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.
Note: Relative to other loop diuretics (eg, furosemide), bumetanide is much more potent; monitor closely during use.
Edema (diuresis): Limited data available: Note: Doses in the higher end of the range may be required for patients with heart failure (Ward 1977):
Preterm: Oral, IM, IV: 0.01 to 0.06 mg/kg/dose every 12 to 48 hours; every 12 to 24 hour dosing interval has been used for oliguria in the setting of acute renal failure (Gal 2007; Oliveros 2011); dosing based on small trials; one retrospective study evaluated 35 preterm neonates and infants (mean GA: 26 ± 2.75 weeks, mean PNA: 24 ± 11.57 days) who received a mean IV dose of 0.03 mg/kg/dose every 12 to 24 hours (range: 0.01 to 0.06 mg/kg/dose) to reverse oliguria in the setting of acute renal failure (Oliveros 2011); IV doses as high as 0.1 mg/kg/dose were reported in a pharmacokinetic study (Lopez-Samblas 1997)
Term: Oral, IM, IV: 0.01 to 0.05 mg/kg/dose every 12 to 24 hours; doses as high as 0.1 mg/kg/dose have been reported (Sullivan 1996; Ward 1977)
Note: Dose equivalency for adult patients with normal renal function (approximate): Bumetanide 1 mg = furosemide 40 mg = torsemide 20 mg = ethacrynic acid 50 mg
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 (Gal 2007; Kliegman 2016; Sullivan 1996)
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. Dosing based on retrospective study of 95 patients (median age: 0.2 years, range: 0 to 15.7 years) who received a mean dose of 5.7 mcg/kg/hour (range: 1 to 10 mcg/kg/hour); negative fluid balance was achieved in 76% of patients within 48 hours of initiation; of note, 60% of patients were receiving concomitant intermittent diuretics (McCallister 2015). Another retrospective, descriptive trial reported higher doses in 40 neonates and children (mean age: 1.6 ± 2.6 years); the reported mean initial dose was 30 mcg/kg/hour (range: 1 to 100 mcg/kg/hour) and the mean maximum dose was 50 mcg/kg/hour (range: 3 to 200 mcg/kg/hour); of note, a complete safety analysis is lacking in this trial (Bulkley 2012).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric-specific recommendations; based on experience in adult patients, high doses are effective in ESRD (Aronoff 2007) but use is contraindicated in anuria; use with caution in renal insufficiency due to increased risk of adverse effects.
There are no pediatric-specific recommendations; 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.
(For additional information see "Bumetanide: Drug information")
Note: Loop diuretic approximate oral dose equivalency for patients with normal renal function: Bumetanide 1 mg = furosemide 40 mg = torsemide 20 mg (ACCF/AHA [Yancy 2013]; Brater 1983; Brater 2022a; Felker 2011). Some experts suggest an approximate oral dose equivalency of bumetanide 1 mg = furosemide 40 mg = torsemide 10 mg (Felker 2012; Vargo 1995).
Edema (eg, peripheral, pulmonary, generalized):
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) (Brater 2011; Sterns 2022).
Note: Oral bioavailability is very good (~80% to 100%); the same IV or oral dose is expected to produce a similar effect (Brater 2011).
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 (see Titration to Effect below) (ACC [Hollenberg 2019]; Brater 2011; Brater 2021b; Colucci 2020).
Continuous infusion: Note: Reserve for patients who have responded to bolus therapy; administer an effective bolus dose then immediately start continuous infusion.
eGFR ≥30 mL/minute/1.73 m2: 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 (Brater 2011; Brater 2021b).
eGFR <30 mL/minute/1.73 m2: IV: Initial: 1 mg/hour; if diuretic response is not adequate, repeat IV bolus dose and increase continuous infusion to 2 mg/hour (Brater 2011; Brater 2021b).
Note: Higher continuous infusion rates are not recommended due to potential for side effects; consider alternative strategies for fluid removal (Brater 2021b).
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 renal failure. The maximum recommended total daily dose is 10 mg/day to avoid toxicity (ACC [Hollenberg 2019]; Brater 2011; Brater 2022a; Brater 2021b).
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 (Brater 2011; Brater 2021b).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution. Contraindicated in anuria.
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.
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 aluminum lake, fd&c yellow #10 aluminum lake]
Bumex: 1 mg [DSC] [contains fd&c yellow #10 (quinoline yellow)]
Bumex: 2 mg [DSC]
Generic: 0.5 mg, 1 mg, 2 mg
Yes
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]
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 (Rudy 1991)
Continuous IV infusion: In pediatric patients, may be administered undiluted or further diluted (Miller 2014; Murray 2014) via an infusion pump
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.
IV: Store vials at 15°C to 30°C (59°F to 86°F). Infusion solutions in D5W, NS, or LR should be used within 24 hours after preparation. Light sensitive; discoloration may occur when exposed to light.
Tablet: Store at 15°C to 30°C (59°F to 86°F); protect from light.
Management of edema secondary to heart failure or hepatic or renal disease, including nephrotic syndrome (FDA approved in adults)
Bumetanide may be confused with Buminate.
Bumex may be confused with Brevibloc, Buprenex.
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 2019]).
Bumex [US] may be confused with Permax brand name for pergolide [multiple international markets].
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)
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)
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).
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)
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
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.
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.
• Renal impairment: Larger doses may be necessary in patients with impaired renal 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 higher doses of loop diuretic treatment, an adequate diuretic response cannot be attained. Diuretic resistance can usually be overcome by intravenous administration, the use of two diuretics together (eg, furosemide and chlorothiazide), or the use of a diuretic with a positive inotropic agent. When such combinations are used, serum electrolytes need to be monitored even more closely (ACC/AHA [Yancy 2013]).
None known.
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
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. 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
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). 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
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. 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
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
Fosphenytoin: May diminish the diuretic effect of Loop Diuretics. Risk C: Monitor therapy
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
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
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. 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
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
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
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
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
Phenytoin: May diminish the diuretic effect of Loop Diuretics. 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
Probenecid: May enhance the adverse/toxic effect of Loop Diuretics. Probenecid may diminish the diuretic effect of Loop Diuretics. Probenecid may increase the serum concentration of Loop Diuretics. Management: Monitor for decreased diuretic effects or increased adverse effects of loop diuretics with concomitant use of probenecid. Bumetanide prescribing information recommends against concomitant use of probenecid. 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 diuretic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. 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. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Risk D: Consider therapy modification
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
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
May cause potassium loss; potassium supplement or dietary changes may be required.
Adverse events have been observed in some animal reproduction studies.
Serum electrolytes (baseline and frequently during therapy); blood pressure; urine output and renal function parameters (baseline and frequently during therapy); fluid balance (body weight; neonatal and young pediatric patients may require more frequent monitoring than older patients); hearing (with high doses or extended duration)
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
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: 0.26 to 0.39 L/kg; 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.
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.
Renal function impairment: The half-life is prolonged.
Solution (Bumetanide Injection)
0.25 mg/mL (per mL): $0.64 - $0.83
Tablets (Bumetanide Oral)
0.5 mg (per each): $0.54 - $2.43
1 mg (per each): $0.54 - $2.70
2 mg (per each): $1.02 - $2.97
Tablets (Bumex Oral)
0.5 mg (per each): $2.70
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