General Administration Information
For storage information, see the specific product information within the How Supplied section.
Oral Solid Formulations
-If patient has difficulty swallowing, furosemide tablets may be crushed.
Oral Liquid Formulations
-When administering furosemide to an infant or child using a medicine dropper or oral syringe, slowly squirt the solution into the side of the child's mouth so that he or she will swallow the liquid naturally. Do not squirt onto the back of the throat because this may cause gagging. Rinse the dropper or syringe in warm water after each use.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-For IV push administration, no dilution necessary.
-For intermittent or continuous infusion, dilute furosemide in NS, Lactated Ringer's, or D5W injection solution; adjust pH to greater than 5.5 when necessary.
-ISMP recommended standard concentrations for continuous and intermittent infusions in neonates: 2 or 10 mg/ml.
-No dilution necessary.
-Inject no faster than 0.5 mg/kg/min; more rapid administration may increase the risk of ototoxicity.
-In adults, doses of 20 to 40 mg can be injected slowly IV over 1-2 minutes.
-For patients receiving extracorporeal membrane oxygenation (ECMO), administer IV furosemide outside of the circuit; the drug is substantially adsorbed by circuit components.
Intermittent IV Infusion
-Infuse at a rate not to exceed 0.5 mg/kg/minute or for high dose therapy, do not exceed 4 mg/minute.
Continuous IV Infusion
NOTE: Furosemide is not approved by the FDA for continuous IV administration.
-Infusion rates of 0.1-0.4 mg/kg/hour after a loading dose of 0.1 mg/kg (minimum 1 mg) have been studied.
-No dilution necessary.
-Inject deeply into a large muscle mass (e.g., anterolateral thigh or deltoid ). Aspirate prior to injection to avoid injection into a blood vessel. When multiple IM injections are necessary, rotate administration sites.
Severe abdominal pain with nausea/vomiting may indicate pancreatitis, which has been attributed to furosemide therapy. Furosemide therapy may cause hepatic encephalopathy in patients with hepatocellular insufficiency. Other adverse gastrointestinal effects of furosemide include anorexia, constipation, cramping, diarrhea, elevated hepatic enzymes, and oral and gastric irritation. Furosemide may rarely cause jaundice due to cholestasis.
Adverse central nervous system effects associated with furosemide therapy include dizziness, lightheadedness, vertigo, headache, blurred vision, xanthopsia, restlessness, and paresthesias.
Polyuria during furosemide therapy can cause excessive fluid loss and dehydration. This results in hypovolemia and electrolyte imbalance. Large doses of furosemide and restricted sodium intake increases this possibility. Hypovolemia can lead to orthostatic hypotension, syncope, and hemoconcentration, potentially more serious in chronic cardiac patients. Close monitoring is necessary to check for hyponatremia, hypokalemia, hypocalcemia, hypochloremia, and hypomagnesemia. Symptoms of fluid or electrolyte imbalance are: lassitude, mental confusion, fatigue, dizziness, muscle cramps, headache, paresthesias, tachycardia, arrhythmia, thirst, anorexia, nausea, or vomiting. Hypokalemia, necessitating potassium supplementation or the addition of aldosterone antagonists, and hypomagnesemia were reported in 38% and 12.4% of adult patients receiving furosemide, respectively. Hyperaldosteronism, secondary to cirrhosis or nephrosis, can predispose patients to developing potassium depletion when furosemide is administered. Hypokalemia and hypochloremia can cause metabolic alkalosis, particularly in patients with other conditions that cause potassium loss including vomiting, diarrhea, or excessive sweating. Administration of potassium supplements and an aldosterone antagonist may be helpful in preventing hypokalemia and metabolic alkalosis. Volume loss secondary to loop diuretic therapy can also cause oliguria and/or azotemia (elevation of BUN), which may lead to a risk factor for nephrotoxicity in selected patients or an allergic interstitial nephritis. If increasing azotemia and oliguria occur during treatment of severe renal disease, discontinue furosemide.
