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Bumetanide: Drug information

Bumetanide: Drug information
(For additional information see "Bumetanide: Patient drug information" and see "Bumetanide: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Fluid/electrolyte loss:

Bumetanide is a potent diuretic which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion. Therefore, careful medical supervision is required and dose and dosage schedule have to be adjusted to the individual patient's needs.

Brand Names: US
  • Bumex
Brand Names: Canada
  • Burinex
Pharmacologic Category
  • Antihypertensive;
  • Diuretic, Loop
Dosing: Adult

Dosage guidance:

Dosing: Loop diuretic approximate oral dose equivalency for patients with normal kidney function: Bumetanide 1 mg = furosemide 40 mg = torsemide 10 to 20 mg (Ref).

Edema or volume overload

Edema or volume overload:

Naive to loop diuretics:

Oral, IV: Initial: 0.5 to 1 mg once, then titrate as needed to an effective dose (see Titration to Effect below) (Ref).

Note: Oral bioavailability is very good (~80% to 100%); the same IV or oral dose is expected to produce a similar effect (Ref).

Refractory edema or acute decompensation in patients taking oral loop diuretics:

IV: Bolus/intermittent dosing: Initial: Administer 1 to 2.5 times the total daily oral maintenance dose once (eg, a patient taking oral bumetanide 1 mg twice daily at home [2 mg/day] can be given 2 to 5 mg IV as an initial bolus), then titrate as needed to an effective dose; maximum effective single dose: 3 to 10 mg depending on kidney function (see "Titration to Effect" below) (Ref).

Titration to effect: If the initial dose does not result in diuresis, double the individual dose (rather than administer the same dose more frequently) until diuresis occurs. Titration of an IV dose can occur at ≥2-hour intervals as needed in hospitalized patients. Once an effective dose is identified, it is typically administered 1 to 3 times daily. The maximum effective dose varies by population; higher than usual doses may be required for patients with nephrotic syndrome or kidney failure; maximum effective single dose: 3 to 10 mg; maximum recommended total daily dose: 10 mg/day (Ref).

Continuous infusion: Note: Reserve for patients who have responded to bolus therapy but need ongoing and sustained diuresis; administer an effective bolus dose then immediately start continuous infusion.

IV: Initial: 0.5 mg/hour; if diuretic response is not adequate, repeat IV bolus dose and increase continuous infusion to 1 mg/hour; continue to bolus and titrate infusion as needed up to 2 mg/hour (Ref).

Note: Higher continuous infusion rates are not recommended due to potential for side effects; consider alternative strategies for fluid removal (Ref).

Transitioning from IV to oral: Give the same IV dose orally (eg, total daily IV dose of 3 mg/day should be converted to an oral dose of 3 mg/day in 1 to 3 divided doses), then monitor urine output and adjust oral dose as needed (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: IV, Oral:

eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary (Ref).

eGFR <30 mL/minute/1.73 m2:

Higher doses may be required to achieve desired diuretic response due to decreased secretion into the tubular fluid. However, single IV or oral doses >8 to 10 mg are unlikely to result in additional diuretic effect (Ref).

Continuous infusion: IV: Initial: 1 mg/hour; if diuretic response is not adequate, repeat IV bolus dose and increase continuous infusion to 2 mg/hour (Ref).

Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzable (highly protein bound) (Ref):

IV, Oral:

Patients with anuria: Use is contraindicated (Ref).

Patients with residual kidney function: Dose as per eGFR <30 mL/minute/1.73 m2 (Ref).

Peritoneal dialysis: Unlikely to be significantly dialyzable (highly protein bound) (Ref):

IV, Oral:

Patients with anuria: Use is contraindicated (Ref).

Patients with residual kidney function: Dose as per eGFR <30 mL/minute/1.73 m2 (Ref).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted.

IV, Oral: In general, use not recommended; fluid management can be more effectively managed using CRRT ultrafiltration (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions (eg, ototoxicity) due to drug accumulation is important.

IV, Oral:

Patients with anuria: There is no expected clinical benefit; use is not recommended (Ref).

Patients with residual kidney function: Dose as per eGFR <30 mL/minute/1.73 m2 (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling. Use is contraindicated in hepatic coma. Use with caution in cirrhosis and ascites due to increased risk of precipitating hepatic coma; initiate with conservative doses and monitoring.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Bumetanide: Pediatric drug information")

Dosage guidance:

Dosing: Dose equivalency for adult patients with normal renal function (approximate): Bumetanide 1 mg = furosemide 40 mg = torsemide 10 to 20 mg. Note: Ethacrynic acid has a relative potency of 0.7 (Ref).

