Questions about Atrial Fibrillation? Get answers from our expert.

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

Introduction

A sulfonamide, loop-type diuretic and antihypertensive agent.1 12 13 14

Uses for Demadex

Edema

Management of edema associated with CHF1 4 14 or hepatic1 or renal1 disease (including chronic renal failure).12 13 14

Slideshow: Newly Approved Weight Loss Drugs: Can They Help You?

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 3 12 13

One of several preferred initial therapies in hypertensive patients with CHF, acute pulmonary edema, or renal disease.2 3

Can be used as monotherapy for initial management of uncomplicated hypertension;1 2 3 12 13 14 however, thiazide diuretics are preferred by JNC 7.11

Demadex 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.1 12

Edema

  • Most experts state that all patients with symptomatic CHF who have evidence for, or a prior history of, fluid retention generally should receive diuretic therapy in conjunction with moderate sodium restriction (≤3 g of sodium daily), an ACE inhibitor, and usually a β-blocker, with or without a cardiac glycoside.4

  • Hospitalization of the patient during initiation of therapy is advisable for patients with hepatic cirrhosis and ascites or chronic renal failure.1 b 12 13

  • Chronic use of any diuretic in hepatic disease has not been adequately studied.1 12 13

Administration

Administer orally, by direct IV injection, or by continuous IV infusion.1 12 13 14

Oral Administration

Administer orally without regard to meals.1 12 13

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.1 12

If torsemide is administered through an IV line, flush the IV line with 0.9% sodium chloride injection before and after administration.12 14

Dilution

For IV infusion, dilute in 5% dextrose, 0.9% sodium chloride, or 0.45% sodium chloride injection.12 14

Rate of Administration

For direct IV injection, administer slowly over a period of 2 minutes.1 12 14

Administer IV injections of torsemide either slowly over 2 minutes (“bolus”) or as a continuous infusion.1 12 14

Dosage

Adults

Edema
CHF
Oral

Initially, 10–20 mg, given as a single dose.1 Increase as necessary by approximately doubling daily dosage until desired diuresis is attained.1 12 Single doses exceeding 200 mg not adequately studied.1 12 13

IV

Initially, 10–20 mg, given as a single dose.1 12 14 Increase as necessary by approximately doubling dosage until desired diuresis is attained.1 12 14 Single doses exceeding 200 mg not adequately studied.1 12 14

Hypertension
Oral

Initially, 5 mg once daily.1 12 13 If adequate hypotensive response not attained in 4–6 weeks, may increase dosage to 10 mg once daily.1 12 13 If adequate response not observed with 10 mg once daily, an additional antihypertensive agent should be added to antihypertensive therapy.1 12 13

IV

Initially, 5 mg once daily.1 12 14 If adequate hypotensive response not attained in 4–6 weeks, may increase dosage to 10 mg once daily.1 12 14 If adequate response not observed with 10 mg once daily, an additional antihypertensive agent should be added to antihypertensive therapy.1 12 14

Prescribing Limits

Adults

Edema
CHF
Oral

Maximum of 200 mg as a single dose (daily).1 12 13

IV

Maximum of 200 mg as a single dose (daily).1 12 14

Hypertension
Oral

Maximum of 10 mg once daily.1 12 13

IV

Maximum of 10 mg once daily.1 12 14

Special Populations

Renal Impairment

Edema
Edema Associated with Chronic Renal Failure
Oral or IV

In adults, initially, 20 mg once daily.1 14 Increase as necessary by approximately doubling dosage until desired diuresis is attained.1 14 Single doses exceeding 200 mg not adequately studied.1 12 13 14

Hepatic Impairment

Chronic use in hepatic disease not adequately studied.1 12 13

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.12 13 14 Increase as necessary by approximately doubling dosage until desired diuresis is attained.12 13 14 Single doses exceeding 40 mg not adequately studied.1 12 13 14

Cautions for Demadex

Contraindications

  • Anuria.1 12 13 14

  • Known hypersensitivity to torsemide or to sulfonylureas.1 12 13 14

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.1 12 13 14

Therapy in such patients is best initiated in the hospital.1 14 Use an aldosterone antagonist or potassium-sparing agent concomitantly with torsemide to prevent hypokalemia and metabolic alkalosis in such patients.1 12 13 14

Ototoxicity

Tinnitus and hearing loss, usually reversible, have been observed following rapid IV injection of other loop diuretics and following oral torsemide administration.1 12 13 14 Administer IV slowly (over 2 minutes); do not exceed 200 mg as a single dose.1 12 14

