WARNING
id: c4fcb0ba-7baf-46a4-be21-925f4c427032
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
id: 1a737640-642d-4691-8253-ecf075389b82
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 USP, 10 mg/mL is a sterile, non-pyrogenic solution in vials for intravenous and intramuscular injection.
Furosemide, USP is a white to slightly yellow 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:
Molecular Formula: C12H11ClN2O5S
Molecular Weight: 330.74
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.
CLINICAL PHARMACOLOGY
id: 0af26152-cbdb-4a8c-9808-c62ce6553d3d
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 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.
INDICATIONS AND USAGE
id: 1665d870-9c1f-46ca-8c08-2324d0539280
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: 1ce749ac-2333-4aa9-a2c1-d495af5678a2
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: a8ecd5ec-87b1-4e29-8b5b-611367c801c5
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 arenter. 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 arenteral 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: 0df6a931-bce0-4b0a-809a-a55350684816
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
|
|
| 1. Hepatic encephalopathy in patients with
|
6. Oral and gastric irritation
|
| hepatocellular insufficiency
|
7. Cramping
|
| 2. Pancreatitis
|
8. Diarrhea
|
| 3. Jaundice (intrahepatic cholestatic jaundice)
|
9. Constipation
|
| 4. Increased liver enzymes
|
10. Nausea
|
| 5. Anorexia
|
11. Vomiting
|
Systemic
Hypersensitivity
Reactions
|
|
| 1. Severe anaphylactic or anaphylactoid
|
3. Interstitial nephritis
|
| reactions (e.g. with shock)
|
4. Necrotizing angiitis
|
| 2. Systemic vasculitis
|
|
Central
Nervous
System
Reactions
|
|
| 1. Tinnitus and hearing loss
|
5. Headache
|
| 2. Paresthesias
|
6. Blurred vision
|
| 3. Vertigo
|
7. Xanthopsia
|
| 4. Dizziness
|
|
Hematologic
Reactions
|
|
| 1. Aplastic anemia
|
5. Leukopenia
|
| 2. Thrombocytopenia
|
6. Anemia
|
| 3. Agranulocytosis
|
7. Eosinophilia
|
| 4. Hemolytic anemia
|
|
Dermatologic
–
Hypersensitivity
Reactions
|
|
| 1. Exfoliative dermatitis
|
6. Urticaria
|
| 2. Bullous pemphigoid
|
7. Rash
|
| 3. Erythema multiforme
|
8. Pruritus
|
| 4. Purpura
|
9. Stevens-Johnson Syndrome
|
| 5. Photosensitivity
|
10. Toxic epidermal necrolysis
|
Cardiovascular Reaction
1 Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates or narcotics.
2. Increase in cholesterol and triglyceride serum levels.
Other
Reactions
|
|
| 1. Hyperglycemia
|
7. Urinary bladder spasm
|
| 2. Glycosuria
|
8. Thrombophlebitis
|
| 3. Hyperuricemia
|
9. Transient injection site pain following
|
| 4. Muscle spasms
|
intramuscular injection
|
| 5. Weakness
|
10. Fever
|
| 6. Restlessness
|
|
Whenever adverse reactions are moderate or severe, furosemide dosage should be reduced or therapy withdrawn.
OVERDOSAGE
id: c79403fd-be8f-4892-9021-cbc94e6384a7
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
id: 4c0e5bdd-33b1-48ac-b368-f69ad5b7b542
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Furosemide injection, USP (10 mg/mL)
| 2 mL single dose amber colored vials
|
Boxes of 25
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NDC 64679-759-01
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| 2 mL single dose amber colored vials
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Boxes of 10
|
NDC 64679-759-07
|
| 2 mL single dose amber colored vials
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Box of 1
|
NDC 64679-759-04
|
|
|
|
|
| 4 mL single dose amber colored vials
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Boxes of 25
|
NDC 64679-759-02
|
| 4 mL single dose amber colored vials
|
Boxes of 10
|
NDC 64679-759-08
|
| 4 mL single dose amber colored vials
|
Box of 1
|
NDC 64679-759-05
|
|
|
|
|
| 10 mL single dose amber colored vials
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Boxes of 25
|
NDC 64679-759-03
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| 10 mL single dose amber colored vials
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Boxes of 10
|
NDC 64679-759-09
|
| 10 mL single dose amber colored vials
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Box of 1
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NDC 64679-759-06
|
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
id: 8141077c-ba9c-4996-929c-05289a201a4a
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
2 mL Vial Label
DRUG: Furosemide
GENERIC: Furosemide
DOSAGE: Injection
ADMINSTRATION: Intramuscular or Intravenous
NDC: 64679-759-99
STRENGTH: 10 mg per mL
QTY: 2 mL Single Dose Vial
4 mL Vial Label
DRUG: Furosemide
GENERIC: Furosemide
DOSAGE: Injection
ADMINSTRATION: Intramuscular or Intravenous
NDC: 64679-759-88
STRENGTH: 10 mg per mL
QTY: 4 mL Single Dose Vial
10 mL Vial Label
DRUG: Furosemide
GENERIC: Furosemide
DOSAGE: Injection
ADMINSTRATION: Intramuscular or Intravenous
NDC: 64679-759-77
STRENGTH: 10 mg per mL
QTY: 10 mL Single Dose Vial
