Furosemide is a sulfonamide, loop-type diuretic and antihypertensive agent.133, 150, 151, 1230
Furosemide is used for the treatment of edema.133, 134, 150, 151, 1230 The drug is commercially available in various oral and parenteral formulations for this use.133, 134, 150, 151, 1230 Furosemide oral tablets and solution and the injection for IV or IM use is specifically indicated for the treatment of edema associated with heart failure, renal disease (including nephrotic syndrome), and hepatic cirrhosis in adult and pediatric patients.133, 150, 151 IV furosemide is also indicated for the treatment of acute pulmonary edema as adjunctive therapy.150
Subcutaneous formulations of furosemide also are available for the treatment of edema.134, 1230 Currently available subcutaneous preparations (Furoscix® and Lasix® ONYU) are administered using a controlled drug delivery device (i.e., infusor).134, 1230 Furosemide 80 mg/10 mL injection (Furoscix®) is specifically indicated for the treatment of edema in adults with chronic heart failure or chronic kidney disease (CKD), including nephrotic syndrome.1230 Furosemide 80 mg/2.67 mL injection (Lasix® ONYU) is specifically indicated for the treatment of edema in adults with chronic heart failure.134
Current guidelines for the management of heart failure recommend guideline-directed medical therapy with a combination of drug therapies to reduce morbidity and mortality, including angiotensin converting enzyme (ACE) inhibitors, sodium-glucose cotransporter 2 inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors (ARNIs), β-blockers, and mineralocorticoid receptor antagonists.800 Diuretics, including furosemide, are recommended on an as-needed basis to improve symptoms of congestion and prevent worsening of disease in patients with fluid retention.800 Once guideline-directed medical therapy is optimized, additional therapies may be considered based on patient-specific factors, including ivabradine, vericiguat, polyunsaturated fatty acids, potassium binders, and digoxin.800
In patients with structural heart disease who do not have any prior or current signs or symptoms of heart failure (i.e., Stage B disease) who have a left ventricular ejection fraction (LVEF) ≤40%, ACE inhibitors should be used to reduce mortality and prevent symptomatic heart failure; angiotensin II receptor antagonists may be used in such patients with a recent MI who are intolerant to ACE inhibitors.800 In patients with heart failure with reduced ejection fraction (HFrEF) and NYHA class II to III symptoms, use of an ARNI is recommended first-line to reduce morbidity and mortality.800, 1005 Angiotensin II receptor antagonists are recommended for such patients only when an ARNI is contraindicated, inaccessible, or poorly tolerated.1005 In patients with symptomatic heart failure with mildly reduced ejection fraction (i.e., LVEF 41-49%), angiotensin II receptor antagonists may be considered (particularly in patients with a LVEF on the lower end of the range) to reduce the risk of hospitalizations for heart failure and cardiovascular mortality.800
Most patients with chronic heart failure require oral loop diuretics for maintenance of fluid balance.1231 Furosemide is the most commonly used loop diuretic for treatment of heart failure, although other loop diuretics (e.g., bumetanide or torsemide) may produce a more favorable response because of better oral bioavailability.800, 1231 The addition of a thiazide diuretic may be considered for patients with diuretic resistance, who do not respond to moderate or high doses of loop diuretics.800, 1231
For patients hospitalized for heart failure, parenteral loop diuretics, given as a continuous IV infusion or as IV boluses, are considered a mainstay of treatment.1231 Furosemide has also been given as a subcutaneous infusion for patients with acute decompensated heart failure.1232 In a systematic review, 20 studies, enrolling 687 adult patients with symptomatic heart failure and volume overload requiring treatment with diuretics were reviewed.1232 Subcutaneous furosemide was associated with improvements in NYHA function class, weight reduction, and symptom improvement.1232 Similar results were reported in the AT HOME-HF trial, comparing subcutaneous furosemide to usual care in patients with chronic heart failure and fluid overload requiring diuretic therapy.1233 No difference was seen in hospitalization for heart failure between subcutaneous furosemide and usual care, with a greater degree of decongestion with subcutaneous furosemide.1233
The Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines on glomerular diseases state that loop diuretics are the preferred agents for management of edema in patients with nephrotic syndrome.1234 Additional treatments for patients with kidney disease may include ACE inhibitors or angiotensin II receptor antagonists in the presence of hypertension and proteinuria.1234
