displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5
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 “DOSAGE AND ADMINISTRATION”.)
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Furosemide is a diuretic which is an anthranilic acid derivative. Furosemide is a white to slightly yellow odorless, crystalline powder. It is practically insoluble in water, sparingly soluble in alcohol, freely soluble in solutions of dilute alkali solutions and insoluble in dilute acids. Chemically, it is 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid with the following structural formula:Furosemide is available in 20 mg, 40 mg and 80 mg tablets for oral administration.The inactive ingredients include corn starch, lactose monohydrate, magnesium stearate, and microcrystalline cellulose.Tested by Dissolution Test 1.
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
Investigations into the mode of action of furosemide 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 furosemide 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 mcg/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 furosemide tablets is 64% of that from an intravenous injection of the drug. 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.
INDICATIONS AND USAGE
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Edema: Furosemide is indicated in adults and pediatric patients for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephritic syndrome. Furosemide is particularly useful when an agent with greater diuretic potential is desired.Hypertension: Oral furosemide 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 furosemide alone.
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Furosemide is contraindicated in patients with anuria and in patients with a history of hypersensitivity to furosemide.
displayName: WARNINGS SECTION
FDA Article Code: 34071-1
In patients with hepatic cirrhosis and ascites, furosemide 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, furosemide should be discontinued.Cases of tinnitus and reversible or irreversible hearing impairment have been reported. Usually, reports indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, doses exceeding several times the usual recommended dose, 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 furosemide per minute has been used).
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
Adverse reactions are categorized below by organ system and listed by decreasing severity.Gastrointestinal System Reactions
Systemic Hypersensitivity Reactions
||4. oral and gastric irritation
|2. jaundice (intrahepatic
Central Nervous System Reactions
|1. systemic vasculitis
||2. interstitial nephritis
||3. necrotizing angiitis
|1. tinnitus and hearing loss
||6. blurred vision
|1. aplastic anemia (rare)
||3. agranulocytosis (rare)
||4. hemolytic anemia
Cardiovascular ReactionOrthostatic hypotension may occur and be aggravated by alcohol, barbiturates or narcotics.Other Reactions
|1. exfoliative dermatitis
|2. erythema multiforme
Whenever adverse reactions are moderate or severe, furosemide dosage should be reduced or therapy withdrawn.
||4. muscle spasm
||7. urinary bladder spasm
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
The principal signs and symptoms of overdose with furosemide are dehydration, blood volume reduction, hypotension, electrolyte imbalance, hypokalemia and hypochloremic alkalosis, and are extensions of its diuretic action.The acute toxicity of furosemide has been determined in mice, rats and dogs. In all three, the oral LD50 exceeded 1000 mg/kg body weight, while the intravenous LD50 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 furosemide 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.
DOSAGE AND ADMINISTRATION
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
EdemaTherapy should be individualized according to patient response to gain maximal therapeutic response and to determine the minimal dose needed to maintain that response.Adults: The usual initial dose of furosemide is 20 to 80 mg given as a single dose. Ordinarily a prompt diuresis ensues. If needed, the same dose can be administered 6 to 8 hours later or the dose may be increased. The dose may be raised by 20 or 40 mg and given not sooner than 6 to 8 hours after the previous dose until the desired diuretic effect has been obtained. The individually determined single dose should then be given once or twice daily (e.g., at 8 am and 2 pm). The dose of furosemide may be carefully titrated up to 600 mg/day in patients with clinically severe edematous states.Edema may be most efficiently and safely mobilized by giving furosemide tablets on 2 to 4 consecutive days each week.When doses exceeding 80 mg/day are given for prolonged periods, careful clinical observation and laboratory monitoring are particularly advisable. (See PRECAUTIONS: Laboratory Tests.)Pediatric Patients: The usual initial dose of oral furosemide in pediatric patients is 2 mg/kg body weight, given as a single dose. If the diuretic response is not satisfactory after the initial dose, dosage may be increased by 1 or 2 mg/kg no sooner than 6 to 8 hours after the previous dose. Doses greater than 6 mg/kg body weight are not recommended. For maintenance therapy in pediatric patients, the dose should be adjusted to the minimum effective level. For ease of administration, and to allow maximum flexibility in dosing, the use of Furosemide Oral Solution is suggested.HypertensionTherapy should be individualized according to the patient’s response to gain maximal therapeutic response and to determine the minimal dose needed to maintain the therapeutic response.Adults: The usual initial dose of furosemide for hypertension is 80 mg, usually divided into 40 mg twice a day. Dosage should then be adjusted according to response. If response is not satisfactory, add other antihypertensive agents.Changes in blood pressure must be carefully monitored when furosemide is used with other antihypertensive drugs, especially during initial therapy. To prevent excessive drop in blood pressure, the dosage of other agents should be reduced by at least 50% when furosemide is added to the regimen. As the blood pressure falls under the potentiating effect of furosemide, a further reduction in dosage or even discontinuation of other antihypertensive drugs may be necessary.
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Furosemide Tablets 20 mg are supplied as white, round unscored tablets, debossed WATSON 300 on one side in bottles of 100 and 1000.Furosemide Tablets 40 mg are supplied as white, round, scored tablets debossed WATSON 301 on one side in bottles of 100 and 1000.Furosemide Tablets 80 mg are supplied as white, round, scored tablets debossed WATSON 302 on one side in bottles of 100 and 500.Note: Dispense in a tight, light-resistant container, as defined in USP, with child-resistant closure. Exposure to light might cause a slight discoloration. Discolored tablets should not be dispensed.Store at controlled room temperature: 20°-25°C (68°-77°F). [See USP.] Protect from light.Watson Laboratories, Inc.
Corona, CA 92880 USA10055-13
Revised: September 2005