Frusema

Frusema

furosemide

Manufacturer:

RiteMED

Distributor:

Carels
Full Prescribing Info
Contents
Furosemide.
Description
Each tablet contains: Furosemide 20 mg or 40 mg.
Each mL solution for injection contains: Furosemide 10 mg.
Action
Pharmacology: Tablet: Furosemide is a potent diuretic with a rapid action. Its effect are evident within 1 hour after a dose by mouth and for about 4 to 6 hours: also promote the excretion of water and electrolytes by the kidneys. Used in treating patients with congestive heart failure, renal or pulmonary disease when salt and water retention has resulted in edema and ascites. Furosemide is incompletely but fairly rapidly absorbed from the gastrointestinal tract. It has a biphasic half-life in a plasma with a terminal elimination phase that has been estimated to range to 1 1/2 hours. It is up to 99% bound to plasma protein and is mainly excreted in the urine, largely unchanged, but also in the form of the glucuronide and free amine metabolites. Variable amount are also excreted in the bile, non-renal elimination being considerably increased in the renal failure. Furosemide crosses the placental barrier and is excreted in milk.
Pharmacodynamics: Injection: Furosemide inhibits primarily the absorption 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.
Furosemide diuresis results in enhanced excretion of sodium, chloride, potassium, hydrogen, calcium, magnesium, ammonia, bicarbonate, and possibly phosphate. Urinary pH usually decreases after furosemide administration; however, increased bicarbonate excretion in some patients may temporarily increase urinary pH. Low doses of furosemide promote uric acid retention while large intravenous (IV) doses may cause temporary uricosuria. Maximum diuresis and electrolyte loss is greater with furosemide than with the thiazide diuretics. The effectiveness of furosemide, like the thiazide diuretics, is independent of the acid-base balance of the patient.
The diuretic response to furosemide is similar after oral or IV administration in patients with normal renal function. However, in uremic patients, diuresis and urinary excretion of sodium and potassium are greater after IV administration than after similar oral furosemide doses.
As with other diuretics, furosemide's blood pressure lowering effect may result from decreased plasma volume. However, furosemide produces only mild decreases in the supine systolic blood pressure and in the erect systolic and diastolic blood pressures when administered alone in the recommended oral dosage.
Furosemide appears to have less effect on carbohydrate metabolism and blood glucose concentrations than do the thiazides; however, furosemide may cause increases in blood glucose, glycosuria and alterations in glucose tolerance possibly as a result of hypokalemia.
After IV administration of furosemide, diuresis occurs within 5 minutes, peaks within 20 to 60 minutes and persists for about 2 hours.
After intramuscular (IM) administration, onset of diuresis occurs later than after IV administration since peak plasma concentrations are attained only after 30 minutes. The diuretic response may be prolonged in patients with severely impaired renal function.
Pharmacokinetics: Injection: 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.
Recent evidence suggests that furosemide glucuronide is the only, or at least the major, bio-transformation product of furosemide in man.
In patients with normal renal function, approximately 80% of an IV or IM dose is excreted in the urine within 24 hours. Urinary excretion is accomplished both by glomerular filtration and proximal tubular secretion, which accounts for roughly 66% of the ingested dose, the remainder being excreted in the feces. A small fraction is metabolized by cleavage of the side chain.
The terminal half-life of furosemide is approximately two hours. Significantly more furosemide is excreted in urine after the IV injection than after the tablet or oral solution.
Special Population: Renal/Hepatic Impairment: In patients with marked renal impairment without liver disease, hepatic and fecal clearance of furosemide is increased so that up to 98% of the drug is removed from the plasma within 24 hours.
Where liver disease is present, biliary elimination is reduced up to 50%.
Elderly: The elimination of furosemide is delayed in the elderly where a certain degree of renal impairment is present.
Indications/Uses
Tablet: For the treatment of edema associated with heart failure, including pulmonary edema, and with renal and hepatic disorders and maybe effective in patients unresponsive to thiazide diuretics.
It is also used in high doses in the management of oliguria due to renal failure or insufficiency.
Furosemide is also used in the treatment of hypertension, either alone or with other antihypertensives.
Injection: Edema: 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 may also be used as an adjunct in the treatment of acute pulmonary edema and cerebral edema where intense and rapid onset of diuresis is desired.
Hypertension: Furosemide may be used as an adjunct to antihypertensive agents in the treatment of hypertensive crisis (especially when associated with acute pulmonary edema or renal failure).