Edema

Edema (diuresis):

Intermittent dosing:

Infants and Children: Limited data available: Oral, IM, IV: 0.01 to 0.1 mg/kg/dose every 6 to 24 hours; maximum adult daily dose: 10 mg/day; a prospective, open-label dose-range study in infants (mean age: 2 months; range: 0 to 6 months) reported a maximal diuretic response at doses 0.035 to 0.04 mg/kg/dose every 6 to 8 hours, and no additional clinical benefit (ie, urine output) at doses >0.05 mg/kg/dose (Ref).

Adolescents: Very limited data: Oral, IM, IV: Initial: 0.5 to 1 mg/dose every 6 to 24 hours; maximum adult daily dose: 10 mg/day. Note: Dosing in adolescents based on experience in adult patients.

Continuous IV infusion: Limited data available: Infants, Children, and Adolescents ≤16 years: 1 to 10 mcg/kg/hour; titrate to effect (Ref). Note: A wide range of doses (1 to 200 mcg/kg/hour) have been reported; a complete safety analysis is lacking for the higher doses (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustment provided in the manufacturer's labeling; based on experience in adult patients, high doses are effective in end-stage kidney disease (Ref), but use is contraindicated in anuria; use with caution in kidney insufficiency due to increased risk of adverse effects.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; based on experience in adult patients, use is contraindicated in hepatic coma. Use with caution in cirrhosis and ascites due to increased risk of precipitating hepatic coma; initiate with conservative doses and monitoring.

Adverse Reactions (Significant): Considerations
Acute kidney injury

Loop diuretics, including bumetanide, may lead to acute kidney injury due to fluid loss.

Mechanism: Dose-related; related to the pharmacologic action (ie, volume depletion) (Ref).

Risk factors:

• Excessive doses (Ref)

• Concurrent administration of nephrotoxic agents (Ref)

• Older adults (Ref)

• Preexisting volume depletion (Ref)

• Reduced blood flow to the kidney or depletion of effective blood volume (eg, bilateral renal artery stenosis, cirrhosis, nephrotic syndrome, heart failure) (Ref)

Fluid/electrolyte loss

Loop diuretics, including bumetanide, may lead to profound diuresis (especially if given in excessive amounts), resulting in hypovolemia and electrolyte loss. Electrolyte disturbances (eg, hypocalcemia, hypokalemia, hypomagnesemia) may predispose a patient to serious cardiac arrhythmias.

Mechanism: Dose-related; related to the pharmacologic action (Ref).

Risk factors:

• Excessive doses with initiation or dose adjustment (Ref)

• Reduced dietary fluid and/or electrolyte intake (Ref)

• Concurrent illness leading to excessive fluid loss (eg, diarrhea, vomiting) (Ref)

• Concomitant administration of an additional diuretic (Ref)

• Very high or very restricted dietary sodium (Ref)

Hypersensitivity (immediate and delayed)

Immediate hypersensitivity reactions, including urticaria, have been reported (Ref) with bumetanide. Delayed hypersensitivity reactions range from nonspecific skin rash to rare severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Mechanism: Non–dose-related; immunologic. Immediate hypersensitivity reactions: IgE-mediated, with specific antibodies formed against a drug allergen following initial exposure (Ref). SCARs: Delayed type IV hypersensitivity reactions involving a T-cell mediated drug-specific immune response (Ref).

Onset: Immediate hypersensitivity reactions: Rapid; generally occurs within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Delayed hypersensitivity reactions: Varied; typically occur 1 to 8 weeks after drug exposure but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref).

Ototoxicity

Loop diuretics, including bumetanide, have been associated with hearing loss (deafness) and tinnitus, which is generally reversible (lasting from 30 minutes to 24 hours after administration) (Ref). There is less risk of ototoxicity with bumetanide compared to furosemide (Ref).

Mechanism: Dose-related; related to the pharmacologic action (ie, inhibition of a secretory isoform of the Na-K-2Cl co-transporter in the inner ear and impacts on ionic composition of cochlear fluids) (Ref).

