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Medication Safety Issues
Sound-alike/look-alike issues:
Furosemide may be confused with torsemide
Lasix® may be confused with Esidrix®, Lanoxin®, Lidex®, Lomotil®, Luvox®, Luxiq®
International issues:
Urex® [Australia] may be confused with Eurax® which is a brand name for crotamiton in the U.S.
Urex® [Australia]: Brand name for methenamine in the U.S.
Pronunciation
(fyoor OH se mide)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of edema associated with congestive heart failure and hepatic or renal disease; alone or in combination with antihypertensives in treatment of hypertension
Pregnancy Risk Factor
C
Pregnancy Considerations
Crosses the placenta. Increased fetal urine production, electrolyte disturbances reported. Generally, use of diuretics during pregnancy is avoided due to risk of decreased placental perfusion.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Crosses into breast milk; may suppress lactation. AAP has NO RECOMMENDATION.
Contraindications
Hypersensitivity to furosemide, any component, or sulfonylureas; anuria; patients with hepatic coma or in states of severe electrolyte depletion until the condition improves or is corrected
Warnings/Precautions
Concerns related to adverse effects:
• Fluid/electrolyte loss: 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.
Adverse Reactions
Frequency not defined.
Cardiovascular: Acute hypotension, chronic aortitis, necrotizing angiitis, orthostatic hypotension, thrombophlebitis, sudden death from cardiac arrest (with I.V. or I.M. administration)
Central nervous system: Blurred vision, dizziness, fever, headache, lightheadedness, restlessness, vertigo, xanthopsia
Dermatologic: Cutaneous vasculitis, erythema multiforme, exfoliative dermatitis, photosensitivity, pruritus, purpura, rash, urticaria
Endocrine & metabolic: Gout, hyperglycemia, hyperuricemia, hypocalcemia, hypochloremia, hypokalemia, hypomagnesemia, hyponatremia, metabolic alkalosis
Gastrointestinal: Anorexia, constipation, cramping, diarrhea, intrahepatic cholestatic jaundice, ischemia hepatitis, nausea, oral and gastric irritation, pancreatitis, vomiting
Genitourinary: Urinary bladder spasm, urinary frequency
Hematological: Agranulocytosis (rare), anemia, aplastic anemia (rare), hemolytic anemia, leukopenia, purpura, thrombocytopenia
Neuromuscular & skeletal: Muscle spasm, paresthesia, weakness
Otic: Hearing impairment (reversible or permanent with rapid I.V. or I.M. administration), reversible deafness (with rapid I.V. or I.M. administration), tinnitus
Renal: Allergic interstitial nephritis, fall in glomerular filtration rate and renal blood flow (due to overdiuresis), glycosuria, transient rise in BUN, vasculitis
Miscellaneous: Anaphylaxis (rare), exacerbate or activate systemic lupus erythematosus
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
Aliskiren: May decrease the serum concentration of Furosemide. 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
Food: Furosemide serum levels may be decreased if taken with food.
Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, and ginseng (may worsen hypertension). Limit intake of natural licorice. Avoid garlic (may have increased antihypertensive effect).
Storage
Furosemide injection should be stored at controlled room temperature and protected from light. Exposure to light may cause discoloration. Do not use furosemide solutions if they have a yellow color. Refrigeration may result in precipitation or crystallization, however, resolubilization at room temperature or warming may be performed without affecting the drugs stability. I.V. infusion solution mixed in NS or D5W solution is stable for 24 hours at room temperature.
Reconstitution
I.V. infusion solution may also be diluted for infusion 1-2 mg/mL (maximum: 10 mg/mL) over 10-15 minutes (following infusion rate parameters).
Compatibility
Stable in D5LR, D5NS, D5W, D10W, D20W, mannitol 20%, LR, NS.
Y-site administration: Compatible: Allopurinol, amifostine, amikacin, amphotericin B cholesteryl sulfate complex, aztreonam, bleomycin, cefepime, cisplatin, cladribine, cyclophosphamide, cytarabine, docetaxel, doxorubicin liposome, epinephrine, etoposide phosphate, fentanyl, fludarabine, fluorouracil, foscarnet, granisetron, heparin, hydrocortisone sodium succinate, hydromorphone, indomethacin, kanamycin, leucovorin, linezolid, lorazepam, melphalan, meropenem, methotrexate, mitomycin, nitroglycerin, norepinephrine, paclitaxel, piperacillin/tazobactam, potassium chloride, propofol, ranitidine, remifentanil, sargramostim, tacrolimus, teniposide, thiotepa, tobramycin, tolazoline, vitamin B complex with C. Incompatible: Alatrofloxacin, amsacrine, chlorpromazine, ciprofloxacin, clarithromycin, diltiazem, droperidol, esmolol, filgrastim, fluconazole, gatifloxacin, gemcitabine, gentamicin, hydralazine, idarubicin, levofloxacin, metoclopramide, midazolam, milrinone, netilmicin, nicardipine, ondansetron, quinidine gluconate, thiopental, vecuronium, vinblastine, vincristine, vinorelbine. Variable (consult detailed reference): Cisatracurium, dobutamine, dopamine, doxorubicin, famotidine, labetalol, meperidine, morphine.