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).1 12 13 14

Excessive diuresis may cause dehydration and blood volume reduction with circulatory collapse and possibly vascular thrombosis and embolism, particularly in geriatric patients.1 12 13 14

Laboratory changes may include altered serum concentrations of sodium, chloride, and potassium; acid-base abnormalities; and increased BUN.1 12 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.1 12 13 14

Risk of hypokalemia, especially with brisk diuresis, with inadequate oral electrolyte intake, in those with cirrhosis, or during concomitant use of corticosteroids or ACTH.1 12 Risk of arrhythmias secondary to hypokalemia in patients with cardiovascular disease, especially those receiving concomitant therapy with a cardiac glycoside.1 12 13

Periodically monitor serum potassium and other electrolyte concentrations.1 12 13 14

General Precautions

Endocrine Effects

Possible increased blood glucose concentrations; hyperglycemia occurred rarely. 1 12 13 14

Renal and Electrolyte Effects

Small, dose-related, reversible increases in BUN, serum creatinine, and uric acid concentrations reported.1 14 12 Symptomatic gout reported at an incidence similar to placebo.1 12 13 14

Slight alterations in calcium and magnesium concentrations.1 12 13

Other Effects

Increases in total plasma cholesterol concentrations may occur; usually subside during chronic therapy.1 12 13 14

Increases in plasma triglyceride concentrations reported.1 12 13

In long-term studies, no clinically important differences in lipid profiles compared to baseline.1 12 14

No clinically important effects on hemoglobin; hematocrit; WBC, erythrocyte, or platelet counts; or serum alkaline phosphatase concentrations.1 12 13 14

Specific Populations

Pregnancy

Category B.1 12 13

Lactation

Not known whether torsemide is distributed into milk.1 12 13 14 Caution if used in nursing women.1 12 13 14

Pediatric Use

Safety and efficacy not established.1 12 13 14

Renal calcifications reported in severely premature infants with edema secondary to patent ductus arteriosus and hyaline membrane disease receiving another loop diuretic.1 12 14 Increased risk of persistent patent ductus arteriosus in premature neonates with hyaline membrane disease receiving another loop diuretic also has been reported.1 12 13 14

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1 12 13 14

Renal Impairment

Seizures reported in patients with acute renal failure receiving higher than recommended dosages of torsemide.1 12 13

Common Adverse Effects

Headache, excessive urination, dizziness, rhinitis, asthenia, diarrhea, ECG abnormality, increased cough.1 12 13 14

Interactions for Demadex

Specific Drugs

Drug

Interaction

Comments

Cholestyramine

Decreased absorption of torsemide in animals1 12 13 14

Avoid simultaneous administration when used concomitantly1 12 13 14

Digoxin

Increased torsemide AUC1 13 14

Torsemide dosage adjustment not necessary1 13 14

Lithium

Reduced renal clearance of lithium and increased risk of lithium toxicity reported with other diuretics 1 12 13 14

Avoid concomitant use or use great caution1 12 13 14

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 function1 12

Probenecid

Reduced secretion of torsemide into proximal tubule and decreased diuretic activity1 12

Salicylates (e.g., aspirin, NSAIAs)

Concomitant use of NSAIAs with another loop diuretic (furosemide) occasionally associated with renal dysfunction.1 12 13 14

Indomethacin may partially inhibit natriuretic effect of torsemide in those with dietary sodium restriction (50 mEq daily) 1 12 13 14

Concomitant use with high dosages of salicylates may result in salicylate toxicity1 12 13 14

Spironolactone

Reduced renal clearance of spironolactone1 12 13 14

Adjustment of spironolactone or torsemide dosage not necessary1 12 13 14

Demadex Pharmacokinetics

Absorption

Bioavailability

Bioavailability is approximately 80%.1

Onset

Following oral administration, onset of diuresis occurs within 1 hour; maximal effect during the first or second hour.1 12

Following IV administration, onset of diuresis occurs within 10 minutes; maximal effect within 1 hour.1 12

Duration

Independent of the route of administration, diuretic effect persists 6–8 hours following oral or IV administration.1 12

Food

Food delays the time to peak plasma concentration following oral dosing but does not affect extent of absorption or diuretic activity.1 12

Plasma Concentrations

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

Distribution

Extent

Not known whether torsemide is distributed into milk.1 12 13 14

Plasma Protein Binding

>99%.1 12

Elimination

Metabolism

Hepatic metabolism accounts for approximately 80% of total clearance.1 12 Carboxylic acid derivative, the major metabolite, is inactive.1 12 13 14

