United States - English - NLM (National Library of Medicine)
FUROSEMIDE- furosemide injection, solution
General Injectables & Vaccines, Inc.
FUROSEMIDE INJECTION, USP
Furosemide is a potent diuretic which, if given in excessive amounts, can lead to a profound
diuresis with water and electrolyte depletion. Therefore, careful medical supervision is required
and dose and dose schedule must be adjusted to the individual patient's needs. (See DOSAGE
Furosemide is a diuretic which is an anthranilic acid derivative.
Chemically, it is 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid.
Furosemide Injection 10 mg/mL is a sterile, non-pyrogenic solution in vials for intravenous and
Furosemide is a white to off-white odorless crystalline powder. It is practically insoluble in water,
sparingly soluble in alcohol, freely soluble in dilute alkali solutions and insoluble in dilute acids.
The structural formula is as follows:
Each mL contains: Furosemide 10 mg, Water for Injection q.s., Sodium Chloride for isotonicity, Sodium
Hydroxide and, if necessary, Hydrochloric Acid to adjust pH between 8.0 and 9.3.
Investigations into the mode of action of furosemide have utilized micropuncture studies is rats, stop
flow experiments in dogs and various clearance studies in both humans and experimental animals. It has
been demonstrated that furosemide inhibits primarily the reabsorption of sodium and chloride not only in
the proximal and distal tubules but also in the loop of Henle. The high degree of efficacy is largely due
to this unique site of action. The action on the distal tubule is independent of any inhibitory effect on
carbonic anhydrase and aldosterone.
Recent evidence suggests that furosemide glucuronide is the only or at least the major
biotransformation product of furosemide in man. Furosemide is extensively bound to plasma proteins,
mainly to albumin. Plasma concentrations ranging from 1 to 400 μg/mL are 91 to 99% bound in healthy
individuals. The unbound fraction averages 2.3 to 4.1% at therapeutic concentrations.
The onset of diuresis following intravenous administration is within 5 minutes and somewhat later after
intramuscular administration. The peak effect occurs within the first half hour. The duration of diuretic
effect is approximately 2 hours.
In fasted normal men, the mean bioavailability of furosemide from furosemide tablets and furosemide
oral solution is 64 % and 60%, respectively, of that from an intravenous injection of the drug. Although
furosemide is more rapidly absorbed from the oral solution (50 minutes) than from the tablet (87
minutes), peak plasma levels and area under the plasma concentration-time curves do not differ
significantly. Peak plasma concentrations increase with increasing dose but times-to-peak do not differ
among doses. The terminal half-life of furosemide is approximately 2 hours.
Significantly more furosemide is excreted in urine following the intravenous injection than after the
tablet or oral solution. There are no significant differences between the two oral formulations in the
amount of unchanged drug excreted in urine.
Furosemide binding to albumin may be reduced in elderly patients. Furosemide is predominantly
excreted unchanged in the urine. The renal clearance of furosemide after intravenous administration in
older healthy male subjects (60-70 years of age) is statistically significantly smaller than in younger
healthy male subjects (20-35 years of age). The intial diuretic effect of furosemide in older subjects is
decreased relative to younger subjects. (See
PRECAUTIONS: Geriatric Use .)
INDICATIONS AND USAGE
Parenteral therapy should be reserved for patients unable to take oral medication or for patients in
emergency clinical situations.
Edema: Furosemide is indicated in adults and pediatric patients for the treatment of edema associated
with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic
syndrome. Furosemide is particularly useful when an agent with greater diuretic potential is desired.
Furosemide is indicated as adjunctive therapy in acute pulmonary edema. The intravenous administration
of furosemide is indicated when a rapid onset of diuresis is desired, e.g., in acute pulmonary edema.
If gastrointestinal absorption is impaired or oral medication is not practical for any reason, furosemide
is indicated by the intravenous or intramuscular route. Parenteral use should be replaced with oral
furosemide as soon as practical.
Furosemide is contraindicated in patients with anuria and in patients with a history of hypersensitivity to
In patients with hepatic cirrhosis and ascites, furosemide therapy is best initiated in the hospital. In
hepatic coma and in states of electrolyte depletion, therapy should not be instituted until the basic
condition is improved. Sudden alterations of fluid and electrolyte balance in patients with cirrhosis may
precipitate hepatic coma; therefore, strict observation is necessary during the period of diuresis.
Supplemental potassium chloride and, if required, an aldosterone antagonist are helpful in preventing
hypokalemia and metabolic alkalosis.
If increasing azotemia and oliguria occur during treatment of severe progressive renal disease,
furosemide should be discontinued.
