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Bumetanide (Monograph)

Drug class: Loop Diuretics

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Warning

  • Bumetanide is a potent diuretic which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion.4

  • Careful medical supervision is required; adjust dosage selection and titration according to the individual patient’s needs.4

Introduction

A sulfonamide loop-type diuretic and antihypertensive agent.4 1200

Uses for Bumetanide

Edema

Management of edema associated with heart failure or hepatic or renal disease (including nephrotic syndrome).3 4 524

May be effective in some patients whose condition is unresponsive or refractory to other diuretics.5 47 49 52

Considered a diuretic of choice for most patients with heart failure.524

Most experts state that all patients with symptomatic heart failure who have evidence for, or a history of, fluid retention generally should receive diuretic therapy in conjunction with moderate sodium restriction, an agent to inhibit the renin-angiotensin-aldosterone (RAA) system (e.g., ACE inhibitor, angiotensin II receptor antagonist, angiotensin receptor-neprilysin inhibitor [ARNI]), a β-adrenergic blocking agent (β-blocker), and in selected patients, an aldosterone antagonist.524 700 713

Short- and long-term management of edema and ascites associated with hepatic disease (e.g., cirrhosis).2 31 36 48 49 50

Management of postoperative† [off-label] or premenstrual edema† [off-label] and edema associated with disseminated carcinoma† [off-label].5

Hypertension

Management of hypertension† [off-label], alone or in combination with other classes of antihypertensive agents.5 92 94 113 127 128 1200

Not considered a preferred agent for initial management of hypertension according to current evidence-based hypertension guidelines;501 502 503 504 other agents (i.e., ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, thiazide diuretics) are preferred for initial management.501 502 503 504 1200

Some experts state that loop diuretics (e.g., bumetanide, furosemide, torsemide) are preferred over thiazides in patients with moderate to severe chronic kidney disease (CKD)502 504 1200 or symptomatic heart failure.524 1200

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults 1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Other hypertension guidelines generally have based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk, and have used higher BP thresholds and target BPs in elderly patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.1200 1220 1229

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, CKD, or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Bumetanide Dosage and Administration

General

Monitoring and BP Treatment Goals

Administration

Administer orally, IV, or IM.4

Oral Administration

Administer orally as a single daily dose in the morning.4 May be preferable to administer single daily dose in the evening for a greater diuretic effect.24 67 81 May administer on alternate days or on 3 or 4 consecutive days alternating with drug-free periods of 1 or 2 days.4

For optimum therapeutic effect in some patients, may administer twice daily (morning and evening).67

Food may delay absorption.22

IV or IM Administration

IV or IM administration may be used in patients unable to take oral medication or who have impaired GI absorption; resume oral administration as soon as possible.4

Rate of Administration

For direct IV injection, administer slowly over a period of 1–2 minutes.4

Dilution

For IV infusion, dilute in 5% dextrose, 0.9% sodium chloride, or lactated Ringer’s injection; use solutions within 24 hours.4

Standardize 4 Safety

Standardized concentrations for IV bumetanide have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care.249 250 Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label.249 250 For additional information on S4S (including updates that may be available), see [Web].249 250

dosing units differ from concentration units

Table 2: Standardize 4 Safety Continuous IV Infusion Standard Concentrations for IV Bumetanide249250

Patient Population

Concentration Standards

Dosing Units

Adults

0.25 mg/mL

mg/hour

Pediatric patients (<50 kg)

0.04 mg/mL

mcg/kg/hour

0.25 mg/mL

Dosage

Individualize dosage according to individual requirements and response.4

Since the diuretic response following oral or parenteral administration is similar, dosage for oral, IV, or IM administration is identical.4

Manufacturer states that bumetanide may be substituted for furosemide in furosemide-allergic patients at approximately a 1:40 ratio (cross-sensitivity between the drugs does not appear to occur).4 49

Pediatric Patients

Heart Failure† [off-label]
IV

Safety and efficacy not established.4

0.015 mg/kg on alternate days to 0.1 mg/kg daily has been used in a limited number of children with heart failure†.42

In infants 4 days to 6 months of age, maximal diuretic effect was observed at a dosage of 0.035–0.04 mg/kg.a

Adults

Edema
Oral

Initially, 0.5–2 mg daily.4 Repeat dose at 4- to 5-hour intervals until desired response is obtained or maximum dosage of 10 mg daily is reached.4