For patients with acute kidney injury, use of furosemide or other loop diuretics may be useful in achieving fluid balance in critically ill patients also requiring mechanical ventilation.1235 However, KDIGO guidelines on treatment of acute kidney injury note that there is no evidence that the use of diuretics, including furosemide, reduces the incidence or severity of acute kidney injury.1235
KDIGO guidelines on chronic kidney disease (CKD) state that there are limited data on clinical outcomes with loop diuretics for the treatment of high blood pressure due to fluid overload in CKD patients.536 Thiazide diuretics in combination with a loop diuretic may be effective at inducing diuresis but may result in hypokalemia and hypomagnesemia.536
Hepatic cirrhosis, although initially asymptomatic, can progress with the development of ascites, bleeding, encephalopathy, and jaundice.1236 For patients with cirrhosis and moderate ascites, furosemide has been used in combination with an anti-mineralocorticoid (e.g., spironolactone) and moderate sodium restriction to reduce edema.1236
Acute pulmonary edema can result from either noncardiac (e.g., direct or indirect lung injury) or cardiac (e.g., left ventricular dysfunction) causes.1237 For acute cardiogenic pulmonary edema, therapy with IV loop diuretics, including furosemide, is recommended as the mainstay of treatment.1237, 1238 Vasodilators may be needed for patients not responding to initial diuretic therapy.1238
Furosemide oral tablets and solution are used for treatment of hypertension alone or in combination with other antihypertensive agents in adult patients.133, 151
Angiotensin II receptor antagonists, ACE inhibitors, calcium-channel blockers, and thiazide diuretics are considered among the preferred antihypertensive drugs for initial management of hypertension according to current evidence-based hypertension guidelines.1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.1200
Angiotensin II receptor antagonists or ACE inhibitors may be particularly useful in the management of hypertension in patients with certain coexisting conditions such as diabetes mellitus or CKD; angiotensin II receptor antagonists also may be preferred, generally as an alternative to ACE inhibitors, in hypertensive patients with heart failure or ischemic heart disease and/or following myocardial infarction (MI).1200 Loop diuretics, including furosemide, are considered secondary agents and are preferred diuretics for patients with symptomatic heart failure.1200 Additionally, these agents are also preferred over thiazide diuretics for patients with moderate-to-severe CKD.1200
Furosemide has been used IV to prevent blood product transfusion-associated circulatory overload†.1239, 1240 However, currently available data are limited and do not support the routine use of loop diuretics prior to blood product transfusions.1240
IV and oral furosemide have been used for management of symptomatic rheumatic carditis† in adult and pediatric patients.1241
For patients with hyperkalemia†, renal potassium excretion can be increased with the use of loop diuretics, including furosemide.1242 Furosemide has also been used in combination with sodium polystyrene sulfonate to reduce the risk of sodium overload†.1242
Furosemide, with saline diuresis, has been used as standard of care for treatment of hypercalcemia†.1243, 1244 However, analysis of available data on this treatment found no significant evidence to support this practice.1243, 1244 Use of furosemide in hypercalcemia should be limited to patients with volume overload.1243
Dispensing and Administration Precautions
Furosemide is administered orally (as tablets or oral solution); the drug can also be administered parenterally (by IM or IV injection, or by subcutaneous infusion using an infusor device).133, 134, 150, 151, 1230
Furosemide 80 mg/mL injection (Furoscix®) is administered by subcutaneous infusion via a single-use On-body Infusor; the drug is contained in a prefilled cartridge that is designed to deliver 80 mg of furosemide in 10 mL solution over 5 hours.1230
Furosemide 80 mg/2.67 mL injection (Lasix® ONYU) is administered by subcutaneous infusion via an Infusor; the drug is contained in a prefilled cartridge that is designed to deliver 80 mg of furosemide in 2.67 mL solution over 5 hours.134 The Infusor consists of a custom Reusable Unit that can be used for close to 50 treatments.134
Administer once or twice daily.133, 151
Store furosemide tablets at 20-25°C (excursions permitted to 15-30°C).133, 151 Exposure of the tablets to light may cause a slight discoloration; do not dispense discolored tablets.133, 151 Store furosemide oral solution at 20-25°C and protect from light.151
IV injections of furosemide should be given slowly over 1-2 minutes.150 If high-dose parenteral furosemide therapy is necessary, the manufacturer recommends that the drug be administered as a controlled infusion at a rate not exceeding 4 mg/minute in adults.150
