Torasemide

Usage

• Torasemide is prescribed for the treatment of edema associated with heart failure, kidney disease, and liver cirrhosis. It is also used to treat hypertension, though it’s not typically a first-line agent.
• Pharmacological classification: Loop diuretic.
• Mechanism of action: Torasemide inhibits sodium and chloride reabsorption in the thick ascending limb of the loop of Henle, leading to increased excretion of water and electrolytes, thus reducing fluid overload and blood pressure.

Alternate Names

• International variations: Torasemid (German), torasémide (French).
• Brand names: Demadex®, Soaanz®.

How It Works

• Pharmacodynamics: Torasemide increases the excretion of sodium, chloride, and water by inhibiting the Na+/K+/2Cl- cotransporter in the loop of Henle. It does not affect renal blood flow or glomerular filtration rate (GFR) under normal physiological conditions.
• Pharmacokinetics:
  • Absorption: Oral bioavailability is approximately 80%. Food does not significantly affect absorption.
  • Metabolism: Primarily metabolized in the liver via oxidation and hydroxylation by cytochrome P450 (CYP) enzymes, predominantly CYP2C9.
  • Elimination: Excreted in urine and feces. The elimination half-life is about 3-4 hours in healthy individuals, but may be prolonged in patients with renal impairment.
• Mode of action: Torasemide acts by binding to the chloride-binding site of the Na+/K+/2Cl- cotransporter in the luminal membrane of the ascending loop of Henle, blocking its function. This blocks the reabsorption of sodium, chloride, and water, leading to increased urine output.
• Elimination pathways: Primarily renal excretion (approximately 80%), with a smaller fraction excreted in feces via biliary elimination.

Dosage

Standard Dosage

Adults:

• Edema (Heart Failure, Renal Disease): 10-20 mg orally once daily initially. If inadequate response, double the dose until the desired effect is achieved, up to a maximum of 200 mg/day.
• Edema (Hepatic Cirrhosis): 5-10 mg orally once daily initially, usually administered with an aldosterone antagonist or potassium-sparing diuretic. If inadequate response, double the dose until the desired effect is achieved, up to a maximum of 40 mg/day.
• Hypertension: 5 mg orally once daily. If inadequate response after 4-6 weeks, increase to 10 mg once daily. If still inadequate, consider adding another antihypertensive agent.

Children:

• Safety and efficacy not fully established. Dosing should be determined on a case-by-case basis by a physician, usually starting with a lower dose based on body weight (0.13-0.25 mg/kg/day) and titrating up as needed based on clinical response.

Special Cases:

• Elderly Patients: Initiate with lower doses and titrate carefully due to potential for reduced renal function.
• Patients with Renal Impairment: Higher doses may be required to achieve the desired effect. No specific dosage adjustments are provided in prescribing information, however, the maximum effective dose in moderate chronic kidney disease (eGFR >30 mL/min/1.73 m2) is 20-50 mg, while in severe CKD (eGFR <30 mL/min/1.73 m2) it is 50-100 mg. Torsemide is not removed by hemodialysis.
• Patients with Hepatic Dysfunction: Use cautiously. Contraindicated in hepatic coma.
• Patients with Comorbid Conditions: Monitor closely for potential drug interactions and electrolyte imbalances.

Clinical Use Cases

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use/Emergency Situations: Torsemide can be administered intravenously when a rapid onset of diuresis is necessary, such as in acute pulmonary edema or other emergency situations. The IV dose is generally equivalent to the oral dose, administered as a bolus over 2 minutes or as a continuous infusion. Dosage should be adjusted based on patient response and clinical status.

Dosage Adjustments

• Dose adjustments may be necessary based on renal or hepatic function, concomitant medications, and electrolyte abnormalities.

Side Effects

Common Side Effects

• Excessive urination
• Dehydration
• Electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia)
• Dizziness
• Headache
• Muscle cramps

Rare but Serious Side Effects

• Ototoxicity (hearing loss)
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Pancreatitis
• Severe allergic reactions

Long-Term Effects

• Potential for electrolyte disturbances with long-term use.
• May exacerbate gout in susceptible patients.

Adverse Drug Reactions (ADR)

• Anaphylaxis
• Severe hypotension

Contraindications

• Hypersensitivity to torsemide or sulfonamides.
• Anuria (complete absence of urine production).
• Hepatic coma.

