2011 ‫ יוני‬:‫ עלון מאושר‬.

"‫"פורמט עלון זה נקבע ע"י משרד הבריאות ותוכנו נבדק ואושר‬

“This leaflet format has been determined by the Ministry of Health and the content thereof has been
checked and approved.” Date of approval: June 2011.

FUSID®
TABLETS

Composition

Each tablet contains:

Active Ingredient
Furosemide 40 mg

Other Ingredients
Lactose*, microcrystalline cellulose, starch, crospovidone, povidone, magnesium
stearate, colloidal silicon dioxide, propylparaben, butylparaben.
* Lactose content per tablet: 36 mg.
Action
Furosemide is a potent diuretic which inhibits the reabsorption of sodium at the
proximal and distal tubules, as well as the ascending limb of Henle's loop. It is
characterized by a high degree of efficacy and rapid onset of action with
comparatively short duration.
The onset of diuresis is within 1 hour following oral administration. The peak effect
occurs within the first or second hour, and the duration of the diuretic effect is
approximately 6-8 hours.

Indications
If gastrointestinal absorption is impaired or oral administration is not practical for any
reason, and for patients in emergency clinical situations, Fusid is indicated by the
intravenous or the intra-muscular route. Parenteral use should be replaced with oral
Fusid as soon as practical.

Treatment of edema associated with congestive heart failure, cirrhosis of the liver,
and renal disease, including the nephrotic syndrome.
Adjunctive therapy in acute pulmonary edema.
Treatment of hypertension.

Contraindications
Known hypersensitivity to furosemide or to sulfonamides.
Electrolyte deficiency (e.g: Severe hypokalaemia, severe hyponatraemia).
Hypovolaemia, dehydration
Renal failure due to nephrotoxic or hepatotoxic agents.
Renal failure associated with hepatic coma.
Pre-comatose and comatose states associated with hepatic encephalopahty/liver
cirrhosis.
Anuria or renal failure with anuria not responding to furosemide.
Breastfeeding.
As furosemide may be capable of displacing bilirubin from albumin at least "in vitro",
it should not be administered to jaundiced newborn infants or to infants suffering from
diseases (e.g. Rh incompatibility, familial non-hemolytic jaundice, etc.) with the
potential of causing hyperbilirubinemia and possibly kernicterus.

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Warnings
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 HAVE TO BE ADJUSTED TO THE
INDIVIDUAL PATIENT'S NEEDS.

Note: Steps should be taken to correct hypotension or hypovolemia before

commencing therapy.
In patients with hepatic cirrhosis and ascites, initiation of therapy with furosemide is
best carried out in a hospital. In hepatic coma and 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, the drug should be discontinued.
Patients with prostatic hypertrophy or impairment of micturition have an increased
risk of developing acute retention.
Use in Pregnancy
Safety of use in pregnancy has not been established. Furosemide should be used
during pregnancy only if the potential benefit to the mother outweighs the possible risk
to the fetus. Treatment during pregnancy requires monitoring of fetal growth because
of the potential for higher birth weights.
Furosemide has been shown to cause unexplained matemal deaths and abortions in
rabblts at 2, 4 and 8 times the maximal recommended human dose.
Use in Breastfeeding
(see Contraindications)
Furosemide appears in breast milk. Therefore, having taken into account the
importance of the drug to the mother, either nursing or the drug should be
discontinued.
Furosemide may inhibit lactation.
Use in Pediatrics
Renal calcifications have occurred in some severely premature infants treated with
intravenous furosemide for edema due to patent ductus arteriosus and hyaline
membrane disease.
Nephrocalcinosis/nephrolithiasis has also been observed in children under 4 years of
age with no history of prematurity who have been treated chronically with furosemide.
Monitor renal function, and renal ultrasonography should be considered, in pediatric
patients receiving furosemide.
If furosemide is administered to premature infants during the first weeks of life, it may
increase the risk of persistence of patent ductus arteriosus.
The concurrent use of cholorothiazide has been reported to decrease hypercalciuria
and to dissolve some calculi.
Hearing loss in neonates has been associated with the use of furosemide injection.
Use in the Elderly
Controlled clinical studies of furosemide did not include sufficient numbers of
subjects aged 65 and over to determine whether they respond differently from
younger subjects. Other reported clinical experience has not identified differences in
responses between the elderly and younger patients. In general, dose selection for
the 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.

