Torsemide: uses, appearance and warnings

Torsemide is a loop diuretic indicated for: the treatment of edema associated with heart failure, renal disease or hepatic disease. ( 1.1 ) the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. ( 1.2 ) 1.1 Edema Torsemide tablets are indicated for the treatment of edema associated with heart failure, renal disease or hepatic disease. 1.2 Hypertension Torsemide tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with torsemide. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. The antihypertensive effects of torsemide are on the average greater in black patients than in nonblack patients [see Clinical Pharmacology (12.2) ]. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Torsemide can be used alone or in combination with other antihypertensive agents.

Torsemide Tablets, USP 5 mg are available as white to off-white, capsule shaped, uncoated tablets, debossed with bisect between “C” and “40” on one side and plain on other side. Torsemide Tablets, USP 10 mg are available as white to off-white, capsule shaped, uncoated tablets, debossed with bisect between “C” and “41” on one side and plain on other side. Torsemide Tablets, USP 20 mg are available as white to off-white, capsule shaped, uncoated tablets, debossed with bisect between “C” and “42” on one side and plain on other side. Torsemide Tablets, USP 100 mg are available as white to off-white, capsule shaped, uncoated tablets, debossed with bisect between “C” and “43” on one side and plain on other side. Tablets: 5 mg, 10 mg, 20 mg and 100 mg ( 3 )

Torsemide Tablets, USP 5 mg are available for oral administration as white to off-white, capsule shaped, uncoated tablets, debossed with bisect between “C” and “40” on one side and plain on other side. They are supplied as follows: Bottles of 90 (62135-818-90) Torsemide Tablets, USP 10 mg are available for oral administration as white to off-white, capsule shaped, uncoated tablets, debossed with bisect between “C” and “41” on one side and plain on other side. They are supplied as follows: Bottles of 90 (62135-819-90) Torsemide Tablets, USP 20 mg are available for oral administration as white to off-white, capsule shaped, uncoated tablets, debossed with bisect between “C” and “42” on one side and plain on other side. They are supplied as follows: Bottles of 90 (62135-820-90) Torsemide Tablets, USP 100 mg are available for oral administration as white to off-white, capsule shaped, uncoated tablets, debossed with bisect between “C” and “43” on one side and plain on other side. They are supplied as follows: Bottles of 90 (62135-821-90) Storage Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP with a child-resistant closure. Keep out of reach of children.

Torsemide tablets are contraindicated in patients with known hypersensitivity to torsemide or to povidone. Torsemide tablets are contraindicated in patients who are anuric. Torsemide tablets are contraindicated in patients with hepatic coma. Hypersensitivity to torsemide or povidone, anuria, and hepatic coma.( 4 )

Hypotension and worsening renal function: monitor volume status and renal function periodically ( 5.1 ) Electrolyte and metabolic abnormalities: monitor serum electrolytes and blood glucose periodically. ( 5.2 ) Ototoxicity ( 5.3 , 7.6 ) 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.

The following risks are discussed in more detail in others sections: Hypotension and Worsening Renal Function [see Warnings and Precautions (5.1) ] Electrolyte and Metabolic Abnormalities [see Warnings and Precautions (5.2) ] Ototoxicity [see Warnings and Precautions (5.3) ] The most common adverse reaction is excessive urination (6.7%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Chartwell RX, LLC at 1-845-232-1683 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. …

Non-steroidal anti-inflammatory drugs (NSAIDs): Reduced diuretic, natriuretic, and antihypertensive effects; risk of renal impairment. ( 7.1 ) CYP2C9: Concomitant use with CYP2C9 inhibitors can decrease torsemide clearance. Torsemide may affect the efficacy and safety of sensitive CYP2C9 substrates or of substrates with a narrow therapeutic range, such as warfarin or phenytoin. ( 7.2 ) Cholestyramine: Decreased exposure of torsemide. ( 7.3 ) Organic anion drugs: may decrease diuretic activity of torsemide. ( 7.4 ) Lithium: Risk of lithium toxicity ( 7.5 ) Renin-angiotensin inhibitors: Increased risk of hypotension and renal impairment. ( 7.7 ) Radiocontrast agents: Increased risk of renal toxicity. ( 7.8 ) Corticosteroids and ACTH: Increased risk of hypokalemia. …