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 TABLET therapy, especially in patients receiving higher doses and a restricted salt intake. Hypokalemia may develop with FUROSEMIDE TABLET, 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 TABLET 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.

Patients allergic to sulfonamides may also be allergic to FUROSEMIDE TABLET. 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.

Patients receiving FUROSEMIDE TABLET 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.

Serum electrolytes (particularly potassium), CO2, creatinine and BUN should be determined frequently during the first few months of FUROSEMIDE TABLET 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 TABLET, even in those suspected of latent diabetes.

FUROSEMIDE TABLET 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.

FUROSEMIDE TABLET may increase the ototoxic potential of aminoglycoside antibiotics, especially in the presence of impaired renal function. Except in life-threatening situations, avoid this combination.

FUROSEMIDE TABLET should not be used concomitantly with ethacrynic acid because of the possibility of ototoxicity. Patients receiving high doses of salicylates concomitantly with FUROSEMIDE TABLET, as in rheumatic disease, may experience salicylate toxicity at lower doses because of competitive renal excretory sites.

FUROSEMIDE TABLET 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 TABLET may add to or potentiate the therapeutic effect of other antihypertensive drugs. Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs.

FUROSEMIDE TABLET may decrease arterial responsiveness to norepinephrine. However, norepinephrine may still be used effectively.

Simultaneous administration of sucralfate and FUROSEMIDE TABLET may reduce the natriuretic and antihypertensive effects of FUROSEMIDE TABLET. Patients receiving both drugs should be observed closely to determine if the desired diuretic and/or antihypertensive effect of FUROSEMIDE TABLET is achieved. The intake of FUROSEMIDE TABLET and sucralfate should be separated by at least two hours.

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 TABLET (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 TABLET should be observed closely to determine if the desired diuretic and/or antihypertensive effect of FUROSEMIDE TABLET is achieved.

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 TABLET 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 TABLET 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.

Because it appears in breast milk, caution should be exercised when FUROSEMIDE TABLET is administered to a nursing mother.

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. 聽Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 聽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. 聽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.)