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Elderly patients may be more sensitive to the hypotensive and electrolyte effects of
diuretics. The excessive diuresis induced by the loop diuretic, furosemide, may result
in dehydration and in reduction of blood volume, with circulatory collapse and with the
possibility of vascular thrombosis and embolism. Elderly patients are also more likely
to have age-related renal function impairment. Adjustment of dosage or of the dosing
interval is required.

Adverse Reactions
Adverse reactions are categorized below by organ system and listed by decreasing
severity.

Gastrointestinal System Reactions

Gastrointestinal System Reactions
(1) hepatic encephalopathy in patients with hepatocellular insufficiency (2)
pancreatitis, (3) jaundice (intrahepatic cholestatic jaundice), (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

Central Nervous 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) leucopenia, (6) anemia, (7) eosinophilia..

Dermatologic-Hypersensitivity Reactions
(1) exfoliative dermatitis, (2) bullous pemphigoid, (3) erythema multiforme, (4)
purpura, (5) photosensitivity, (6) urticaria, (7) rash, (8) pruritus, (9) Stevens-Johnson
Syndrome, (10) toxic epidermal necrolysis.

Cardiovascular Reaction
(1) Orthostatic hypotension may occur and may 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) fever.

Whenever adverse reactions are moderate or severe, furosemide dosage should be

reduced or therapy withdrawn.

Miscellaneous
Blood urea nitrogen (BUN) levels may be increased. Serum calcium, magnesium,
potassium and sodium levels may be decreased.

Metabolism and Nutrition Disorders: Transitory increases in blood creatinine and urea
levels, increase in cholesterol and triglyceride serum levels, increase in uric acid
serum levels and attacks of gout, decrease of glucose tolerance.
Vascular Disorders: Hypotension including orthostatic hypotension, tendency for
thromboses.

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Congenital and Familiar/Genetic Disorders: Increased risk of persistence of patent
ductus arteriosus when furosemide is administered to premature infants during the
first weeks of life.

Precautions
Where indicated, steps should be taken to correct hypotension or hypovolemia before
commencing therapy.
Excessive diuresis may result in dehydration and reduction in blood volume with
circulatory collapse, together with the possibility of vascular thrombosis and embolism,
particularly in elderly patients.
Electrolyte depletion may occur during therapy, especially in patients receiving
higher doses and a restricted salt intake. Frequent serum electrolyte, CO2 and BUN
determinations should be performed during the first few months of therapy and
periodically thereafter, in order to correct abnormalities or if necessary, withdraw the
drug temporarily.
Furosemide may lower serum calcium levels, and rare cases of tetany have been
reported. Accordingly, periodic serum calcium levels should be obtained.
Hypokalemia may develop with furosemide especially with brisk diuresis, inadequate
oral electrolyte intake, concomitant abuse of laxatives, when liver 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 the following signs
and 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, patients who are at risk from a pronounced fall in blood
pressure, 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.
In patients with severe symptoms of urinary retention (because of bladder emptying
disorders, prostatic hyperplasia, urethral narrowing), the administration of furosemide
can cause acute urinary retention related to increased production and retention of
urine. Thus, these patients require careful monitoring, especially during the initial
stages of treatment. In patients at high risk for radiocontrast nephropathy furosemide
can lead to a higher incidence of deterioration in renal function after receiving
radiocontrast compared to high-risk patients who received only intravenous hydration
prior to receiving radiocontrast.
In patients with hypoproteinemia (e.g., associated with nephrotic syndrome) the
effect of furosemide may be weakened and its ototoxicity potentiated.
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.
Serum cholesterol and triglyceride levels may rise during furosemide treatment.
During long- term therapy they will usually return to normal within 6 months.

Careful monitoring is also necessary in:

- patients with hypotension.
- patients who are at risk from a pronounced fall in blood pressure.
- patients where latent diabetes may become manifest or the insulin requirements of
diabetic patients may increase.
- patients with gout
- patients with hepatorenal syndrome
-patients with hypoproteinaemia, e.g. associated with nephritic syndrome (the effect of
furosemide may be weakened and its ototoxicity potentiated). Cautious dose titration
is required.

