NDC 21695-721 Furosemide

NDC Product Code 21695-721

NDC CODE: 21695-721

Proprietary Name: Furosemide What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • Furosemide is used to reduce extra fluid in the body (edema) caused by conditions such as heart failure, liver disease, and kidney disease. This can lessen symptoms such as shortness of breath and swelling in your arms, legs, and abdomen. This drug is also used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Furosemide is a "water pill" (diuretic) that causes you to make more urine. This helps your body get rid of extra water and salt.

NDC Code Structure

  • 21695 - Rebel Distributors Corp

NDC 21695-721-25

Package Description: 25 VIAL, SINGLE-DOSE in 1 BOX > 2 mL in 1 VIAL, SINGLE-DOSE

This product is EXCLUDED from the official NDC directory because the listing data was inactivated by the FDA.

NDC Product Information

Furosemide with NDC 21695-721 is a product labeled by Rebel Distributors Corp. The product's dosage form is and is administered via form. The RxNorm Crosswalk for this NDC code indicates a single RxCUI concept is associated to this product: 1719290.

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • SODIUM CHLORIDE (UNII: 451W47IQ8X)
  • WATER (UNII: 059QF0KO0R)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Rebel Distributors Corp
Labeler Code: 21695
Start Marketing Date: 11-30-1983 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2017 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: I - INACTIVATED, the listing data was inactivated by the FDA. What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

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Information for Patients

Furosemide Injection

Furosemide Injection is pronounced as (fure oh' se mide)

Why is furosemide injection medication prescribed?
Furosemide injection is used to treat edema (fluid retention; excess fluid held in body tissues) caused by various medical problems, including heart failure, pulmonary ed...
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Furosemide Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Other

Rx Only

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: 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 WARNINGS, above).

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.

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.

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".)

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.

Clinical Pharmacology

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.

Indications And Usage

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

Contraindications

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

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).

General Precautions

General: Excessive diuresis may cause dehydration and blood volume reduction with circulatory collapse and possibly vascular thrombosis and embolism, particularly in elderly patients. As with any effective diuretic, electrolyte depletion may occur during furosemide therapy, especially in patients receiving higher doses and a restricted salt intake. Hypokalemia may develop with furosemide, especially with brisk diuresis, inadequate oral electrolyte intake, when cirrhosis is present, or during concomitant use of corticosteroids or ACTH. Digitalis therapy may exaggerate metabolic effects of hypokalemia, especially myocardial effects.All patients receiving furosemide therapy should be observed for these signs or symptoms of fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia, hypomagnesemia or hypocalcemia): dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia or gastrointestinal disturbances such as nausea and vomiting.Increases in blood glucose and alterations in glucose tolerance tests (with abnormalities of the fasting and 2-hour postprandial sugar) have been observed, and rarely, precipitation of diabetes mellitus has been reported.Asymptomatic hyperuricemia can occur and gout may rarely be precipitated.Patients allergic to sulfonamides may also be allergic to furosemide.The possibility exists of exacerbation or activation of systemic lupus erythematosus.As with many other drugs, patients should be observed regularly for the possible occurrence of blood dyscrasias, liver or kidney damage, or other idiosyncratic reactions.

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.

Laboratory Tests

Laboratory Tests: Serum electrolytes, (particularly potassium), CO2, creatinine and BUN should be determined frequently during the first few months of furosemide therapy and periodically thereafter. Serum and urine electrolyte determinations are particularly important when the patient is vomiting profusely or receiving parenteral fluids. Abnormalities should be corrected or the drug temporarily withdrawn. Other medications may also influence serum electrolytes.Reversible elevations of BUN may occur and are associated with dehydration, which should be avoided, particularly in patients with renal insufficiency. Urine and blood glucose should be checked periodically in diabetics receiving furosemide, even in those suspected of latent diabetes.Furosemide may lower serum levels of calcium (rarely cases of tetany have been reported) and magnesium. Accordingly, serum levels of these electrolytes should be determined periodically.

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.

Carcinogenesis & Mutagenesis & Impairment Of Fertility

Carcinogenesis, Mutagenesis, Impairment of Fertility: Furosemide was tested for carcinogenicity by oral administration in one strain of mice and one strain of rats. A small but significantly increased incidence of mammary gland carcinomas occurred in female mice at a dose 17.5 times the maximum human dose of 600 mg. There were marginal increases in uncommon tumors in male rats at a dose of 15 mg/kg (slightly greater than the maximum human dose) but not at 30 mg/kg.Furosemide was devoid of mutagenic activity in various strains of Salmonella typhimurium when tested in the presence or absence of an in vitro metabolic activation system, and questionably positive for gene mutation in mouse lymphoma cells in the presence of rat liver S9 at the highest dose tested. Furosemide did not induce sister chromatid exchange in human cells in vitro, but other studies on chromosomal aberrations in human cells in vitro gave conflicting results. In Chinese hamster cells it induced chromosomal damage but was questionably positive for sister chromatid exchange. Studies on the induction by furosemide of chromosomal aberrations in mice were inconclusive. The urine of rats treated with this drug did not induce gene conversion in Saccharomyces cerevisiae.Furosemide produced no impairment of fertility in male or female rats, at 100 mg/kg/day (the maximum effective diuretic dose in the rat and 8 times the maximal human dose of 600 mg/day).

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.

Nursing Mothers

Nursing Mothers: Because it appears in breast milk, caution should be exercised when furosemide is administered to a nursing mother.

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.

Adverse Reactions

  • Adverse reactions are categorized below by organ system and listed by decreasing severity.Gastrointestinal System ReactionsPancreatitisJaundice (intrahepatic cholestatic jaundice)AnorexiaOral and gastric irritationCrampingDiarrheaConstipationNauseaVomitingSystemic Hypersensitivity ReactionsSystemic vasculitisInterstitial nephritisNecrotizing angiitisCentral Nervous System ReactionsTinnitus and hearing lossParesthesiasVertigoDizzinessHeadacheBlurred visionXanthopsiaHematologic ReactionsAplastic anemia (rare)ThrombocytopeniaAgranulocytosis (rare)Hemolytic anemiaLeukopeniaAnemiaDermatologic-Hypersensitivity ReactionsExfoliative dermatitisErythema multiformePurpuraPhotosensitivityUrticariaRashPruritusCardiovascular ReactionOrthostatic hypotension may occur and be aggravated by alcohol, barbiturates or narcotics.Other ReactionsHyperglycemiaGlycosuriaHyperuricemiaMuscle spasmWeaknessRestlessnessUrinary bladder spasmThrombophlebitisTransient injection site pain following intramuscular injectionFeverWhenever adverse reactions are moderate or severe, furosemide dosage should be reduced or therapy withdrawn.

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 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.

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.

How Supplied

Furosemide Injection, USP (10 mg/mL)NDC 21695-721-252 mL single dose amber colored vialsBoxes of 25Do not use if solution is discolored.Store at controlled room temperature 15°-30°C (59°-86°F) (See USP).Protect from light.IN5702Rev. 4/01MG #7822AMERICANREGENTLABORATORIES, INC.SHIRKEY, NY 11967Repackaged by:Rebel Distributors CorpThousand Oaks, CA 91320

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