Furosemide Tablets, USP

WARNING

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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.)

DESCRIPTION

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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Furosemide is a diuretic which is an anthranilic acid derivative. Chemically, it is 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid. 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 structural formula is as follows: Furosemide is available in 20 mg, 40 mg and 80 mg tablets for oral administration. Inactive ingredients include lactose monohydrate, magnesium stearate, pregelatinized starch (corn) and starch (corn). Meets USP Dissolution Test 1.

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

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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.

WARNINGS

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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 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 )

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 toxic epidermal necrolysis
Stevens-Johnson Syndrome
erythema multiforme
drug rash with eosinophilia and systemic symptoms
acute generalized exanthematous pustulosis
exfoliative dermatitis
bullous pemphigoid
purpura
photosensitivity
rash
pruritis
urticaria 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

Repackaged by Aphena Pharma Solutions – TN. See Repackaging Information for available configurations.

Furosemide tablets, USP, for oral administration, are available as: 20 mg: round, white, scored tablets, debossed GG 21 on one side and plain on the reverse side, and supplied as: NDC 0781-1818-01 bottles of 100 NDC 0781-1818-05 bottles of 500 NDC 0781-1818-10 bottles of 1000 40 mg: round, white, scored tablets, debossed GG 201 on one side and plain on the reverse side, and supplied as: NDC 0781-1966-60 bottles of 60 NDC 0781-1966-01 bottles of 100 NDC 0781-1966-05 bottles of 500 NDC 0781-1966-10 bottles of 1000 80 mg: round, white, scored tablets, debossed GG 80 on one side and plain on the reverse side, and supplied as: NDC 0781-1446-01 bottles of 100 NDC 0781-1446-05 bottles of 500 Exposure to light might cause a slight discoloration. Discolored tablets should not be dispensed. Store at 20°-25°C (68°-77°F) (see USP Controlled Room Temperature). Dispense in a tight, light-resistant container.

Repackaging Information

id: c78e3959-61db-44b2-99f1-a807517b0653
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5

Please reference the How Supplied section listed above for a description of individual tablets or capsules. This drug product has been received by Aphena Pharma – TN in a manufacturer or distributor packaged configuration and repackaged in full compliance with all applicable cGMP regulations. The package configurations available from Aphena are listed below:

Count	40mg
30	67544-075-30
45	67544-075-45
60	67544-075-53
90	67544-075-60
180	67544-075-80
270	67544-075-92
360	67544-075-94

Count	20mg
30	43353-737-30
45	43353-737-45
60	43353-737-53
90	43353-737-60
180	43353-737-80
270	43353-737-92
360	43353-737-94

Store between 20°-25°C (68°-77°F). See USP Controlled Room Temperature. Dispense in a tight light-resistant container as defined by USP. Keep this and all drugs out of the reach of children. Repackaged by:

Cookeville, TN 38506

20140512SC

PRINCIPAL DISPLAY PANEL – 40mg

id: 16a294c9-efa5-4f14-b4d0-ac540bd67221
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

NDC 67544-075 – Furosemide 40mg – Rx Only