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- premature infants (possible development nephrocalcinosis/nephrolithiasis; renal

function must be monitored and renal ultrasonography performed).
As with many other drugs, patients should be observed regularly for the possible
occurrence of blood dyscrasias, liver damage, or other idiosyncratic reactions.
In patients who are at high risk for radiocontrast nephropathy, furosemide is not
recommended to be used for diuresis as part of the preventative measures against
radiocontrast-induced nephropathy.

Drug Interactions
Furosemide/Other Antihypertensive Drugs: Furosemide may intensify the therapeutic
effect of other antihypertensive drugs. Concurrent administration requires dosage
adjustment.
Furosemide/Salicylates in High Doses: Furosemide and salicylates have competitive
renal excretory sites. Therefore patients receiving high doses of salicylates
concomitantly administered with furosemide, such as in rheumatic diseases, may
experience salicylate toxicity a lower furosemide doses than usual. Therefore, caution
should be exercised when administering this combination.
Furosemide/Ototoxic and/or Nephrotoxic Medications Concurrent and/or sequential
administration of furosemide with ototoxic and /or nephrotoxic medications such as
parenteral amphotericin B, aminoglycoside antibiotics, the cephalosporin antibiotics
cephaloridine and cephalothin, parenteral amphotericin, cisplatin, should be avoided
because of the potential for these toxicities being increased. This is especially
important in patients presenting with renal function impairment.
Impairment of renal function may develop in patients receiving concurrent treatment
with furosemide and high doses of certain cephalosporins
Furosemide/Cardiac Glycosides: Concurrent use may increase the possibility of
digitalis toxicity associated with hypokalemia.
Furosemide/Risperidone: Caution should be exercised and the risks and benefits of
the combination or co-treatment with furosemide or with other potent diuretics should
be considered prior to the decision to use.
In risperidone placebo controlled trials in elderly patients with dementia, a higher
incidence of mortality was observed in patients treated with furosemide plus
risperidone when compared to patients treated with risperidone alone or furosemide
alone. Concomitant use of risperidone with other diuretics (mainly thiazide diuretics
used in low dose) was not associated with similar findings. No pathophysiological
mechanism has been identified to explain this finding, and no consistent pattern for
cause of death observed Cautions should be exercised and the risks and benefits of
this combination or co-treatment should be considered prior to the decision to use.
Dehydration should be avoided.
Furosemide/ACE Inhibitors/Angiotensin ll Receptor Antagonists: A marked fall in blood
pressure and deterioration in renal function may be seen when ACE inhibitors or
angiotensin II receptor antagonists are added to furosemide therapy, or their dose
level increased. The dose of furosemide should be reduced for at least three days, or
the drug stopped, before initiating the ACE inhibitor or angiotensin II receptor
antagonist or increasing their dose.
Furosemide/Carbamazepine/Aminoglutethimide: Concomitant administration of
carbamazepine or aminoglutethimide may increase the risk of hyponatremia.
Furosemide/Hypoglycemics: Furosemide may raise blood glucose levels or interfere
with the hypoglycemic effects of these agents. For adult-onset diabetics, dosage
adjustment of hypoglycemic medications may be necessary during and after therapy.
Furosemide/Antigout Medications: Furosemide may raise the level of blood uric acid.
Dosage adjustment of antigout medications may be necessary to control
hyperuricemia and gout.

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Furosemide/Corticosteroids or Corticotropin (ACTH)/Carbenoxolone/Liquorice/2

