FUROSEMIDE TABLETS, USP Rx only

SPL UNCLASSIFIED SECTION

SPL UNCLASSIFIED SECTION

WARNING 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 ).

DESCRIPTION

DESCRIPTION SECTION

Furosemide is a diuretic which is an anthranilic acid derivative. Furosemide tablets, USP for oral administration contain furosemide, USP as the active ingredient and the following inactive ingredients: corn starch, lactose monohydrate, magnesium stearate, pregelatinized starch, and sodium starch glycolate. Chemically, it is 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid. Furosemide , USP is available as white to off white round tablets for oral administration in dosage strengths of 20, 40 and 80 mg. Furosemide, USP is a white to slightly yellow odorless crystalline powder. It is practically insoluble in water, soluble in 15 parts of acetone, freely soluble in dimethylformamide and in solution of alkali hydroxides; soluble in methanol; sparingly soluble in alcohol; very slightly soluble in chloroform. The CAS Registry Number is 54-31-9. It has a molecular formula of C 12 H 11 ClN 2 O 5 S and a molecular weight of 330.75. The molecular structure is as follows: Tested by USP Dissolution Test 1

CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

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 mcg/mL 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 and furosemide 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.

INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

Furosemide tablets are contraindicated in patients with anuria and in patients with a history of hypersensitivity to furosemide.

WARNINGS

WARNINGS SECTION

In patients with hepatic cirrhosis and ascites, furosemide tablets 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 tablets should be discontinued. 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. 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) (see PRECAUTIONS: Drug Interactions ) .

PRECAUTIONS

PRECAUTIONS SECTION

ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

Adverse reactions are categorized below by organ system and listed by decreasing severity.

OVERDOSAGE

OVERDOSAGE SECTION

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 LD 50 exceeded 1000 mg/kg body weight, while the intravenous LD 50 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

DOSAGE & ADMINISTRATION SECTION

HOW SUPPLIED

HOW SUPPLIED SECTION

Furosemide tablets, USP 20 mg, 40 mg and 80 mg are supplied as white to off-white, round tablets. 40 mg tablets and 80 mg tablets have functional scoring. Furosemide tablets, USP 20 mg are debossed with 'RE22' on one side and plain on the other side and are supplied as follows: NDC 83980-002-97 Bottles of 10 NDC 83980-002-01 Bottles of 100 NDC 83980-002-10 Bottles of 1,000 Furosemide tablets, USP 40 mg are debossed with 'RE23' on one side and break-line on the other side and are supplied as follows: NDC 83980-003-97 Bottles of 10 NDC 83980-003-01 Bottles of 100 NDC 83980-003-10 Bottles of 1,000 Furosemide tablets, USP 80 mg are debossed with 'RE24' on one side and break-line on the other side and are supplied as follows: NDC 83980-004-97 Bottles of 10 NDC 83980-004-01 Bottles of 100 NDC 83980-004-05 Bottles of 500 NDC 83980-004-10 Bottles of 1,000 Note: Dispense in well-closed, light-resistant containers. Exposure to light might cause a slight discoloration. Discolored tablets should not be dispensed Store at 20°C to 25°C (68°F to 77°F); [See USP Controlled Room Temperature]. Protect from light.

SPL UNCLASSIFIED SECTION

SPL UNCLASSIFIED SECTION

Distributed by: Unichem Pharmaceuticals (USA), Inc. East Brunswick, NJ 08816, USA July 2024 IBZZN4