Cases of tinnitus and reversible or irreversible hearing impairment and deafness have been reported.
Reports usually indicate that furosemide ototoxicity is associated with rapid injection, severe renal
impairment, the use of higher than recommended doses, hypoproteinemia, or concomitant therapy with
aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If the physician elects to use high
dose parenteral therapy, controlled intravenous infusion is advisable (for adults, an infusion rate not
exceeding 4 mg furosemide per minute has been used) (See PRECAUTIONS, Drug Interactions.)
Pediatric Use: In premature neonates with respiratory distress syndrome, diuretic treatment with
furosemide in the first few weeks of life may increase the risk of persistent patent ductus arteriosus
(PDA), possibly through a prostaglandin-E-mediated process.
Literature reports indicate that premature infants with post conceptual age (gestational plus postnatal)
less than 31 weeks receiving doses exceeding 1 mg/kg/24 hours may develop plasma levels which
could be associated with potential toxic effects including ototoxicity.
Hearing loss in neonates has been associated with the use of furosemide injection (see WARNINGS,
General: Excessive diuresis may cause dehydration and blood volume reduction with circulatory
collapse and possibly vascular thrombosis and embolism, particularly in elderly patients. As with any
effective diuretic, electrolyte depletion may occur during furosemide therapy, especially in patients
receiving higher doses and a restricted salt intake. Hypokalemia may develop with furosemide,
especially with brisk diuresis, inadequate oral electrolyte intake, when cirrhosis is present, or during
concomitant use of corticosteroids, ACTH, licorice in large amounts, or prolonged use of laxatives.
Digitalis therapy may exaggerate metabolic effects of hypokalemia, especially myocardial effects.
All patients receiving furosemide therapy should be observed for these signs or symptoms of fluid or
electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia, hypomagnesemia or
hypocalcemia): dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or
cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia or gastrointestinal disturbances
such as nausea and vomiting. Increases in blood glucose and alterations in glucose tolerance tests (with
abnormalities of the fasting and 2-hour postprandial sugar) have been observed, and rarely, precipitation
of diabetes mellitus has been reported.
In patients with severe symptoms of urinary retention (because of bladder emptying disorders, prostatic
hyperplasia, urethral narrowing), the administration of furosemide can cause acute urinary retention
related to increased production and retention of urine. Thus, these patients require careful monitoring,
especially during the initial stages of treatment.
In patients at high risk for radiocontrast nephropathy, furosemide can lead to a higher incidence of
deterioration in renal function after receiving radiocontrast compared to high-risk patients who
received only intravenous hydration prior to receiving radiocontrast.
In patients with hypoproteinemia (e.g., associated with nephrotic syndrome) the effect of furosemide
may be weakened and its ototoxicity potentiated.
Asymptomatic hyperuricemia can occur and gout may rarely be precipitated.
Patients allergic to sulfonamides may also be allergic to furosemide.
The possibility exists of exacerbation or activation of systemic lupus erythematosus.
As with many other drugs, patients should be observed regularly for the possible occurrence of blood
dyscrasias, liver or kidney damage, or other idiosyncratic reactions.
Information for Patients: Patients receiving furosemide should be advised that they may experience
symptoms from excessive fluid and/or electrolyte losses.
The postural hypotension that sometimes occurs can usually be managed by getting up slowly.
Potassium supplements and/or dietary measures may be needed to control or avoid hypokalemia.
Patients with diabetes mellitus should be told that furosemide may increase blood glucose levels and
thereby affect urine glucose tests. The skin of some patients may be more sensitive to the effects of
sunlight while taking furosemide.
Hypertensive patients should avoid medications that may increase blood pressure, including over-the-
counter products for appetite suppression and cold symptoms.
Laboratory Tests: Serum electrolytes, (particularly potassium), CO , creatinine and BUN should be
determined frequently during the first few months of furosemide therapy and periodically thereafter.
Serum and urine electrolyte determinations are particularly important when the patient is vomiting
profusely or receiving parenteral fluids. Abnormalities should be corrected or the drug temporarily
withdrawn. Other medications may also influence serum electrolytes.
Reversible elevations of BUN may occur and are associated with dehydration, which should be
avoided, particularly in patients with renal insufficiency. Urine and blood glucose should be checked
periodically in diabetics receiving furosemide, even in those suspected of latent diabetes.
Furosemide may lower serum levels of calcium (rarely cases of tetany have been reported) and
magnesium. Accordingly, serum levels of these electrolytes should be determined periodically. In
premature infants furosemide may precipitate nephrocalcinosis/nephrolithiasis, therefore renal function
must be monitored and renal ultrasonography performed. (See PRECAUTIONS, Pediatric Use.)
