Geriatric Population 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 initial diuretic effect of furosemide in older subjects is decreased relative to younger subjects. LASIX is particularly useful when an agent with greater diuretic potential is desired.
Hypertension Oral LASIX may be used in adults for the treatment of hypertension alone or in combination with other antihypertensive agents. Hypertensive patients who cannot be adequately controlled with thiazides will probably also not be adequately controlled with LASIX alone.
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, LASIX should be discontinued. Cases of tinnitus and reversible or irreversible hearing impairment and deafness have been reported. Reports usually indicate that LASIX 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 LASIX per minute has been used. 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: 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. Asymptomatic hyperuricemia can occur and gout may rarely be precipitated. 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.
The postural hypotension that sometimes occurs can usually be managed by getting up slowly. 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 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. 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, 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. Drug Interactions LASIX may increase the ototoxic potential of aminoglycoside antibiotics, especially in the presence of impaired renal function. Except in life-threatening situations, avoid this combination. LASIX should not be used concomitantly with ethacrynic acid because of the possibility of ototoxicity. Patients receiving high doses of salicylates concomitantly with LASIX, as in rheumatic disease, may experience salicylate toxicity at lower doses because of competitive renal excretory sites.
In addition, nephrotoxicity of nephrotoxic drugs such as cisplatin may be enhanced if LASIX is not given in lower doses and with positive fluid balance when used to achieve forced diuresis during cisplatin treatment.
LASIX 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. LASIX may add to or potentiate the therapeutic effect of other antihypertensive drugs, necessitating a reduction in the dosage of these drugs.
Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs. LASIX may decrease arterial responsiveness to norepinephrine. However, norepinephrine may still be used effectively. In isolated cases, intravenous administration of LASIX within 24 hours of taking chloral hydrate may lead to flushing, sweating attacks, restlessness, nausea, increase in blood pressure and tachycardia.
The cephalosporin antibiotics should be used with caution in the presence of even minor transient renal impairment and particularly if LASIX is being given concurrently Concomitant use of cyclosporine and LASIX is associated with increased risk of gouty arthritis secondary to LASIX-induced hyperurecemia 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 LASIX furosemide in some patients by inhibiting prostaglandin synthesis. Indomethacin may also affect plasma renin levels, aldosterone excretion, and renin profile evaluation. 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 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. There are no adequate and well-controlled studies in pregnant women.
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.
Precautions 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: 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. 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. The postural hypotension that sometimes occurs can usually be managed by getting up slowly. 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.
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 this combination.
Furosemide should not be used concomitantly with ethacrynic acid because of the possibility of ototoxicity. Patients receiving high doses of salicylates concomitantly with furosemide, as in rheumatic disease, 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 treatment. 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.
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