Bumetanide

Pronunciation (byoo MET a nide)

• Heart Failure
• Sulfonamide Derivatives

U.S. Brand Names Bumex®

Generic Available Yes

Canadian Brand Names Bumex®; Burinex®

Pharmacologic Category Diuretic, Loop

Use Management of edema secondary to congestive heart failure or hepatic or renal disease including nephrotic syndrome; may be used alone or in combination with antihypertensives in the treatment of hypertension; can be used in furosemide-allergic patients

Pregnancy Risk Factor C (manufacturer); D (expert analysis)

Lactation Excretion in breast milk unknown/use caution

Contraindications Hypersensitivity to bumetanide, any component of the formulation, or sulfonylureas; anuria; patients with hepatic coma or in states of severe electrolyte depletion until the condition improves or is corrected; pregnancy (based on expert analysis)

Warnings/Precautions Adjust dose to avoid dehydration. In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Ototoxicity is associated with I.V. rapid administration, renal impairment, excessive doses, and concurrent use of other ototoxins. Hypersensitivity reactions can rarely occur. Monitor fluid status and renal function in an attempt to prevent oliguria, azotemia, and reversible increases in BUN and creatinine. Close medical supervision of aggressive diuresis required. Watch for and correct electrolyte disturbances. Coadministration of antihypertensives may increase the risk of hypotension.

Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonylurea allergy is specifically contraindicated in product labeling, however a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.

Loop diuretics are potent diuretics; excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation is required; 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.

>10%:

1% to 10%:

<1% (Limited to important or life-threatening): Hypotension, orthostatic hypotension, headache, nausea, encephalopathy (in patients with pre-existing liver disease), impaired hearing, pruritus, weakness, hives, abdominal pain, arthritic pain, musculoskeletal pain, rash, vomiting, vertigo, chest pain, ear discomfort, fatigue, dehydration, diaphoresis, hyperventilation, dry mouth, upset stomach, renal failure, asterixis, itching, nipple tenderness, diarrhea, premature ejaculation, hypernatremia

Overdosage/Toxicology Symptoms of overdose include electrolyte depletion and volume depletion. Treatment is symptomatic and supportive.

ACE inhibitors: Hypotensive effects and/or renal effects are potentiated by hypovolemia.

Antidiabetic agents: Glucose tolerance may be decreased.

Antihypertensive agents: Hypotensive effects may be enhanced.

Cholestyramine or colestipol may reduce bioavailability of bumetanide.

Digoxin: Bumetanide-induced hypokalemia may predispose to digoxin toxicity; monitor potassium.

Indomethacin (and other NSAIDs) may reduce natriuretic and hypotensive effects of diuretics.

Lithium: Renal clearance may be reduced. Isolated reports of lithium toxicity have occurred; monitor lithium levels.

NSAIDs: Risk of renal impairment may increase when used in conjunction with diuretics.

Ototoxic drugs (aminoglycosides, cis-platinum): Concomitant use of bumetanide may increase risk of ototoxicity, especially in patients with renal dysfunction.

Peripheral adrenergic-blocking drugs or ganglionic blockers: Effects may be increased.

Salicylates (high-dose) with diuretics may predispose patients to salicylate toxicity due to reduced renal excretion or alter renal function.

Sparfloxacin, gatifloxacin, and moxifloxacin: Risk of hypokalemia and cardiotoxicity may be increased; avoid use.

Thiazides: Synergistic diuretic effects occur.

Ethanol/Nutrition/Herb Interactions Herb/Nutraceutical: Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid dong quai if using for hypertension (has estrogenic activity). Avoid garlic (may have increased antihypertensive effect).

