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Furosemide (Lasix®) versus Torsemide (Demadex®)

Based on "Treatment of Myocardial Ischemia and Hypertension"
written by Thomas Michel, MD, PhD, and Brian B. Hoffman, MD

Difference between Furosemide and Torsemide

Table 1. Comparison of Furosemide and Torsemide

Furosemide	Torsemide
Brand names
Lasix®	Demadex®
Drug class
High-Ceiling (Loop) Diuretic
Dose formulations
• tablets • injectable solution • oral solution	• tablets • injectable solution (Roche discontinued Demadex® injection)
Legal status
Rx only Not a controlled drug
FDA-approved indications
• Edema associated with heart failure, renal disease or liver cirrhosis • High blood pressure
• Acute pulmonary edema
"Off-label" uses
	• Acute pulmonary edema2.
Mechanism of action
• Loop diuretics block Na+/K+/2Cl- cotransport in the thick ascending limb of the loop of Henle, resulting in diuresis and natriuresis.
	•Antialdosterone - inhibites aldosterone secretion • Antifibrotic • Inhibits angiotensin II-induced vasoconstriction and vascular growth-promoting activity
Onset of action
• ~ 1 hour (oral)	• within 1 hour (oral)
Duration of action
• Duration of diuresis for 6 - 8 hours hours	• Duration of diuresis for 6-8 hours
Half-life
• 0.8 hours	• 3 hours
Oral bioavailability
•40–70% variable bioavailability	• 90%
Metabolism, Elimination
• Furosemide is eliminated via kidney by glomerular filtration of tubular secretion.	• About 80% of torsemide is cleared by the liver (the process involves the cytochrome P450 system) and 20% is eliminated unchanged in urine.
Contraindications
• Hypersensitivity to furosemide or sulfonamides	• Hypersensitivity to torsemide • Hepatic coma
• Anuria (absence of urine production)
Side effects
• Excessive urination • Hypotension • Dehydration • Hypovolemia (decreased blood volume) • Hypokalemia (potassium loss) • Hypomagnesemia (Low magnesium) • Hyponatremia (low sodium) • Hypocalcemia (urinary loss of calcium) • Ototoxicity (hearing loss or ear ringing) • Increased blood glucose levels • Retain of uric acid, which can lead to precipitation or worsening of gout Note: Torsemide causes less kaliuresis than furosemide
Drug interactions
• May increase the ototoxic potential of aminoglycoside. • Lithium - risk of lithium toxicity. • ACE inhibitors, Angiotensin II receptor blockers - increased risk of hypotension and renal damage.
• Furosemide does not undergo extensive liver metabolism.	• CYP2C9 inhibitors (e.g. amiodarone, fluconazole, miconazole) - decreased torsemide clearance. • CYP2C9 inducers (e.g. carbamazepine, rifampin) - increased torsemide clearance.
Pregnancy category
C	B

Furosemide advantages over Torsemide

Furosemide is by far the most prescribed and researched loop diuretic.
Lower potential for drug interactions.

Torsemide advantages over Furosemide

Pharmacological advantages. Compared with furosemide, torsemide has longer half-life, longer duration of action, and higher and less-variable bioavailability.
Torsemide has more potent natriuretic and chloruretic effects than furosemide.
Torsemide has beneficial effects on myocardial fibrosis, the neurohormonal axis, and ventricular structure3,4.
There is some evidence that torsemide therapy is associated with reduction in all-cause mortality 5.
Furosemide carries a higher risk of accumulation and subsequent ototoxicity compared with torsemide.
According to the clinical trials6 torsemide decreases hospitalizations for heart failure and hospital stay, improves exercise tolerance, quality of life, left ventricular function, cardiac sympathetic nerve activity, myocardial fibrosis, pulmonary congestion, edema, and blood pressure compared with furosemide.
Torsemide has more convenient dosing schedule. It can be taken once daily while furosemide needs to be taken two or three times a day.

Head-to-head comparative studies

Heart failure

Torsemide is a more cost-effective medication for long-term treatment of patients with heart failure7.
Torasemide provides greater improvements in functional and social restrictions than furosemide and reduces the frequency of hospitalisations in patients with chronic heart failure 10.

Cirrhosis

Torasemide produces more pronounced diuresis and natriuresis than furosemide8.
Both diuretics have similar effect on body weight, urinary volume, and fractional excretion of uric acid, sodium, and chloride.
Torasemide has higher sparing effect than furosemide on calcium, inorganic phosphate, and magnesium excretion and stronger action on free water clearance 9.

Acute renal failure

Both torsemide and furosemide are effective in increasing urine output in patients with renal failure.
Torsemide has a longer duration of diuretic action and does not accumulate in renal failure11.
Furosemide induces less pronounced serum creatinine and serum urea nitrogen elimination.

References

1. Uchida T, Yamanaga K, Nishikawa M, Ohtaki Y, Kido H, Watanabe M. Anti-aldosteronergic effect of torasemide. Eur J Pharmacol. 1991 Nov 26;205(2):145-50.
2. Stringer KA, Watson W, Gratton M, Wolfe R. Intravenous torsemide as adjunctive therapy in patients with acute pulmonary edema. J Clin Pharmacol. 1994 Nov;34(11):1083-7. PubMed
3. Lopez B, Querejeta R, Gonzalez A, Sanchez E, Larman M, Diez J. Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure. J Am CollCardiol. 2004;43:2028–2035.
4. Mentz RJ, Buggey J, Fiuzat M, et al. Torsemide versus furosemide in heart failure patientsJ CardiovascPharmacol. 2015 May;65(5):438-43. PubMed
5. Cosín J, Díez J; TORIC investigators. Torasemide in chronic heart failure: results of the TORIC study. Eur J Heart Fail. 2002 Aug;4(4):507-13. PubMed
6. DiNicolantonio JJ. Should torsemide be the loop diuretic of choice in systolic heart failure? Future Cardiol. 2012 Sep;8(5):707-28.
7. Spannheimer A, Goertz A, Dreckmann-Behrendt B. Comparison of therapies with torasemide or furosemide in patients with congestive heart failure from a pharmacoeconomic viewpoint. Int J Clin Pract. 1998 Oct;52(7):467-71. PubMed
8. Laffi G, Marra F, Buzzelli G, Azzena G, Meacci E, De Feo ML, La Villa G, Gentilini P. Comparison of the effects of torasemide and furosemide in nonazotemic cirrhotic patients with ascites: a randomized, double-blind study. Hepatology. 1991 Jun;13(6):1101-5.
9. Fiaccadori F, Pedretti G, Pasetti G, et al. Torasemide versus furosemide in cirrhosis: a long-term, double-blind, randomized clinical study. Clin Investig. 1993 Jul;71(7):579-84.
10. Müller K, Gamba G, Jaquet F, Hess B. Torasemide vs. furosemide in primary care patients with chronic heart failure NYHA II to IV--efficacy and quality of life. Eur J Heart Fail. 2003 Dec;5(6):793-801. PubMed
11. Vargas Hein O, Staegemann M, Wagner D, von Heymann C, Martin M, Morgera S, Spies C.Torsemide versus furosemide after continuous renal replacement therapy due to acute renal failure in cardiac surgery patients.Ren Fail. 2005;27(4):385-92.