Dosage/Direction for Use
Tablet: For Oedema: Adults: Initially 40 mg in the morning; maintenance of 20 mg to 40 mg daily, increased in resistance oedema to 80 mg daily or more.
Children: Initially 1 mg to 3 mg/Kg daily, maximum of 40 mg daily.
For hypertension: 40 to 80 mg daily, either alone or in conjunction with other antihypertensives.
For Oliguria in chronic renal impairment: An initial dose of 250 mg may be given, increase if necessary in steps of 250 mg every 4 to 6 hours to a maximum of 1.5 g in 24 hours. Or as prescribed by the physician.
20 mg Tablet: Adult: 20 to 80 mg single dose daily preferably in the morning dose may be titrated and given in divided doses every 6-8 hours.
Children: Start with 2 mg/kg/dose, if diuretic response is not achieved, increase dose by 1-2 mg/Kg every 6-8 hours. After initial dose, maximum 6 mg/Kg with an interval of at least 2 hours between doses. Or, as prescribed by the physician.
Injection: General Dosing Recommendations: Parenteral furosemide 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.
Furosemide IV must be injected or infused slowly over 1 to 2 minutes; administer as a controlled IV infusion at a rate not exceeding 4 mg/min. In patients with severe renal function impairment (serum creatinine >5 mg/dL), it is recommended that an infusion rate of 2.5 mg/min must not be exceeded to minimize the risk of ototoxicity.
IM administration must be restricted to exceptional cases where neither oral nor IV administration is feasible. Note that IM administration is not suitable for the treatment of acute conditions such as pulmonary edema.
A continuous furosemide infusion is generally preferred to repeated bolus injections to achieve optimum efficacy and suppress counter-regulation. Where continuous furosemide infusion is not feasible for follow-up treatment after one or several acute bolus doses, a follow-up regimen with low doses given at short intervals (about 4 hours) is preferred to a regimen with higher bolus doses at longer intervals.
For IV infusion, furosemide must be diluted with an infusion solution of 0.9% sodium chloride, lactated Ringer's or 5% dextrose, adjusting the pH to greater than 5.5 when necessary.
Inspect the ampule visually for particulate matter and discoloration before administration. Do not use if discolored.
Strict aseptic technique should be observed when drawing up the contents of the ampule. If contaminated, it has the potential to become a source of infection to patients.
Dosing must be individualized and adjusted according to patient response.
Recommended Furosemide IV/IM Dose: See table.

Click on icon to see table/diagram/image
Overdosage
Injection: Manifestations of furosemide overdosage include dehydration, blood volume reduction, hypotension or severe hypotension (progressing to shock), electrolyte imbalance, cardiac arrhythmias (including atrioventricular block and ventricular fibrillation), hypokalemia and hypochloremic alkalosis, acute renal failure, thrombosis, delirious states, flaccid paralysis, apathy, confusion and extensions of its diuretic action.
Treatment is supportive and consists of replacement of excessive fluid and electrolyte losses. Gastric lavage may be useful if ingestion is recent. Serum electrolytes, carbon dioxide level and blood pressure must be frequently determined. Adequate drainage must be assured in patients with urinary bladder outlet obstruction such as prostatic hypertrophy.
Hemodialysis does not accelerate furosemide elimination.
Contraindications
Tablet: Best avoided during pregnancy. Anuria in patients receiving lithium therapy.
Injection: Hypersensitivity to furosemide or sulfonamides, or to any component of the product. Patients allergic to sulfonamides may show cross sensitivity to furosemide.
Anuria or renal failure with anuria not responding to furosemide.
Increasing azotemia and oliguria during treatment of severe progressive renal disease.
Severe hypokalemia, hyponatremia, hypovolemia, or hypotension until serum electrolytes, fluid balance and blood pressure have been restored to normal levels.
Hepatic coma or pre-coma and conditions producing electrolyte depletion until the underlying conditions have been corrected or ameliorated.
Newborns presenting jaundice or infants with conditions which might induce hyperbilirubinemia or kernicterus (e.g., Rhesus incompatibility, familial non-hemolytic jaundice, etc.) because of furosemide's in vitro potential to displace bilirubin from albumin.
Digitalis intoxication.
Porphyria.
Breastfeeding.
Warnings
20 mg Tablet: This product contains FDC Yellow #5 (Tartrazine) which may cause allergic reaction including bronchial asthma in certain susceptible persons.
Special Precautions
Tablet: Furosemide should be used with care to patients with prostatic hypertrophy or impairment of micturition, caution in patients with impaired hearing, and pregnancy. Furosemide should not be given in pre-comatose states associated with hepatic cirrhosis.
