Torsemide for Treatment of Congestive Heart Failure in Dogs & Cats

Torsemide (ie, torasemide) is a potent loop diuretic used for management of congestive heart failure (CHF) in dogs and cats. Compared with furosemide, torsemide provides higher oral bioavailability, longer duration of action, and greater diuretic potency.

Clinical Applications

Oral administration of torsemide produces sustained diuresis in dogs due to a longer duration of action compared with furosemide, often permitting once-daily administration,^1-4 which may improve pet owner compliance compared with twice-daily furosemide.²

Dogs

In dogs with CHF secondary to myxomatous mitral valve disease, torsemide provides noninferior control of pulmonary edema and clinical signs compared with furosemide.^1,2 Prospective clinical trials have reported significantly reduced risk for reaching a composite cardiac endpoint (defined as pooled occurrence of cardiac death, euthanasia, or CHF worsening) in dogs administered once-daily torsemide as compared with twice-daily furosemide of equivalent dose.^1,2 This benefit was primarily driven by a reduction in CHF worsening (either progression of modified New York Heart Association class in the TEST study or requiring escalation of diuretic dose in the CARPODIEM study) rather than a statistically significant difference in cardiac-related death alone.

Torsemide is used in dogs with CHF when clinical response to furosemide is inadequate or frequent administration becomes impractical.^1,5 Onset of action is rapid after oral administration, and the duration of diuresis typically approaches 12 hours.^6,7

Cats

In cats with CHF, torsemide can be used as a first-choice diuretic or a second-choice loop diuretic when furosemide response is inadequate or administration frequency is difficult.^8,9 Studies of torsemide in cats are limited; however, a retrospective case series on cats with CHF and a prospective study of healthy cats have suggested acceptable short-term tolerance and clinical efficacy, and one pharmacokinetic study supports once-daily oral administration.^8-10 The longer duration of action may be advantageous in cats that are difficult to medicate multiple times daily.^8,9

Administration Considerations

In dogs, torsemide is ≈10 to 20 times more potent than furosemide on a mg/kg basis, depending on dose range.^1,3,5,6 Because of this difference in potency, initial torsemide doses are commonly calculated as 5% to 10% of the total daily furosemide dose (0.13-0.25 mg/kg every 24 hours for first-onset CHF in dogs), with lower ratios used at higher furosemide doses.^1,4 In cats, studied oral doses range from ≈0.16 to 0.4 mg/kg every 24 hours.^8,9 Small dose adjustments can result in large changes in diuretic effect because of the potency of this drug.^3,5 Once-daily torsemide administration may be appropriate for first-onset CHF, but an escalated frequency of administration is often necessary with worsening heart failure.²

Mechanism of Action

Torsemide inhibits the Na⁺/K⁺/2Cl⁻ cotransporter in the thick ascending limb of the loop of Henle, producing natriuresis and diuresis.⁵ Compared with furosemide, torsemide has higher and more predictable oral bioavailability in dogs (≈80%-100%) and cats (88%), as well as a longer elimination half-life in dogs (torsemide, 6-12.3 hours; furosemide, 3 hours) and cats (torsemide, 12.9 hours; furosemide, 1.2-2.3 hours).^3,6,8,11 Feeding may slightly delay time to peak onset but has no effect on maximal plasma concentrations (ie, can be given with or without food).

Effects on the Renin-Angiotensin-Aldosterone System

Loop diuretics activate the renin-angiotensin-aldosterone system (RAAS) via volume depletion and inhibition of the Na⁺/K⁺/2Cl⁻ transport at the macula densa, impairing sodium chloride sensing and stimulating renin release from the juxtaglomerular apparatus.⁵ In a crossover study of healthy dogs, torsemide did not result in significant differences in BUN, sodium, potassium, blood pressure, or heart rate compared with furosemide. Torsemide administration resulted in a similar level of RAAS activation and was considered equipotent at approximately one-twentieth of the furosemide dose.⁴ Experimental and clinical studies have demonstrated that torsemide increases circulating renin and angiotensin peptides and may increase aldosterone concentrations during therapy.^3,4,12 When administered at approximately equipotent diuretic doses, torsemide and furosemide produce comparable degrees of RAAS activation in dogs. Concurrent RAAS-modulating therapy (eg, ACE inhibitors, angiotensin-receptor blockers, spironolactone) remains indicated when clinically appropriate.^1,2

Adverse Effects

Expected adverse effects (eg, polyuria, polydipsia, electrolyte depletion, prerenal azotemia) parallel those of other loop diuretics.^1,2,12,13 In the CARPODIEM study, dogs administered torsemide experienced at least one nonserious renal adverse effect by the end of the study. Although not statistically significant, more dogs in the torsemide group were withdrawn from the study for renal adverse effects (7/161 vs 1/158 in the furosemide group), and torsemide overall had more adverse effects (49/161 vs 21/158).² Renal laboratory abnormalities occur more frequently with torsemide than with furosemide, reflecting greater potency.

One study of 7 dogs with stable CHF revealed statistically significant increases in BUN and creatinine, with decreases in serum chloride and urine specific gravity.⁷ In the TEST study, renal adverse effects were more common with torsemide (18%) than with furosemide (4%), although renal-related mortality did not differ.¹ Azotemia is a common adverse effect of loop diuretics in cats and appears dose dependent.^9,14

Cautions

Torsemide should be initiated cautiously in patients with kidney disease or systemic hypotension.^15,16 Renal values and electrolytes should be reassessed shortly after initiation and after dose escalation to monitor for azotemia or electrolyte decreases, which may necessitate diuretic dose reduction, a dose decrease in concurrent CHF medications with known renal adverse effects (eg, ACE inhibitors), and/or electrolyte supplementation. Accurate tablet splitting and owner education are essential, particularly for cats and small dogs.

Formulations & Regulatory Considerations

A torsemide oral solution (2 mg/mL) has been conditionally approved by the FDA for use in dogs only; extra-label use of conditionally approved drugs is not permitted by the FDA. Chewable tablets (1 mg, 2 mg, 4 mg) are available for dogs. A human-labeled product (oral tablets [5 mg, 10 mg, 20 mg, 40 mg, 60 mg, 100 mg]) should be used when prescribing torsemide for an extra-label indication or dose in a dog or another species. IV torsemide may be available outside of the United States.