Nephrocalcinosis (calcium nephrolithiasis) has occurred in some premature neonates treated with furosemide for edema. Nephrolithiasis has also been reported in children < 4 years of age who received furosemide chronically. Monitor renal function in pediatric patients receiving furosemide, and the manufacturer recommends considering renal ultrasonography in these patients as well. The concurrent use of chlorothiazide has been reported to decrease hypercalciuria and dissolve some calculi. In addition, when furosemide is used in premature neonates during the first week of life, it may increase the risk of a persistent patent ductus arteriosus.
Furosemide can cause asymptomatic hyperuricemia and rarely may precipitate gout.
Ototoxicity, manifested as tinnitus and reversible or permanent hearing loss has occurred during furosemide therapy and is usually associated with rapid administration of parenteral doses, severe renal impairment, use of higher than recommended doses, hypoproteinemia, or concomitant therapy with other ototoxic drugs. Cases of deafness have been reported. If parenteral therapy is used, the administration rate should not exceed 0.5 mg/kg/min or 4 mg/min. Ototoxicity increased proportionately as the rate of infusion of parenteral furosemide increased from 4 mg/min (no ototoxicity), to 5.6 mg/min (no ototoxicity), to 25 mg/min (9/15 patients developed reversible hearing loss), to 67 mg/min (10/10 patients developed tinnitus and deafness that persisted for 90 minutes).
Furosemide can produce impaired glucose tolerance, glycosuria, and hyperglycemia. There have been occasional reports of precipitation of diabetes mellitus.
Diuretics, particularly thiazide and loop diuretics such as furosemide, have been shown to cause hypercholesterolemia, hypertriglyceridemia, as well as increased plasma concentrations of LDL. Some studies have suggested that these effects may decrease or cease with long-term therapy, and are not clinically important.
Adverse hematologic effects reported during furosemide therapy include anemia, hemolytic anemia, aplastic anemia, leukopenia, thrombocytopenia, eosinophilia, and agranulocytosis. Fever and weakness also may occur with furosemide therapy; if a patient presents with fever and/or weakness, carefully evaluate the patient for possible blood dyscrasias.
Dermatitis and/or photosensitivity can occur during furosemide therapy. Patients who are sensitive to sulfonamides may also have a hypersensitivity reaction to furosemide. Systemic lupus erythematosus may be exacerbated or activated. Other dermatologic adverse reactions to furosemide therapy include: exfoliative dermatitis, bullous rash (i.e., bullous pemphigoid), erythema multiforme, purpura, urticaria, rash (unspecified), drug reaction with eosinophilia and systemic symptoms (DRESS), pruritus, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Furosemide has been associated with acute generalized exanthematous pustulosis (AGEP). The nonfollicular, pustular, erythematous rash starts suddenly and is associated with fever above 38 degrees C. Drugs are the main cause of AGEP. A period of 2 to 3 weeks after an inciting drug exposure appears necessary for a first episode of AGEP. Unintentional reexposure may cause a second episode within 2 days.
Severe systemic hypersensitivity reactions to furosemide therapy are possible including anaphylaxis or anaphylactoid reactions including anaphylactic shock. Other hypersensitivity reactions include systemic vasculitis, interstitial nephritis, and necrotizing vasculitis (necrotizing angiitis).
Bladder spasm and muscle spasm (muscle cramps) may occur with the administration of furosemide.
An injection site reaction such as transient injection site pain may occur after the intramuscular injection of furosemide.
Thrombo-phlebitis has been reported with furosemide. In addition, excessive diuresis may possibly result in vascular thrombosis and thromboembolism. Carefully monitor clinical status and avoid dehydration.