Injection: Furosemide is a potent diuretic which, if given in excessive amounts, may lead to a profound diuresis with water and electrolyte depletion. Therefore, careful medical supervision is required and dose schedule must be adjusted to the individual patient's needs (see Dosage & Administration).
Furosemide is best initiated in the hospital in patients with hepatic cirrhosis and ascites. 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; thus, closely monitor patients during the period of diuresis. Supplemental potassium and chloride and, if required, an aldosterone antagonist are helpful in preventing hypokalemia and metabolic acidosis.
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 therapy, especially in patients receiving higher doses and a restricted salt intake. All patients receiving furosemide should be observed for signs or symptoms of fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia, hypomagnesemia or hypocalcemia). Periodic determinations of serum electrolytes to detect a possible imbalance should be performed at appropriate intervals, as well as creatinine, blood urea, carbon dioxide content determinations. This is particularly important when the patient is vomiting excessively or receiving parenteral fluids. Warning signs of an imbalance (irrespective of cause) include 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. Hypovolemia or dehydration as well as any significant electrolyte and acid-base disturbances must be corrected. This may require temporary discontinuation of furosemide.
Hypokalemia may develop with furosemide, especially with brisk diuresis, inadequate oral electrolyte intake, when cirrhosis is present, or during concomitant use of corticosteroids. Digitalis therapy may exaggerate metabolic effects of hypokalemia, especially myocardial effects.
There have been reports of tinnitus and reversible or irreversible hearing impairment. Usually, reports indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, doses exceeding several times the usual recommended dose, concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs, and hypoproteinemia. In patients with hypoproteinemia (e.g., associated with nephrotic syndrome), the effect of furosemide may be weakened and its ototoxicity potentiated. Cautious dose titration is required.
If the physician elects to use high dose parenteral therapy, controlled IV infusion is advisable [for adults, an infusion rate not exceeding 4 mg/min has been used (see Dosage & Administration).
Furosemide should be used with care, particularly in the initial stages, in patients with micturition impairment (e.g., prostatic hypertrophy). Urinary outflow must be secured. Increased production of urine may provoke or aggravate complaints in patients with partial obstruction of urinary outflow (e.g., in patients with bladder-emptying disorders, prostatic hyperplasia or narrowing of the urethra). Thus, these patients require careful monitoring.
In premature infants, there is the possible development of nephrocalcinosis/nephrolithiasis and therefore renal function should be monitored and renal ultrasonography performed. Furosemide administered during the first weeks of life may increase the risk of persistence of Botallo's duct in premature infants.
Careful monitoring is required in patients with gout, in patients at risk from hypotension (e.g., in patients with coronary artery stenosis), in patients with latent or manifest diabetes mellitus, and in patients with hepatorenal syndrome.
Rigid sodium restriction is conducive to both hyponatremia and hypokalemia, thus strict restriction of sodium intake is not advisable in patients receiving furosemide.
A high potassium diet (lean meat, potatoes, banana, tomatoes, cauliflower, spinach, dried fruit, etc.) is recommended during long-term therapy. Potassium supplements may be required, especially when high doses are used for prolonged periods. Particular caution with potassium is necessary when the patient is on digitalis glycosides, potassium depleting steroids or in the case of infants and children. Potassium supplementation, diminution in dose, or discontinuation of furosemide may be required.
It is advisable to discontinue furosemide for one week before any elective surgery.
Asymptomatic hyperuricemia may occur and gout may rarely be precipitated.
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.
Periodic checks of urine and blood glucose should be made in diabetics and even those suspected of latent diabetes when receiving furosemide. 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.
Furosemide may lower calcium levels, and rare cases of tetany have been observed. Accordingly, periodic serum calcium levels must be obtained.
Reversible increases in blood urea nitrogen may be seen. These have been observed in association with dehydration, which should be avoided, particularly in patients with renal insufficiency.
In patients who are at risk for radiocontrast nephropathy, furosemide is not recommended to be used for diuresis as part of the preventative measures against radiocontrast-induced nephropathy.
Some adverse effects (e.g., an undesirable pronounced fall in blood pressure) may impair the patient's ability to concentrate and react and therefore constitute a risk in situations where these abilities are of special importance (e.g., operating a vehicle or machinery).
Use in Children: A sustained diuretic effect is seen in the newborn, possibly due to immature tubular function.
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.