Compatibility in syringe: Compatible: Bleomycin, cisplatin, cyclophosphamide, fluorouracil, heparin, leucovorin, methotrexate, mitomycin. Incompatible: Doxapram, doxorubicin, droperidol, metoclopramide, milrinone, vinblastine, vincristine.
Compatibility when admixed: Compatible: Amikacin, aminophylline, ampicillin, atropine, bumetanide, calcium gluconate, cefamandole, cefoperazone, cefuroxime, cimetidine, dexamethasone sodium phosphate, diamorphine, digoxin, epinephrine, heparin, isosorbide, kanamycin, lidocaine, meropenem, morphine, nitroglycerin, penicillin G, potassium chloride, ranitidine, scopolamine, sodium bicarbonate, sulfadimidine, theophylline, tobramycin. Incompatible: Buprenorphine, chlorpromazine, diazepam, dobutamine, erythromycin lactobionate, isoproterenol, meperidine, metoclopramide, netilmicin, prochlorperazine edisylate, promethazine. Variable (consult detailed reference): Amiodarone, gentamicin, hydrocortisone sodium succinate, verapamil.
Mechanism of Action
Inhibits reabsorption of sodium and chloride in the ascending loop of Henle and distal renal tubule, interfering with the chloride-binding cotransport system, thus causing increased excretion of water, sodium, chloride, magnesium, and calcium
Pharmacodynamics/Kinetics
Onset of action: Diuresis: Oral: 30-60 minutes; I.M.: 30 minutes; I.V.: ?5 minutes
Peak effect: Oral: 1-2 hours
Duration: Oral: 6-8 hours; I.V.: 2 hours
Absorption: Oral: 60% to 67%
Protein binding: >98%
Metabolism: Minimally hepatic
Half-life elimination: Normal renal function: 0.5-1.1 hours; End-stage renal disease: 9 hours
Excretion: Urine (Oral: 50%, I.V.: 80%) within 24 hours; feces (as unchanged drug); nonrenal clearance prolonged in renal impairment
Dosage
Infants and Children:
Oral: 0.5-2 mg/kg/dose increased in increments of 1 mg/kg/dose with each succeeding dose until a satisfactory effect is achieved to a maximum of 6 mg/kg/dose no more frequently than 6 hours.
I.M., I.V.: 1 mg/kg/dose, increasing by each succeeding dose at 1 mg/kg/dose at intervals of 6-12 hours until a satisfactory response up to 6 mg/kg/dose.
Adults:
Oral: 20-80 mg/dose initially increased in increments of 20-40 mg/dose at intervals of 6-8 hours; usual maintenance dose interval is twice daily or every day; may be titrated up to 600 mg/day with severe edematous states.
Hypertension (JNC 7): 20-80 mg/day in 2 divided doses
I.M., I.V.: 20-40 mg/dose, may be repeated in 1-2 hours as needed and increased by 20 mg/dose until the desired effect has been obtained. Usual dosing interval: 6-12 hours; for acute pulmonary edema, the usual dose is 40 mg I.V. over 1-2 minutes. If not adequate, may increase dose to 80 mg. Note: ACC/AHA 2005 guidelines for chronic congestive heart failure recommend a maximum single dose of 160-200 mg.
Continuous I.V. infusion: Initial I.V. bolus dose 20-40 mg, followed by continuous I.V. infusion doses of 10-40 mg/hour. If urine output is <1 mL/kg/hour, double as necessary to a maximum of 80-160 mg/hour. The risk associated with higher infusion rates (80-160 mg/hour) must be weighed against alternative strategies. Note: ACC/AHA 2005 guidelines for chronic congestive heart failure recommend 40 mg I.V. load, then 10-40 mg/hour infusion.
Refractory heart failure: Oral, I.V.: Doses up to 8 g/day have been used.
Elderly: Oral, I.M., I.V.: Initial: 20 mg/day; increase slowly to desired response.
Dosing adjustment/comments in renal impairment: Acute renal failure: High doses (up to 1-3 g/day - oral/I.V.) have been used to initiate desired response; avoid use in oliguric states.
Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.
Dosing adjustment/comments in hepatic disease: Diminished natriuretic effect with increased sensitivity to hypokalemia and volume depletion in cirrhosis; monitor effects, particularly with high doses.
Administration: Oral
May be taken with or without food.
Administration: I.V.
I.V. injections should be given slowly. In adults, undiluted direct I.V. injections may be administered at a rate of 40 mg over 1-2 minutes; maximum rate of administration for IVPB or continuous infusion: 4 mg/minute. In children, a maximum rate of 0.5 mg/kg/minute has been recommended.
Administration: I.V. Detail
As a general guideline, I.V. bolus doses may be infused at a rate <20 mg/minute.
pH: 8-9.3
Monitoring Parameters
Monitor weight and I & O daily; blood pressure, orthostasis, serum electrolytes, renal function; in high doses, monitor hearing
Dietary Considerations
May cause a potassium loss; potassium supplement or dietary changes may be required. Administer on an empty stomach. May be administered with food or milk if GI distress occurs. Do not mix with acidic solutions.
