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
Lasix (furosemide) therapy, especially in patients receiving higher doses and a restricted
salt intake. Hypokalemia may develop with Lasix (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 Lasix (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 Lasix (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 Lasix (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 Lasix (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.
Laboratory Tests
Serum electrolytes (particularly potassium), CO2, creatinine and BUN should
be determined frequently during the first few months of Lasix (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
Lasix (furosemide) , even in those suspected of latent diabetes.
Lasix (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 Lasix (furosemide) 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
cerevisiae.
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
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 (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 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.
Nursing Mothers
Because it appears in breast milk, caution should be exercised when Lasix (furosemide) is
administered to a nursing mother.
Lasix (furosemide) may inhibit lactation.
Pediatric Use
In premature infants Lasix (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 Lasix (furosemide) . Monitor renal function, and renal ultrasonography should be considered,
in pediatric patients receiving Lasix (furosemide) .
If Lasix (furosemide) is administered to premature infants during the first weeks of life,
it may increase the risk of persistence of patent ductus arteriosus
Geriatric Use
Controlled clinical studies of Lasix (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).
Last reviewed on RxList: 11/15/2010
This monograph has been modified to include the generic and brand name in many instances.