Stability I.V. infusion solutions should be used within 24 hours after preparation; light sensitive, discoloration may occur when exposed to light

Compatibility Stable in D₅W, NS, LR

Y-site administration: Compatible: Allopurinol, amifostine, aztreonam, cefepime, cisatracurium, cladribine, clarithromycin, diltiazem, docetaxel, etoposide, filgrastim, gemcitabine, granisetron, lorazepam, melphalan, meperidine, milrinone, morphine, piperacillin/tazobactam, propofol, remifentanil, teniposide, thiotepa, vinorelbine. Incompatible: Midazolam

Compatibility in syringe: Compatible: Doxapram

Compatibility when admixed: Compatible: Floxacillin, furosemide. Incompatible: Dobutamine, milrinone

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

Onset of action: Oral, I.M.: 0.5-1 hour; I.V.: 2-3 minutes

Duration: 6 hours

Distribution: V_d: 13-25 L/kg

Protein binding: 95%

Metabolism: Partially hepatic

Half-life elimination: Infants <6 months: Possibly 2.5 hours; Children and Adults: 1-1.5 hours

Excretion: Primarily urine (as unchanged drug and metabolites)

Oral, I.M., I.V.:

Adults:

Administration Administer I.V. slowly, over 1-2 minutes; an alternate-day schedule or a 3-4 daily dosing regimen with rest periods of 1-2 days in between may be the most tolerable and effective regimen for the continued control of edema; reserve I.V. administration for those unable to take oral medications

Monitoring Parameters Blood pressure, serum electrolytes, renal function

Dietary Considerations May require increased intake of potassium-rich foods.

Patient Information May be taken with food to reduce GI effects. Take single dose early in day (single dose) or last dose early in afternoon (twice daily) to prevent sleep interruptions. Include orange juice or bananas (or other sources of potassium-rich foods) in your daily diet but do not take supplemental potassium without consulting prescriber. You may experience dizziness, hypotension, lightheadedness, or weakness; use caution when changing position (rising from sitting or lying position), when driving, exercising, climbing stairs, or performing hazardous tasks, and avoid excessive exercise in hot weather. Report swelling of ankles or feet, weight increase or decrease more than 3 pounds in any one day, increased fatigue, muscle cramps or trembling, and any changes in hearing. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant; contraceptives may be recommended. Consult prescriber if breast-feeding.

Nursing Implications Be alert to complaints about hearing difficulty

Anesthesia and Critical Care Concerns/Other Considerations If given the morning of surgery it may render the patient volume depleted and blood pressure may be labile during general anesthesia.

Patients with impaired hepatic function must be monitored carefully, often requiring reduced doses; larger doses may be necessary in patients with impaired renal function to obtain the same therapeutic response

Bumetanide is a potent diuretic that may be used in patients who cannot tolerate or who may be allergic to furosemide. It is important that patients be closely followed for hypokalemia, hypomagnesemia, and volume depletion because of significant diuresis.

Cardiovascular Considerations Bumetanide is a potent diuretic that may be used in patients who cannot tolerate or who may be allergic to furosemide. It is important that patients be closely followed for hypokalemia, hypomagnesemia, and volume depletion because of significant diuresis.

Dental Health: Effects on Dental Treatment No effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions No information available to require special precautions

Mental Health: Effects on Mental Status May cause dizziness

Mental Health: Effects on Psychiatric Treatment Lithium excretion may be decreased; monitor serum lithium levels

Injection, solution: 0.25 mg/mL (2 mL, 4 mL, 10 mL)

Tablet: 0.5 mg, 1 mg, 2 mg

Montgomery PA and Christen C, "Policy to Restrict Use of I.V. Bumetanide,"Am J Health Syst Pharm, 1995, 52(16):1802-4.

Ward A and Heel RC, "Bumetanide: A Review of Its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Use,"Drugs, 1984, 28(5):426-64.

Wells TG, "The Pharmacology and Therapeutics of Diuretics in the Pediatric Patient,"Pediatr Clin North Am, 1990, 37(2):463-504.

International Brand Names Aneiromox® (ES); Aquazone® (ES); Bumedyl® (MX); Bumet® (IN); Bumetanid® (CY, YU); Bumex® (CA); Bumid® (TR); Burinax® (BR); Burinex® (AU); Burinex (AT, BE, CA, DK, FI, FR, DE, GB, HK, IE, IT, LU, NL, NZ, NO, ZA, SE, CH); Butinat® (AR); Butinat (ES); Drenural® (MX); Farmadiuril® (ES); Fluxil® (BR); Fontego (IT); Fordiuran (DE, ES); Lixil-Leo® (DK); Lunetoron® (JP); Miccil® (MX); Salurin® (TR); Yurinex® (YU)