Furosemide is contraindicated in patients with known hypersensitivity to this drug. Because cross-sensitivity with furosemide has rarely been observed, bumetanide can be substituted for furosemide in patients allergic to furosemide. The risk of an allergic reaction after administration of a loop diuretic in a patient with sulfonamide hypersensitivity or thiazide diuretic hypersensitivity appears to be very low. Although furosemide is a sulfonamide derivative, sulfonamide cross-sensitivity has been rarely documented. Furosemide does not contain the N4-aromatic amine or the N1-substituent which are present in sulfonamide antibiotics. Non-arylamine sulfonamide derivatives, such as loop diuretics, have been proposed to have a lower risk of allergic reactions in patients with sulfonamide allergy, presumably due to lack of an arylamine group at the N4 position (a proposed structural site of action for sulfonamide allergy). One large retrospective cohort study has reported that in patients with the presence of an allergic reaction after exposure to a sulfonamide antibiotic, 9.9% had an allergic reaction after receiving a non-antibiotic sulfonamide derivative, while in patients who lacked an allergic reaction after sulfonamide antibiotic exposure, 1.6% had an allergic reaction after administration of a non-antibiotic sulfonamide derivative (adjusted odds ratio 2.8; 95% CI, 2.1-3.7). A causal relationship between sulfonamide hypersensitivity and allergic reactions with non-arylamine sulfonamide derivatives has not been definitively established and remains controversial. In general, patients with a documented sulfonamide allergy are considered to be predisposed for development of allergic drug reactions.
Correct preexisting electrolyte imbalance such as severe hyponatremia, hypokalemia, hypocalcemia, hypochloremia, or hypomagnesemia before initiating furosemide therapy. Loop diuretics may induce metabolic alkalosis associated with hypokalemia and hypochloremia; this acid/base imbalance is effectively treated with potassium chloride replacement.
Assess blood and urine glucose levels in patients with diabetes mellitus or hyperglycemia during treatment with furosemide; loop diuretics can impair glucose tolerance.
Monitor patients with ventricular arrhythmias, heart failure, potassium-losing nephropathy, aldosterone excess, or diarrhea closely since furosemide-induced hypokalemia can exacerbate these conditions.
Correct pre-existing hypovolemia or hypotension before furosemide is initiated. Orthostatic hypotension may occur during treatment with loop diuretics. Excessive hypotension can result in syncope.
Furosemide is contraindicated in patients with anuria. Use furosemide cautiously in any patient with renal disease such as severe renal impairment or renal failure. Drug-induced hypovolemia can precipitate azotemia in these patients. The presence of hypoproteinemia (e.g., nephrotic syndrome) may weaken the effect of furosemide and increase its potential for ototoxicity. The risk of ototoxicity may also be increased when furosemide is administered to patients with severe renal impairment. Furosemide is an effective diuretic for many patients with renal impairment. However, renal impairment may reduce clearance; furosemide may be less effective in these patients and delayed excretion of drug may increase the risk of toxicity.
Furosemide has been reported to activate or exacerbate systemic lupus erythematosus (SLE); use with caution in patients with SLE.
Since furosemide can reduce the clearance of uric acid, patients with gout or hyperuricemia can have exacerbations of their disease.
High doses and accumulation of furosemide may cause ototoxicity. Use furosemide with caution in patients with hearing impairment. Do not exceed the recommended rate of infusion when IV doses are administered.
Furosemide has been reported to cause pancreatitis; use with caution in patients with a history of pancreatitis.
Although diuretics are often part of the medical management of patent ductus arteriosus (PDA), the manufacturer states that premature neonates who receive furosemide in the first few weeks of life may have an increased risk of persistent PDA.
The manufacturer recommends initiating furosemide therapy in the hospital in patients with hepatic disease (i.e., hepatic cirrhosis) and ascites. Do not initiate furosemide therapy in hepatic encephalopathy (hepatic coma) or in patients with electrolyte depletion until the condition is improved. Rapid fluctuations in fluid and serum electrolyte concentrations can precipitate hepatic coma in patients with cirrhosis. The presence of cirrhosis may also increase the potential for the development of hypokalemia in patients receiving furosemide therapy. Hypokalemia and metabolic alkalosis may be prevented with potassium supplementation and, if necessary, an aldosterone antagonist.