Store furosemide injection at 20-25°C (excursions permitted to 15-30°C) and protect from light.150
Subcutaneous preparations of furosemide are administered using a prefilled cartridge with a wearable infusor device.134, 1230 Prepare the drug-device combination by loading the prefilled cartridge of furosemide into the infusor.134, 1230 Peel away the adhesive liner on the infusor and apply to a clean, dry area of the abdomen between the top of the beltline and bottom of the ribcage.134, 1230 The application site should not be tender, bruised, red, or indurated.134, 1230 For additional details on administration of each drug-device combination (Furoscix®or Lasix®ONYU), refer to the manufacturer's Instructions for Use.134, 1230 Rotate the injection site for each subcutaneous administration.134, 1230
Store furosemide subcutaneous drug-device combinations in their carton between 20-25°C (excursions permitted between 15-30°C) and protect from light; do not refrigerate or freeze.134, 1230 Protect the infusor from water.134, 1230
Standardized concentrations for IV furosemide have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care .249, 250Multidisciplinary expert panels were convened to determine recommended standard concentrations. 249, 250Because recommendations from the S4S panels may differ from the manufacturer's prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. 249, 250 For additional information on S4S (including updates that may be available), see [Web].249, 250
Patient Population | Concentration Standards | Dosing Units |
|---|---|---|
Adults | 2 mg/mL 10 mg/mL | mg/hour |
Pediatric patients (<50 kg) | 2 mg/mL 10 mg/mL | mg/kg/hour |
Furosemide injection for IV or IM administration is available as the sodium salt; dosage is expressed in terms of furosemide.150 Furosemide dosage must be adjusted according to the patient's requirements and response.133, 151
The usual initial adult oral dose of furosemide for the management of edema is 20-80 mg given as a single dose, preferably in the morning.133, 151 In adults who do not respond, the second and each succeeding oral dose may be increased in 20- to 40-mg increments every 6-8 hours until the desired diuretic response is obtained.133, 151 The effective dose may be given once or twice daily thereafter, or, in some cases, by intermittent administration on 2-4 consecutive days each week.133, 151 Adult oral dosage of furosemide may be carefully titrated up to 600 mg daily in severely edematous patients.133, 151
For the management of fluid retention (e.g., edema) associated with heart failure, some experts recommend initiating furosemide at a low dosage (e.g., 20-40 mg once or twice daily) and increasing the dosage (maximum of 600 mg daily) until urine output increases and weight decreases, generally by 0.5-1 kg daily.800
For infants and children, the usual initial oral dose of furosemide for the management of edema is 2 mg/kg administered as a single dose.133, 151 If necessary, dosage may be increased in increments of 1 or 2 mg/kg every 6-8 hours to maximum individual doses of 6 mg/kg.133, 151 For maintenance, the minimum effective dosage should be employed.133, 151
As a diuretic, the usual adult IM or IV dose is 20-40 mg given as a single injection.150 In adults who do not respond to the initial parenteral dose of furosemide, the second and each succeeding dose may be increased in 20-mg increments and given not more often than every 2 hours until the desired diuretic response is obtained.150 The effective single dose may then be given once or twice daily.150
For the management of acute pulmonary edema in adults, 40 mg of furosemide may be slowly injected IV over 1-2 minutes.150 If the initial adult dose does not produce a satisfactory response within 1 hour, the dose may be increased to 80 mg IV given over 1-2 minutes.150
For infants and children, the usual initial IV or IM dose of furosemide for the management of acute pulmonary edema or edema associated with heart failure or renal disease is 1 mg/kg.150, 1245 If necessary, the initial dose may be increased by 1 mg/kg no more often than every 2 hours until the desired effect has been obtained.150 Maximum individual parenteral doses recommended by the manufacturer for infants and children are 6 mg/kg.150 For premature infants, the maximum parenteral dose should not exceed 1 mg/kg per day.150
Furoscix®: The single-use On-body Infusor with prefilled cartridge is pre-programmed to deliver a dosage of 30 mg of furosemide over the first hour, followed by 12.5 mg per hour for the subsequent 4 hours.1230
Lasix®ONYU: The Infusor with single-dose prefilled cartridge is pre-programmed to deliver a dosage of 30 mg of furosemide over the first hour, followed by 12.5 mg per hour for the subsequent 4 hours.134 The manufacturer states to administer once or twice daily as needed for edema.134
