Bumetanide

Bumetanide is a loop diuretic about 40 times more potent than furosemide by weight, so 1 mg is roughly equal to 40 mg of furosemide. It has better and more predictable oral absorption, a shorter duration of action, and a lower risk of ototoxicity. It treats oedema from heart failure, liver and kidney disease, and acute pulmonary oedema. In East Africa it is available in tertiary hospitals but not in many district formularies.

Classification. Loop diuretic (sulphonamide).

Mechanism. Blocks the sodium potassium 2 chloride cotransporter in the thick ascending limb of the loop of Henle.

Pharmacodynamics. Oral onset within 30 to 60 minutes, peak at 1 to 2 hours, duration 4 to 6 hours. IV onset within 5 minutes, peak at 15 to 30 minutes, duration 2 to 3 hours.

Pharmacokinetics. Oral bioavailability 80 to 100% (more predictable than furosemide, even in gut oedema). Half life about 1 to 1.5 hours. About 50% excreted unchanged in urine; the rest is metabolised in the liver. Protein binding about 95%.

Oedema (heart failure, cirrhosis, kidney disease), adult (oral).

• Start 1 mg once daily (0.5 mg in older adults).

• A second dose 6 to 8 hours later if the response is poor.

• Usual maintenance 1 to 2 mg daily, in 1 to 2 doses; severe oedema up to 5 mg daily; maximum 10 mg daily.

• Intermittent dosing on alternate days or 3 to 4 days a week reduces electrolyte loss in chronic use.

Acute pulmonary oedema and acute decompensated heart failure, adult (IV).

• 1 to 2 mg IV over 1 to 2 minutes; repeat after 20 minutes if no response, then every 2 to 3 hours as needed.

• Maximum 10 mg daily.

• Infusion in specialist units: 0.5 to 2 mg/hour.

Oedema in chronic kidney disease, adult. 2 to 5 mg once or twice daily (higher oral doses are needed at low eGFR); maximum 10 mg daily.

Children. Specialist use only. Weight based; typical oral 15 to 50 micrograms/kg once or twice daily, with a maximum of 1 mg daily in a small child. Avoid in neonates unless closely monitored because of bilirubin displacement and nephrocalcinosis.

Contraindications. Anuria not responding to a test dose; severe hypovolaemia; severe hypokalaemia or hyponatraemia; hepatic coma and precoma; hypersensitivity.

Warnings. Hypokalaemia, hyponatraemia, hypomagnesaemia, hypochloraemic alkalosis, hyperuricaemia, hyperglycaemia. Hypovolaemia and kidney injury. Muscle pain and cramps with higher doses. Ototoxicity less than with furosemide but still present with high doses or aminoglycosides. May trigger hepatic encephalopathy. Hypersensitivity to sulphonamides: possible cross reaction.

Adverse effects. Dizziness, hypotension, muscle cramp, hypokalaemia, hyponatraemia, nausea, rash, tinnitus (rare), gout, rarely thrombocytopenia.

Interactions. Aminoglycosides and cisplatin: ototoxicity and nephrotoxicity. Digoxin: hypokalaemia raises toxicity. Lithium: raised levels. Non steroidal anti-inflammatory drugs: blunt effect and kidney injury. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers: first dose hypotension. Probenecid: reduces effect. Corticosteroids and amphotericin B: more potassium loss. Indometacin blocks the response.

Special groups.

• Pregnancy: avoid unless essential; risk of reduced placental perfusion.

• Breastfeeding: avoid or use short courses; no data.

• Patients of African ancestry: no change.

• Older adults: start at 0.5 mg; risk of dehydration and falls.

• Kidney impairment: higher doses may be needed (2 to 5 mg); monitor creatinine and electrolytes.

• Liver impairment: start low; use with spironolactone to protect potassium.

Formulations. Tablets 0.5, 1, 5 mg; oral solution 1 mg/5 mL; injection 0.25 mg/mL.

Administration. Oral in the morning with or without food. IV: slow injection over 1 to 2 minutes; may be diluted in 0.9% sodium chloride or 5% glucose and used within 24 hours.

Baseline. Weight, blood pressure, volume status, sodium, potassium, magnesium, creatinine and eGFR, urate, glucose.

Monitoring. Daily weight and fluid balance in hospital. Sodium, potassium, magnesium and creatinine 1 to 2 weeks after starting or each dose increase, then every 3 to 6 months. Acute use: daily electrolytes and creatinine. Replace potassium when below 3.5 mmol/L. Stop or reduce if symptomatic hypotension, creatinine rise over 30%, or sodium below 125 mmol/L.

Stopping. Taper to the lowest effective dose. Hold on sick days with vomiting or diarrhoea.

Common prescribing errors. Confusing the dose with furosemide (1 mg equals about 40 mg furosemide) and giving 40 mg of bumetanide; omitting potassium monitoring; starting at 2 mg or more in older adults; giving in the evening; combining with aminoglycosides without hearing checks.