Torsemide is a loop diuretic that belongs to the pyridine -sulfonylurea class.[1] It received approval for use in the united states in 1993. The effect of torsemide is dose-dependent. The maximum effective dose is the dose required to attain maximum sodium excretion. Torsemide is available in oral and IV form. The bioavailability of oral torsemide is high, so the efficacy of oral and IV forms is equivocal.[1]
Indications of torsemide are:
1. Edema secondary to the following
a. Heart failure: Diuretics are the mainstay of treatment in edema due to heart failure.[2] The initial dose is 5 to 10 mg once daily; the dose can be double until reaching the desired diuretic effect. The maximum daily dose is 200 mg /day.[3]
b. Chronic renal disease: Initial oral dose is 20 mg once daily, and the dose can double until obtaining the desired diuretic effect. The maximum dose is 200 mg/day. Doses over 200 mg have not been adequately studied.[1]
c. Hepatic cirrhosis: Initial oral dose is 5 to 10 mg once daily. The dose may be increased slowly by doubling the doses until achieving the desired diuretic effect. The maximum recommended daily dose is 40 mg. The usual recommendation is to administer with an aldosterone antagonist or a potassium-sparing diuretic.[1][4]
2. Hypertension (Not a first-line agent)[5]: Initial oral dose is 5 mg once daily, and the dose may increase to 10 mg daily after 4 to 6 weeks. The maximum daily dose is 10 mg.[5][1] Usually used in combination with other oral antihypertensives.
Torsemide causes excretion of sodium chloride and water by inhibiting sodium and chloride reabsorption in the ascending loop of Henle and distal collecting tubule. The effect is caused by blocking the chloride-binding site of the Na+/K+/2Cl- cotransport mechanism. Torsemide does not affect renal blood flow or glomerular filtration rate (GFR).
However, studies have also shown that genetics can play a role in drug response of various loop diuretics, including torsemide.[6]
Torsemide is available in two forms. IV form and oral form.
Patients may take the oral form with or without food. IV administration is the recommendation for inpatient settings, and when rapid action of the drug is needed.
Bioavailability of torsemide is approximately 80%, which allows equivalency between oral and IV to 1 to 1, unlike furosemide (oral to IV is 2 to 1 ).
The onset of diuresis occurs within 1 hr with a peak in 1 to 2 hours after oral administration. With IV administration, the onset of action is within 10 mins with a peak in one hour. The duration of action of the drug is around 6 to 8 hours, irrespective of the route of administration. The drug is primarily metabolized by the liver (80%) and excreted in the urine. Half-life elimination is approximately 3.5 hours.
Although torsemide does not offer significant advantages over other loop diuretics, it may provide benefits in patients who show an inadequate response to or do did not tolerate other agents.[4]
Contraindications for using torsemide can classify as either absolute or relative.
Absolute contraindications
Relative contraindications
Toxicity usually occurs with medications that can increase serum concentrations of torsemide like methotrexate etc. No antidote is available for the treatment of toxicity. In cases of toxicities, close monitoring of kidney function and electrolytes are essential to promptly identify and treat acute kidney injury and severe electrolyte abnormalities.
Ototoxicity and nephrotoxicity occur with concomitant use of nephro- or ototoxic medications. Animal studies have shown temporary ototoxicity with no permanent effect.[9] Further research is necessary for confirmation of temporary vs. permanent ototoxic effects in humans.
In patients with decompensated heart failure, both renal and hepatic clearance becomes reduced due to decreased renal plasma flow and hepatic congestion, respectively. As a result of reduced renal clearance, only a fraction of the given dose is delivered to the site of action in the kidney, causing less natriuresis in patients with heart failure than in normal subjects at any given dose.
A meta-analysis, including randomized clinical trials (RCTs) and observational studies, including heart failure patients, has shown that torsemide is associated with significant improvement in functional status and reduced cardiac mortality compared to furosemide. Findings also denote that there is no statistically significant difference in all-cause mortality or side effects experienced among the two diuretics[10]. However, further research in the future is needed to implement the findings in clinical practice.
In chronic kidney disease, dose adjustment of diuretics inversely relates to GFR.
In moderate chronic kidney disease (CKD) (estimated GFR >30 mL/min/1.73 m), the maximum effective dose of torsemide is approximately 20 to 50 mg.
In severe CKD (estimated GFR <30 mL/min/1.73 m), the maximum effective dose of torsemide is approximately 50 to 100 mg.
In cases of acute kidney injury with oliguria, a higher dose is necessary for a diuretic response.
It's important to note that torsemide does not get removed by hemodialysis, so no dosing adjustment is necessary for dialysis patients.
It is essential to note in clinical practice the oral dose equivalency of different loop diuretics, which is as follows: torsemide 20 mg = bumetanide 1 mg = furosemide 40 mg.
[1] | Blose JS,Adams KF Jr,Patterson JH, Torsemide: a pyridine-sulfonylurea loop diuretic. The Annals of pharmacotherapy. 1995 Apr; [PubMed PMID: 7633019] |
[2] | Cody RJ,Kubo SH,Pickworth KK, Diuretic treatment for the sodium retention of congestive heart failure. Archives of internal medicine. 1994 Sep 12; [PubMed PMID: 8074594] |
[3] | Yancy CW,Jessup M,Bozkurt B,Butler J,Casey DE Jr,Drazner MH,Fonarow GC,Geraci SA,Horwich T,Januzzi JL,Johnson MR,Kasper EK,Levy WC,Masoudi FA,McBride PE,McMurray JJ,Mitchell JE,Peterson PN,Riegel B,Sam F,Stevenson LW,Tang WH,Tsai EJ,Wilkoff BL, 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013 Oct 15; [PubMed PMID: 23741057] |
[4] | Fowler SF,Murray KM, Torsemide: a new loop diuretic. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 1995 Aug 15; [PubMed PMID: 8528833] |
[5] | Malha L,Mann SJ, Loop Diuretics in the Treatment of Hypertension. Current hypertension reports. 2016 Apr; [PubMed PMID: 26951244] |
[6] | Vormfelde SV,Brockmöller J, The genetics of loop diuretic effects. The pharmacogenomics journal. 2012 Feb; [PubMed PMID: 20877298] |
[7] | Juang P,Page RL 2nd,Zolty R, Probable loop diuretic-induced pancreatitis in a sulfonamide-allergic patient. The Annals of pharmacotherapy. 2006 Jan; [PubMed PMID: 16352777] |
[8] | Byrd DR,Ahmed I, Photosensitive lichenoid reaction to torsemide--a loop diuretic. Mayo Clinic proceedings. 1997 Oct; [PubMed PMID: 9379695] |
[9] | Klinke R,Mertens M, Quantitative assessment of torasemide ototoxicity. Arzneimittel-Forschung. 1988 Jan; [PubMed PMID: 3370060] |
[10] | Abraham B,Megaly M,Sous M,Fransawyalkomos M,Saad M,Fraser R,Topf J,Goldsmith S,Simegn M,Bart B,Azzo Z,Mesiha N,Sharma R, Meta-Analysis Comparing Torsemide Versus Furosemide in Patients With Heart Failure. The American journal of cardiology. 2020 Jan 1; [PubMed PMID: 31699358] |