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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.
Medication Safety Issues
Sound-alike/look-alike issues:
Bumetanide may be confused with Buminate®
Bumex® may be confused with Brevibloc®, Buprenex®, Permax®
Pronunciation
(byoo MET a nide)
U.S. Brand Names
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
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
Boxed warnings:
• Fluid/electrolyte loss: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Fluid/electrolyte loss: [U.S. Boxed Warning]: Loop diuretics are potent diuretics; excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration.
• Hyperuricemia: Asymptomatic hyperuricemia has been reported with use.
• Nephrotoxicity: 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.
• Ototoxicity: Rapid I.V. administration, renal impairment, excessive doses, and concurrent use of other ototoxins is associated with ototoxicity.
• Sulfa allergy: 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. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns:
• Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.
Concurrent drug therapy issues:
• Antihypertensives: Coadministration of antihypertensives may increase the risk of hypotension.
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.
Adverse Reactions
>10%:
Endocrine & metabolic: Hyperuricemia (18%), hypochloremia (15%), hypokalemia (15%)
Renal: Azotemia (11%)
1% to 10%:
Central nervous system: Dizziness (1%)
Endocrine & metabolic: Hyponatremia (9%); hyperglycemia (7%); variations in phosphorus (5%), CO2 content (4%), bicarbonate (3%), and calcium (2%)
Neuromuscular & skeletal: Muscle cramps (1%)
Otic: Ototoxicity (1%)
Renal: Serum creatinine increased (7%)
<1% (Limited to important or life-threatening): Hypotension, orthostatic hypotension, headache, nausea, encephalopathy (in patients with pre-existing liver disease), hearing impaired, 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
Drug Interactions
ACE Inhibitors: Loop Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Loop Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. 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 Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Aminoglycosides: Loop Diuretics may enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Loop Diuretics. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Dofetilide: Loop Diuretics may enhance the QTc-prolonging effect of Dofetilide. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. 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
Nonsteroidal Anti-Inflammatory Agents: May diminish the diuretic effect of Loop Diuretics. Risk C: Monitor therapy
Phenytoin: May diminish the diuretic effect of Loop Diuretics. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
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).
Storage
I.V.: Store vials at 15°C to 30°C (59°F to 86°F). Infusion solutions 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).
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
Pharmacodynamics/Kinetics
Onset of action: Oral, I.M.: 0.5-1 hour; I.V.: 2-3 minutes
Duration: 4-6 hours
Distribution: Vd: 13-25 L/kg
Protein binding: 95%
Metabolism: Partially hepatic
Half-life elimination: Neonates: ?6 hours; Infants (1 month): ?2.4 hours; Adults: 1-1.5 hours
Excretion: Primarily urine (as unchanged drug and metabolites)
Dosage
Oral, I.M., I.V.:
Neonates (see Warnings/Precautions): 0.01-0.05 mg/kg/dose every 24-48 hours
Infants and Children: 0.015-0.1 mg/kg/dose every 6-24 hours (maximum dose: 10 mg/day)
Adults:
Edema:
Oral: 0.5-2 mg/dose (maximum dose: 10 mg/day) 1-2 times/day
I.M., I.V.: 0.5-1 mg/dose; may repeat in 2-3 hours for up to 2 doses if needed (maximum dose: 10 mg/day)
Continuous I.V. infusion: Initial: 1 mg I.V. load then 0.5-2 mg/hour (ACC/AHA 2005 practice guidelines for chronic heart failure)
Hypertension: Oral: 0.5 mg daily (maximum dose: 5 mg/day); usual dosage range (JNC 7): 0.5-2 mg/day in 2 divided doses
Administration: I.V.
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.
Administration: I.V. Detail
pH: 6.8-7.8 (adjusted)
Monitoring Parameters
Blood pressure, serum electrolytes, renal function
Dietary Considerations
May require increased intake of potassium-rich foods.
Patient Education
Do not take any new medication during therapy unless approved by prescriber. May be taken with food to reduce GI effects. If taking one dose daily, take single dose early in day; if taking twice daily, take last dose early in afternoon 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. If you have diabetes, monitor glucose levels closely (glucose tolerance may be decreased by loop diuretics), and notify prescriber of noted changes (hypoglycemic agent may need to be adjusted). May cause dizziness, hypotension, lightheadedness, or weakness (use caution when changing position from sitting or lying position, when driving, exercising, climbing stairs, or performing hazardous tasks until response to drug is known). Report palpitations or chest pain; swelling of ankles or feet; weight increase or decrease (>3 lb 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 become pregnant; contraceptives may be recommended. Consult prescriber if breast-feeding.
Geriatric Considerations
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, particularly in the elderly. Severe loss of sodium and/or increases in BUN can cause confusion; for any change in mental status in patients on bumetanide, monitor electrolytes and renal function.
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.
It is important that patients be closely followed for hypokalemia, hypomagnesemia, and volume depletion because of significant diuresis.
Cardiovascular Considerations
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 significant 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
Nursing: Physical Assessment/Monitoring
Assess history of allergies, renal, electrolyte, hepatic, and pregnancy status prior to beginning treatment. Assess other pharmacological or herbal products patient may be taking for potential interactions (eg, increased risk of hyperglycemia, hypotension, arrhythmias, ototoxicity). Blood pressure, weight, and fluid status should be monitored at beginning of therapy and periodically during therapy. Glucose levels for patients with diabetes should be monitored closely (glucose tolerance may be decreased by loop diuretics, requiring adjustment of hypoglycemic agents). Assess results of laboratory tests (electrolytes and renal function), therapeutic effectiveness (reduced edema and cardiopulmonary symptoms), and adverse effects (hypotension, electrolyte imbalance, ototoxicity). Teach patient proper use, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, solution: 0.25 mg/mL (2 mL, 4 mL, 10 mL)
Tablet: 0.5 mg, 1 mg, 2 mg
Bumex®: 0.5 mg [DSC]; 1 mg; 2 mg [DSC]
Pricing: U.S. (www.drugstore.com)
Tablets (Bumetanide)
2 mg (100): $82.39
References
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Hunt SA, Abraham WT, Chin MH , et al, "ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure)," available at http://www.acc.org/qualityandscience/clinical/guidelines/failure/update/index.pdf.
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
Lexi-Comp.com
Last full review/revision September 2008
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