute renal failure particularly in salt-depleted patients or those taking renin- angiotensin aldosterone inhibitors. Worsening of renal function can also occur with concomitant use of nephrotoxic drugs (e.g., aminoglycosides, cisplatin, and NSAIDs). Monitor volume status and renal function periodically.

5.2 Electrolyte and Metabolic Abnormalities

Torsemide can cause potentially symptomatic hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, and hypochloremic alkalosis. Treatment with torsemide can cause an increase in blood glucose levels and hyperglycemia. Asymptomatic hyperuricemia can occur and gout may rarely be precipitated. Monitor serum electrolytes and blood glucose periodically.

5.3 Ototoxicity

Tinnitus and hearing loss (usually reversible) have been observed with loop diuretics, including torsemide. Higher than recommended doses, severe renal impairment, and hypoproteinemia, appear to increase the risk of ototoxicity.

2 DOSAGE AND ADMINISTRATION

2.1 Treatment of Edema

Edema associated with heart failure

The recommended initial dose is 10 mg or 20 mg oral torsemide once daily. If the diuretic response is inadequate, titrate upward by approximately doubling until the desired diuretic response is obtained. Doses higher than 200 mg have not been adequately studied.

Edema associated with chronic renal failure

The recommended initial dose is 20 mg oral torsemide once daily. If the diuretic response is inadequate, titrate upward by approximately doubling until the desired diuretic response is obtained. Doses higher than 200 mg have not been adequately studied.

Edema associated with hepatic cirrhosis

The recommended initial dose is 5 mg or 10 mg oral torsemide once daily, administered together with an aldosterone antagonist or a potassium-sparing diuretic. If the diuretic response is inadequate, titrate upward by approximately doubling until the desired diuretic response is obtained. Doses higher than 40 mg have not been adequately studied in this population.

2.2 Treatment of Hypertension

The recommended initial dose is 5 mg once daily. If the 5 mg dose does not provide adequate reduction in blood pressure within 4 to 6 weeks, increase to 10 mg once daily. If the response to 10 mg is insufficient, add another antihypertensive agent to the treatment regimen.