FUROSEMIDE INJECTION, USP, 10 mg/mL

WARNING

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displayName: BOXED WARNING SECTION
FDA Article Code: 34066-1

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

id: 6947af02-f4ea-7f9c-e053-2a91aa0a45cd
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 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: Furosemide 10 mg, 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.

CLINICAL PHARMACOLOGY

id: 6947af02-f4eb-7f9c-e053-2a91aa0a45cd
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

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 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 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.

Geriatric Population

id: 6947af02-f4ec-7f9c-e053-2a91aa0a45cd
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5

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 (60-70 years of age) is statistically significantly smaller than in younger healthy male subjects (20-35 years of age). The initial diuretic effect of furosemide in older subjects is decreased relative to younger subjects. (See
PRECAUTIONS: Geriatric Use .)

INDICATIONS AND USAGE

id: 6947af02-f4ed-7f9c-e053-2a91aa0a45cd
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

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

CONTRAINDICATIONS

id: 6947af02-f4ef-7f9c-e053-2a91aa0a45cd
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

id: 6947af02-f4f0-7f9c-e053-2a91aa0a45cd
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

id: 6947af02-f4fc-7f9c-e053-2a91aa0a45cd
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
Transient injection site pain following intramuscular injection
Fever Whenever adverse reactions are moderate or severe, furosemide dosage should be reduced or therapy withdrawn.

OVERDOSAGE

id: 6947af02-f4fd-7f9c-e053-2a91aa0a45cd
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 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.

HOW SUPPLIED

id: 6947af02-f504-7f9c-e053-2a91aa0a45cd
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Furosemide Injection, USP (10 mg/mL)

PRINCIPAL PANEL DISPLAY- 4 mL Vial Label

id: 69481572-42c7-68ea-e053-2a91aa0a0e98
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

Rx Only FUROSEMIDE

INJECTION, USP
40 mg/4 mL

(10 mg/mL)
FOR IV OR IM USE 4 mL SINGLE DOSE VIAL Manufactured for:

Claris Lifesciences Inc.

North Brunswick, NJ 08902

PRINCIPAL DISPLAY PANEL: OUTER PACKAGE LABEL

id: 69481572-42c9-68ea-e053-2a91aa0a0e98
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4