Risk factors:

• Concurrent kidney disease (Ref)

• Excessive doses (Ref)

• IV administration (Ref): bolus (higher risk) versus continuous infusion (Ref)

• Concurrent use of other ototoxic agents (eg, aminoglycosides) can lead to ototoxicity at lower doses (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Endocrine & metabolic: Hyperuricemia (18%), hypochloremia (15%), hypokalemia (15%)

Genitourinary: Azotemia (11%)

1% to 10%:

Endocrine & metabolic: Abnormal lactate dehydrogenase (1%), abnormal serum calcium (2%), hyperglycemia (7%), hyponatremia (9%), variations in bicarbonate (3%)

Hematologic & oncologic: Abnormal serum phosphorus level (5%)

Nervous system: Dizziness (1%)

Neuromuscular & skeletal: Muscle cramps (1%)

Renal: Increased serum creatinine (7%)

Respiratory: Variations in CO2 concentration (4%)

<1%:

Cardiovascular: Chest pain, ECG changes, hypotension

Dermatologic: Diaphoresis, pruritus, skin rash, urticaria (Earl 2003)

Endocrine & metabolic: Abnormal alanine aminotransferase, abnormal aspartate transaminase, alkaline phosphatase abnormal, blood cholesterol abnormal, dehydration, glycosuria

Gastrointestinal: Abdominal pain, diarrhea, dyspepsia, nausea, vomiting, xerostomia

Genitourinary: Erectile dysfunction, nipple tenderness, premature ejaculation, proteinuria

Hematologic & oncologic: Abnormal hematocrit, abnormal hemoglobin level, change in prothrombin time, change in serum protein, change in WBC count, thrombocytopenia

Hepatic: Abnormal bilirubin levels

Nervous system: Asterixis, encephalopathy (in patients with preexisting hepatic disease), fatigue, headache, vertigo

Neuromuscular & skeletal: Arthritic pain, asthenia, musculoskeletal pain

Otic: Auditory impairment, otalgia

Renal: Acute kidney injury (Hansrivijit 2020)

Respiratory: Hyperventilation

Postmarketing: Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis

Contraindications

Hypersensitivity to bumetanide or any component of the formulation; anuria; hepatic coma; patients in states of severe electrolyte depletion until the condition improves or is corrected.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to other sulfonamide derivatives; hepatic encephalopathy; galactose intolerance, glucose-galactose malabsorption, or congenital lactase deficiency.

Note: Although the FDA-approved product labeling states this medication is contraindicated in patients with hypersensitivity to sulfonamide-containing drugs, the scientific basis of this cross-sensitivity has been challenged. See “Warnings/Precautions” for more detail.

Warnings/Precautions

Concerns related to adverse effects:

• Hyperuricemia: Asymptomatic hyperuricemia has been reported with use.

• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are not well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

• Bariatric surgery: Dehydration: Avoid diuretics in the immediate postoperative period after bariatric surgery; electrolyte disturbances and dehydration may occur. Diuretics may be resumed, if indicated, once oral fluid intake goals are met (Ziegler 2009).

• Hepatic impairment: Use caution in patients with cirrhosis; initiate bumetanide therapy with conservative dosing and close monitoring of electrolytes; avoid sudden changes in fluid and electrolyte balance and acid/base status which may lead to hepatic encephalopathy.

• Kidney impairment: Larger doses may be necessary in patients with impaired kidney function to obtain the same therapeutic response (Brater 1998).

Special populations:

• Neonates: In vitro studies using pooled sera from critically-ill neonates have shown bumetanide to be a potent displacer of bilirubin; avoid use in neonates at risk for kernicterus.

• Surgical patients: If given the morning of surgery, bumetanide may render the patient volume depleted and blood pressure may be labile during general anesthesia.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

Other warnings and precautions:

• Diuretic resistance: For some patients, despite high doses of loop diuretic, an adequate diuretic response cannot be attained. Diuretic resistance may be overcome by IV rather than oral administration or the use of 2 diuretics together (eg, a loop diuretic in combination with a thiazide diuretic). When such combinations are used, serum electrolytes need to be monitored even more closely (ACC [Hollenberg 2019]).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

Generic: 0.25 mg/mL (4 mL, 10 mL)

Tablet, Oral:

Bumex: 0.5 mg [contains fd&c blue #1 (brill blue) aluminum lake, quinoline (d&c yellow #10) aluminum lake]

Bumex: 1 mg [DSC] [contains quinoline yellow (d&c yellow #10)]

Bumex: 2 mg [DSC]

Generic: 0.5 mg, 1 mg, 2 mg

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Bumetanide Injection)

0.25 mg/mL (per mL): $0.68 - $0.91

Tablets (Bumetanide Oral)

0.5 mg (per each): $0.41 - $2.43

1 mg (per each): $0.82 - $2.70

2 mg (per each): $0.41 - $2.97

Tablets (Bumex Oral)

0.5 mg (per each): $2.70

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Burinex: 0.5 mg

Burinex: 1 mg, 5 mg [contains corn starch]

Administration: Adult

IV: Administer IV slowly, over 1 to 2 minutes. Undiluted direct IV injections may be administered at a rate of 0.5 to 1 mg over 1 to 2 minutes.

