CONTRAINDICATIONS
Furosemide is contraindicated in patients with anuria and in patients with a history of
hypersensitivity to furosemide.
WARNINGS
Tablets, Injection, and Oral Solution
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 have been reported. Usually,
reports indicate that furosemide ototoxicity is associated with rapid injection, severe renal
impairment, doses exceeding several times the usual recommended dose, 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).
Injection
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.
Hearing loss in neonates has been associated with the use of furosemide injection (see
WARNINGS).
PRECAUTIONS
Tablets, Injection, and Oral Solution
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 or ACTH. 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.
Asymptomatic hyperuricemia can occur and gout may rarely be precipitated.
Oral Solution
The sorbitol present in the vehicle may cause diarrhea (especially in children) when higher doses of
furosemide oral solution are given.
Tablets, Injection, and Oral Solution
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 the Patient: 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), CO2, 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.
Carcinogenesis, Mutagenesis, and 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 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 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.
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 dose of 600 mg/day). In another study, a dose of
50 mg/kg (4 times the maximal recommended human 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 a 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 the treated dams as compared with the incidence in 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.
Injection
Pediatric Use: 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 hypercalciuria and dissolve some calculi.