The administration of furosemide to patients with severe symptoms of urinary retention (due to bladder emptying disorders or urethral stricture) can precipitate acute urinary retention. This is related to increased production and retention of urine. Monitor these patients carefully, especially during the initiation of furosemide therapy.
Use high doses of furosemide cautiously in patients with thyroid disease. At high doses (more than 80 mg in adults), furosemide may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations.
Description: Furosemide is a sulfonamide-derived loop diuretic indicated for the management of edema. It is used for the the management of peripheral edema associated with renal disease, including the nephrotic syndrome, as well as pulmonary edema. Furosemide is effective in managing edema associated with congestive heart failure, and it may be useful in patients who are unresponsive to other diuretics or who have renal impairment. Other uses include the adjunctive treatment of mild to moderate hypertension, especially in patients with concomitant renal disease. Furosemide is associated with lower rates of ototoxicity compared to some other loop diuretics, such as ethacrynic acid, and is therefore commonly used in pediatric patients. Furosemide is FDA approved in pediatric patients as young as neonates.
For the treatment of edema, including peripheral and pulmonary edema associated with chronic lung disease (CLD), heart failure, nephrotic syndrome, and acute or chronic renal failure (renal impairment):
Premature Neonates <= 32 weeks postconceptional age: Initially, 1-2 mg/kg/dose PO. Because of the risk for accumulation, chronic doses should not be administered more frequently than every 24 hours. Bioavailability is variable.
Premature and Term Neonates > 32 weeks postconceptional age: Initially, 1-2 mg/kg/dose PO, given 1-2 times daily. Bioavailability is variable.
Infants, Children, and Adolescents: Initially, 1-2 mg/kg/dose PO every 6-12 hours. If response is not adequate 6-8 hours after the dose, increase by 1-2 mg/kg/dose (Max: 6 mg/kg/dose). Adjust to minimum effective dose for maintenance ; large doses are not recommended for chronic use. Alternatively, for the management of nephrotic syndrome, some experts recommend 1-2 mg/kg/day PO given as a single daily dose or divided into 2 daily doses.
Intermittent Intravenous or Intramuscular dosage:
Premature Neonates <= 32 weeks postconceptional age: 1 mg/kg/dose IV. Because of the risk for accumulation, doses should not be administered more frequently than every 24 hours.
Premature and Term Neonates > 32 weeks postconceptional age: 1-2 mg/kg/dose IV or IM every 12-24 hours. Use the lowest effective dose.
Infants, Children, and Adolescents: 1-2 mg/kg/dose IV or IM every 6-12 hours. If the diuretic response is not adequate after 2 hours, increase the dose by 1 mg/kg/dose IV (Max: 6 mg/kg/dose IV). Use the lowest effective dose.
Continuous Intravenous infusion dosage*:
Neonates, Infants, and Children: A loading dose of 0.1 mg/kg IV (minimum 1 mg IV) followed by a continuous IV infusion of 0.1 mg/kg/h has been studied for short durations (<= 24 hours) in postoperative cardiac patients. The infusion was doubled every 2 hours to a maximum of 0.4 mg/kg/h continuous IV in patients whose urine output remained < 1 mL/kg/hour. Compared to patients receiving intermittent IV doses, patients receiving continuous infusions had a greater urine output per dose of drug, less variability in urine output, and lower urinary losses of sodium and chloride.
Adolescents: Specific dosing information for adolescents is not available; however, a bolus dose of 0.1 mg/kg IV followed by a continuous infusion of 0.1-0.4 mg/kg/hour IV has been used for short durations in children after cardiac surgery and a bolus dose of 40 mg IV followed by a continuous infusion of 10-40 mg/hour is recommended in adult patients with chronic heart failure.
