Torsemide - Drug Monograph

Introduction

Torsemide is a potent loop diuretic medication used primarily in the management of edema associated with congestive heart failure, renal disease, and hepatic cirrhosis. As a sulfonylurea-class diuretic, it acts on the thick ascending limb of the loop of Henle to promote sodium and water excretion. Torsemide offers several advantages over other loop diuretics, including more predictable absorption, longer duration of action, and dual hepatic and renal elimination pathways.

Mechanism of Action

Torsemide inhibits the Na+/K+/2Cl- cotransporter in the thick ascending limb of the loop of Henle in the kidneys. This action prevents the reabsorption of sodium, chloride, and potassium, resulting in increased excretion of water, sodium, chloride, magnesium, calcium, and potassium. The drug's diuretic effect leads to reduced plasma volume and decreased preload, making it particularly effective in managing fluid overload states.

Indications

• FDA-approved indications:

- Edema associated with congestive heart failure - Edema associated with chronic renal failure - Edema associated with hepatic cirrhosis

• Off-label uses:

- Hypertension (though not FDA-approved for this indication) - Diuretic-resistant edema - Prevention of contrast-induced nephropathy

Dosage and Administration

• Congestive heart failure: 10-20 mg once daily (may increase to 200 mg daily in divided doses)
• Chronic renal failure: 20 mg once daily (may increase to 200 mg daily)
• Hepatic cirrhosis: 5-10 mg once daily (may increase to 40 mg daily)

• Route: Oral or intravenous
• Timing: Usually administered in the morning to avoid nocturia
• IV administration: May be given as slow injection (over 2 minutes) or infusion

• Renal impairment: No dosage adjustment necessary
• Hepatic impairment: Use with caution; monitor for electrolyte imbalances
• Elderly: Start with lower doses due to increased sensitivity
• Pediatrics: Safety and efficacy not established

Pharmacokinetics

• Absorption: Rapid and complete (80-90% bioavailability) with minimal food effect
• Distribution: Volume of distribution: 12-15 L; Protein binding: >99%
• Metabolism: Primarily hepatic via CYP2C9 (80%) with minor CYP2C8 and CYP2C19 involvement
• Elimination: Half-life: 3-4 hours; Dual elimination: 80% hepatic metabolism, 20% renal excretion
• Onset/Duration: Oral: onset 1 hour, peak 1-2 hours, duration 6-8 hours; IV: onset 10 minutes, peak 1 hour

Contraindications

• Hypersensitivity to torsemide, sulfonylureas, or any component of the formulation
• Anuria
• Hepatic coma or severe electrolyte depletion
• Patients with documented sulfonamide allergy

Warnings and Precautions

• Electrolyte imbalances: Monitor for hypokalemia, hyponatremia, hypochloremia, hypocalcemia, hypomagnesemia
• Ototoxicity: Risk increased with rapid IV administration, high doses, or concomitant use of other ototoxic drugs
• Renal function: May cause prerenal azotemia in susceptible patients
• Photosensitivity: May increase sensitivity to sunlight
• Diabetes: May alter glucose tolerance
• Gout: May increase uric acid levels

Drug Interactions

• Lithium: Increased lithium levels and toxicity risk
• NSAIDs: Reduced diuretic and antihypertensive effects
• Probenecid: Reduced diuretic effect
• Digoxin: Hypokalemia may potentiate digoxin toxicity
• Antihypertensives: Enhanced hypotensive effect
• Aminoglycosides: Increased risk of ototoxicity and nephrotoxicity
• CYP2C9 inhibitors/inducers: Altered torsemide concentrations (e.g., fluconazole, rifampin)

Adverse Effects

• Headache (5.4%)
• Excessive urination (4.8%)
• Dizziness (3.2%)
• Rhinitis (2.6%)
• Asthenia (2.5%)
• ECG abnormalities (2.5%)

• Severe electrolyte disturbances
• Ototoxicity (hearing loss)
• Stevens-Johnson syndrome
• Acute interstitial nephritis
• Pancreatitis
• Blood dyscrasias

Monitoring Parameters

• Baseline and periodic:

- Electrolytes (sodium, potassium, chloride, magnesium, calcium) - Renal function (BUN, creatinine) - Liver function tests - Blood pressure and weight - Hearing assessment (with high doses or prolonged therapy)

• Frequency:

- Within first 1-2 weeks of therapy - Periodically during maintenance therapy - After dosage adjustments

Patient Education

• Take medication in the morning to avoid nighttime urination
• Report signs of electrolyte imbalance: muscle cramps, weakness, dizziness, excessive thirst
• Use sun protection due to photosensitivity risk
• Weigh yourself daily at the same time and report sudden weight changes
• Maintain consistent potassium intake through diet or supplements as directed
• Avoid sudden position changes to prevent dizziness
• Inform all healthcare providers about torsemide use
• Do not stop medication without consulting your physician

References

1. FDA Prescribing Information: Torsemide Tablets (2022) 2. Brater DC. Pharmacology of diuretics. Am J Med Sci. 2000;319(1):38-50. 3. Ellison DH. Diuretic therapy and resistance in congestive heart failure. Cardiology. 2001;96(3-4):132-143. 4. Murray MD, Haag KM, Black PK, et al. Variable furosemide absorption and poor predictability of response in elderly patients. Pharmacotherapy. 1997;17(1):98-106. 5. Knauf H, Mutschler E. Clinical pharmacokinetics and pharmacodynamics of torasemide. Clin Pharmacokinet. 1998;34(1):1-24. 6. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th Edition 7. Lexicomp Online, Torsemide Monograph