Furosemide Injection

Furosemide injection is used to treat edema (fluid retention; excess fluid held in body tissues) caused by various medical problems, including heart failure, pulmonary edema (excess fluid in the lungs), kidney, and liver disease. Furosemide is in a class of medications called diuretics ('water pills'). It works by causing the kidneys to get rid of unneeded water and salt from the body into the urine.

Furosemide may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• frequent urination
• blurred vision
• headache
• constipation
• diarrhea

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately:

• fever
• ringing in the ears
• loss of hearing
• ongoing pain that begins in the stomach area, but may spread to the back
• rash
• hives
• blisters or peeling skin
• itching
• difficulty breathing or swallowing
• yellowing of the skin or eyes
• light-colored stools
• dark urine
• pain in the upper right part of the stomach

Furosemide may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

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In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For furosemide, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to furosemide or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of furosemide injection in children. However, premature babies are more likely to have unwanted effects (e.g., kidney stones, hearing problems), which may require caution in patients receiving furosemide injection.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of furosemide injection in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving furosemide injection.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving furosemide, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using furosemide with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Desmopressin

Using furosemide with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Amikacin
• Amtolmetin Guacil
• Arsenic Trioxide
• Aspirin
• Bepridil
• Bromfenac
• Bufexamac
• Celecoxib
• Chloral Hydrate
• Choline Salicylate
• Cisplatin
• Clonixin
• Dasabuvir
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Diflunisal
• Digitoxin
• Dipyrone
• Dofetilide
• Droperidol
• Droxicam
• Ethacrynic Acid
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Flurbiprofen
• Foscarnet
• Gentamicin
• Ibuprofen
• Indomethacin
• Kanamycin
• Ketanserin
• Ketoprofen
• Ketorolac
• Levomethadyl
• Lithium
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Metolazone
• Morniflumate
• Nabumetone
• Naproxen
• Neomycin
• Nepafenac
• Netilmicin
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Phenylbutazone
• Piketoprofen
• Piroxicam
• Proglumetacin
• Propyphenazone
• Proquazone
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sodium Salicylate
• Sotalol
• Streptomycin
• Sulindac
• Tenoxicam
• Tiaprofenic Acid
• Tobramycin
• Tolfenamic Acid
• Tolmetin
• Valdecoxib
• Vasopressin

Using furosemide with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alacepril
• Aliskiren
• Benazepril
• Captopril
• Carbamazepine
• Cephaloridine
• Cilazapril
• Clofibrate
• Cyclosporine
• Delapril
• Dibekacin
• Enalapril
• Enalaprilat
• Fludrocortisone
• Fosinopril
• Germanium
• Ginseng
• Gossypol
• Imidapril
• Licorice
• Lisinopril
• Moexipril
• Pancuronium
• Pentopril
• Perindopril
• Quinapril
• Ramipril
• Spirapril
• Temocapril
• Trandolapril
• Tubocurarine
• Vecuronium
• Zofenopril

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of furosemide. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy to sulfa drugs (such as sulfamethoxazole, sulfasalazine, sulfisoxazole, Azulfidine®, Bactrim®, Gantrisin®, or Septra®) or
• Bladder problem with urinating or
• Blood or bone marrow problems or
• Dehydration or
• Electrolyte imbalance (e.g., low sodium, calcium, magnesium, or potassium in the blood) or
• Enlarged prostate or
• Gout or
• Hearing problems or
• Hyperuricemia (high uric acid in the blood) or
• Hypovolemia (low blood volume) or
• Liver disease, severe (e.g., cirrhosis, hepatic coma) or
• Systemic lupus erythematosus (SLE) or
• Tinnitus (ringing in the ears) or
• Trouble urinating—Use with caution. May make these conditions worse.

• Anuria (not able to pass urine)—Should not be used in patients with this condition.

• Diabetes—furosemide may increase the amount of sugar in the blood.

• Hypertension (high blood pressure)—Your dose of antihypertensive medicines may need to be adjusted to prevent your blood pressure from falling too low.