For maintenance therapy, effective dose may be administered intermittently.4

For management of fluid retention associated with heart failure, some experts recommend initiating at a low dosage (e.g., 0.5–1 mg once or twice daily) and increasing dosage (maximum 10 mg daily) until urine output increases and weight decreases, generally by 0.5–1 kg daily.524

IV or IM

Initially, 0.5–1 mg.4 Repeat dose at 2- to 3-hour intervals until desired diuretic response is obtained or a maximum dosage of 10 mg daily is reached.4

Hypertension†
Oral

Initially, 0.5 mg daily.92 94 111

Some experts state that usual dosage range is 0.5–2 mg daily administered in 2 divided doses.1200

Prescribing Limits

Adults

Edema
Oral

Maximum recommended by manufacturer and some experts: 10 mg daily.4 524

IV or IM

Maximum recommended by manufacturer: 10 mg daily.4

Special Populations

Hepatic Impairment

Edema

Use minimum effective dosage; titrate carefully.4

Renal Impairment

Edema
Oral or IV

Up to 20 mg daily has been administered.37 55 IV doses >2 mg needed to achieve a diuretic response in patients with Clcr <5 mL/minute.2 54 High dosages may be needed to produce an adequate diuretic response in patients with severe renal impairment (i.e., GFR <10 mL/minute).5

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.a

Detailed Bumetanide dosage information

Cautions for Bumetanide

Contraindications

Warnings/Precautions

Warnings

Fluid, Electrolyte, and Cardiovascular Effects

Careful etiologic diagnosis should precede use of any diuretic.d Titrate dosage carefully; excessive dosage, administration frequency, or prolonged therapy may lead to profound water loss, electrolyte depletion, dehydration, reduction in blood volume, and circulatory collapse with the possibility of vascular thrombosis and embolism, especially in geriatric patients.4 (See Boxed Warning.)

Observe carefully for signs of electrolyte depletion, especially hypokalemia.4 Excessive fluid and electrolyte loss may be minimized by careful monitoring and initiating therapy with small doses, careful dosage adjustment, and an intermittent dosage schedule if possible.4

Hypokalemia may occur; evaluate serum potassium concentration periodically.4 Hypokalemia is particularly likely and important to prevent in patients with hyperaldosteronism and normal renal function, hepatic cirrhosis and ascites, potassium-losing renal diseases, or certain diarrheal conditions and may require particular attention in patients with heart failure receiving cardiac glycosides and diuretics, those with a history of ventricular arrhythmias, and those with other conditions in which hypokalemia represents a risk.4

Periodic determination of other serum electrolyte concentrations recommended for patients receiving high dosages or chronic therapy, especially when sodium intake is restricted.4 If excessive diuresis and/or electrolyte abnormalities occur, discontinue therapy or reduce dosage until corrected.76 81 82

Ototoxicity

Produces ototoxicity in animals at high dosages.4 Serum concentrations associated with ototoxicity in humans unlikely; consider possibility of ototoxicity following IV administration, especially at high dosages,4 after too rapid administration,81 in patients with impaired renal function, and/or in patients receiving other ototoxic drugs (e.g., aminoglycosides).4

Thrombocytopenia.

Rare postmarketing experience reports; monitor regularly.4

Sensitivity Reactions

Sulfonamides

Patients allergic to sulfonamides may be hypersensitive to bumetanide; use with extreme caution.4 Does not appear to exhibit cross-sensitivity in patients allergic to furosemide.4 69 2

General Precautions

Electrolyte Effects

Hypomagnesemia, hypocalcemia, and/or hypophosphatemia may occur.4 31

Endocrine Effects

Possible effects on glucose metabolism should be considered.4 Changes in plasma insulin, glucagon, or growth hormone concentration or in glucose tolerance or diabetic control generally have not been observed; diuretic-induced hyperglycemia occurs rarely.2 3 4 5 18 19 24 83 84 May result from potassium depletion, which has been associated with impaired insulin secretion.2 3 4 5 18 19 83 84

Other Effects

Blood dyscrasias (especially thrombocytopenia), liver damage, or idiosyncratic reactions have been reported occasionally.4

Hyperuricemia may occur; most reported cases have been asymptomatic.4 25 31 32 43

Specific Populations

Pregnancy

Category C.4

Lactation

Not known whether bumetanide is distributed into milk.4 Use not recommended.4

Pediatric Use

Safety and efficacy not established in children <18 years of age.4

Has been used effectively as a diuretic for up to 40 weeks in a limited number of infants 2 weeks to 7 months of age with congenital heart disease and heart failure†.42

