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Bumetanide

Pronunciation

Class: Loop Diuretics
VA Class: CV702
Chemical Name: 3-(Aminosulfonyl)-5-(butylamino)-4-phenoxybenzoic acid
Molecular Formula: C17H20N2O5S
CAS Number: 28395-03-1
Brands: Bumex

Warning(s)

  • 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; dosage selection and titration should be adjusted to the individual patient’s needs.4 (See Dosage and Administration.)

Introduction

A sulfonamide, loop-type diuretic and antihypertensive agent.4 130

Uses for Bumetanide

Edema

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

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

Congestive Heart Failure

Short- and long-term management of edema associated with congestive heart failure.2 25 35 39 44 45 46 73 Also relieves other signs and symptoms of congestive heart failure such as dyspnea, rales, and hepatomegaly.2 45 46

Loop diuretics (e.g., bumetanide, ethacrynic acid, furosemide, torsemide) are diuretics of choice for most patients with congestive heart failure.d

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Hepatic Disease

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

Appears to be as effective as furosemide in reducing body weight and in causing diuresis and increased urinary excretion of sodium, potassium, and chloride in patients with hepatic cirrhosis and ascites.31 50 53

Renal Disease

Management of edema in patients with impaired renal function, including nephrotic syndrome3 4 .34 37 54 55 56

Appears to be as effective as furosemide in reducing edema, body weight, and abdominal girth in patients with edema secondary to renal disease.34

Other Edematous Conditions

Used for the management of postoperative or premenstrual edema and edema associated with disseminated carcinoma.5

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).5 92 94 112 113 127 128 130

One of several preferred initial therapies in hypertensive patients with congestive heart failure, acute pulmonary edema, or renal disease.5 112 113 130

Can be used as monotherapy for initial management of uncomplicated hypertension.5 92 94 112 113 127 128 130 However, JNC 7 recommends that thiazides be used as initial therapy for the treatment of uncomplicated hypertension in most patients, either alone or combined with other classes of antihypertensive drugs with demonstrated benefit (e.g., ACE inhibitors, angiotensin II receptor antagonists, β-blockers, calcium-channel blockers).92 93 112 113 127 128 130

Bumetanide Dosage and Administration

General

  • Excessive fluid and electrolyte loss may be minimized by monitoring the patient carefully and by initiating therapy with small doses, adjusting dosage carefully, and using an intermittent dosage schedule if possible.4 (See Boxed Warning.)

  • Supplemental therapy with potassium chloride or potassium-sparing diuretics (e.g., spironolactone) may be necessary for the prevention of hypokalemia and/or metabolic alkalosis in some patients.4

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

For solution and drug compatibility information, see Compatibility under Stability.

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

When possible, use vials instead of ampuls to prepare large doses to prevent large quantities of glass particles from entering the solutions; if ampuls must be used, filter through a sterile membrane filter before use.81 82

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 (See Sensitivity Reactions under Cautions.)

Pediatric Patients

Congestive Heart Failure
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 congestive 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 (See Administration under Dosage and Administration.)

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 94 111 112 0.5–2 mg daily administered in 2 divided doses is recommended by JNC 7.130

Maintenance dosages of 1–4 mg daily have been used.43 57 112 Higher dosages may be necessary in some patients (e.g., those with renal insufficiency).92 (See Renal Impairment under Dosage and Administration.)

Prescribing Limits

Adults

Edema
Oral

Maximum recommended by manufacturer: 10 mg daily.4

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

Hypertension
Oral

Dosages >1–2 mg daily may be necessary for the management of hypertension in adults with renal insufficiency.92 94 Dosage may be increased until the desired therapeutic response is achieved, adverse effects become intolerable, or a maximum dosage of 10 mg daily, in 2 divided doses, is attained.92 If an adequate response is not achieved with this maximum dosage, another hypotensive agent (e.g., an adrenergic inhibitor that preserves glomerular filtration rate and renal blood flow) may be added or substituted.92 93 Risk of adverse effects (e.g., ototoxicity) at these high dosages should be considered.4 (See Ototoxicity under Cautions.)

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

Cautions for Bumetanide

Contraindications

  • Anuria.4

  • Marked increases in BUN or serum creatinine concentration or development of oliguria during treatment of progressive renal disease.4

  • Hepatic coma or severe electrolyte depletion, until condition is improved or corrected.4

  • Known hypersensitivity to bumetanide or any ingredient in the formulation.4

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 CHF receiving cardiac glycosides and diuretics, those with a history of ventricular arrhythmias, and those with other conditions in which hypokalemia represents a risk.4 (See Hepatic Impairment under Cautions.)

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 (See Specific Drugs under Interactions.)

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 CHF.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 (See Distribution: Special Populations, under Pharmacokinetics.)

Elimination appears to be slower in neonates than in adults, possibly because of immature renal and hepatobiliary functions.4 (See Elimination: Special Populations, under Pharmacokinetics.)

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 (See Fluid, Electrolyte, and Cardiovascular Effects under Cautions.) 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 (See Renal Impairment under Dosage and Administration.)