Drug Interactions: Furosemide may increase the ototoxic potential of aminoglycoside antibiotics,
especially in the presence of impaired renal function. Except in life-threatening situations, avoid the
Furosemide should not be used concomitantly with ethacrynic acid because of the possibility of
Patients receiving high doses of salicylates concomitantly with furosemide, as in rheumatic diseases,
may experience salicylate toxicity at lower doses because of competitive renal excretory sites.
There is a risk of ototoxic effects if cisplatin and furosemide are given concomitantly. In addition,
nephrotoxicity of nephrotoxic drugs such as cisplatin may be enhanced if furosemide is not given in
lower doses and with positive fluid balance when used to achieve forced diuresis during cisplatin
Furosemide has a tendency to antagonize the skeletal muscle relaxing effect of tubocurarine and may
potentiate the action of succinylcholine.
Lithium generally should not be given with diuretics because they reduce lithium's renal clearance and
add a high risk of lithium toxicity.
Furosemide combined with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers
may lead to severe hypotension and deterioration in renal function, including renal failure. An
interruption or reduction in the dosage of furosemide, angiotensin converting enzyme inhibitors, or
angiotensin receptor blockers may be necessary.
Furosemide may add to or potentiate the therapeutic effect of other antihypertensive drugs. Potentiation
occurs with ganglionic or peripheral adrenergic blocking drugs.
Furosemide may decrease arterial responsiveness to norepinephrine. However, norepinephrine may still
be used effectively.
In isolated cases, intravenous administration of furosemide within 24 hours of taking chloral hydrate
may lead to flushing, sweating attacks, restlessness, nausea, increase in blood pressure, and tachycardia.
Use of furosemide concomitantly with chloral hydrate is therefore not recommended.
Phenytoin interferes directly with renal action of furosemide.
Methotrexate and other drugs that, like furosemide, undergo significant renal tubular secretion may
reduce the effect of furosemide. Conversely, furosemide may decrease renal elimination of other drugs
that undergo tubular secretion. High-dose treatment of both furosemide and these other drugs may result
in elevated serum levels of these drugs and may potentiate their toxicity as well as the toxicity of
Furosemide can increase the risk of cephalosporin-induced nephrotoxicity even in the setting of minor
or transient renal impairment.
Concomitant use of cyclosporine and furosemide is associated with increased risk of gouty arthritis
secondary to furosemide-induced hyperuricemia and cyclosporine impairment of renal urate excretion.
One study in six subjects demonstrated that the combination of furosemide and acetylsalicylic acid
temporarily reduced creatinine clearance in patients with chronic renal insufficiency. There are case
reports of patients who developed increased BUN, serum creatinine and serum potassium levels, and
weight gain when furosemide was used in conjunction with NSAIDs.
Literature reports indicate that coadministration of indomethacin may reduce the natriuretic and
antihypertensive effects of furosemide in some patients by inhibiting prostaglandin synthesis.
Indomethacin may also affect plasma renin levels, aldosterone excretion, and renin profile evaluation.
Patients receiving both indomethacin and furosemide should be observed closely to determine if the
desired diuretic and/or antihypertensive effect of furosemide is achieved.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Furosemide was tested for carcinogenicity
by oral administration in one strain of mice and one strain of rats. A small but significantly increased
incidence of mammary gland carcinomas occurred in female mice at a dose 17.5 times the maximum
human dose of 600 mg. There were marginal increases in uncommon tumors in male rats at a dose of 15
mg/kg (slightly greater than the maximum human dose) but not at 30 mg/kg.
Furosemide was devoid of mutagenic activity in various strains of Salmonella typhimurium when tested
in the presence or absence of an in vitro metabolic activation system, and questionably positive for gene
mutation in mouse lymphoma cells in the presence of rat liver S9 at the highest dose tested. Furosemide
did not induce sister chromatid exchange in human cells in vitro, but other studies on chromosomal
aberrations in human cells in vitro gave conflicting results. In Chinese hamster cells it induced
chromosomal damage but was questionably positive for sister chromatid exchange. Studies on the
induction by furosemide of chromosomal aberrations in mice were inconclusive. The urine of rats
treated with this drug did not induce gene conversion in Saccharomyces cerevisiae.
Furosemide produced no impairment of fertility in male or female rats, at 100 mg/kg/day (the maximum
effective diuretic dose in the rat and 8 times the maximal human dose of 600 mg/day).