Use in Elderly: In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Use In Pregnancy & Lactation
Injection: Use in Pregnancy: Pregnancy Category C. Furosemide must not be given during pregnancy unless there are compelling medical reasons.
Treatment during pregnancy requires monitoring of fetal growth.
Thiazides, related diuretics and loop diuretics enter the fetal circulation and may cause electrolyte disturbances. There have been reports of neonatal thrombocytopenia associated with thiazides and related diuretics. Loop diuretics, like furosemide, are probably also associated with this risk. During the latter part of pregnancy, products of this type should only be given on sound indications and in the lowest effective dose. In pregnancy, furosemide must only be used in patients with a marked reduction in glomerular filtration.
Use in Lactation: Furosemide is excreted in breast milk. Thus, the mother should discontinue breastfeeding when furosemide therapy is indicated.
Adverse Reactions
Tablet: The most common adverse effect associated with furosemide therapy is fluid and electrolyte imbalance after either single large doses or prolonged administration. Other side effects are relatively uncommon and include allergy, nausea, diarrhea, blurred vision, dizziness, headache, pancreatitis, photosensitivity, skin rashes, muscle spasm and hypotension. Hyponatraemia, hypokalemia, & hypomagnesaemia, hypochloraemic alkalosis, increased calcium excretion, hypotension; less commonly nausea, gastro-intestinal disturbances, hyperuricaemia & gout; hyperglycemia, temporary increase in plasma cholesterol & triglyceride concentrations; rarely rashes, photosensitivity, & bone marrow depression (withdrawal treatment).
Injection: Body as a whole: Excessive sweating, fever, headache, malaise.
Cardiovascular: Cardiac arrhythmias, circulatory collapse, disorders of cardiac rhythm, hypotension, ischemic complications in the elderly.
Dermatologic and hypersensitivity reactions: Allergic reaction, anaphylactic shock, angioedema, bullous pemphigoid, dermatitis, erythema multiforme, exacerbation or activation of systemic lupus erythematosus, exfoliative dermatitis, itching, necrotizing angiitis, photosensitivity, pruritus, purpura, rash, Stevens-Johnson syndrome, systemic vasculitis, urticaria, transient pain at injection site after intramuscular injection.
Gastrointestinal: Anorexia, constipation, cramping, dehydration, diarrhea, dry mouth, gastrointestinal drainage, nausea, oral and gastric irritation, pancreatitis, vomiting.
Genitourinary: Acute urinary retention with overflow incontinence in elderly men; decreased glomerular filtration rate (GFR); increased risk of persistence of patent ductus arteriosus, calcium depletion and nephrocalcinosis/nephrolithiasis in premature infants; interstitial nephritis; obstructed micturition (e.g., uretostenosis, hydronephrosis); urinary bladder spasm; urinary frequency; prostatic hyperplasia; transient increases in creatinine and blood urea nitrogen (BUN).
Hematologic: Agranulocytosis (rare), anemia, aplastic anemia (rare), bone marrow depression (rare), eosinophilia, hemoconcentration, hemolytic anemia, hypovolemia, leukopenia, thrombocytopenia, thrombophilia, thrombophlebitis.
Hepatobiliary: Distention of biliary tree which is already obstructed, hepatic encephalopathy in patients with hepatocellular insufficiency, increased liver transaminase and bile flow, intrahepatic cholestatic jaundice, jaundice, liver dysfunction, pancreatitis.
Metabolic: Fluid and electrolyte imbalance; glycosuria; gout; hyperglycemia; hyperuricemia; hypokalemia; hypomagnesemia; increased insulin requirements in diabetic patients; latent diabetes mellitus; aggravated pre-existing metabolic alkalosis (e.g., due to compensated liver cirrhosis); alterations in glucose tolerance possibly as a result of hypokalemia.
Elevations in the following: blood glucose, serum cholesterol, triglyceride, total cholesterol, low-density lipoprotein cholesterol, very low density lipoprotein cholesterol, serum uric acid levels.
Musculoskeletal: Calf muscle spasm, flank and loin pain, muscle spasm, weakness.
Nervous: Apathy, confusion, dizziness, drowsiness, lightheadedness, neuromuscular irritability, paresthesia, restlessness, tetany, vertigo, xanthopsia.
Special senses: Blurred vision, visual impairment, deafness, reversible hearing impairment and tinnitus (rare), permanent tinnitus and impairment of hearing in patients with markedly reduced renal function or hypoproteinemia (e.g., in nephrotic syndrome).
