What is the difference between Torsemide and Furosemide (Frusemide) in terms of diuretic effect?

From the Guidelines

Torsemide is generally more potent and longer-acting than furosemide, making it a preferred choice for patients with heart failure or significant fluid overload. The difference in diuretic effect between Torsemide and Furosemide (Frusemide) is notable, with torsemide having approximately 4 times the diuretic potency on a milligram-to-milligram basis 1. While furosemide typically has a duration of action of 6-8 hours, torsemide works for 12-16 hours, allowing for once-daily dosing compared to furosemide's often twice-daily regimen. Some key points to consider when choosing between these medications include:

• Torsemide's more predictable oral bioavailability (80-100%) versus furosemide's variable absorption (10-100%) 1
• The equivalent dosing between the two medications, with 10-20mg of torsemide being approximately equivalent to 40-80mg of furosemide
• Torsemide's potential advantages in patients with heart failure or cirrhosis due to its more reliable absorption even in patients with edema or poor gut perfusion Both medications work by inhibiting the sodium-potassium-chloride cotransporter in the ascending loop of Henle, but torsemide's pharmacokinetic advantages often make it more effective in clinical practice, particularly in patients with significant fluid overload 1.

From the FDA Drug Label

Torsemide increases the urinary excretion of sodium, chloride, and water, but it does not significantly alter glomerular filtration rate, renal plasma flow, or acid-base balance. With oral dosing, the onset of diuresis occurs within 1 hour and the peak effect occurs during the first or second hour and diuresis lasts about 6 to 8 hours.

Furosemide inhibits primarily the absorption of sodium and chloride not only in the proximal and distal tubules but also in the loop of Henle The onset of diuresis following oral administration is within 1 hour. The peak effect occurs within the first or second hour. The duration of diuretic effect is 6 to 8 hours

The main difference between Torsemide and Furosemide (Frusemide) in terms of diuretic effect is their site of action and mechanism of action.

• Torsemide acts from within the lumen of the thick ascending portion of the loop of Henle, where it inhibits the Na+/K+/2Cl–-carrier system.
• Furosemide inhibits primarily the absorption of sodium and chloride not only in the proximal and distal tubules but also in the loop of Henle. Both drugs have a similar onset of action (within 1 hour) and duration of diuretic effect (6 to 8 hours) 2 3. Key differences include:
• Bioavailability: Torsemide has a higher bioavailability (approximately 80%) compared to Furosemide (64% from tablets and 60% from oral solution).
• Protein binding: Both drugs are extensively bound to plasma proteins, but Torsemide has a higher binding rate (>99%) compared to Furosemide (91-99%).

From the Research

Diuretic Effect Comparison

• The diuretic effect of Torsemide and Furosemide has been compared in several studies, with some suggesting that Torsemide may have a more efficient diuretic effect due to its oral bioavailability and half-life 4.
• However, a study published in the Journal of the American Society of Nephrology found that oral Torsemide was not superior to Furosemide in measures of renal tubular delivery or duration of action, and that a dose equivalence of approximately 40 mg oral Furosemide:10 mg oral Torsemide resulted in similar natriuresis 5.
• Another study published in JAMA found that among patients discharged after hospitalization for heart failure, Torsemide compared with Furosemide did not result in a significant difference in all-cause mortality over 12 months 6.

Clinical Outcomes

• A systematic review and meta-analysis of randomized controlled trials found that Torsemide significantly reduced hospitalizations for heart failure and cardiovascular causes, and improved left ventricular ejection fraction (LVEF) compared with Furosemide 7.
• A meta-analysis published in The American Journal of Cardiology found that Torsemide was associated with a numerically lower risk of hospitalization due to heart failure, and a statistically significant improvement in functional status and lower cardiac mortality compared with Furosemide 4.
• A retrospective cohort study published in Pharmacoepidemiology and Drug Safety found that compared with Furosemide, initiation of Torsemide was associated with a slightly lower risk of a composite of all-cause mortality or heart failure hospitalization and urgent visits with intravenous diuretics, but a slightly higher risk of acute kidney injury 8.

Dosage and Efficacy

• The optimal dosage of Torsemide and Furosemide is still a topic of debate, with some studies suggesting that a dose equivalence of approximately 4:1 (Torsemide:Furosemide) may result in similar natriuresis 5.
• The efficacy of Torsemide and Furosemide may also depend on individual patient characteristics, such as renal function and comorbidities, and further studies are needed to determine the optimal treatment strategy for different patient populations 5, 6, 7, 4, 8.