FUROSEMIDE
INJECTION, USP
10 mg/mL

Rx Only

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".)

Furosemide is a diuretic which is an anthranilic acid derivative.

Chemically, it is 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid.

Furosemide Injection 10 mg/mL is a sterile, non-pyrogenic solution in vials for intravenous and intramuscular injection.

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:

Each mL contains: 10 mg Furosemide, Water for Injection q.s., Sodium Chloride for isotonicity, Sodium Hydroxide and, if necessary, Hydrochloric Acid to adjust pH between 8.0 and 9.3.

Investigations into the mode of action of furosemide have utilized micropuncture studies is 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 reabsorption 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 this 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 μg/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 intravenous administration is within 5 minutes and somewhat later after intramuscular administration. The peak effect occurs within the first half hour. The duration of diuretic effect is approximately 2 hours.

In fasted normal men, the mean bioavailability of furosemide from furosemide tablets and furosemide oral solution is approximately 60% of that from an intravenous injection of the drug. Although furosemide is more rapidly absorbed from the oral solution than from the tablet, 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 intravenous 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.

Parenteral therapy should be reserved for patients unable to take oral medication or for patients in emergency clinical situations.

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

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).

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

Gastrointestinal System Reactions

• Pancreatitis
• Jaundice (intrahepatic cholestatic jaundice)
• Anorexia
• Oral and gastric irritation
• Cramping
• Diarrhea
• Constipation
• Nausea
• Vomiting

Systemic Hypersensitivity Reactions

• 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 (rare)
• Thrombocytopenia
• Agranulocytosis (rare)
• Hemolytic anemia
• Leukopenia
• Anemia

Dermatologic-Hypersensitivity Reactions

• Exfoliative dermatitis
• Erythema multiforme
• Purpura
• Photosensitivity
• Urticaria
• Rash
• Pruritus

Cardiovascular Reaction

Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates or narcotics.

Other Reactions

• Hyperglycemia
• Glycosuria
• Hyperuricemia
• Muscle spasm
• Weakness
• Restlessness
• Urinary bladder spasm
• Thrombophlebitis
• Transient injection site pain following intramuscular injection
• Fever

Whenever adverse reactions are moderate or severe, furosemide dosage should be reduced or therapy withdrawn.

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.

Furosemide Injection, USP (10 mg/mL)

Do not use if solution is discolored.
Store at controlled room temperature 15°-30°C (59°-86°F) (See USP).
Protect from light.

IN5702
Rev. 4/01
MG #7822

AMERICAN
REGENT
LABORATORIES, INC.
SHIRKEY, NY 11967