Lasix Description

Lasix®is a diuretic which is an anthranilicacid derivative. Lasix tablets for oral administration containfurosemide as the active ingredient and the following inactiveingredients: lactose monohydrate NF, magnesium stearate NF, starch NF,talc USP, and colloidal silicon dioxide NF. Chemically, it is4-chloro-N-furfuryl-5-sulfamoylanthranilic acid. Lasix is available aswhite tablets for oral administration in dosage strengths of 20, 40 and80 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.

Lasix - Clinical Pharmacology

Investigations into the mode of action of Lasix have utilizedmicropuncture studies in rats, stop flow experiments in dogs andvarious clearance studies in both humans and experimental animals. Ithas been demonstrated that Lasix inhibits primarily the absorption ofsodium and chloride not only in the proximal and distal tubules butalso in the loop of Henle. The high degree of efficacy is largely dueto the unique site of action. The action on the distal tubule isindependent of any inhibitory effect on carbonic anhydrase andaldosterone.

Recent evidence suggests that furosemide glucuronide is the only orat 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% boundin healthy individuals. The unbound fraction averages 2.3 to 4.1% attherapeutic concentrations.

The onset of diuresis following oral administration is within 1hour. The peak effect occurs within the first or second hour. Theduration of diuretic effect is 6 to 8 hours.

In fasted normal men, the mean bioavailability of furosemide fromLasix Tablets and Lasix Oral Solution is 64% and 60%, respectively, ofthat from an intravenous injection of the drug. Although furosemide ismore rapidly absorbed from the oral solution (50 minutes) than from thetablet (87 minutes), peak plasma levels and area under the plasmaconcentration-time curves do not differ significantly. Peak plasmaconcentrations increase with increasing dose but times-to-peak do notdiffer among doses. The terminal half-life of furosemide isapproximately 2 hours.

Significantly more furosemide is excreted in urine following the IVinjection than after the tablet or oral solution. There are nosignificant differences between the two oral formulations in the amountof unchanged drug excreted in urine.

Geriatric Population

Furosemide binding to albumin may be reduced in elderly patients.Furosemide is predominantly excreted unchanged in the urine. The renalclearance of furosemide after intravenous administration in olderhealthy male subjects (60–70 years of age) is statisticallysignificantly smaller than in younger healthy male subjects (20–35years of age). The initial diuretic effect of furosemide in oldersubjects is decreased relative to younger subjects. 

Indications and Usage for Lasix

Edema

Lasix is indicated in adults and pediatric patients for the treatment of edema associated with congestive heartfailure, cirrhosis of the liver, and renal disease, including thenephrotic syndrome. Lasix is particularly useful when an agent withgreater diuretic potential is desired.

Hypertension

Oral Lasix may be used in adults for the treatment of hypertensionalone or in combination with other antihypertensive agents.Hypertensive patients who cannot be adequately controlled withthiazides will probably also not be adequately controlled with Lasixalone.

Contraindications

Lasix is contraindicated in patients with anuria and in patients with a history of hypersensitivity to furosemide.

Warnings

In patients with hepatic cirrhosis and ascites, Lasix therapy isbest initiated in the hospital. In hepatic coma and in states ofelectrolyte depletion, therapy should not be instituted until the basiccondition is improved. Sudden alterations of fluidand electrolyte balance in patients with cirrhosis may precipitatehepatic coma; therefore, strict observation is necessary during theperiod of diuresis. Supplemental potassium chloride and, if required,an aldosterone antagonist are helpful in preventing hypokalemia andmetabolic 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 impairmenthave been reported. Usually, reports indicate that Lasix ototoxicity isassociated with rapid injection, severe renal impairment, dosesexceeding several times the usual recommended dose, or concomitanttherapy with aminoglycoside antibiotics, ethacrynic acid, or otherototoxic drugs. If the physician elects to use high dose parenteraltherapy, controlled intravenous infusion is advisable (for adults, aninfusion rate not exceeding 4 mg Lasix per minute has been used).

Precautions

General

Excessive diuresis may cause dehydration and blood volume reductionwith circulatory collapse and possibly vascular thrombosis andembolism, particularly in elderly patients. As with any effectivediuretic, electrolyte depletion may occur during Lasix therapy,especially in patients receiving higher doses and a restricted saltintake. Hypokalemia may develop with Lasix, especially with briskdiuresis, inadequate oral electoletyintake, when cirrhosis is present, or during concomitant use ofcorticosteroids or ACTH. Digitalis therapy may exaggerate metaboliceffects of hypokalemia, especially myocardial effects.

All patients receiving Lasix therapy should be observed for thesesigns 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 asnausea and vomiting. Increases in blood glucoseand alterations in glucose tolerance tests (with abnormalities of thefasting 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 Lasix. Thepossibility exists of exacerbation or activation of systemic lupuserythematosus.

As with many other drugs, patients should be observed regularly forthe possible occurrence of blood dyscrasias, liver or kidney damage, orother idiosyncratic reactions.

Information for Patients

Patients receiving Lasix should be advised that they may experiencesymptoms from excessive fluid and/or electrolyte losses. The posturalhypotension that sometimes occurs can usually be managed by getting upslowly. Potassium supplements and/or dietary measures may be needed tocontrol or avoid hypokalemia.

Patients with diabetes mellitus should be told that furosemide mayincrease 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.

Overdosage

The principal signs and symptoms of overdose with Lasix aredehydration, blood volume reduction, hypotension, electrolyteimbalance, hypokalemia and hypochloremic alkalosis, and are extensionsof its diuretic action.

The acute toxicity of Lasix has been determined in mice, rats and dogs. In all three, the oral LD50exceeded 1000 mg/kg body weight, while the intravenous LD50ranged 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 ofexcessive fluid and electrolyte losses. Serum electrolytes, carbondioxide 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.