Furosemide drug-device combinations for subcutaneous administration are not for chronic use and should be replaced with oral diuretics as soon as possible.134, 1230
The manufacturer states that the usual adult oral dosage of furosemide for the management of hypertension is 40 mg twice daily initially and for maintenance.133, 151 If a satisfactory lowering of blood pressure does not occur, dosage can be increased gradually.133, 151 If a satisfactory lowering of blood pressure does not occur when 40 mg is administered orally twice daily, the manufacturer recommends adding other antihypertensive agents rather than increasing the dosage of furosemide.133, 151 Some experts state that the usual oral antihypertensive dosage of furosemide for adults is 20-80 mg daily given in 2 divided doses.1200
For the management of hypertension in children†, some experts have recommended an initial oral dosage of 0.5-2 mg/kg administered once or twice daily.149 Such experts have suggested that the dosage may be increased as necessary up to 6 mg/kg daily.149
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.133, 134, 150, 151, 1230
Sudden shifts in fluid and electrolyte balance can precipitate hepatic encephalopathy and coma in patients with hepatic cirrhosis and ascites.133, 150, 151, 1230 In such patients, treatment with furosemide should be administered in a setting (e.g., hospital) where clinical status and electrolyte balance can be carefully monitored.133, 150, 151, 1230
Significant renal impairment can affect response to furosemide.134, 1230
Furosemide drug-device combinations for subcutaneous administration deliver a maximum furosemide dose of 80 mg; patients with significant renal impairment may require additional diuretic therapy.134, 1230
The manufacturer makes no specific dosage recommendations for geriatric patients.133, 150, 151, 1230 In general, dosage selection in geriatric patients should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.133, 150, 151, 1230
A boxed warning about the risk of profound diuresis, resulting in fluid and electrolyte depletion, is included in the prescribing information for furosemide tablets and oral solution.133, 151 Fluid and electrolyte depletion are especially likely to occur when large doses are given and/or in patients with restricted sodium intake.133, 151
Fluid, Electrolyte, and Metabolic Abnormalities
Furosemide may cause fluid, electrolyte, and metabolic abnormalities, including hypovolemia, hypokalemia, azotemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypocalcemia, hyperglycemia, or hyperuricemia.134, 150, 1230 Patients receiving higher doses, those with inadequate oral electrolyte intake, and geriatric patients are particularly at risk for these abnormalities.150, 1230 Excessive diuresis may also cause dehydration and blood volume reduction with circulatory collapse and possibly vascular thrombosis and embolism; geriatric patients are particularly at risk.133, 150, 151, 1230 Observe patients for signs or symptoms of fluid or electrolyte imbalance (e.g., dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramping, muscle fatigue, hypotension, oliguria, tachycardia, arrhythmia, or GI disturbances) during treatment with furosemide.133, 151 Monitor serum electrolytes, CO2, BUN, creatinine, glucose, and uric acid frequently during treatment with furosemide.150, 1230
Sudden shifts in fluid and electrolyte balance may precipitate hepatic encephalopathy and coma in patients with hepatic cirrhosis and ascites.133, 150, 151 In such patients, treatment is best initiated in the hospital with small doses and careful monitoring of the patient's electrolyte balance and clinical status.133, 150, 151
Furosemide can cause dehydration and azotemia.134, 150, 1230 If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, discontinue furosemide.133, 150, 151, 1230
Use of furosemide in the first year of life, particularly in patients born pre-term, may precipitate nephrocalcinosis/nephrolithiasis.150 If furosemide is administered in this age group, monitor renal function and consider renal ultrasonography.150
Tinnitus, reversible or permanent hearing impairment, or reversible deafness have occurred.133, 134, 150, 151, 1230 Otic effects are most likely to occur in patients receiving furosemide at higher than recommended doses or via rapid injection, in those with severe impairment of renal function, in patients with hypoproteinemia, and/or in patients receiving other ototoxic drugs (e.g., aminoglycosides).133, 150, 151, 1230 If high-dose parenteral furosemide therapy is necessary in patients with severely impaired renal function, the manufacturers recommend that the drug be infused in adults at a rate not exceeding 4 mg/minute.133, 150, 151, 1230
Hearing loss has also been reported in neonates, including premature neonates, following use of furosemide injection.150