-for the prevention of adverse hemodynamic effects and/or pulmonary edema associated with blood product transfusions*:
Premature Neonates: Although use in clinical practice is not uncommon, limited published data are available evaluating furosemide 1 mg/kg IV prior to or after the administration of blood products. One prospective, unblinded trial evaluated furosemide after transfusions of 10 mL/kg of packed red blood cells (PRBC) in 24 cases of neonates (mean gestational age 32.5 +/- 3.4 weeks) with CLD. The PRBCs were administered at a rate of 5 mL/kg/hour, and furosemide was given in 16 of the 24 cases. The infants that received furosemide demonstrated an improvement in lung compliance, tidal volume, and minute ventilation compared to baseline. There was no observed improvement in these values in the untreated group. The authors noted no difference in the clinical respiratory status between the 2 groups. Some authors caution against the routine use of furosemide following PRBC transfusions due to a lack of efficacy data and the potential for electrolyte imbalance.
For the treatment of hypertension*:
Infants, Children, and Adolescents: Initially, 0.5-2 mg/kg/dose PO, given 1-2 times daily. The American Academy of Pediatrics states that furosemide may be useful as adjunctive therapy in patients with resistant hypertension, especially if concomitant renal disease is present. The manufacturer recommends initial doses of 1-2 mg/kg/dose PO every 6-12 hours for the treatment of edema. Increase the dose by 1-2 mg/kg/dose PO (Max: 6 mg/kg/dose).
Maximum Dosage Limits:
Premature Neonates <= 32 weeks postconceptional age: 1 mg/kg/dose IV every 24 hours; the maximum PO dose has not been established in neonates.
Premature and Term Neonates > 32 weeks postconceptional age: 2 mg/kg/dose IV every 12 hours; the maximum PO dose has not been established in neonates.
6 mg/kg/dose PO/IV.
6 mg/kg/dose PO/IV.
6 mg/kg/dose PO/IV.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Use diuretics with caution in patients with hepatic disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available. In adults with renal impairment, higher doses may be needed. Monitor fluid status and electrolytes closely; delayed excretion may occur. The clearance of furosemide does not appear to be effected by hemodialysis (< 10%).
Monograph content under development
Mechanism of Action: Furosemide is a loop diuretic that inhibits sodium and chloride resorption by competing with chloride for the Na+/K+/2Cl- co-transporter in the ascending limb of the loop of Henle. The manufacturer also states that furosemide inhibits the absorption of sodium and chloride in the proximal and distal tubules. A profound diuresis results from the increased urinary excretion of sodium, chloride, potassium, and hydrogen ions. In addition, furosemide increases the excretion of calcium, magnesium, bicarbonate, ammonium, and phosphate. The diuresis caused by furosemide can lead to increased aldosterone production, resulting in increased sodium resorption, and increased potassium and hydrogen excretion. Excessive loss of these electrolytes can lead to metabolic alkalosis.
Furosemide's effectiveness is independent of the acid-base status of the patient. Renal vasodilation occurs following administration of furosemide; renal vascular resistance decreases, and renal blood flow is enhanced. Reduced peripheral vascular resistance and increased peripheral venous capacitance also occur, and the subsequent decrease in left ventricular filling pressure may contribute to the drug's beneficial effect in patients with congestive heart failure. Initially, diuretics lower blood pressure by causing hypovolemia (decreased plasma and extracellular fluid), a temporary increase in glomerular filtration rate, and a decreased cardiac output. Cardiac output eventually returns to normal, but peripheral resistance is now reduced, resulting in lower blood pressure. In general, diuretics worsen left ventricular hypertrophy (LVH) and glucose tolerance. In addition, loop diuretics have been associated with hypercholesterolemia and hypertriglyceridemia.
