Bumetanide

Approved Indications:

• Edema associated with:
• Congestive heart failure (CHF)
• Hepatic cirrhosis
• Renal disease, including nephrotic syndrome
• Acute pulmonary edema (when rapid diuresis is required)
• Hypertension (off-label; generally as an adjunct to other antihypertensives in resistant cases)

Off-label / Clinically Accepted Uses:

• Hypercalcemia (adjunctive treatment to promote calcium excretion)
• Oliguria in acute kidney injury (AKI) (off-label, with caution)
• Chronic kidney disease (CKD) with fluid overload (as part of volume control strategies)

Route: Oral or Intravenous (IV)

Adults:

• Oral:
• Initial: 0.5 to 2 mg once daily
• Titrate as needed every 4–5 hours; usual range: 0.5–10 mg/day in 1–2 divided doses
• IV/IM:
• Initial: 0.5–1 mg IV or IM; may repeat in 2–3 hours if needed
• Max dose: 10 mg/day

Elderly:

• Start at lower end of dosing range (e.g., 0.5 mg once daily)
• Adjust slowly based on renal function and response

Pediatrics:

• Limited data; consult pediatric specialist
• Off-label dosing: 0.015–0.1 mg/kg/dose IV every 6–24 hours, adjusted as per clinical need

Renal Impairment:

• May require higher doses due to reduced efficacy in advanced renal dysfunction
• Monitor serum electrolytes and renal function closely

Hepatic Impairment:

• Use with caution; monitor for electrolyte imbalance and encephalopathy

Administration Notes:

• Can be taken with or without food
• IV formulation should be administered slowly to avoid hypotension

Bumetanide is a potent loop diuretic that selectively inhibits the Na⁺-K⁺-2Cl⁻ co-transporter (NKCC2) in the thick ascending limb of the loop of Henle. This action results in decreased reabsorption of sodium, potassium, and chloride, leading to significant diuresis and natriuresis. The reduction in plasma volume decreases preload and cardiac workload, providing relief from fluid overload conditions such as CHF or renal disease-related edema.

• Absorption: Rapid and nearly complete oral absorption (~80–95%)
• Onset of action: Oral: ~30–60 minutes; IV: ~5 minutes
• Peak effect: 1–2 hours (oral); 15–30 minutes (IV)
• Bioavailability: ~80–90%
• Distribution: Widely distributed; ~95% protein bound
• Metabolism: Hepatic (~50% via cytochrome-mediated oxidation)
• Half-life: 1–1.5 hours (shorter in renal impairment)
• Excretion: Primarily via kidneys (half unchanged, half metabolites); minor biliary elimination

• Pregnancy: Not assigned a formal FDA category under the updated labeling rule; however, data are limited. Animal studies show potential fetal risk. Use only if the benefit outweighs the risk.
• Lactation: Unknown if excreted into human milk. Due to potential for serious adverse effects (e.g., electrolyte imbalance) in the infant, either discontinue the drug or breastfeeding, depending on clinical necessity.
• Recommendation: Use during pregnancy or lactation only if clearly indicated and closely monitor electrolytes.

• Primary Class: Loop Diuretic
• Subclass: Sulfonamide-type loop diuretic
• Potency: Approximately 40 times more potent than furosemide

• Known hypersensitivity to bumetanide or any sulfonamide-derived drugs
• Anuria (no urine output)
• Severe electrolyte depletion (e.g., hypokalemia, hyponatremia) uncorrected
• Hepatic coma or states of hepatic encephalopathy
• Severe renal failure with increasing azotemia and oliguria

• Volume depletion: May cause profound diuresis with water/electrolyte loss
• Electrolyte imbalances: Risk of hypokalemia, hyponatremia, hypochloremia, hypomagnesemia
• Ototoxicity: Rare; usually with high-dose IV use or in combination with other ototoxic agents
• Nephrotoxicity: Monitor serum creatinine and BUN in long-term use
• Gout: May raise serum uric acid; caution in gout patients
• Diabetes mellitus: May cause hyperglycemia; monitor blood glucose
• Hypotension: Risk increases with volume depletion or concurrent antihypertensives
• Photosensitivity: Rare but reported
• Sulfa allergy caution: Although cross-reactivity is low, caution advised in patients with sulfa allergy

Common:

• Renal/Fluid Balance:
• Hypokalemia, hypomagnesemia, hyponatremia
• Dehydration, increased urination
• Cardiovascular:
• Hypotension, dizziness
• Gastrointestinal:
• Nausea, vomiting, abdominal cramps
• Neurological:
• Headache, confusion (especially in elderly)

Serious:

• Ototoxicity (hearing loss, tinnitus)
• Stevens-Johnson Syndrome (rare)
• Pancreatitis (very rare)
• Hepatic encephalopathy (in liver disease)

Major interactions:

• Aminoglycosides & vancomycin: ↑ risk of ototoxicity and nephrotoxicity
• Digitalis glycosides (e.g., digoxin): ↑ toxicity risk due to hypokalemia
• NSAIDs: May blunt diuretic efficacy
• Lithium: ↑ risk of lithium toxicity due to sodium depletion
• ACE inhibitors/ARBs: Additive hypotension and hyperkalemia risk
• Corticosteroids: ↑ risk of hypokalemia

Metabolic pathway:

• Minor involvement of CYP450 (CYP2C9), but not clinically significant

• Heart failure guidelines (AHA/ACC 2022): Bumetanide is recognized as an alternative to furosemide in patients not responsive or intolerant to other loop diuretics.
• KDIGO CKD guidelines: Recommends bumetanide as part of volume control therapy in fluid-overloaded patients with renal impairment, especially when furosemide is ineffective.

• Oral Tablets:
• Store below 30°C
• Protect from moisture and direct light
• Injection (IV/IM):
• Store at 15°C to 30°C
• Do not freeze
• Use immediately after opening vial
• Protect from light