Use with caution in critically ill or jaundiced neonates at risk for kernicterus; in vitro studies indicate bumetanide may displace bilirubin from albumin.4

Elimination appears to be slower in neonates than in adults, possibly because of immature renal and hepatobiliary functions.4

Geriatric Use

Response in patients ≥65 years of age does not appear to differ from that in younger adults; however, use with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in geriatric patients.4 Monitor renal function.4

Hepatic Impairment

Use with caution in patients with hepatic cirrhosis and ascites; sudden alterations in electrolyte balance may precipitate hepatic encephalopathy and coma.4 Therapy in such patients is best initiated in the hospital with small doses and careful monitoring of clinical status and electrolyte balance.4 Supplemental potassium and/or concomitant potassium-sparing diuretics (e.g., spironolactone) may be used to prevent hypokalemia and metabolic alkalosis.4 31 48 50

Renal Impairment

Patients with renal impairment may require high dosages to achieve an adequate diuretic response.5

The risk of adverse effects (e.g., ototoxicity) at high dosages should be considered.4

Common Adverse Effects

Muscle cramps, dizziness, hypotension, headache, nausea, encephalopathy, hyperuricemia, hypochloremia, hypokalemia, azotemia, hyponatremia, increased serum creatinine, hyperglycemia.4 38 81 82

Drug Interactions

Specific Drugs

Drug

Interaction

Comments

Anticoagulants, oral (e.g., warfarin)

Plasma prothrombin activity or warfarin metabolism not affected 4 65 66

Antihypertensive agents

Additive antihypertensive effect3 4

Reduction in dosage of both drugs may be required.3 4

Concomitant therapy generally used to therapeutic advantage; orthostatic hypotension may occur.34

Cardiac glycosides (e.g., digoxin)

Possible electrolyte disturbances (e.g., hypokalemia, hypomagnesemia) may predispose to digitalis toxicity, possibly fatal cardiac arrhythmias3 4 77 79

Renal excretion and serum digoxin concentrations not affected3 4 59

Monitor electrolytes; correct hypokalemia4 79 80

Diuretics

Increased diuretic and natriuretic effects3 25

Diuretics, potassium- sparing (e.g., amiloride, spironolactone, triamterene)

Possible reduction in potassium loss3 25

Concomitant therapy may be used to therapeutic advantage3 25

Indomethacin

Decreased diuretic and natriuretic effect3 4 60 61 62 78

Concomitant therapy not recommended4

If concomitant therapy is necessary, increased bumetanide dosage may overcome decreased diuretic effect82 .

Other drugs causing potassium loss (corticosteroids, corticotropin, amphotericin B)79 81

Additive hypokalemic effects 81

Monitor electrolytes; correct hypokalemia4 81

Lithium

Reduced renal clearance of lithium and increased risk of lithium toxicity3 4

Concomitant use generally contraindicated; if concomitant therapy is necessary, monitor serum lithium concentrations and adjust dosage3 4 81

Nondepolarizing neuromuscular blocking agents (e.g., atracurium besylate, tubocurarine chloride)

Potential for prolonged neuromuscular blockade, possibly due to potassium depletion and/or decreased urinary excretion of neuromuscular blocking agent79 85 86

Clinical importance unknown; use with caution81

Nephrotoxic drugs

Possible increased nephrotoxic effects; no clinical experience to date 4

Avoid concomitant use4

Ototoxic drugs (e.g., aminoglycoside antibiotics, cisplatin)

Possible additive ototoxic effect, especially in patients with impaired renal function3 4

Avoid concomitant parenteral administration of bumetanide and aminoglycoside antibiotics, except in life-threatening conditions4

Probenecid

Decreased diuretic and natriuretic effects, inhibition of bumetanide-induced increase in plasma renin activity3 4 8 62 63

Avoid concomitant use4
Bumetanide drug interactions (more detail)

Bumetanide Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely (85–95%)2 3 20 21 22 absorbed following oral administration;22 23 peak plasma concentrations generally attained within 0.5–2 hours.3 13 14 20 21 22 23

Appears to be completely absorbed following IM administration.2

Onset

Diuresis begins within 30–60 minutes following oral administration,3 4 about 40 minutes following IM administration,73 and within a few minutes following IV administration.4 Peak diuretic activity generally occurs within 1–2 hours following oral or IM administration14 20 22 24 25 73 and within 15–30 minutes after IV administration.4 21 22

Duration

Diuresis is dose-dependent and generally complete within 4–6 hours following oral or IM administration.3 4 14 20 24 25 73

