Lasix Information
Lasix () Warning
Lasix () (furosemide) is a potent diuretic which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion. Therefore, careful medical supervision is required and dose and dose schedule must be adjusted to the individual patient's needs. (See .)
Lasix () Description
Lasix () is a diuretic which is an anthranilic acid derivative. Lasix () tablets for oral administration contain furosemide as the active ingredient and the following inactive ingredients: lactose monohydrate NF, magnesium stearate NF, starch NF, talc USP, and colloidal silicon dioxide NF. Chemically, it is 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid. Lasix () is available as white tablets for oral administration in dosage strengths of 20, 40 and 80 mg. Furosemide is a white to off-white odorless crystalline powder. It is practically insoluble in water, sparingly soluble in alcohol, freely soluble in dilute alkali solutions and insoluble in dilute acids.
The CAS Registry Number is 54-31-9.
The structural formula is as follows:
Lasix () Clinical Pharmacology
Investigations into the mode of action of Lasix () have utilized micropuncture studies in rats, stop flow experiments in dogs and various clearance studies in both humans and experimental animals. It has been demonstrated that Lasix () inhibits primarily the absorption of sodium and chloride not only in the proximal and distal tubules but also in the loop of Henle. The high degree of efficacy is largely due to the unique site of action. The action on the distal tubule is independent of any inhibitory effect on carbonic anhydrase and aldosterone.
Recent evidence suggests that furosemide glucuronide is the only or at least the major biotransformation product of furosemide in man. Furosemide is extensively bound to plasma proteins, mainly to albumin. Plasma concentrations ranging from 1 to 400 μg/mL are 91 to 99% bound in healthy individuals. The unbound fraction averages 2.3 to 4.1% at therapeutic concentrations.
The onset of diuresis following oral administration is within 1 hour. The peak effect occurs within the first or second hour. The duration of diuretic effect is 6 to 8 hours.
In fasted normal men, the mean bioavailability of furosemide from Lasix () Tablets and Lasix () Oral Solution is 64% and 60%, respectively, of that from an intravenous injection of the drug. Although furosemide is more rapidly absorbed from the oral solution (50 minutes) than from the tablet (87 minutes), peak plasma levels and area under the plasma concentration-time curves do not differ significantly. Peak plasma concentrations increase with increasing dose but times-to-peak do not differ among doses. The terminal half-life of furosemide is approximately 2 hours.
Significantly more furosemide is excreted in urine following the IV injection than after the tablet or oral solution. There are no significant differences between the two oral formulations in the amount of unchanged drug excreted in urine.
Lasix () Contraindications
Lasix () is contraindicated in patients with anuria and in patients with a history of hypersensitivity to furosemide.
Lasix () Warnings
In patients with hepatic cirrhosis and ascites, Lasix () 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, 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). (See )
Lasix () Precautions
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 potentiated.
Asymptomatic hyperuricemia can occur and gout may rarely be precipitated.
Patients allergic to sulfonamides may also be allergic to Lasix () . 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 Lasix () 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), CO, 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 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.
In premature infants Lasix () may precipitate nephrocalcinosis/nephrolithiasis, therefore renal function must be monitored and renal ultrasonography performed. (See )
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.
There is a risk of ototoxic effects if cisplatin and Lasix () are given concomitantly. 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 () 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 Lasix () , angiotensin converting enzyme inhibitors, or angiotensin receptor blockers may be necessary.
Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs.
Lasix () may decrease arterial responsiveness to norepinephrine. However, norepinephrine may still be used effectively.
Simultaneous administration of sucralfate and Lasix () tablets may reduce the natriuretic and antihypertensive effects of Lasix () . Patients receiving both drugs should be observed closely to determine if the desired diuretic and/or antihypertensive effect of Lasix () is achieved. The intake of Lasix () and sucralfate should be separated by at least two hours.
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. Use of Lasix () concomitantly with chloral hydrate is, therefore, not recommended.
Phenytoin interferes directly with renal action of Lasix () . There is evidence that treatment with phenytoin leads to decrease intestinal absorption of Lasix () , and consequently to lower peak serum furosemide concentrations.
Methotrexate and other drugs that, like Lasix () , undergo significant renal tubular secretion may reduce the effect of Lasix () . Conversely, Lasix () may decrease renal elimination of other drugs that undergo tubular secretion. High-dose treatment of both Lasix () and these other drugs may result in elevated serum levels of these drugs and may potentiate their toxicity as well as the toxicity of Lasix () .
Lasix () can increase the risk of cephalosporin-induced nephrotoxicity even in the setting of minor or transient renal impairment.
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. Patients receiving both indomethacin and Lasix () should be observed closely to determine if the desired diuretic and/or antihypertensive effect of Lasix () 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 when tested in the presence or absence of an 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 , but other studies on chromosomal aberrations in human cells 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 .
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).
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 arteriosus
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 and .)
Lasix () Adverse Reactions
Adverse reactions are categorized below by organ system and listed by decreasing severity.
Whenever adverse reactions are moderate or severe, Lasix () dosage should be reduced or therapy withdrawn.
Lasix () Overdosage
The principal signs and symptoms of overdose with Lasix () are dehydration, blood volume reduction, hypotension, electrolyte imbalance, hypokalemia and hypochloremic alkalosis, and are extensions of its diuretic action.
The acute toxicity of Lasix () has been determined in mice, rats and dogs. In all three, the oral LD exceeded 1000 mg/kg body weight, while the intravenous LD ranged from 300 to 680 mg/kg. The acute intragastric toxicity in neonatal rats is 7 to 10 times that of adult rats.
The concentration of Lasix () in biological fluids associated with toxicity or death is not known.
Treatment of overdosage is supportive and consists of replacement of excessive fluid and electrolyte losses. Serum electrolytes, carbon dioxide level and blood pressure should be determined frequently. Adequate drainage must be assured in patients with urinary bladder outlet obstruction (such as prostatic hypertrophy).
Hemodialysis does not accelerate furosemide elimination.
Lasix () How Supplied
Lasix () (furosemide) Tablets 20 mg are supplied as white, oval, monogrammed tablets in Bottles of 100 (NDC 0039-0067-10), and 1000 (NDC 0039-0067-70). The 20 mg tablets are imprinted with "Lasix () " on one side.
Lasix () Tablets 40 mg are supplied as white, round, monogrammed, scored tablets in Bottles of 100 (NDC 0039-0060-13), 500 (NDC 0039-0060-50), and 1000 (NDC 0039-0060-70). The 40 mg tablets are imprinted with "Lasix () 40" on one side.
Lasix () Tablets 80 mg are supplied as white, round, monogrammed, facetted edge tablets in Bottles of 50 (NDC 0039-0066-05) and 500 (NDC 0039-0066-50). The 80 mg tablets are imprinted with "Lasix () 80" on one side.
Lasix ()
Lasix () Principal Display Panel - Mg Bottle Label
Lasix () Principal Display Panel - Mg Bottle Label
Lasix () Principal Display Panel - Mg Bottle Label
