Bumetanide - Drug Monograph

Introduction

Bumetanide is a potent loop diuretic medication used primarily for the management of edema associated with congestive heart failure, hepatic disease, and renal impairment. As a sulfonamide derivative, it belongs to the same class as furosemide but demonstrates approximately 40 times greater potency on a milligram-to-milligram basis. First approved by the FDA in 1983, bumetanide remains an important therapeutic option in fluid overload conditions.

Mechanism of Action

Bumetanide exerts its diuretic effect by specifically inhibiting the sodium-potassium-chloride (Na-K-2Cl) cotransporter in the thick ascending limb of the loop of Henle. This inhibition reduces the reabsorption of sodium, chloride, and potassium, resulting in increased excretion of water and electrolytes. The drug also promotes calcium and magnesium excretion. By reducing sodium reabsorption by approximately 20-25%, bumetanide creates a significant osmotic gradient that prevents water reabsorption, leading to profound diuresis.

Indications

FDA-approved indications:

• Edema associated with congestive heart failure
• Hepatic cirrhosis with ascites
• Nephrotic syndrome
• Renal edema

Off-label uses:

• Hypercalcemia
• Hypertension (particularly when thiazides are ineffective)
• Ascites refractory to other diuretics

Dosage and Administration

• Oral: 0.5-2 mg once daily; may increase to maximum 10 mg daily
• IV/IM: 0.5-1 mg; may repeat every 2-3 hours as needed

• Renal impairment: No dosage adjustment needed, but monitor response
• Hepatic impairment: Use cautiously due to electrolyte imbalance risk
• Elderly: Start with lower doses (0.5 mg) due to increased sensitivity
• Pediatrics: 0.015-0.1 mg/kg/dose every 6-24 hours (not FDA-approved under age 18)

• Oral administration: May be taken with food to reduce GI upset
• IV administration: Administer slowly over 1-2 minutes
• Timing: Morning administration recommended to avoid nocturia

Pharmacokinetics

Contraindications

• Hypersensitivity to bumetanide or sulfonamides
• Anuria
• Hepatic coma or severe electrolyte depletion
• Patients in whom diuresis would be inappropriate (e.g., dehydrated patients)

Warnings and Precautions

• Electrolyte imbalances: Monitor for hypokalemia, hyponatremia, hypochloremia
• Ototoxicity: Risk increased with rapid IV administration, high doses, or concomitant use of other ototoxic drugs
• Hyperuricemia and gout: May occur due to reduced uric acid excretion
• Photosensitivity: May increase sensitivity to sunlight
• Orthostatic hypotension: May occur due to volume depletion
• Use in pregnancy: Category C (risk cannot be ruled out)
• Lactation: Excreted in breast milk; use cautiously

Drug Interactions

• Aminoglycosides: Increased risk of ototoxicity and nephrotoxicity
• Lithium: Reduced lithium clearance leading to toxicity
• Probenecid: Reduces diuretic effect
• NSAIDs: May diminish diuretic and antihypertensive effects
• Digoxin: Hypokalemia may potentiate digoxin toxicity
• Antihypertensives: Enhanced hypotensive effect
• Corticosteroids: Enhanced potassium wasting

Adverse Effects

• Dehydration (12%)
• Hypokalemia (10-15%)
• Muscle cramps (5%)
• Dizziness (3%)
• Headache (2%)
• Nausea (1.5%)

• Stevens-Johnson syndrome
• Thrombocytopenia
• Neutropenia
• Acute pancreatitis
• Ototoxicity (usually reversible)
• Anaphylactic reactions
• Severe electrolyte disturbances

Monitoring Parameters

• Complete metabolic panel (especially electrolytes, BUN, creatinine)
• Liver function tests
• Urinalysis
• Weight and fluid status assessment

• Serum electrolytes (particularly potassium, sodium, magnesium) weekly initially, then periodically
• Renal function (BUN, creatinine)
• Body weight daily
• Blood pressure (standing and supine)
• Hearing assessment with high doses or prolonged therapy
• Uric acid levels in susceptible patients
• Signs of dehydration or volume depletion

Patient Education

• Take in morning to avoid nighttime urination
• Report signs of electrolyte imbalance: muscle weakness, cramps, fatigue, dizziness
• Weigh yourself daily at same time and report sudden weight changes
• Maintain adequate fluid intake unless otherwise directed
• Avoid excessive sun exposure and use sunscreen
• Rise slowly from sitting/lying position to prevent dizziness
• Do not take NSAIDs without consulting healthcare provider
• Report hearing changes or ringing in ears immediately
• Follow prescribed dietary recommendations, especially regarding potassium-rich foods
• Inform all healthcare providers about bumetanide use before any new medications

References

1. FDA Prescribing Information: Bumex (bumetanide) tablets and injection 2. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 13th ed. McGraw-Hill Education; 2017 3. Lexicomp Online. Bumetanide monograph. Wolters Kluwer Clinical Drug Information 4. Ellison DH. Diuretic therapy and resistance in congestive heart failure. Cardiology. 2001;96(3-4):132-143 5. Sica DA. Pharmacotherapy in heart failure: a review of bumetanide. Expert Opin Pharmacother. 2018;19(4):341-351 6. McEvoy GK, ed. AHFS Drug Information. American Society of Health-System Pharmacists; 2023 7. National Kidney Foundation. KDOQI Clinical Practice Guideline for Hypertension and Antihypertensive Agents in CKD. Am J Kidney Dis. 2004;43(5 Suppl 1):S1-290