In patients with severe symptoms of urinary retention due to bladder emptying disorders, prostatic hyperplasia, or urethral narrowing, administration of furosemide can cause acute urinary retention related to increased production and retention of urine.133, 134, 150, 151, 1230 Such patients require careful monitoring, especially during therapy initiation.133, 150, 151, 1230
Incomplete Administration of Subcutaneous Infusion
When furosemide is administered subcutaneously via wearable infusor devices, the infusor should not be allowed to get wet from water or any other fluids.134, 1230 If the circuit board comes in contact with fluids, it can lead to device errors and premature termination of the infusion.134, 1230
The drug-device combination is intended for use in a setting where the patient can limit activity throughout the duration of the infusion.134, 1230 Certain movements can interrupt adherence of the device to the skin, causing premature termination of the infusion.134, 1230
The infusor device should only be used in patients who are able to detect and respond to alarms; this ensures that the complete dose is administered.134, 1230
Available data from published observational studies, case reports, and postmarketing reports over decades of use have not demonstrated a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes with furosemide use during pregnancy.150, 1230 However, untreated congestive heart failure and hepatic cirrhosis can lead to adverse outcomes in both the mother and fetus.150, 1230 In reproduction studies involving rabbits, administration of furosemide caused unexplained abortions and maternal and fetal deaths.133, 150, 151, 1230 In addition, an increased incidence of hydronephrosis occurred in fetuses of animals treated with the drug.133, 151, 1230
Furosemide is distributed into human milk;133, 150, 151, 1230 there are no data on the effects on the breast-fed infant or on milk production.150, 1230 Doses associated with clinically significant diuresis may impair milk production.133, 150, 151, 1230 The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for furosemide and any potential adverse effects on the breast-fed infant from furosemide or from the underlying maternal condition.150, 1230
Females and Males of Reproductive Potential
Reproduction studies in male and female rats using furosemide dosages of 100 mg/kg daily (the maximum effective diuretic dosage in rats and 7-8 times the maximum human dosage based on formulation) have not revealed evidence of impaired fertility.133, 150, 151, 1230
Safety and efficacy of subcutaneous administration of furosemide via on-body infusor have not been established in pediatric patients.1230
In premature neonates, diuretic therapy with furosemide during the first weeks of life may increase the risk of persistent patent ductus arteriosus (PDA).133, 151
Hearing loss has been reported in neonates receiving furosemide.150 Therefore, the manufacturer states that parenteral furosemide dosages should not exceed 1 mg/kg per 24 hours in premature neonates with <31 weeks postconception age (gestational age at birth plus postnatal age), because higher dosages may be associated with potentially toxic plasma concentrations of the drug.150
Furosemide may precipitate nephrocalcinosis/nephrolithiasis in premature neonates.133, 150, 151 Nephrocalcinosis/nephrolithiasis has also been observed in patients ≤4 years of age with no history of prematurity receiving chronic treatment with furosemide.133, 151 Monitor renal function and consider renal ultrasonography in pediatric patients receiving furosemide.133, 151
Clinical studies of furosemide did not include sufficient numbers of patients to determine whether those who were ≥65 years of age responded differently from younger patients.133, 150, 151, 1230 Other reported clinical experience has not identified differences in response between geriatric and younger patients.133, 150, 151, 1230 In general, dose selection should be cautious in geriatric patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in this population.133, 150, 151, 1230
Binding of furosemide to albumin may be reduced in geriatric patients.133, 150, 151, 1230 Furosemide is predominantly excreted unchanged in the urine.133, 150, 151, 1230 Following IV administration, the renal clearance of furosemide is substantially smaller in older healthy male patients (60-70 years of age) compared to younger healthy male patients (20-35 years of age).133, 150, 151, 1230 The initial diuretic effect of furosemide is also generally decreased in geriatric patients relative to younger patients.133, 150, 151
Sudden shifts in fluid and electrolyte balance can precipitate hepatic encephalopathy and coma in patients with hepatic cirrhosis and ascites.133, 150, 151, 1230 In such patients, treatment with furosemide should be administered in a setting (e.g., hospital) where clinical status and electrolyte balance can be carefully monitored.133, 150, 151, 1230
Significant renal impairment can affect response to furosemide.134, 1230
