furosemide 40 MG in 4 ML Injection
WARNINGS
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).
Pediatric Use: In premature neonates with respiratory distress syndrome, diuretic treatment with furosemide in the first few weeks of life may increase the risk of persistent patent ductus arteriosus (PDA), possibly through a prostaglandin-E-mediated process.
Literature reports indicate that premature infants with post conceptual age (gestational plus postnatal) less than 31 weeks receiving doses exceeding 1 mg/kg/24 hours may develop plasma levels which could be associated with potential toxic effects including ototoxicity.
Hearing loss in neonates has been associated with the use of furosemide injection (see ).
DRUG INTERACTIONS
Drug Interactions: Furosemide may increase the ototoxic potential of aminoglycoside antibiotics, especially in the presence of impaired renal function.
Except in life-threatening situations, avoid the combination.
Furosemide should not be used concomitantly with ethacrynic acid because of the possibility of ototoxicity.
Patients receiving high doses of salicylates concomitantly with furosemide, as in rheumatic diseases, may experience salicylate toxicity at lower doses because of competitive renal excretory sites.
Furosemide has a tendency to antagonize the skeletal muscle relaxing effect of tubocurarine and may potentiate the action of succinylcholine.
Lithium generally should not be given with diuretics because they reduce lithium’s renal clearance and add a high risk of lithium toxicity.
Furosemide may add to or potentiate the therapeutic effect of other antihypertensive drugs.
Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs.
Furosemide may decrease arterial responsiveness to norepinephrine.
However, norepinephrine may still be used effectively.
One study in six subjects demonstrated that the combination of furosemide and acetylsalicylic acid temporarily reduced creatinine clearance in patients with chronic renal insufficiency.
There are case reports of patients who developed increased BUN, serum creatinine and serum potassium levels, and weight gain when furosemide was used in conjunction with NSAIDs.
Literature reports indicate that coadministration of indomethacin may reduce the natriuretic and antihypertensive effects of furosemide in some patients by inhibiting prostaglandin synthesis.
Indomethacin may also affect plasma renin levels, aldosterone excretion, and renin profile evaluation.
Patients receiving both indomethacin and furosemide should be observed closely to determine if the desired diuretic and/or antihypertensive effect of furosemide is achieved.
OVERDOSAGE
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.
DESCRIPTION
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.
Furosemide Structural Formula
HOW SUPPLIED
Product: 63739-464
INDICATIONS AND USAGE
Parenteral therapy should be reserved for patients unable to take oral medication or for patients in emergency clinical situations.
Edema: Furosemide 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.
Furosemide is indicated as adjunctive therapy in acute pulmonary edema.
The intravenous administration of furosemide is indicated when a rapid onset of diuresis is desired, e.g., in acute pulmonary edema.
If gastrointestinal absorption is impaired or oral medication is not practical for any reason, furosemide is indicated by the intravenous or intramuscular route.
Parenteral use should be replaced with oral furosemide as soon as practical.
PEDIATRIC USE
Pediatric Use: Renal calcifications (from barely visible on x-ray to staghorn) have occurred in some severely premature infants treated with intravenous furosemide for edema due to patent ductus arteriosus and hyaline membrane disease.
The concurrent use of chlorothiazide has been reported to decrease hypercalcinuria and dissolve some calculi.
PREGNANCY
Pregnancy: Teratogenic Effects: Pregnancy Category C.
Furosemide has been shown to cause unexplained maternal deaths and abortions in rabbits at 2, 4, and 8 times the maximal recommended human oral dose.
There are no adequate and well-controlled studies in pregnant women.
Furosemide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
The effects of furosemide on embryonic and fetal development and on pregnant dams were studied in mice, rats and rabbits.
Furosemide caused unexplained maternal deaths and abortions in the rabbit at the lowest dose of 25 mg/kg (2 times the maximal recommended human oral dose of 600 mg/day).
In another study, a dose of 50 mg/kg (4 times the maximal recommended human oral dose of 600 mg/day) also caused maternal deaths and abortions when administered to rabbits between Days 12 and 17 of gestation.
