FUROSEMIDE TABLETS USP

DESCRIPTION

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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

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 C₁₂H₁₁ClN₂O₅S and a molecular weight of 330.75. The molecular structure is as follows:

CLINICAL PHARMACOLOGY

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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 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.

CONTRAINDICATIONS

id: 279df64d-71ff-4649-871c-552b7ce2458b
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

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

WARNINGS

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displayName: WARNINGS SECTION
FDA Article Code: 34071-1

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 PRECAUCTIONS: Drug Interactions ).

ADVERSE REACTIONS

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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 hepatic encephalopathy in patients with hepatocellular insufficiency
pancreatitis
jaundice (intrahepatic cholestatic jaundice)
increased liver enzymes
anorexia
oral and gastric irritation
cramping
diarrhea
constipation
nausea
vomiting Systemic Hypersensitivity Reactions severe anaphylactic or anaphylactoid reactions (e.g. with shock)
systemic vasculitis
interstitial nephritis
necrotizing angiitis Central Nervous System Reactions tinnitus and hearing loss
paresthesias
vertigo
dizziness
headache
blurred vision
xanthopsia Hematologic Reactions aplastic anemia
thrombocytopenia
agranulocytosis
hemolytic anemia
leukopenia
anemia
eosinophilia Dermatologic-Hypersensitivity Reactions exfoliative dermatitis
bullous pemphigoid
erythema multiforme
purpura
photosensitivity
urticaria
rash
pruritus
Stevens-Johnson Syndrome
toxic epidermal necrolysis Cardiovascular Reaction Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates or narcotics.
Increase in cholesterol and triglyceride serum levels Other Reactions hyperglycemia
glycosuria
hyperuricemia
muscle spasm
weakness
restlessness
urinary bladder spasm
thrombophlebitis
fever Whenever adverse reactions are moderate or severe, furosemide dosage should be reduced or therapy withdrawn.

OVERDOSAGE

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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.

HOW SUPPLIED

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displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Furosemide tablets, USP 20 mg, 40 mg and 80 mg are supplied as white to off-white, round tablets. Furosemide tablets, USP 20 mg are debossed with ‘RE22’ on one side and plain on the other side and are supplied as follows: NDC 50742-104-01           Bottles of 100 NDC 50742-104-10           Bottles of 1000 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 50742-105-01           Bottles of 100 NDC 50742-105-10           Bottles of 1000 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 50742-106-01           Bottles of 100 NDC 50742-106-05           Bottles of 500 Note: Dispense in well-closed, light-resistant containers. Exposure to light might cause a slight discoloration. Discolored tablets should not be dispensed. Tested by USP Dissolution Test 1 Store at 20 – 25° C (68 – 77° F) [See USP Controlled Room Temperature]. You may report side effects to FDA at 1-800-FDA-1088. Manufactured for: Ingenus Pharmaceuticals, LLC
4190 Millenia Boulevard
Orlando, FL 32839-6408
Customer complaint toll free number : 877-748-1970 by: Ipca Laboratories Limited
48, Kandivli Ind. Estate, Mumbai 400 067, India. January 2011 Repackaged by:

Contract Pharmacy Services-PA
125 Titus Ave Suite 200
Warrington, PA 18976 USA Original–12/2011–NJW

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL

id: a5447935-1de6-47e7-85dc-10d0328de5b5
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4