Subcutaneous drug-device combinations deliver a maximum furosemide dose of 80 mg; patients with significant renal impairment may require additional diuretic therapy.134, 1230
Adverse effects associated with oral administration of furosemide (categorized by body system and listed in order of severity) are: GI system reactions (hepatic encephalopathy in patients with hepatocellular insufficiency, pancreatitis, jaundice [intrahepatic cholestatic jaundice], increased liver enzymes, anorexia, oral/gastric irritation, cramping, diarrhea, constipation, nausea, and vomiting); systemic hypersensitivity reactions (severe anaphylactic or anaphylactoid reactions, systemic vasculitis, interstitial nephritis, necrotizing angiitis); CNS reactions (tinnitus and hearing loss, paresthesias, vertigo, dizziness, headache, blurred vision, xanthopsia); hematologic reactions (aplastic anemia, thrombocytopenia, agranulocytosis, hemolytic anemia, leukopenia, anemia, eosinophilia); dermatologic-hypersensitivity reactions (toxic epidermal necrolysis, Stevens-Johnson Syndrome, erythema multiforme, drug rash with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, exfoliative dermatitis, bullous pemphigoid, purpura, photosensitivity, rash, pruritus, urticaria); cardiovascular reactions (orthostatic hypotension, increase in serum cholesterol and triglycerides); and various other reactions (hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weakness, restlessness, urinary bladder spasm, thrombophlebitis, fever).133, 151
The most common adverse effects associated with intramuscular or IV administration of furosemide are related to fluid and electrolyte imbalance.150
Common adverse effects associated with subcutaneous administration of furosemide via infusors include administration site and skin reactions, including erythema, bruising, edema, and infusion site pain.134, 1230
Drugs Affected by or Causing Potassium Depletion
Furosemide reportedly antagonizes the skeletal muscle relaxing effect in patients receiving nondepolarizing neuromuscular blocking agents and may potentiate the action of succinylcholine.133, 150, 151, 1230 Furosemide may also cause decreased arterial responsiveness to norepinephrine.133, 150, 151, 1230
Concomitant use of furosemide with nephrotoxic drugs (e.g., cisplatin, cephalosporins) can enhance the nephrotoxicity of such agents.133, 150, 151, 1230 If furosemide is administered during cisplatin treatment, administer at lower doses and with positive fluid balance when used to achieve forced diuresis.133, 150, 151, 1230 Monitor renal function.150, 1230
Drugs That Undergo Renal Tubular Secretion
Drugs that undergo renal tubular secretion (e.g., methotrexate) may reduce the effect of furosemide.133, 150, 151, 1230 Conversely, furosemide may decrease renal elimination of other drugs that undergo renal tubular secretion.133, 150, 151, 1230 High-dose treatment with furosemide or other drugs that undergo renal tubular secretion may cause an elevation in serum levels of furosemide or the other drug(s), leading to toxicity.133, 150, 151, 1230 If administered concomitantly, monitor serum levels and adjust the dosage if needed.150, 1230
The antihypertensive effect of hypotensive agents may be enhanced when given concomitantly with furosemide.133, 150, 151, 1230 When furosemide is combined with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, it may lead to severe hypotension and deterioration in renal function, including renal failure.133, 150, 151, 1230 Monitor for changes in blood pressure and renal function if furosemide is used with other hypotensive drugs.150, 1230 An interruption or reduction in the dosage of one or both drugs may be necessary.133, 150, 151, 1230
Concomitant administration of furosemide and aminoglycoside antibiotics or other ototoxic drugs (e.g., cisplatin, ethacrynic acid) may result in an increased incidence of ototoxicity and concomitant use of these drugs should be avoided.133, 150, 151, 1230
Nonsteroidal Anti-inflammatory Agents
Furosemide and salicylates reportedly have competitive renal excretory sites and, therefore, patients receiving high doses of salicylates with furosemide may experience salicylate toxicity at a lower dosage than usual.133, 150, 151, 1230 Concomitant administration of furosemide and aspirin reportedly has been associated with a transient reduction in creatinine clearance in a few patients with chronic renal insufficiency.133, 150, 151, 1230 Weight gain and increases in BUN, serum creatinine, and serum potassium concentrations also have been reported in patients receiving furosemide in combination with other nonsteroidal anti-inflammatory agents (NSAIAs).133, 150, 151, 1230
High doses of furosemide (i.e., >80 mg) may inhibit the binding of thyroid hormones to carrier proteins, resulting in transient increases in free thyroid hormones, followed by an overall decrease in total thyroid hormone levels.133, 150, 151, 1230 Monitor total thyroid hormone levels.150, 1230