Following IV administration, diuresis generally persists for 2–3 hours.21

Food

Limited data suggest food may delay GI absorption.22

Special Populations

Bioavailability appears similar in patients with impaired renal or hepatic function.23

Distribution

Extent

Distribution has not been fully characterized.2 3 20

Not known whether bumetanide crosses the blood-brain barrier or the placenta or is distributed into milk.3 4

Bumetanide and its metabolites are distributed into bile.3 4 20 Following oral administration of radiolabeled bumetanide in one patient with a biliary T tube in place, 1.8% of the dose was distributed into bile as unchanged drug and 12.6% as metabolites.20

Does not appear to bind to erythrocytes.2 3 21

Following IV administration in healthy adults, the steady-state volume of distribution (Vss) ranged from 9.45–19.7 L and the volume of distribution of the central compartment (Vc) ranged from 3.26–5.84 L.14 21 22 29

Plasma Protein Binding

Approximately 93–96%.21 29

Special Populations

Following IV administration in neonates, the mean volume of distribution ranged from 0.26–0.38 L/kg.4

May increase serum concentrations of free (unbound) bilirubin by displacement from albumin when administered to critically ill neonates.4 28

Protein binding may be decreased in patients with renal impairment; binding appears to be correlated with plasma albumin concentration.91

Vss may be increased in patients with renal impairment.91

Vss may be decreased in patients with hepatic impairment.23

Elimination

Metabolism

Bumetanide is partially metabolized by oxidation in the liver to at least 5 metabolites.3 20 21 Major urinary metabolite is the 3′-alcohol derivative.20 The major metabolite excreted in bile and/or feces is the 2′-alcohol derivative.20 Minor metabolites include the 4′-alcohol, N-desbutyl, and 3′-acid derivatives.20

Metabolites in urine and bile are present as conjugates, principally glucuronide conjugates.20 Conjugates of bumetanide and its metabolites do not appear in feces.20

Elimination Route

Bumetanide and its metabolites are excreted principally in urine.3 4 20 21 22 29 Renal excretion appears to occur mainly via glomerular filtration;3 22 29 91 tubular secretion also may occur.22 29 91

Following oral or IV administration in healthy adults, about 80% of a dose is excreted in urine and 10–20% in feces within 48 hours;3 20 21 29 about 50% of a dose is excreted unchanged in urine.3 20 21 29 Excreted in feces almost completely as metabolites, apparently via biliary elimination;20 less than 2% of a dose is excreted unchanged in feces within 48 hours.20

Half-life

1–1.5 hours in healthy adults following oral administration.3 4 20

Plasma concentrations generally decline in a monophasic or biphasic manner;2 14 20 21 22 however, plasma concentrations may decline in a triphasic manner following IV administration.22 29

Following IV administration in adults with normal renal and hepatic function, t½α averages 5–6.9 minutes, t½β averages 46–47 minutes, and t½γ averages 3.1–3.4 hours.22 29

Special Populations

Clearance decreased in patients with impaired renal function, with or without concurrent hepatic impairment;29 91 101 in patients with only renal impairment, nonrenal clearance of the drug is about 90% or more of total body clearance.29 91 101 Serum concentrations may be higher and the terminal elimination half-life prolonged in patients with impaired renal and/or hepatic function.23 91

In neonates and infants, elimination appears slower than in older pediatric patients and adults, possibly because of immature renal and hepatobiliary functions.4 Mean serum elimination half-life decreased considerably during the first month of life from 6 hours in neonates to 2.4 hours in infants 1 month of age.a Mean serum elimination half-life is 2.5 and 1.5 hours in infants younger than 2 months of age and in those 2–6 months of age, respectively.4 Limited data indicate that the apparent elimination half-life may be prolonged to about 6 hours (with a range up to 15 hours) after IV administration in premature or full-term neonates with respiratory disorders.4

Stability

Storage

Oral

Tablets

15–30°C in tight, light resistant containers.3 4 95

Parenteral

Injection

15–30°C; protect from light.b

If diluted with infusion solution, use within 24 hours of preparation.b

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Bumetanide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

0.5 mg*

Bumetanide Tablets

1 mg*

Bumetanide Tablets

2 mg*

Bumetanide Tablets

Parenteral

Injection

0.25 mg/mL*

Bumetanide Injection

AHFS DI Essentials™. © Copyright 2025, Selected Revisions June 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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4. Roche Laboratories. Bumex (bumetanide) tablets and injection prescribing information. Nutley, NJ; 1999 Feb.

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