Usage
- Bumetanide is prescribed for the treatment of edema associated with heart failure, hepatic cirrhosis, and renal dysfunction, including nephrotic syndrome. It can also be used for acute pulmonary edema and sometimes for hypertension (off-label).
- Pharmacological Classification: Loop diuretic.
- Mechanism of Action: Bumetanide inhibits sodium and chloride reabsorption in the ascending limb of the loop of Henle, leading to increased excretion of water, sodium, chloride, potassium, magnesium, calcium, and phosphate.
Alternate Names
- No widely recognized alternate generic names.
- Brand Names: Bumex, Burinex.
How It Works
- Pharmacodynamics: Bumetanide’s primary effect is to increase the excretion of water and electrolytes from the body by inhibiting the sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle. This leads to decreased reabsorption of sodium and chloride, resulting in increased urine output and reduced fluid volume. It also affects calcium and magnesium excretion.
- Pharmacokinetics: Bumetanide is readily absorbed orally and intravenously with high bioavailability (80-100%). It is highly protein-bound (95%). It is metabolized in the liver, primarily by oxidation of the butyl side chain, and excreted mainly in the urine (partially as unchanged drug). Its half-life is 1 to 1.5 hours, and it has a volume of distribution of approximately 25 liters. The plasma clearance is 225-228 mL/min.
- Mode of Action: Bumetanide acts by inhibiting NKCC2, preventing the reabsorption of sodium, chloride, and potassium in the loop of Henle. It also indirectly affects calcium and magnesium reabsorption.
- Receptor Binding/Enzyme Inhibition: Bumetanide’s primary mechanism is the inhibition of NKCC2. It doesn’t have significant receptor binding activity.
- Elimination Pathways: Bumetanide is primarily eliminated via hepatic metabolism (butyl side chain oxidation) and renal excretion (both as metabolites and unchanged drug).
Dosage
Standard Dosage
Adults:
- Oral: 0.5 mg to 2 mg once daily, usually as a single morning dose. May increase to 10 mg/day divided into multiple doses, as needed. Maximum dose: 10 mg per day.
- Intravenous/Intramuscular: 0.5 mg to 1 mg initially, administered slowly over 1-2 minutes. May repeat every 2-3 hours as needed, up to a maximum of 10 mg per day. Continuous IV infusion: 1 mg/hour up to 12 mg/day.
Children:
- Dosage must be determined by a doctor based on weight and age.
- < 6 months: 0.01-0.05 mg/kg every 24-48 hours.
- ≥ 6 months: 0.015-0.1 mg/kg every 24-48 hours. Maximum dose: 10 mg/day.
- Pediatric safety considerations: Close monitoring of electrolytes is crucial in children.
Special Cases:
- Elderly Patients: Start with a lower dose (e.g., 0.5 mg daily) and adjust as needed.
- Patients with Renal Impairment: Use cautiously; high dosages (up to 20 mg daily) may be needed. Reduce dosage based on creatinine clearance.
- Patients with Hepatic Dysfunction: Start with the lowest dose and titrate very carefully. Monitor closely for adverse effects.
- Patients with Comorbid Conditions: Individualize dosage based on the specific comorbidity and monitor for potential interactions.
Clinical Use Cases
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: IV administration is typically preferred in these settings, starting with 0.5-1 mg, with subsequent doses and continuous infusions as needed based on patient response and fluid status.
- Emergency Situations (e.g., pulmonary edema): IV administration of 0.5 to 1 mg is indicated for rapid diuresis.
Dosage Adjustments:
- Adjust dosage based on patient response, renal function, and hepatic function. Monitor electrolyte levels closely, particularly potassium, sodium, and chloride.
Side Effects
Common Side Effects:
- Muscle cramps, dizziness, hypotension, headache, nausea, vomiting, electrolyte imbalances (hypokalemia, hypochloremia, hyponatremia), increased uric acid levels (hyperuricemia).
Rare but Serious Side Effects:
- Electrolyte disturbances (severe hypokalemia, hypomagnesemia, hypochloremic alkalosis), dehydration, hypotension, ototoxicity (hearing impairment), increased blood urea nitrogen (BUN) and creatinine, hepatic encephalopathy.
Long-Term Effects:
- With prolonged use, potential electrolyte imbalances may occur, including hypokalemia, hypomagnesemia, and hypochloremic alkalosis. Regular monitoring of electrolytes is essential.
Adverse Drug Reactions (ADR):
- Severe allergic reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Contraindications
- Anuria
- Hepatic coma
- Severe electrolyte depletion
- Hypersensitivity to bumetanide or sulfonamides
Drug Interactions
- Aminoglycoside antibiotics (increased risk of ototoxicity)
- Lithium (increased lithium levels)
- Probenecid (decreased diuretic effect)
- Indomethacin (decreased diuretic effect)
- Digoxin (hypokalemia can potentiate digoxin toxicity)
- NSAIDs (can decrease the effectiveness of bumetanide)
- Corticosteroids (can exacerbate hypokalemia)
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Consult a physician)
- Bumetanide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is unknown if bumetanide is excreted in human milk.
Drug Profile Summary
- Mechanism of Action: Inhibits sodium and chloride reabsorption in the ascending limb of the loop of Henle.
- Side Effects: Muscle cramps, dizziness, hypotension, electrolyte imbalances, nausea.
- Contraindications: Anuria, hepatic coma, severe electrolyte depletion.
- Drug Interactions: Aminoglycosides, lithium, probenecid, indomethacin, digoxin, NSAIDs.
- Pregnancy & Breastfeeding: Use with caution; potential fetal risk.
- Dosage: Adult: 0.5–2 mg/day. Pediatric: Dose adjusted by weight. Max 10 mg/day for adults and peds.
- Monitoring Parameters: Electrolytes (potassium, sodium, chloride, magnesium, calcium), renal function (BUN, creatinine), blood pressure.
Popular Combinations
- Often combined with ACE inhibitors, ARBs, or beta-blockers in heart failure.
- May be used with potassium-sparing diuretics (e.g., spironolactone) to mitigate hypokalemia.
Precautions
- General Precautions: Monitor electrolytes, renal function, and blood pressure.
- Specific Populations: Close monitoring during pregnancy and lactation, dose adjustments in elderly and those with hepatic or renal impairment.
- Lifestyle Considerations: Encourage patients to limit salt and fluid intake as directed by their physician.
FAQs (Frequently Asked Questions)
A: Adults: Initial 0.5-2 mg/day orally, IV, or IM; can be increased as needed up to 10 mg/day. Children: Dose is determined by weight and age; max 10 mg/day. Elderly: Start with a low dose and titrate cautiously.
A: Bumetanide is approximately 40 times more potent than furosemide on a milligram-to-milligram basis but has a shorter duration of action.
A: Aminoglycosides, lithium, probenecid, indomethacin, digoxin, NSAIDs, and corticosteroids.
A: Yes, but with caution. Higher doses may be required, and careful monitoring of renal function is necessary. Dose reductions are recommended according to level of dysfunction.
A: Severe dehydration, electrolyte imbalances, hypotension, circulatory collapse.
A: Only if the potential benefit outweighs the risk to the fetus. It’s categorized as Pregnancy Category C.
A: Orally, intravenously (slowly over 1-2 minutes), or intramuscularly.
A: Hypokalemia, hypomagnesemia, and hypochloremic alkalosis.
A: Serum electrolytes (potassium, sodium, chloride, magnesium, calcium), renal function (BUN, creatinine), blood pressure, and signs of dehydration.
A: It can be effective in some patients who do not respond to other diuretics, although higher doses may be required.
