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 LASIX therapy, especially in patients
receiving higher doses and a restricted salt intake. Hypokalemia may develop
with LASIX, 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 LASIX 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
LASIX 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 LASIX may be weakened and its ototoxicity
Asymptomatic hyperuricemia can occur and gout may rarely
Patients allergic to sulfonamides may also be allergic to
LASIX. The possibility exists of exacerbation or activation of systemic lupus
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.
Serum electrolytes (particularly potassium), CO2,
creatinine and BUN should be determined frequently during the first few months
of LASIX 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
Reversible elevations of BUN may occur and are associated
with dehydration, which should be avoided, particularly in patients with renal
Urine and blood glucose should be checked periodically in
diabetics receiving LASIX, even in those suspected of latent diabetes.
LASIX 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 LASIX may precipitate
nephrocalcinosis/nephrolithiasis, therefore renal function must be monitored
and renal ultrasonography performed. (See PRECAUTIONS: Pediatric Use)
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
LASIX (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. LASIX 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 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 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.
Because it appears in breast milk, caution should be
exercised when LASIX is administered to a nursing mother.
LASIX may inhibit lactation.
In premature infants LASIX 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 LASIX. Monitor renal function, and renal
ultrasonography should be considered, in pediatric patients receiving LASIX.
If LASIX is administered to premature infants during the
first weeks of life, it may increase the risk of persistence of patent ductus
Controlled clinical studies of LASIX 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