Drug Interactions

• NSAIDs: May reduce diuretic and antihypertensive effects and increase risk of renal impairment.
• Aminoglycosides (e.g., gentamicin, amikacin): Increased risk of ototoxicity and nephrotoxicity.
• CYP2C9 inhibitors (e.g., amiodarone, fluconazole): May decrease torsemide clearance.
• Digoxin: May potentiate digoxin toxicity due to electrolyte imbalances.
• Lithium: May increase lithium levels.
• Antihypertensives: Additive hypotensive effect.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (FDA). Use with caution if benefits outweigh risks.
• Fetal risks: Potential for electrolyte imbalances and reduced placental perfusion.
• Breastfeeding: Torsemide is excreted in breast milk. Use with caution or avoid breastfeeding while taking torsemide.

Drug Profile Summary

• Mechanism of Action: Inhibits Na+/K+/2Cl- cotransporter in the loop of Henle, increasing excretion of water and electrolytes.
• Side Effects: Excessive urination, electrolyte imbalances, dizziness, headache, muscle cramps. Rarely: ototoxicity, severe skin reactions, pancreatitis.
• Contraindications: Hypersensitivity, anuria, hepatic coma.
• Drug Interactions: NSAIDs, aminoglycosides, CYP2C9 inhibitors, digoxin, lithium, antihypertensives.
• Pregnancy & Breastfeeding: Category C; use with caution. Excreted in breast milk.
• Dosage: See dosage section above.
• Monitoring Parameters: Electrolytes (sodium, potassium, magnesium, calcium), creatinine, blood glucose, uric acid, blood pressure, urine output, weight, and renal function.

Popular Combinations

• Often combined with potassium-sparing diuretics (e.g., spironolactone, amiloride) or aldosterone antagonists in patients with cirrhosis to prevent hypokalemia.
• May be used with other antihypertensive agents to achieve better blood pressure control.

Precautions

• General Precautions: Monitor renal function, electrolytes, and blood pressure regularly. Assess for volume depletion.
• Specific Populations: Monitor pregnant women, breastfeeding mothers, children, and elderly patients closely.
• Lifestyle Considerations: Advise patients to avoid alcohol, maintain adequate hydration, and take precautions when driving or operating machinery due to potential for dizziness.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Torasemide?

A: See dosage section above.

Q2: What are the most common side effects of Torsemide?

A: Excessive urination, electrolyte imbalances (hypokalemia, hyponatremia), dizziness, and headache.

Q3: What are the contraindications to Torasemide use?

A: Hypersensitivity to torsemide or sulfonamides, anuria, and hepatic coma.

Q4: How does Torasemide interact with other medications?

A: See drug interactions section above. Notably, NSAIDs, aminoglycosides, and CYP2C9 inhibitors can have clinically significant interactions.

Q5: Can Torasemide be used during pregnancy or breastfeeding?

A: Torsemide is FDA Pregnancy Category C. Use cautiously if benefits outweigh risks. Torsemide is excreted in breast milk. Use with caution during breastfeeding.

Q6: How should Torasemide be administered?

A: Torsemide is available in oral and IV formulations. Oral tablets can be taken with or without food. IV administration should be given as a bolus over 2 minutes or as a continuous infusion.

Q7: What monitoring parameters are essential while prescribing Torasemide?

A: Regular monitoring of electrolytes (especially potassium, sodium, and magnesium), renal function (serum creatinine, eGFR), blood glucose, uric acid, blood pressure, and urine output is essential.

Q8: Can Torsemide be used in patients with renal impairment?

A: Yes, but caution and dose adjustments are often necessary. Higher doses may be needed to achieve a diuretic response, but excessive dosing can lead to adverse effects.

Q9: What is the difference between Torsemide and Furosemide?

A: Both are loop diuretics, but Torsemide has a longer half-life and improved oral bioavailability compared to Furosemide. The equivalent doses are approximately 1 mg of Bumetanide = 20 mg of Torsemide = 40 mg of Furosemide.

Q10: Is there a maximum daily dose of Torsemide?

A: For heart failure and renal disease, the maximum recommended daily dose is generally 200 mg. For hepatic cirrhosis, the maximum recommended dose is typically 40 mg.