Pharmacokinetics: Furosemide is administered orally and intravenously. It is 91-99% plasma protein-bound, mainly to albumin. Furosemide undergoes minimal metabolism in the liver, with 50-80% of a dose excreted in the urine within 24 hours; significantly more furosemide is excreted in the urine after IV administration as compared to oral. The remainder of the drug is eliminated through nonrenal mechanisms including excretion in the feces. In patients with significant renal impairment, nonrenal elimination can increase to 98%. The half-life of furosemide is approximately 2 hours.
Affected cytochrome P450 isoenzymes: none
Furosemide is absorbed erratically following an oral dose, and food will delay this absorption but will not alter the diuretic response. The bioavailability of the tablet and solution in healthy fasted volunteers is 64% and 60%, respectively. Although furosemide solution is more rapidly absorbed compared to the tablet, peak plasma concentrations and the AUC are not significantly different between the 2 dosage forms. Diuresis generally begins 30 to 60 minutes after oral administration, with the peak effect occurring within 1-2 hours. The duration of diuresis is 6-8 hours.
Diuresis generally begins about 5 minutes after IV administration of furosemide. The peak effect occurs within the first 30 minutes and the duration is approximately 2 hours.
The elimination of furosemide is prolonged in premature and term neonates compared to older pediatric patients due to immature renal function. Although no relationship was seen between half-life or clearance and postconceptional age (PCA) in patients receiving a single dose, a positive correlation was seen between half-life and PCA in premature and term neonates receiving multiple doses. The plasma half-life ranged from 1.8-67.3 hours in 10 premature neonates (mean gestational age 26.6 weeks) receiving multiple doses of furosemide 1 mg/kg/dose IV or 2-3 mg/kg/dose enterally every 12-24 hours. The most premature neonates had the longest half-life with the majority of those < 31 weeks PCA having half-lives > 24 hours. As the patients matured, half-life decreased, declining to < 12 hours by 33 weeks PCA and to approximately 4 hours as the PCA neared term. The bioavailability of oral furosemide was highly variable, ranging from 56-106%. The mean half-life was 19.9 hours (range 8.7-46 hours), the mean volume of distribution was 0.239 L/kg (range 0.1-0.54 L/kg), and the mean plasma clearance was 0.18 ml/kg/min (range 0.04-0.49 ml/kg/min) in 14 normovolemic premature neonates (gestational age 26-36 weeks, postnatal age 1-20 days) after a single IV dose of furosemide 1 mg/kg. In 7 term neonates (gestational age 37-41 weeks, postnatal age 1-18 days), the mean half-life was 13.4 hours (range 4.7-29.2 hours), the mean volume of distribution was 0.523 L/kg (range 0.161-1.3 L/kg), and the mean plasma clearance was 0.196 ml/kg/min (range 0.04-0.5 ml/kg/min) after a single IV doses of furosemide 1-1.13 mg/kg.
The mean half-life was 1.98 +/- 1.25 hours, the mean volume of distribution was 0.49 +/- 0.61 L/kg, and the mean plasma and renal clearance were 3.02 +/- 3.25 ml/min/kg, and 1.48 +/- 1.98 ml/min/kg, respectively, in 10 infants with a mean age 24 +/- 33 weeks (dose not specified). The plasma clearance of furosemide was positively correlated with postnatal age in 26 neonates and infants 1 day-4 months of age (r = 0.79).
Children and Adolescents
The mean +/- SD half-life of furosemide in 17 pediatric patients with nephrotic syndrome and 7 pediatric control patients (2.5-15 years of age) after single oral doses of 2 mg/kg was 2.06 +/- 0.96 hours and 2.14 +/- 0.69 hours, respectively.
In 2 pediatric patients (ages 5 and 13 years) with chronic renal failure on hemodialysis, the half-life of furosemide was prolonged and renal clearance of furosemide was lower compared to normal adult values. The half-life was 3.6-4.5 hours, the volume of distribution was 0.16-0.24 L/kg, and the renal clearance was 0.19 ml/kg/min after a single dose of 1 mg/kg IV of furosemide. Hemodialysis clearance was < 10% of total clearance after chronic oral dosing in 7 pediatric patients.