Oral: May administer with or without food. An intermittent dose schedule, such as an alternate-day schedule or administering for 3 to 4 days with rest periods of 1 to 2 days in between, may be the most tolerable and effective regimen for the continued control of edema.

Administration: Pediatric

Oral: May be administered with or without regard to food.

Parenteral: IV:

Intermittent IV: May be administered undiluted by direct IV injection or further diluted and administered over 5 minutes (Ref).

Continuous IV infusion: In pediatric patients, may be administered undiluted or diluted via an infusion pump.

Usual Infusion Concentrations: Pediatric

IV infusion: 0.04 mg/mL or 0.25 mg/mL (undiluted).

Use: Labeled Indications

Edema or volume overload: Management of edema secondary to heart failure or hepatic or kidney disease (including nephrotic syndrome).

Medication Safety Issues
Sound-alike/look-alike issues:

Bumetanide may be confused with Buminate.

Bumex may be confused with Brevibloc, Buprenex.

Older Adult: High-Risk Medication:

Beers Criteria: Diuretics are identified in the Beers Criteria as a potentially inappropriate medication to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2023]).

International issues:

Bumex [US] may be confused with Permax brand name for pergolide [multiple international markets].

Metabolism/Transport Effects

Substrate of OAT1/3

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Allopurinol: Loop Diuretics may enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Amikacin Liposome (Oral Inhalation): Loop Diuretics may enhance the nephrotoxic effect of Amikacin Liposome (Oral Inhalation). Loop Diuretics may enhance the ototoxic effect of Amikacin Liposome (Oral Inhalation). Risk C: Monitor therapy

Aminoglycosides: Loop Diuretics may enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Angiotensin II Receptor Blockers: Loop Diuretics may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Loop Diuretics may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antihypertensive Agents: Loop Diuretics may enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Arsenic Trioxide: Loop Diuretics may enhance the hypotensive effect of Arsenic Trioxide. Loop Diuretics may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as the loop diuretics. Risk D: Consider therapy modification

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Beta2-Agonists: May enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy

Bilastine: Loop Diuretics may enhance the QTc-prolonging effect of Bilastine. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Loop Diuretics. Risk C: Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Canagliflozin: May enhance the hypotensive effect of Loop Diuretics. Risk C: Monitor therapy

Cardiac Glycosides: Loop Diuretics may enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of loop diuretics. Risk C: Monitor therapy

Cefaloridine [Cephaloridine]: Loop Diuretics may enhance the nephrotoxic effect of Cefaloridine [Cephaloridine]. Loop Diuretics may increase the serum concentration of Cefaloridine [Cephaloridine]. Risk X: Avoid combination

Cefazedone: May enhance the nephrotoxic effect of Loop Diuretics. Risk C: Monitor therapy

Cefotiam: Loop Diuretics may enhance the nephrotoxic effect of Cefotiam. Risk C: Monitor therapy

Cefpirome: Loop Diuretics may enhance the nephrotoxic effect of Cefpirome. Risk C: Monitor therapy

Ceftizoxime: Loop Diuretics may enhance the nephrotoxic effect of Ceftizoxime. Risk C: Monitor therapy

Cephalothin: Loop Diuretics may enhance the nephrotoxic effect of Cephalothin. Risk C: Monitor therapy

Cephradine: May enhance the nephrotoxic effect of Loop Diuretics. Risk C: Monitor therapy

CISplatin: Loop Diuretics may enhance the nephrotoxic effect of CISplatin. Loop Diuretics may enhance the ototoxic effect of CISplatin. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy

CycloSPORINE (Systemic): May enhance the adverse/toxic effect of Loop Diuretics. Specifically, the risk for hyperuricemia and gout may be increased. Risk C: Monitor therapy

Desmopressin: May enhance the hyponatremic effect of Loop Diuretics. Risk X: Avoid combination

