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Torsemide

Class: Loop Diuretics
- Diuretics, Loop
VA Class: CV702
Chemical Name: N-[[(1-Methylethyl)amino]carbonyl]-4-[(3-methylphenyl) amino]-3-pyridinesulfonamide
Molecular Formula: C16H20N4O3S
CAS Number: 56211-40-6
Brands: Demadex

Medically reviewed by Drugs.com on Mar 15, 2022. Written by ASHP.

Introduction

A sulfonamide, loop-type diuretic and antihypertensive agent.

Uses for Torsemide

Edema

Management of edema associated with heart failure or hepatic or renal disease (including chronic renal failure).

Most experts state that all patients with symptomatic heart failure who have evidence for, or a history of, fluid retention generally should receive diuretic therapy in conjunction with moderate sodium restriction, an agent to inhibit the renin-angiotensin-aldosterone (RAA) system (e.g., ACE inhibitor, angiotensin II receptor antagonist, angiotensin receptor-neprilysin inhibitor [ARNI]), a β-adrenergic blocking agent (β-blocker), and in selected patients, an aldosterone antagonist.

Hypertension

Management of hypertension alone or in combination with other classes of antihypertensive agents.

Not considered a preferred agent for initial management of hypertension according to current evidence-based hypertension guidelines; other agents (i.e., ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, thiazide diuretics) are preferred for initial management.

Some experts state that loop diuretics (e.g., bumetanide, furosemide, torsemide) are preferred over thiazides in patients with moderate to severe chronic kidney disease (CKD) or symptomatic heart failure.

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension. (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP. However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk. In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg. These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.

Other hypertension guidelines generally have based target BP goals on age and comorbidities. Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk, and have used higher BP thresholds and target BPs in elderly patients compared with those recommended by the 2017 ACC/AHA hypertension guideline.

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors. ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.

Adults with hypertension and diabetes mellitus, CKD, or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg. Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP. Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.

Torsemide Dosage and Administration

General

  • The manufacturers state that since oral and IV doses of torsemide are therapeutically equivalent, torsemide dosage is identical for oral or IV administration.

Edema

  • Hospitalization of the patient during initiation of therapy is advisable for patients with hepatic cirrhosis and ascites or chronic renal failure.

  • Chronic use of any diuretic in hepatic disease has not been adequately studied.

  • For the management of fluid retention (e.g., edema) associated with heart failure, experts state that diuretics should be administered at a dosage sufficient to achieve optimal volume status and relieve congestion without inducing an excessively rapid reduction in intravascular volume, which could result in hypotension, renal dysfunction, or both.

Monitoring and BP Treatment Goals

  • Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.

  • Assess patient's renal function and electrolytes 2–4 weeks after initiation of diuretic therapy.

  • If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.

  • If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., ACE inhibitor, angiotensin II receptor antagonist, calcium-channel blocker). Many patients will require at least 2 drugs from different pharmacologic classes to achieve this BP goal; if goal BP still not achieved with 2 antihypertensive agents, add a third drug.

Administration

Administer orally, by direct IV injection, or by continuous IV infusion.

Oral Administration

Administer orally without regard to meals.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

May use IV administration when a rapid onset of diuresis is desired or when oral therapy is not practical.

If torsemide is administered through an IV line, flush the IV line with 0.9% sodium chloride injection before and after administration.

Dilution

For IV infusion, dilute in 5% dextrose, 0.9% sodium chloride, or 0.45% sodium chloride injection.

Rate of Administration

For direct IV injection, administer slowly over a period of 2 minutes.

Administer IV injections of torsemide either slowly over 2 minutes (“bolus”) or as a continuous infusion.

Dosage

Adults

Edema
Heart Failure
Oral

Initially, 10–20 mg daily, given as a single dose. Increase as necessary by approximately doubling daily dosage until desired diuresis is attained. Single doses exceeding 200 mg not adequately studied. Some experts recommend initiating at a low dosage and increasing the dosage until urine output increases and weight decreases, generally by 0.5–1 kg daily.

IV

Initially, 10–20 mg, given as a single dose. Increase as necessary by approximately doubling dosage until desired diuresis is attained. Single doses exceeding 200 mg not adequately studied.

Hypertension
Oral

Initially, 5 mg once daily. If adequate hypotensive response not attained in 4–6 weeks, may increase dosage to 10 mg once daily. If adequate response not observed with 10 mg once daily, an additional antihypertensive agent should be added to antihypertensive therapy.