Drug Interactions
Tablet: Furosemide may enhance the nephrotoxicity of cephalosporin antibacterials such as cefalotin and can enhance the ototoxicity of aminoglycoside antibacterials and other ototoxic drugs. The interactions of furosemide that are due to its effects on fluids and electrolyte balance are similar to those of hydrochlorothiazide. Diuretic-induced hypokalaemia may enhance the toxicity of digitalis glycosides and may also increase the risk of arrhythmias with drugs that prolong the QT interval such as astemizole, terfenadine, halofantrine, pimozide, and sotalol.
Injection: Aminogluthethimide, carbamazepine: Increase risk of hyponatremia.
Amphotericin: May result in excessive loss of potassium.
Antibiotics [e.g., aminoglycosides, certain cephalosporins (cephaloridine)]: Increase ototoxic potential especially in the presence of impaired renal function. Avoid this combination except in life-threatening situations.
Anticonvulsants (e.g., chloral hydrate): May lead to diaphoresis, sensation of heat, flushes, nausea, tachycardia and increased blood pressure; thus, avoid this combination.
Barbiturates, narcotics, alcohol: Orthostatic hypotension may occur.
Carbenoxolone, corticosteroids, prolonged use of laxatives or ingestion of licorice in large amounts: May predispose a patient to hypokalemia.
Chlorothiazide: Concurrent use of chlorothiazide and furosemide has been reported to decrease hypercalciuria and dissolve some calculi.
Ciclosporin: Increases risk of gouty arthritis secondary to furosemide-induced hyperuricemia and ciclosporin-induced impairment of renal urate excretion.
Curare-type muscle relaxants: Furosemide may potentiate the effects of these drugs.
Digitalis and medicines inducing QT intervals prolongation syndrome: May be potentiated by changes in electrolyte concentrations (e.g., hypokalemia, hypomagnesemia) due to furosemide.
Ethacrynic acid, cisplatin: Should not be used concomitantly because of the possibility of ototoxicity.
Ganglionic or peripheral adrenergic blockers: Furosemide potentiates the effects of these drugs.
Indomethacin: Reduces natriuretic effect and antihypertensive effect of furosemide by inhibiting prostaglandin synthesis. Closely observe patients receiving indomethacin and furosemide.
Lithium: Should not be given with diuretics since they reduce lithium's renal clearance and add a high risk of lithium toxicity.
Methotrexate, probenecid, reboxetine and other medicines which undergo significant renal tubular secretion: Reduce the effects of furosemide. Conversely, furosemide may decrease renal elimination of these medicines.
Nonsteroidal antiinflammatory drugs (NSAIDs, e.g., aspirin): Reduce creatinine clearance in patients with chronic renal insufficiency. There were reports of patients who developed increased BUN, serum creatinine and serum potassium levels, and weight gain when furosemide was used in conjunction with NSAIDs.
Norepinephrine: Furosemide may decrease arterial responsiveness; however, norepinephrine may still be used effectively.
Phenytoin: Attenuates the effect of furosemide.
Risperidone: Exercise caution; the risks and benefits of the combination or cotreatment with furosemide or with other potent diuretics should be considered prior to the decision to use. There was no increased incidence of mortality among patients taking other diuretics as concomitant treatment with risperidone. Irrespective of treatment, dehydration was an overall risk factor for mortality and should therefore be avoided in elderly patients with dementia.
Salicylates (high doses): Salicylate toxicity at lower doses because of competitive renal excretory site.
Succinylcholine: Furosemide may potentiate the action of succinylcholine.
Sucralfate: Reduces the natriuretic effect and antihypertensive effect of furosemide. The intake of furosemide and sucralfate should be separated by at least 2 hours.
Theophylline: Furosemide potentiates the effects of theophylline.
Tubocurarine: Furosemide (dependent on the dose) may potentiate or antagonize the skeletal muscle relaxing effect of tubocurarine.
Other antihypertensive drugs: Furosemide may add to or potentiate the therapeutic effect of other antihypertensive drug. Furosemide combined with angiotensin II converting enzyme (ACE) inhibitors or angiotensin II receptor blockers may lead to severe hypertension and deterioration in renal function, including renal failure.
Storage
Store at temperatures not exceeding 30°C. Protect from light.
MIMS Class
ATC Classification
C03CA01 - furosemide ; Belongs to the class of high-ceiling sulfonamide diuretics.
Presentation/Packing
Tab 20 mg x 100's. 40 mg x 100's. Soln for inj (amp) 20 mg/2 mL (clear, colorless to slightly yellow, sterile, nonpyrogenic) x 2 mL x 10's.
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