DESCRIPTION:
id: c32550fc-44f6-4950-9498-e3d0dd25f186
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 slightly yellow, odorless, crystalline powder. Practically insoluble in water; freely soluble in acetone, in dimethylformamide, and in solutions of alkali hydroxides; soluble in methanol; sparingly soluble in alcohol; slightly soluble in ether; very slightly soluble in chloroform.
The structural formula is as follows:
Furosemide Injection, USP is a sterile, nonpyrogenic solution of furosemide in Water for Injection prepared with the aid of sodium hydroxide for intramuscular (IM) or intravenous (IV) use.
Each mL contains: Furosemide 10 mg; Water for Injection q.s.; sodium chloride to adjust isotonicity; sodium hydroxide and if necessary hydrochloric acid to adjust pH between 8.0 and 9.3.
CLINICAL PHARMACOLOGY:
id: e6b9032d-3097-4c1a-8557-1c1280bad57b
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 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 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 IV administration is within five minutes and somewhat later after IM administration. The peak effect occurs within the first half hour. The duration of diuretic effect is approximately two hours.
In fasted normal men, the mean bioavailability of furosemide from tablets and 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 two 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.
INDICATIONS AND USAGE:
id: 2ded724f-9f62-4789-b638-5c8a820d25f5
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: 5bd81ec4-fd0b-4117-b980-1ddea4897984
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: 972fbdb1-b577-4c5e-b5cd-77ce3ae1b4ba
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: 8ae5cc39-a900-4f10-af70-ef9f1f0884e9
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
Adverse reactions are categorized below by organ system and listed by decreasing severity.
OVERDOSAGE:
id: b80afa6c-db88-4c37-9bad-0de80eb51b34
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 1,000 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:
id: 5617755f-0882-4005-8ef0-8fda78d3281b
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Furosemide injection, USP
Product
No.
|
NDC
No.
|
Strength
|
Volume
|
PRX28002
|
63323-280-16
|
20 mg per 2 mL
(10 mg per mL)
|
2 mL in a 2 mL amber vial.
|
| PRX28004
|
63323-280-26
|
40 mg per 4 mL
(10 mg per mL)
|
4 mL in a 5 mL amber vial.
|
PRX28010
|
63323-280-36
|
100 mg per 10 mL
(10 mg per mL)
|
10 mL in a 10 mL amber vial.
|
2 mL, 4 mL and 10 mL sizes are single dose vials, packaged 25 vials per tray.
Preservative Free.
Discard unused portion.
Use only if solution is clear and seal intact.
PROTECT FROM LIGHT. Do not use if solution is discolored.
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