Some experts state usual dosage is 5–10 mg once daily.

IV

Initially, 5 mg once daily. If adequate hypotensive response not attained in 4–6 weeks, may increase dosage to 10 mg once daily. If adequate response not observed with 10 mg once daily, an additional antihypertensive agent should be added to antihypertensive therapy.

Prescribing Limits

Adults

Edema
Heart Failure
Oral

Maximum of 200 mg as a single dose (daily).

IV

Maximum of 200 mg as a single dose (daily).

Hypertension
Oral

Maximum of 10 mg once daily.

IV

Maximum of 10 mg once daily.

Special Populations

Renal Impairment

Edema
Edema Associated with Chronic Renal Failure
Oral or IV

In adults, initially, 20 mg once daily. Increase as necessary by approximately doubling dosage until desired diuresis is attained. Single doses exceeding 200 mg not adequately studied.

Hepatic Impairment

Chronic use in hepatic disease not adequately studied.

Edema
Edema Associated with Hepatic Cirrhosis
Oral or IV

In adults, initially, 5–10 mg once daily, given concomitantly with an aldosterone antagonist or a potassium-sparing diuretic. Increase as necessary by approximately doubling dosage until desired diuresis is attained. Single doses exceeding 40 mg not adequately studied.

Cautions for Torsemide

Contraindications

  • Anuria.

  • Known hypersensitivity to torsemide or to sulfonylureas.

Warnings/Precautions

Warnings

Hepatic Effects

Sudden alterations of electrolyte balance in patients with cirrhosis may precipitate hepatic coma; use with caution in patients with hepatic cirrhosis and ascites.

Therapy in such patients is best initiated in the hospital. Use an aldosterone antagonist or potassium-sparing agent concomitantly with torsemide to prevent hypokalemia and metabolic alkalosis in such patients.

Ototoxicity

Tinnitus and hearing loss, usually reversible, have been observed following rapid IV injection of other loop diuretics and following oral torsemide administration. Administer IV slowly (over 2 minutes); do not exceed 200 mg as a single dose.

Fluid, Electrolyte, and Cardiovascular Effects

Observe carefully for manifestations of fluid and electrolyte depletion (e.g., dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, nausea, vomiting).

Excessive diuresis may cause dehydration and blood volume reduction with circulatory collapse and possibly vascular thrombosis and embolism, particularly in geriatric patients.

Laboratory changes may include altered serum concentrations of sodium, chloride, and potassium; acid-base abnormalities; and increased BUN. If electrolyte imbalance, hypovolemia, or prerenal azotemia develops, torsemide should be discontinued until the abnormality is corrected; treatment then may be restarted at a reduced dosage.

Risk of hypokalemia, especially with brisk diuresis, with inadequate oral electrolyte intake, in those with cirrhosis, or during concomitant use of corticosteroids or ACTH. Risk of arrhythmias secondary to hypokalemia in patients with cardiovascular disease, especially those receiving concomitant therapy with a cardiac glycoside.

Periodically monitor serum potassium and other electrolyte concentrations.

General Precautions

Endocrine Effects

Possible increased blood glucose concentrations; hyperglycemia occurred rarely.

Renal and Electrolyte Effects

Small, dose-related, reversible increases in BUN, Scr, and uric acid concentrations reported. Symptomatic gout reported at an incidence similar to placebo.

Slight alterations in calcium and magnesium concentrations.

Other Effects

Increases in total plasma cholesterol concentrations may occur; usually subside during chronic therapy.

Increases in plasma triglyceride concentrations reported.

In long-term studies, no clinically important differences in lipid profiles compared to baseline.

No clinically important effects on hemoglobin; hematocrit; WBC, erythrocyte, or platelet counts; or serum alkaline phosphatase concentrations.

Specific Populations

Pregnancy

Category B.

Lactation

Not known whether torsemide is distributed into milk. Caution if used in nursing women.

Pediatric Use

Safety and efficacy not established.

Renal calcifications reported in severely premature infants with edema secondary to patent ductus arteriosus and hyaline membrane disease receiving another loop diuretic. Increased risk of persistent patent ductus arteriosus in premature neonates with hyaline membrane disease receiving another loop diuretic also has been reported.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.