Patient Education
Do not take any new medication during therapy unless approved by prescriber. Take as directed with food or milk (to reduce GI distress) early in the day (daily), or if twice daily, take last dose in late afternoon in order to avoid sleep disturbance and achieve maximum therapeutic effect. Keep medication in original container, away from light; do not use discolored medication. Follow dietary advice of prescriber; include bananas or orange juice or other potassium-rich foods in daily diet. Do not take potassium supplements without advice of prescriber. If you have diabetes, monitor glucose levels closely (this medication may alter glucose tolerance requiring an adjustment in the dose of hypoglycemic agent). Weigh yourself each day, at the same time, in the same clothes when beginning therapy and weekly on long-term therapy. Report unusual or unanticipated weight gain or loss. May cause dizziness, blurred vision, or drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known); postural hypotension (use caution when rising from lying or sitting position or when climbing stairs); or sensitivity to sunlight (use sunblock or wear protective clothing and sunglasses). Report signs of edema (eg, weight gains; swollen ankles, feet, or hands), trembling, numbness or fatigue, cramping or muscle weakness, palpitations, unresolved nausea or vomiting, or change in hearing. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. 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 increase in BUN can cause confusion. For any change in mental status in patients on furosemide, monitor electrolytes and renal function.
Anesthesia and Critical Care Concerns/Other Considerations
It is important that patients be closely followed for hypokalemia, hypomagnesemia, and volume depletion because of significant diuresis. If given the morning of surgery, it may render the patient volume depleted and blood pressure may be labile during general anesthesia.
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
Dizziness is common
Mental Health: Effects on Psychiatric Treatment
Orthostatic hypotension is common; use caution with low potency antipsychotics and TCAs; may rarely cause agranulocytosis; caution with clozapine and carbamazepine; may decrease renal clearance of lithium resulting in elevated serum levels and risk for toxicity; more common with thiazide diuretics; monitor lithium levels
Nursing: Physical Assessment/Monitoring
Assess for allergy to sulfonylurea before beginning therapy. Assess potential for interactions with other pharmacological agents or herbal products patient may be taking (especially anything that may impact fluid balance, electrolyte balance, or increase potential for ototoxicity or hypotension). For intravenous use, see Administration specifics. Assess results of laboratory tests (electrolytes), therapeutic effectiveness, and adverse response on a regular basis during therapy (eg, dehydration, electrolyte imbalance, postural hypotension). Caution patients with diabetes about closely monitoring glucose levels (glucose tolerance may be decreased). Teach patient appropriate use, possible side effects/appropriate interventions, and adverse symptoms to report.
Oncology: Emetic Potential
Very low (<10%)
Oncology: Vesicant
No
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: 10 mg/mL (2 mL, 4 mL, 8 mL, 10 mL)
Solution, oral: 10 mg/mL (60 mL, 120 mL) [orange flavor]; 40 mg/5 mL (5 mL, 500 mL) [pineapple-peach flavor]
Tablet: 20 mg, 40 mg, 80 mg
Lasix®: 20 mg
Lasix®: 40 mg, 80 mg [scored]
Pricing: U.S. (www.drugstore.com)
Solution (Furosemide)
10 mg/mL (60): $16.99
10 mg/mL (120): $15.98
Tablets (Furosemide)
20 mg (100): $13.99
40 mg (100): $13.99
80 mg (30): $12.99
Tablets (Lasix)
20 mg (30): $20.60
40 mg (30): $23.86
80 mg (30): $30.37
References
Brown CB, Ogg CS, and Cameron JS, “High-Dose Frusemide in Acute Renal Failure: A Controlled Trial,” Clin Nephrol, 1981, 15(2):90-6.
Chaudhry AY, Bing RF, Castleden CM, et al, “The Effect of Aging on the Response to Frusemide in Normal Subjects,” Eur J Clin Pharmacol, 1984, 27(3):303-6.
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.
Gerlag PG and van Meijel JJ, “High-Dose Furosemide in the Treatment of Refractory Congestive Heart Failure,” Arch Intern Med, 1988, 148(2):286-91.
Howard PA and Dunn MI, “Aggressive Diuresis for Severe Heart Failure in the Elderly,” Chest, 2001, 119(3):807-10.
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.
Kuchar DL and O'Rourke MF, “High Dose Furosemide in Refractory Cardiac Failure,” Eur Heart J, 1985, 6(11):954-8.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents,” Pediatrics, 2004, 114(2 Suppl):555-76.
Rudy DW, Voelker JR, Greene PK, et al, “Loop Diuretics for Chronic Renal Insufficiency: A Continuous Infusion Is More Efficacious Than Bolus Therapy,” Ann Intern Med, 1991, 115(5):360-6.
Schuller D, Lynch JP, and Fine D, “Protocol-Guided Diuretic Management: Comparison of Furosemide by Continuous Infusion and Intermittent Bolus,” Crit Care Med, 1997, 25(12):1969-75.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
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