Bumetanide has United States Food and Drug Administration (FDA) approval for the management of various edematous conditions secondary to cardiac failure with or without ascites, hepatic or renal disease, including the nephrotic syndrome. It may also be indicated for refractory edema due to other loop diuretics. Bumetanide may be an appropriate option in case of a medical history of an allergic reaction due to furosemide, another loop diuretic.

Based on recent studies, seizures, and behavioral problems in patients with tuberous sclerosis may be treated by agents that enhance GABA-anergic transmission by influencing chloride regulation. Using bumetanide for this purpose is non-FDA approved. Loop diuretics, such as bumetanide, may also be therapeutic for the initial treatment of hypertension and acute hypercalcemia.[1][2][3]

Diuretics play a crucial role in the treatment of edema and hypertension by causing the induction of a negative balance of solute and water. Loop diuretics are physiologically the most potent family of diuretics. Although they have no direct epithelial effect on segments such as thin descending limb of Henle and thick ascending limb of Henle, many of the diuretics decrease fluid reabsorption by abolishing the papillary osmotic gradient. Most of the loop diuretics have a direct inhibitory effect on the cotransport process, specifically by interfering with the active chloride transport secondary to the presence of sodium, located on the luminal membrane of the segment. Loop diuretics (furosemide, bumetanide, ethacrynic acid) inhibit the concentrating mechanisms in the medullary segment, whereas diuretics such as thiazides are effective primarily in the cortical segment and inhibit the urinary diluting mechanism.[4][5]

Bumetanide inhibits the reabsorption of sodium and chloride in the ascending loop of Henle and proximal renal tubule, which interferes with the chloride-binding cotransport system. This mechanism increases the excretion of water, magnesium phosphate, sodium chloride, magnesium phosphate, and calcium. It decreases both free water clearance and solute free water reabsorption, increases excretion of sodium chloride to the distal tubule (natriuresis), calciuria, phosphaturia, and minimal bicarbonaturia. Studies have shown the onset of diuretic action to occur during 0 to 30 minutes following intravenous use and 30 to 60 min following oral administration. The diuretic effect and the total duration of action last for 3 to 4 hours (270 min) with similar net urine output between intravenous and oral administration.[6] The peak of the drug's action occurs at 90 minutes after oral administration.[1]

To control edema, a staggered dosing schedule or a 3 to 4 times daily dosing schedule with half-day rest intervals between is recommended to increase tolerability and efficacy. It is the safest and most effective method for the continued control of edema. Oral and injectable administrations (intravenous, intramuscular) are available. Bumetanide is rapidly absorbed after oral and intravenous formulations. 95% of the drug extensively bounds to plasma proteins and is eliminated by the metabolism of the butyl side chain and partially removed through urine excretion. The apparent half-life is 1.2 to 1.5 hours, and the volume of distribution is about 25 liters. Plasma clearance is 225 to 228 ml/min. The different modes of administration of bumetanide with dosages are the following:

• Bumetanide intramuscular injection solution: 0.25 mg/1 mL
• Bumetanide intravenous injection solution: 0.25 mg/1mL
• Bumetanide oral tablet: 0.5 mg, 1 mg, 2 mg

Oral Administration: The total daily dosage of bumetanide is 0.5 mg to 2 mg, usually given as a single dose. If the diuretic response after the initial dose of bumetanide is not adequate, a second or third dose is possible at 4- to 5-hour intervals, with a maximum daily dose of 10 mg. In patients with hepatic failure, dosing should remain at a minimum level and, if necessary, should be increased very carefully.[1][6]

The primary adverse effects of bumetanide include hypocalcemia, azotemia, metabolic alkalosis, hyperglycemia, hypomagnesemia, hyponatremia, hypokalemia, tenderness, and myalgia. All loop diuretics decrease urate excretion, which can lead to hyperuricemia. Bumetanide may potentially cause ototoxicity, but there have been very few recorded instances. The most frequent clinical adverse reactions related to bumetanide are muscle cramps.[7][8][9]

Bumetanide is contraindicated in patients with hypersensitivity to the drug or components of the formulation. It is also contraindicated in patients with hypersensitivity to loop diuretics, hepatic disease, hepatic encephalopathy, severe electrolyte depletion, and anuria. Bumetanide is in the FDA pregnancy risk category C classification. The safety and efficacy of bumetanide use have not been established in neonates, infants, children, and adolescents under age 18 years.[10]