Renal Impairment

Seizures reported in patients with acute renal failure receiving higher than recommended dosages of torsemide.

Common Adverse Effects

Headache, excessive urination, dizziness, rhinitis, asthenia, diarrhea, ECG abnormality, increased cough.

Interactions for Torsemide

Specific Drugs

Drug

Interaction

Comments

Cholestyramine

Decreased absorption of torsemide in animals

Avoid simultaneous administration when used concomitantly

Digoxin

Increased torsemide AUC

Torsemide dosage adjustment not necessary

Lithium

Reduced renal clearance of lithium and increased risk of lithium toxicity reported with other diuretics

Avoid concomitant use or use great caution

Ototoxic drugs (e.g., aminoglycoside antibiotics, ethacrynic acid)

Possible additive ototoxic effect when ototoxic drugs used concomitantly with other diuretics, especially in those with impaired renal function

Probenecid

Reduced secretion of torsemide into proximal tubule and decreased diuretic activity

Salicylates (e.g., aspirin, NSAIAs)

Concomitant use of NSAIAs with another loop diuretic (furosemide) occasionally associated with renal dysfunction

Indomethacin may partially inhibit natriuretic effect of torsemide in those with dietary sodium restriction (50 mEq daily)

Concomitant use with high dosages of salicylates may result in salicylate toxicity

Spironolactone

Reduced renal clearance of spironolactone

Adjustment of spironolactone or torsemide dosage not necessary

Torsemide Pharmacokinetics

Absorption

Bioavailability

Bioavailability is approximately 80%.

Onset

Following oral administration, onset of diuresis occurs within 1 hour; maximal effect during the first or second hour.

Following IV administration, onset of diuresis occurs within 10 minutes; maximal effect within 1 hour.

Duration

Independent of the route of administration, diuretic effect persists 6–8 hours following oral or IV administration.

Food

Food delays the time to peak plasma concentration following oral dosing but does not affect extent of absorption or diuretic activity.

Plasma Concentrations

Following oral administration, peak plasma concentrations achieved within 1 hour.

Distribution

Extent

Not known whether torsemide is distributed into milk.

Plasma Protein Binding

>99%.

Elimination

Metabolism

Hepatic metabolism accounts for approximately 80% of total clearance. Carboxylic acid derivative, the major metabolite, is inactive.

Elimination Route

Urinary excretion accounts for approximately 20% of total clearance in patients with normal renal function. Most renal clearance occurs via active secretion of the drug by the proximal tubules into tubular urine.

Half-life

Approximately 3.5 hours.

Special Populations

In patients with decompensated heart failure, hepatic and renal clearance are reduced, resulting in delivery of less drug to the intraluminal site of action and decreased natriuretic effect. Total clearance is about half of that of healthy individuals; half-life and AUC increased.

In patients with renal failure, renal clearance (but not total clearance) is reduced, resulting in delivery of less drug to the intraluminal site of action and decreased natriuretic effect.

In patients with hepatic cirrhosis, renal clearance (but not total clearance) and half-life are increased.

In geriatric patients, decreased renal clearance.

Stability

Storage

Oral

Tablets

15–30°C.

Parenteral

Injection

20–25°C. Do not freeze.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in water

Sodium chloride 0.45 or 0.9%

Y-Site CompatibilityHID

Compatible

Milrinone lactate

Actions

  • Acts from within the lumen of the thick ascending portion of the loop of Henle, where it inhibits the sodium/potassium/chloride carrier system.

  • Increases urinary excretion of sodium, chloride, and water without having an important effect on glomerular filtration rate, renal plasma flow, or acid-base balance.

Advice to Patients

  • Risks associated with excessive fluid loss or electrolyte imbalance.

  • Potential for postural hypotension; importance of rising slowly from a seated position.

  • Importance of informing patients with diabetes mellitus that blood glucose concentrations may increase.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Torsemide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

5 mg*

Demadex

Roche

Torsemide Tablets

10 mg*

Demadex (scored)

Roche

Torsemide Tablets

20 mg*

Demadex (scored)

Roche

Torsemide Tablets

100 mg*

Demadex (scored)

Roche

Torsemide Tablets

Parenteral

Injection, for IV use

10 mg/mL

Torsemide Injection

AHFS DI Essentials™. © Copyright 2022, Selected Revisions March 25, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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