• Hypoproteinemia (low protein in the blood) from a kidney problem or
• Radiocontrast nephropathy (kidney problem), history of—May cause side effects to become worse.

• Kidney disease, severe—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hard stools (constipation).
• Loose stools (diarrhea).
• Dizziness.
• Upset stomach or throwing up.
• Headache.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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 crystalline powder. It is practically insoluble in water, sparingly soluble in alcohol, freely soluble in dilute alkali solutions and insoluble in dilute acids. It has the following structural formula:

Molecular formula: C12H1 1 CI N20sS Molecular weight: 330.75

Furosemide Injection, USP is a sterile solution intended for intramuscular or intravenous administration. Each mL contains furosemide 10 mg and sodium chloride sufficient to render solution isotonic in water for injection. Contains sodium hydroxide and may contain hydrochloric acid for pH adjustment. pH 9.0 (8.0to9.3).

The plastic syringe is molded from a specially  formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life.

Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts;however, biological testing was supportive of the safety of the syringe material.

Contains no preservative.

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).

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).

Adverse reactions are categorized below by organ system and listed by decreasing

severity.

GastrointestinalSystem Reactions

(1) Hepatic encephalopathy in patients with hepatocellular insufficiency

(2) Pancreatitis (3) Jaundice (intrahepatic cholestaticjaundice) (4) Increased liver

enzymes (5) Anorexia (6) Oral and gastric irritation (7) Cramping (8) Diarrhea

(9) Constipation (10) Nausea (11) Vomiting

Systemic Hypersensitivity Reactions

(1) Severe anaphylactic or anaphylactoid reactions (e.g., with shock) (2) Systemic

vasculitis (3) Interstitial nephritis (4) Necrotizing angiitis

CentralNervous System Reactions

(1) Tinnitus and hearing loss (2) Paresthesias (3) Vertigo (4) Dizziness (5) Headache

(6) Blurred vision (7) Xanthopsia

Hematologic Reactions

(1) Aplastic anemia (2)Thrombocytopenia (3) Agranulocytosis (4) Hemolytic

anemia (5) Leukopenia (6) Anemia (7) Eosinophilia.

Dermatologic-Hypersensitivity Reactions

(1) Toxic epidermal necrolysis (2) Stevens-Johnson Syndrome (3) Erythema multiforme (4) Drug rash with eosinophila and systemic symptoms

(5) Acute generalized exanthematous pustulosis (6) Exfoliative dermatitis (7) Bullous pemphigoid (8) Purpura (9) Photosensitivity (1 0) Rash (11) Pruritus (12) Urticaria

Cardiovascular  Reactions

(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 (2) Glycosuria (3) Hyperuricemia (4) Muscle spasm (5) Weakness

(6) Restlessness (7) Urinary bladder spasm (8) Thrombophlebitis (9) Transient injection site pain following intramuscular injection (10) Fever.

Whenever adverse reactions are moderate or severe, furosemide dosage should be reduced or therapy withdrawn.

Adults

Parenteral therapy with Furosemide Injection,USP 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.

When furosemide is given for prolonged periods, careful clinical observation and laboratory monitoring are particularly advisable. (See PRECAUTIONS:Laboratory Tests.)

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 Injection 5%, 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 the 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.q., labetalol. ciorofloxacin. 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.

Geriatric patients

In general, dose selection for the elderly patient should be cautious, usually starting at the low end of the dosing range (see PRECAUTIONS,Geriatric Use).

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. Do not use if solution is discolored.

To prevent needle-stick injuries, needles should not be recapped, purposely bent, or broken by hand.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: ethacrynic acid, lithium.

Some products have ingredients that could raise your blood pressure or worsen your swelling. Tell your pharmacist what products you are using, and ask how to use them safely (especially cough-and-cold products, diet aids, or NSAIDs such as ibuprofen/naproxen).

This medication may interfere with certain lab tests (such as thyroid hormone levels), possibly causing false test results. Make sure lab personnel and all your doctors know you use this drug.