Pregnancy: Teratogenic Effects: Pregnancy Category C. Furosemide has been shown to cause
unexplained maternal deaths and abortions in rabbits at 2, 4, and 8 times the maximal recommended human
oral dose. There are no adequate and well-controlled studies in pregnant women. Furosemide should be
used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Treatment during pregnancy requires monitoring of fetal growth because of the potential for higher
fetal birth weights.
The effects of furosemide on embryonic and fetal development and on pregnant dams were studied in
mice, rats and rabbits.
Furosemide caused unexplained maternal deaths and abortions in the rabbit at the lowest dose of 25
mg/kg (2 times the maximal recommended human oral dose of 600 mg/day). In another study, a dose of
50 mg/kg (4 times the maximal recommended human oral dose of 600 mg/day) also caused maternal
deaths and abortions when administered to rabbits between Days 12 and 17 of gestation. In a third study,
none of the pregnant rabbits survived an oral dose of 100 mg/kg. Data from the above studies indicate
fetal lethality that can precede maternal deaths.
The results of the mouse study and one of the three rabbit studies also showed an increased incidence
and severity of hydronephrosis (distention of the renal pelvis and, in some cases, of the ureters) in
fetuses derived from treated dams as compared with the incidence of fetuses from the control group.
Nursing Mothers: Because it appears in breast milk, caution should be exercised when furosemide is
administered to a nursing mother.
Furosemide may inhibit lactation.
Pediatric Use: In premature infants furosemide may precipitate nephrocalcinosis/nephrolithiasis.
Nephrocalcinosis/nephrolithiasis has also been observed in children under 4 years of age with no
history of prematurity who have been treated chronically with furosemide. Monitor renal function, and
renal ultrasonography should be considered, in pediatric patients receiving furosemide.
If furosemide is administered to premature infants during the first weeks of life, it may increase the risk
of persistence of patent ductus arteriosus.
Renal calcifications (from barely visible on x-ray to staghorn) have occurred in some severely
premature infants treated with intravenous furosemide for edema due to patent ductus arteriosus and
hyaline membrane disease. The concurrent use of chlorothiazide has been reported to decrease
hypercalcinuria and dissolve some calculi.
Geriatric Use: Controlled clinical studies of furosemide did not include sufficient numbers of subjects
aged 65 and over to determine whether they respond differently from younger subjects. Other reported
clinical experience has not identified differences in responses between the elderly and younger
patients. In general, dose selection for the elderly patient 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.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug
may be greater in patients with impaired renal function. Because elderly patients are more likely to have
decreased renal function, care should be taken in dose selection and it may be useful to monitor renal
function. (See PRECAUTIONS: General and DOSAGE AND ADMINISTRATION.)
Adverse reactions are categorized below by organ system and listed by decreasing severity.
Gastrointestinal System Reactions
1.Hepatic encephalopathy in patients with hepatocellular insufficiency
3.Jaundice (intrahepatic cholestatic jaundice)
4.Increased liver enzymes
6.Oral and gastric irritation
Systemic Hypersensitivity Reactions
1.Severe anaphylactic or anaphylactoid reactions (e.g. with shock)
Central Nervous System Reactions
1.Tinnitus and hearing loss
10.Toxic epidermal necrolysis
1.Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates or narcotics.
2.Increase in cholesterol and triglyceride serum levels.
7.Urinary bladder spasm
9.Transient injection site pain following intramuscular injection
Whenever adverse reactions are moderate or severe, furosemide dosage should be reduced or therapy
The principal signs and symptoms of overdose with furosemide are dehydration, blood volume
reduction, hypotension, electrolyte imbalance, hypokalemia and hypochloremic alkalosis, and are
extensions of its diuretic action.
The acute toxicity of furosemide has been determined in mice, rats and dogs. In all three, the oral
LD50exceeded 1000 mg/kg body weight, while the intravenous LD50 ranged from 300 to 680 mg/kg.
The acute intragastric toxicity in neonatal rats is 7 to 10 times that of adult rats.
The concentration of furosemide in biological fluids associated with toxicity or death is not known.
Treatment of overdosage is supportive and consists of replacement of excessive fluid and electrolyte
losses. Serum electrolytes, carbon dioxide level and blood pressure should be determined frequently.
Adequate drainage must be assured in patients with urinary bladder outlet obstruction (such as prostatic
Hemodialysis does not accelerate furosemide elimination.
DOSAGE AND ADMINISTRATION
Adults: Parenteral therapy with Furosemide Injection should be used only in patients unable to take oral
medication or in emergency situations and should be replaced with oral therapy as soon as practical.