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

Common Adverse Effects

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

Interactions for Bumetanide

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 glycoside (e.g., digoxin)

Possible electrolyte disturbances (e.g., hypokalemia, hypomagnesemia) may predispose to digitalis toxicity, possibly fatal cardiac arrhythmias.3 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 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

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Physically and chemically compatible in glass and PVC containers.3 b

Solution CompatibilityHID

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Ringer’s injection, lactated

Drug Compatibility
Admixture CompatibilityHID

Compatible

Furosemide

Incompatible

Dobutamine HCl

Y-Site CompatibilityHID

Compatible

Allopurinol sodium

Amifostine

Aztreonam

Bivalirudin

Caspofungin acetate

Ceftaroline fosamil

Cisatracurium besylate

Cladribine

Dexmedetomidine HCl

Diltiazem HCl

Docetaxel

Doripenem

Etoposide phosphate

Filgrastim

Gemcitabine HCl

Granisetron HCl

Hetastarch in lactated electrolyte injection (Hextend)

Lorazepam

Melphalan HCl

Meperidine HCl

Micafungin sodium

Milrinone lactate

Morphine sulfate

Oxaliplatin

Pemetrexed disodium

Piperacillin sodium–tazobactam sodium

Propofol

Remifentanil HCl

Teniposide

Thiotepa

Vinorelbine tartrate

Incompatible

Fenoldopam mesylate

Midazolam HCl

Nesiritide

Actions

  • Loop diuretic with a rapid onset and short duration of action.4

  • Approximately 40 times the diuretic activity of furosemide on a weight basis;2 3 4 5 11 25 relative potency may vary with different dosages and/or routes of administration.3 12 73

  • Decreases electrolyte reabsorption by inhibiting the active chloride and sodium transport systems in the ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption.4 6 7 8 13 51 89

  • Increases urinary excretion of sodium, chloride, potassium, hydrogen, calcium, magnesium, ammonium and possibly phosphate and bicarbonate.3 4 6 7 8 9 10 13 14 15

  • The chloruretic effect of the drug is greater than its natriuretic effect, and its effect on urinary calcium and magnesium excretion is less than that on sodium excretion.3 4 6 7 13 15

  • Increases potassium secretion in the distal renal tubule in a dose-related manner secondary to increased sodium load in the tubule.3 4 5 7 10 72

  • Induces phosphaturia and bicarbonate excretion; appears to inhibit sodium phosphate-linked transport in the proximal renal tubule.2 4 5 6 7 8 9

  • Decreases uric acid excretion and increases serum uric acid concentration.4 7 8 14 25

  • Produces renal vascular dilation and substantially increases renal blood flow.3 7 16

  • Produces variable but substantial increases in plasma renin activity (PRA).13

  • Produces hypotensive effects and decreases body weight resulting from decreased plasma volume.3 4

  • Reduces mean pulmonary venous pressure, left ventricular end-diastolic pressure, mean pulmonary artery pressure, and mean right atrial pressure in patients with valvular heart disease.3

  • Reduces cardiac output, cardiac index, stroke volume, stroke index, and diastolic pressures in patients with coronary artery disease.3

Advice to Patients

  • Importance of informing patients to report any signs and symptoms of electrolyte imbalance (weakness, dizziness, fatigue, faintness, mental confusion, lassitude, muscle cramps, headache, paresthesia, thirst, anorexia, nausea, and/or vomiting) to their clinician.3 75 76 81 82

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.4

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.4

  • Importance of informing patients of other important precautionary information.4 (See Cautions.)

Preparations

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

* 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

Bumex (scored)

Roche

1 mg*

Bumetanide Tablets

Bumex (scored)

Roche

2 mg*

Bumetanide Tablets

Bumex (scored)

Roche

Parenteral

Injection

0.25 mg/mL*

Bumetanide Injection

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Bumetanide 0.5MG Tablets (TEVA PHARMACEUTICALS USA): 90/$18.99 or 180/$27.97

Bumetanide 1MG Tablets (TEVA PHARMACEUTICALS USA): 90/$28.97 or 180/$57.94

Bumetanide 2MG Tablets (TEVA PHARMACEUTICALS USA): 30/$20.99 or 60/$35.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 18, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

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3. Roche Laboratories. Bumex comprehensive product information. Nutley, NJ; 1983 Mar.

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

5. Flamenbaum W, Friedman R. Pharmacology, therapeutic efficacy, and adverse effects of bumetanide, a new “loop” diuretic. Pharmacotherapy. 1982; 2:213-22. [IDIS 154854] [PubMed 6763204]

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7. Olsen UB. The pharmacology of bumetanide. Acta Pharmacol Toxicol (Copenh). 1977; 41(Suppl. 3):1-24. [PubMed 331869]

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23. Marcantonio LA, Auld WHR, Murdock WR et al. The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease. Br J Clin Pharmacol. 1983; 15:245-52. [IDIS 166487] [PubMed 6849758]

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26. Cohen MR, Hinsch E, Vergona R et al. A comparative diuretic and tissue distribution study of bumetanide and furosemide in the dog. J Pharmacol Exp Ther. 1976; 197:697-702. [PubMed 932999]

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31. Herlong HF, Hunter FM, Koff RS et al. A comparison of bumetanide and furosemide in the treatment of ascites: cooperative study. J Clin Pharmacol. 1981; 21:701-5. [IDIS 149074] [PubMed 7338582]

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