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Dichlorphenamide: Loop Diuretics may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy

Dofetilide: Loop Diuretics may enhance the QTc-prolonging effect of Dofetilide. Management: Monitor serum potassium and magnesium more closely when dofetilide is combined with loop diuretics. Electrolyte replacements will likely be required to maintain potassium and magnesium serum concentrations. Risk D: Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Empagliflozin: May enhance the hypotensive effect of Loop Diuretics. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Management: Avoid use of fexinidazole with OAT1/3 substrates when possible. If combined, monitor for increased OAT1/3 substrate toxicities. Risk D: Consider therapy modification

Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Foscarnet: Loop Diuretics may increase the serum concentration of Foscarnet. Management: When diuretics are indicated during foscarnet treatment, thiazides are recommended over loop diuretics. If patients receive loop diuretics during foscarnet treatment, monitor closely for evidence of foscarnet toxicity. Risk D: Consider therapy modification

Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Iodinated Contrast Agents: Loop Diuretics may enhance the nephrotoxic effect of Iodinated Contrast Agents. Risk C: Monitor therapy

Ipragliflozin: May enhance the adverse/toxic effect of Loop Diuretics. Specifically, the risk for intravascular volume depletion may be increased. Risk C: Monitor therapy

Ivabradine: Loop Diuretics may enhance the arrhythmogenic effect of Ivabradine. Risk C: Monitor therapy

Leflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy

Levosulpiride: Loop Diuretics may enhance the adverse/toxic effect of Levosulpiride. Risk X: Avoid combination

Licorice: May enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy

Lithium: Loop Diuretics may decrease the serum concentration of Lithium. Loop Diuretics may increase the serum concentration of Lithium. Risk C: Monitor therapy

Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Risk X: Avoid combination

Methotrexate: May diminish the therapeutic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Methotrexate. Methotrexate may increase the serum concentration of Loop Diuretics. Risk C: Monitor therapy

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Netilmicin (Ophthalmic): Loop Diuretics may enhance the nephrotoxic effect of Netilmicin (Ophthalmic). Risk X: Avoid combination

Neuromuscular-Blocking Agents: Loop Diuretics may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Loop Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitisinone: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended. Risk D: Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Loop Diuretics. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Opioid Agonists: May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Polyethylene Glycol-Electrolyte Solution: Diuretics may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy

Pretomanid: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy

Probenecid: May diminish the diuretic effect of Loop Diuretics. Probenecid may increase the serum concentration of Loop Diuretics. Risk C: Monitor therapy

Promazine: Loop Diuretics may enhance the QTc-prolonging effect of Promazine. Risk X: Avoid combination

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Reboxetine: May enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy

RisperiDONE: Loop Diuretics may enhance the adverse/toxic effect of RisperiDONE. Risk C: Monitor therapy

Salicylates: May diminish the therapeutic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Risk C: Monitor therapy

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy

Taurursodiol: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid combination

Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy

Teriflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy

Tobramycin (Oral Inhalation): Loop Diuretics may enhance the nephrotoxic effect of Tobramycin (Oral Inhalation). Loop Diuretics may enhance the ototoxic effect of Tobramycin (Oral Inhalation). Risk C: Monitor therapy

Topiramate: Loop Diuretics may enhance the hypokalemic effect of Topiramate. Risk C: Monitor therapy

Urapidil: Antihypertensive Agents may enhance the hypotensive effect of Urapidil. Risk C: Monitor therapy

Vaborbactam: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy

Vancomycin: Loop Diuretics may enhance the nephrotoxic effect of Vancomycin. Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Xipamide: May enhance the adverse/toxic effect of Loop Diuretics. Specifically, the risk of hypovolemia, electrolyte disturbances, and prerenal azotemia may be increased. Risk C: Monitor therapy

Zoledronic Acid: Loop Diuretics may enhance the hypocalcemic effect of Zoledronic Acid. Risk C: Monitor therapy

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies.

Breastfeeding Considerations

It is not known if bumetanide is present in breast milk. Breastfeeding is not recommended by the manufacturer. Diuretics have the potential to decrease milk volume and suppress lactation.

Dietary Considerations

May cause potassium loss; potassium supplement or dietary changes may be required.

Monitoring Parameters

Blood pressure; serum electrolytes, kidney function; fluid intake and output.