The usual initial dose of furosemide is 20 to 40 mg given as a single dose, injected intramuscularly or
intravenously. The intravenous dose should be given slowly (1 to 2 minutes). Ordinarily a prompt
diuresis ensues. If needed, another dose may be administered in the same manner 2 hours later or the
dose may be increased. The dose may be raised by 20 mg and given not sooner than 2 hours after the
previous dose until the desired diuretic effect has been obtained. This individually determined single
dose should then be given once or twice daily. Therapy should be individualized according to patient
response to gain maximal therapeutic response and to determine the minimal dose needed to maintain that
response. Close medical supervision is necessary.
When furosemide is given for prolonged periods, careful clinical observation and laboratory
monitoring are particularly advisable. (See PRECAUTIONS: Laboratory Tests.)
If the physician elects to use high dose parenteral therapy, add the furosemide to either Sodium
Chloride Injection USP, Lactated Ringer's Injection USP, or Dextrose (5%) Injection USP after pH has
been adjusted to above 5.5, and administer as a controlled intravenous infusion at a rate not greater than 4
mg/min. Furosemide Injection is a buffered alkaline solution with a pH of about 9 and drug may
precipitate at pH values below 7. Care must be taken to ensure that the pH of the prepared infusion
solution is in the weakly alkaline to neutral range. Acid solutions, including other parenteral medications
(e.g., labetalol, ciprofloxacin, amrinone, milrinone) must not be administered concurrently in the same
infusion because they may cause precipitation of the furosemide. In addition, furosemide injection
should not be added to a running intravenous line containing any of these acidic products.
Acute Pulmonary Edema
The usual initial dose of furosemide is 40 mg injected slowly intravenously (over 1 to 2 minutes). If a
satisfactory response does not occur within 1 hour, the dose may be increased to 80 mg injected slowly
intravenously (over 1 to 2 minutes).
If necessary, additional therapy (e.g., digitalis, oxygen) may be administered concomitantly.
In general, dose selection for the elderly patient should be cautious, usually starting at the low end of
the dosing range. (See PRECAUTIONS: Geriatric Use.)
Pediatric Patients: Parenteral therapy should be used only in patients unable to take oral medication or
in emergency situations and should be replaced with oral therapy as soon as practical.
The usual initial dose of Furosemide Injection (intravenously or intramuscularly) in pediatric patients is
1 mg/kg body weight and should be given slowly under close medical supervision. If the diuretic
response to the initial dose is not satisfactory, dosage may be increased by 1 mg/kg not sooner than 2
hours after the previous dose, until the desired diuretic effect has been obtained. Doses greater than 6
mg/kg body weight are not recommended.
Literature reports suggest that the maximum dose for premature infants should not exceed 1 mg/kg/day
(see WARNINGS, Pediatric Use).
Furosemide Injection should be inspected visually for particulate matter and discoloration before
Furosemide Injection, USP (10 mg/mL)
Do not use if solution is discolored.
Store at 20° to 25°C (68° to 77°F) ; excursions permitted to 15˚ to 30˚C (59˚ to 86˚F) [see USP
Controlled Room Temperature]
Protect from light.
Baxter Healthcare Corporation
Deerfield, IL 60015 USA
Baxter Pharmaceuticals India Private Ltd
Ahmedabad 382213, India
Issue date: 2018-10-27
furosemide injection, solution
Product T ype
HUMAN PRESCRIPTION DRUG
Ite m Code (Source )
NDC:5258 4-28 4(NDC:36 0 0 0 -28 4)
Route of Administration
Active Ingredient/Active Moiety
Basis of Strength
Stre ng th
FURO SEMIDE (UNII: 7LXU5N7ZO5) (FUROSEMIDE - UNII:7LXU5N7ZO5)
10 mg in 1 mL
Stre ng th
WATER (UNII: 0 59 QF0 KO0 R)
SO DIUM CHLO RIDE (UNII: 451W47IQ8 X)
SO DIUM HYDRO XIDE (UNII: 55X0 4QC32I)
General Injectables & Vaccines, Inc.
HYDRO CHLO RIC ACID (UNII: QTT1758 2CB)
Marketing Start Date Marketing End Date
NDC:5258 4-28 4-25 1 in 1 BAG
0 8 /15/20 19
1 mL in 1 VIAL, GLASS; Type 0 : No t a Co mbinatio n Pro duct
Marke ting Cate gory
Application Numbe r or Monograph Citation
Marke ting Start Date
Marke ting End Date
0 8 /15/20 19
General Injectables & Vaccines, Inc. (108250663)