In a third study, none of the pregnant rabbits survived an oral dose of 100 mg/kg.
Data from the above studies indicate fetal lethality that can precede maternal deaths.
The results of the mouse study and one of the three rabbit studies also showed an increased incidence and severity of hydronephrosis (distention of the renal pelvis and, in some cases, of the ureters) in fetuses derived from treated dams as compared with the incidence of fetuses from the control group.
NUSRING MOTHERS
Nursing Mothers: Because it appears in breast milk, caution should be exercised when furosemide is administered to a nursing mother.
BOXED WARNING
WARNING 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” .)
INFORMATION FOR PATIENTS
Information for Patients: Patients receiving furosemide should be advised that they may experience symptoms from excessive fluid and/or electrolyte losses.
The postural hypotension that sometimes occurs can usually be managed by getting up slowly.
Potassium supplements and/or dietary measures may be needed to control or avoid hypokalemia.
Patients with diabetes mellitus should be told that furosemide may increase blood glucose levels and thereby affect urine glucose tests.
The skin of some patients may be more sensitive to the effects of sunlight while taking furosemide.
Hypertensive patients should avoid medications that may increase blood pressure, including over-the-counter products for appetite suppression and cold symptoms.
DOSAGE AND ADMINISTRATION
Adults: Parenteral therapy with Furosemide Injection should be used only in patients unable to take oral medication or in emergency situations and should be replaced with oral therapy as soon as practical.
Edema The usual initial dose of furosemide is 20 to 40 mg given as a single dose, injected intramuscularly or intravenously.
The intravenous dose should be given slowly (1 to 2 minutes).
Ordinarily a prompt diuresis ensues.
If needed, another dose may be administered in the same manner 2 hours later or the dose may be increased.
The dose may be raised by 20 mg and given not sooner than 2 hours after the previous dose until the desired diuretic effect has been obtained.
This individually determined single dose should then be given once or twice daily.
Therapy should be individualized according to patient response to gain maximal therapeutic response and to determine the minimal dose needed to maintain that response.
Close medical supervision is necessary.
If the physician elects to use high dose parenteral therapy, add the furosemide to either Sodium Chloride Injection USP, Lactated Ringer’s Injection USP, or Dextrose (5%) Injection USP after pH has been adjusted to above 5.5, and administer as a controlled intravenous infusion at a rate not greater than 4 mg/min.
Furosemide Injection is a buffered alkaline solution with a pH of about 9 and drug may precipitate at pH values below 7.
Care must be taken to ensure that the pH of the prepared infusion solution is in the weakly alkaline to neutral range.
Acid solutions, including other parenteral medications (e.g., labetalol, ciprofloxacin, amrinone, milrinone) must not be administered concurrently in the same infusion because they may cause precipitation of the furosemide.
In addition, furosemide injection should not be added to a running intravenous line containing any of these acidic products.
Acute Pulmonary Edema The usual initial dose of furosemide is 40 mg injected slowly intravenously (over 1 to 2 minutes).
If a satisfactory response does not occur within 1 hour, the dose may be increased to 80 mg injected slowly intravenously (over 1 to 2 minutes).
If necessary, additional therapy (e.g., digitalis, oxygen) may be administered concomitantly.
Pediatric Patients: Parenteral therapy should be used only in patients unable to take oral medication or in emergency situations and should be replaced with oral therapy as soon as practical.
The usual initial dose of Furosemide Injection (intravenously or intramuscularly) in pediatric patients is 1 mg/kg body weight and should be given slowly under close medical supervision.
If the diuretic response to the initial dose is not satisfactory, dosage may be increased by 1 mg/kg not sooner than 2 hours after the previous dose, until the desired diuretic effect has been obtained.
Doses greater than 6 mg/kg body weight are not recommended.
Literature reports suggest that the maximum dose for premature infants should not exceed 1 mg/kg/day (see WARNINGS, Pediatric Use ).
Furosemide Injection should be inspected visually for particulate matter and discoloration before administration.