Furosemide Tablets, USP, Rx only

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. 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  40 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 C₁₂H₁₁C_lN₂O₅S and a molecular weight of 330.75. Tested by USP Dissolution Test 1 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. Geriatric Population Furosemide binding to albumin may be reduced in elderly patients. Furosemide is predominantly excreted unchanged in the urine.  The renal clearance of furosemide after intravenous administration in older healthy male subjects (60 to 70 years of age) is statistically significantly smaller than in younger healthy male subjects (20 to 35 years of age). The initial diuretic effect of furosemide in older subjects is decreased relative to younger subjects. (PRECAUTIONS: Geriatric Use.)

INDICATIONS AND USAGE

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displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Edema Furosemide tablets, USP 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 nephrotic syndrome. Furosemide is particularly useful when an agent with greater diuretic potential is desired. Hypertension Furosemide tablets, USP 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.

CONTRAINDICATIONS

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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 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.

DOSAGE AND ADMINISTRATION

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displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Edema Therapy 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 tablets, USP 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 tablets, USP 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, USP 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) Geriatric patients — In general, dose selection for the elderly patient should be cautious, usually starting at the low end of the dosing range (see PRECAUTIONS: Geriatric Use). Pediatric patients — The usual initial dose of furosemide tablets, USP 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. Hypertension Therapy 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 tablets, USP 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 tablets, USP are 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 percent when furosemide tablets, USP are added to the regimen. As the blood pressure falls under the potentiating effect of furosemide tablets, USP a further reduction in dosage or even discontinuation of other antihypertensive drugs may be necessary. Geriatric patients — In general, dose selection and dose adjustment for the elderly patient should be cautious, usually starting at the low end of the dosing range (see PRECAUTIONS: Geriatric Use).

HOW SUPPLIED

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

Furosemide tablets, USP 40 mg are supplied as white to off-white, round tablets. 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 58517-400-30          Bottles of 30 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 – 25°C (68 – 77°F) [See USP Controlled Room Temperature]. You may report side effects to FDA at 1-800-FDA-1088. Distributed by:
New Horizon Rx Group, LLC
Kenner, LA 70062 Manufactured by:
Ipca Laboratories Limited
48, Kandivli Ind. Estate, Mumbai 400 067, India. Rev. 11/13

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4