Elimination Route

Urinary excretion accounts for approximately 20% of total clearance in patients with normal renal function.1 12 Most renal clearance occurs via active secretion of the drug by the proximal tubules into tubular urine.1 12

Half-life

Approximately 3.5 hours.1 12 13 14

Special Populations

In patients with decompensated CHF, hepatic and renal clearance are reduced, resulting in delivery of less drug to the intraluminal site of action and decreased natriuretic effect.1 12 13 14 Total clearance is about half of that of healthy individuals; half-life and AUC increased.1 12 13 14

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.1 12 13 14

In patients with hepatic cirrhosis, renal clearance (but not total clearance) and half-life are increased.1 12 13 14

In geriatric patients, decreased renal clearance.1 12 13 14

Stability

Storage

Oral

Tablets

15–30°C.1 12 13

Parenteral

Injection

20–25°C.1 14 Do not freeze.1 14

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.1 12 13 14

  • Increases urinary excretion of sodium, chloride, and water without having an important effect on glomerular filtration rate, renal plasma flow, or acid-base balance.1 12 13 14

Advice to Patients

  • Risks associated with excessive fluid loss or electrolyte imbalance.1 12

  • Potential for postural hypotension; importance of rising slowly from a seated position.1

  • Importance of informing patients with diabetes mellitus that blood glucose concentrations may increase.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

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

* 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

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Demadex 10MG Tablets (MEDA PHARMACEUTICALS): 30/$43.69 or 90/$110.37

Demadex 100MG Tablets (MEDA PHARMACEUTICALS): 30/$160.99 or 90/$455.97

Demadex 20MG Tablets (MEDA PHARMACEUTICALS): 30/$57.99 or 90/$154.97

Torsemide 10MG Tablets (TEVA PHARMACEUTICALS USA): 30/$20.99 or 90/$59.97

Torsemide 100MG Tablets (AUROBINDO PHARMA): 30/$89.99 or 90/$249.96

Torsemide 20MG Tablets (TEVA PHARMACEUTICALS USA): 30/$22.99 or 90/$59.98

Torsemide 5MG Tablets (CAMBER PHARMACEUTICALS): 30/$18.99 or 90/$45.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 15, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Boehringer Mannheim. Demadex (torsemide) tablets and injection prescribing information. Rockville, MD: 1993 Oct.

2. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health. (NIH publication No. 98-4080.)

3. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80. [IDIS 365188] [PubMed 8622249]

4. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: approaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9-38A.

5. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. [PubMed 10818056]

6. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. [PubMed 10818055]

7. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61. [IDIS 452007] [PubMed 10977801]

8. Associated Press (American Diabetes Association). Diabetics urged: drop blood pressure. Chicago, IL; 2000 Aug 29. Press Release from web site.

9. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-42. [IDIS 490723] [PubMed 12479770]

10. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. [IDIS 490721] [PubMed 12479763]

11. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) Express. Bethesda, MD: May 14 2003. From NIH website. (http://www.nhlbi.nih.gov/guidelines/hypertension/jncintro.htm). (Also published in JAMA. 2003; 289:2560-72.

12. Roche Pharmaceuticals. Demadex (torsemide) tablets and injection prescribing information. Nutley, NJ: 2003 Apr.

13. Meda Demadex (torsemide) tablets prescribing information. Somerset, NJ: 2010 Feb.

14. American Regent. Torsemide injection prescribing information. Shirley, NY: 2009 Dec.

15. American Society of Health-System Pharmacists: Shortage and resumed manufacturing of torsemide Injection. http://www.ashp.org/Drug Shortages/Current/bulletin.aspx?id=344. Accessed Oct. 4 2011

16. Vargo DL, Kramer WG, Black PK et al. Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide and furosemide in patients with congestive heart failure. Clin Pharmacol Ther. 1995; 57:601-9 [PubMed 7781259]

17. American Regent announces increased production and availability of torsemide injection. New York; 2011;Feb 8. Press Release. . Clin Pharmacol Ther. 1994;56:48-54.

18. Kramer WG , Smith WB, Ferguson J et al. Pharmacodynamics of torsemide administered as an intravenous injection and as a continuous infusion to patients with congestive heart failure. J Clinical Pharmacol. 1996;36:265-270.

b. AHFS Drug Information 2007. McEvoy GK, ed. Furosemide. American Society of Health-System Pharmacists; 2007: 2690-4.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1581.

Hide
(web4)