Mechanism of Action

Inhibits reabsorption of sodium and chloride in the ascending loop of Henle and proximal renal tubule, interfering with the chloride-binding cotransport system, thus causing increased excretion of water, sodium, chloride, magnesium, phosphate, and calcium; it does not appear to act on the distal tubule

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Oral: 0.5 to 1 hour; IV: 2 to 3 minutes.

Peak effect: Oral: 1 to 2 hours; IV: 15 to 30 minutes.

Duration: Oral: 4 to 6 hours; IV: 2 to 3 hours.

Distribution: Vd: Neonates and Infants: 0.15 to 0.39 L/kg (Lopez-Samblas 1997; manufacturer's labeling); Adults: 9 to 25 L.

Protein binding: 94% to 96%; Neonates: 97%.

Metabolism: Partially hepatic.

Bioavailability: 59% to 89% (median: 80%); 80% to 100% (Brater 2011).

Half-life elimination:

Premature and full term neonates: 6 hours (range up to 15 hours).

Infants <2 months: 2.5 hours.

Infants 2 to 6 months: 1.5 hours.

Adults: 1 to 1.5 hours.

Excretion: Urine (81% of total dose; 45% of which is unchanged drug); feces (2% of total dose).

Clearance:

Preterm and full term neonates: 0.2 to 1.1 mL/minute/kg (Lopez-Samblas 1997; manufacturer's labeling).

Infants <2 months: 2.17 mL/minute/kg.

Infants 2 to 6 months: 3.8 mL/minute/kg.

Adults: 2.9 ± 0.2 mL/minute/kg.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: The half-life is relatively preserved (~1.6 hours) in patients with CrCl <30 mL/minute/1.73 m2 (Voelker 1987).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Burinex;
  • (AR) Argentina: Butinat | Segurex;
  • (AT) Austria: Burinex;
  • (AU) Australia: Burinex;
  • (BD) Bangladesh: Bumecard | Conart | Urinide;
  • (BE) Belgium: Burinex;
  • (BR) Brazil: Burinax | Fluxil;
  • (CH) Switzerland: Burinex;
  • (CL) Chile: Subit;
  • (CN) China: Chang su | Li liao;
  • (CO) Colombia: Poliurene;
  • (CZ) Czech Republic: Burinex;
  • (DE) Germany: Burinex;
  • (DO) Dominican Republic: Burinex | Miccil;
  • (EC) Ecuador: Miccil;
  • (EE) Estonia: Burinex;
  • (EG) Egypt: Burinex | Edemex;
  • (ES) Spain: Fordiuran;
  • (FI) Finland: Burinex;
  • (FR) France: Burinex;
  • (GB) United Kingdom: Betinex | Bumetanide almus | Bumetanide arrow | Bumetanide cox | Bumetanide kent | Burinex;
  • (GR) Greece: Burinex;
  • (HK) Hong Kong: Burinex;
  • (ID) Indonesia: Burinex;
  • (IE) Ireland: Burinex;
  • (IT) Italy: Fontego;
  • (JO) Jordan: Burinex;
  • (JP) Japan: Lunetoron;
  • (KR) Korea, Republic of: Burinex;
  • (LB) Lebanon: Burinex;
  • (LU) Luxembourg: Burinex;
  • (LV) Latvia: Burinex;
  • (MX) Mexico: Bumedyl | Bumetanida | Drenural | Durin | Miccil;
  • (MY) Malaysia: Bumet | Burinex;
  • (NL) Netherlands: Bumetanide Actavis | Bumetanide CF | Bumetanide ratiopharm | Bumetanide sandoz | Burinex;
  • (NO) Norway: Bumetanide centrafarm | Burinex;
  • (NZ) New Zealand: Burinex;
  • (PE) Peru: Miccil;
  • (PH) Philippines: Burinex;
  • (PL) Poland: Burinex;
  • (PR) Puerto Rico: Bumex;
  • (PY) Paraguay: Burinex;
  • (RU) Russian Federation: Buphenox;
  • (SA) Saudi Arabia: Burinex;
  • (SE) Sweden: Burinex;
  • (SG) Singapore: Burinex;
  • (SI) Slovenia: Burinex;
  • (TH) Thailand: Burinex;
  • (TR) Turkey: Bumid;
  • (TW) Taiwan: Budema | Buedor | Bumeta | Burinex | Busix | Butanide | Urenide;
  • (UA) Ukraine: Buphenox;
  • (VE) Venezuela, Bolivarian Republic of: Biulan | Bumelex;
  • (ZA) South Africa: Burinex
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