Concomitant use of furosemide and cyclosporine is associated with an increased risk of gouty arthritis secondary to furosemide-induced hyperuricemia and cyclosporine impairment of renal urate excretion.133, 150, 151, 1230 If used concomitantly, monitor serum urate levels.150, 1230
Renal clearance of lithium is decreased in patients receiving diuretics, and lithium toxicity may result.133, 150, 151, 1230 Furosemide and lithium should generally not be given together.133, 150, 151, 1230
In some patients, indomethacin may reduce the natriuretic and hypotensive effects of furosemide.133, 150, 151, 1230 The mechanism(s) of these interactions is uncertain but has been attributed to indomethacin-induced inhibition of prostaglandin synthesis.133, 150, 151, 1230 When indomethacin and furosemide are administered concurrently, patients should be observed closely to determine if the desired diuretic and/or hypotensive effect is obtained.133, 150, 151, 1230
Phenytoin directly interferes with the renal action of furosemide.133, 150, 151, 1230 There is evidence that administration of phenytoin leads to decreased intestinal absorption of furosemide, leading to reduced peak serum concentrations of furosemide.133, 151, 1230 If given concomitantly, monitor the diuretic effects of furosemide and adjust the dosage if needed.150, 1230
Coadministration of furosemide tablets and sucralfate may reduce the natriuretic and hypotensive effects of furosemide.133, 151 Patients receiving both drugs should be observed closely to determine if the desired diuretic and/or hypotensive effect of furosemide is achieved.133, 151 Separate administration of furosemide and sucralfate by ≥2 hours.133, 151
Furosemide works by inhibiting the reabsorption of electrolytes in the ascending limb of the loop of Henle.133, 150, 151, 1230 The drug also decreases reabsorption of sodium and chloride in the distal renal tubule.133, 150, 151, 1230 Furosemide does not inhibit carbonic anhydrase and is not an aldosterone antagonist.133, 150, 151, 1230
In a clinical study evaluating subcutaneous infusion of furosemide as the Furoscix®preparation, the bioavailability was 99.6%, with peak plasma concentration reached at a median of 4 hours relative to IV furosemide at a dose of 80 mg.1230 The bioavailability of the subcutaneous infusion of furosemide as the Lasix®ONYU preparation is 112% with a median time to peak plasma concentration of 5 hours relative to IV furosemide administered at a dose of 80 mg.134 The impact of edema at the administration site of subcutaneous formulations of furosemide on drug absorption is not known.134, 1230 In fasted normal men, the mean bioavailability of furosemide tablets and oral solution is 64 and 60%, respectively.133, 151 While the oral solution is absorbed more rapidly than the tablet (50 versus 87 minutes, respectively), peak plasma levels and AUC do not differ substantially.133, 151 Peak plasma concentrations increase as the dose increases, but times-to-peak do not differ among doses.133, 151 The diuretic effect of orally administered furosemide is apparent within 1 hour and is maximal in the first or second hour.133 The duration of action is usually 6-8 hours.133 After IV administration of furosemide, diuresis occurs within 5 minutes, reaches a maximum within 30 minutes, and persists for approximately 2 hours.150 After IM administration, peak plasma concentrations are attained within 30 minutes; onset of diuresis occurs somewhat later than after IV administration.150
Furosemide is extensively (91-99%) bound to plasma proteins, mainly to albumin.133, 150, 151, 1230
Evidence suggests that furosemide glucuronide is the only, or at least the major, biotransformation product of furosemide.133, 150, 151, 1230 The drug is predominantly excreted unchanged in the urine.133 Significantly more furosemide is excreted in the urine following IV injection compared to oral administration;133, 150, 151, 1230 however, there are no substantial differences in urinary excretion between the 2 oral formulations.133, 151 The terminal half-life of furosemide is approximately 2 hours.133, 150, 151, 1230
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Solution | 40 mg/5 mL* | Furosemide Solution | |
10 mg/mL* | Furosemide Solution | |||
Tablets | 20 mg* | Furosemide Tablets | ||
40 mg* | Furosemide Tablets | |||
Lasix® (scored) | Sanofi-Aventis | |||
80 mg* | Furosemide Tablets | |||
Lasix® | Sanofi-Aventis | |||
Parenteral | Injection, for IV or IM use | 10 mg/mL* | Furosemide Injection | |
Injection, for subcutaneous use | 80 mg/10 mL | Furoscix® (available as a single-dose prefilled cartridge co-packaged with the On-body Infusor) | ||
80 mg/2.67 mL | Furoscix® (available as a single-dose prefilled cartridge co-packaged with a single-use Disposable Unit of the Infusor) | SQ Innovation |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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