Sympathomimetics in Large Amounts/Prolonged Use of Laxatives, Reboxetine and
Amphotericin: Concurrent use of corticosteroids, carbenoxolone, liquorice, B2
sympathomimetics in large amounts, prolonged use of laxatives, reboxetine and
amphotericin may increase the risk of developing hypokalemia.
Furosemide/Probenecid/Methotrexate: Probenecid, methotrexate and other drugs
which, like furosemide, undergo significant renal tubular secretion may reduce the
effect of furosemide. Conversely, furosemide may decrease renal elimination of these
drugs. In case of high-dose treatment (in particular, of both furosemide and the other
drugs), this may lead to increased serum levels and an increased risk of adverse
effects due to furosemide or the concomitant medication.
Furosemide/Ciclosporin: Concomitant use of ciclosporin and furosemide is associated
with increased risk of gouty arthritis.
Furosemide/Lithium Salts: Concurrent use may provoke lithium toxicity because of
reduced renal clearance. It is not recommended unless the patient can be closely
monitored.
Furosemide/Alcohol/Barbiturates/Narcotics: Orthostatic hypotension due to
furosemide may be aggravated by alcohol, barbiturates or narcotics.
Furosemide/Indomethacin: Literature reports indicate that co- administration 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.
Furosemide/Other Non-Steroidal Anti-Inflammatory Agents (NSAIAs): 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
NSAIAs .
Furosemide/Tubocurarine: Furosemide has a tendency to antagonize the skeletal
muscle relaxing effect of tubocurarine and may potentiate the action of
succinylcholine.
Furosemide/Norepinephrine: Furosemide may decrease arterial responsiveness to
norepinephrine.
Furosemide/Amiodarone: Concurrent use may lead to an increased risk of arrhythmias
associated with hypokalemia.
Furosemide/Theophyllines: Concurrent administration may lead to increased diuresis.
Furosemide/Hydantoins (e.g. Phenytoin): Concurrent administration may reduce the
efficacy of furosemide.
Furosemide/Chloral Hydrate: In isolated cases intravenous administration of
furosemide within 24 hours of taking chloral hydrate may lead to flushing, sweating
attacks, restlessness, nausea, increase in blood pressure and tachycardia. Use of
furosemide concomitantly with chloral hydrate is, therefore, not recommended.
Furosemide/Metolazone: Severe diuresis may occur if metolazone is administered
concomitantly.
Furosemide/antidiabetics: The effects of antidiabetic drugs may be reduced.
Furosemide/Chlorothiazides: The concurrent use of furosemide with chlorothiazide
has been reported to decrease hypercalciuria and to dissolve some calculi.
Oral Furosemide/Sucralfate: Simultaneous administration of sucralfate and furosemide
tablets may reduce the natriuretic and antihypertensive effects of furosemide. Patients
receiving both drugs should be observed closely to determine if the desired diuretic
and/or antihypertensive effect of furosemide is achieved. The intake of furosemide
and sucralfate should be separated by at least two hours.

Effects on Ability to Drive and Use Machines

Reduced mental alertness may impair ability to drive or operate dangerous
machinery.

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Diagnostic Interference
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 (including patients where
latent diabetes may become manifest or the insulin requirements of diabetic patients
may increase).
Furosemide may lower serum levels of calcium (rarely cases of tetany have been
reported) and magnesium. Accordingly, serum levels should be determined
periodically.

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

Since furosemide is a potent diuretic which, if given in excessive amounts, can lead
to profound diuresis with water and electrolyte depletion, careful medical supervision
is required. Dosage should be adjusted to the individual needs of each patient.

Adults
Edema: The usual initial dose is 20-80 mg/day administered as a single dose.
Usually, prompt diuresis ensues. Depending on the response, a second dose should
be administered 6-8 hours later. If the diuretic response is unsatisfactory, the dose
should be increased by increments of 20 or 40 mg, no sooner than 6-8 hours after
previous dose, until the desired diuretic effect has been obtained. This individually-
determined dose should then be administered 1-2 times a day. In patients with severe
edema, dosage may be titrated up to 600 mg/day.
Mobilization of edema may be most efficiently and safely accomplished with an
intermittent dosage schedule. Furosemide should be administered on 2-4 consecutive
days, each week. With doses exceeding 80 mg/day, clinical and laboratory
observations are recommended.

Hypertension: The usual initial dosage is 40 mg, twice a day. Dosage should be
adjusted according to response. If a patient does not respond, other antihypertensive
agents should be added. Blood pressure changes should be observed when used
with other antihypertensives, especially during initial therapy. The dosage of other
agents should be reduced by at least 50% as soon as furosemide is added, to prevent
excessive drop in blood pressure. As blood pressure falls, either the dose should be
reduced or the other antihypertensives discontinued.

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Infants and Children

The usual initial dose of furosemide in infants and children is 2 mg/kg body weight.
If diuretic response after the initial dose is unsatisfactory, dosage may be increased
by 1-2 mg/kg body weight, but no sooner than 6-8 hours after the first dose. Doses
greater than 6 mg/kg are not recommended. For maintenance therapy, the dose
should be adjusted to the minimum effective level.

Overdosage
Manifestations
The principal signs and symptoms are dehydration, blood volume reduction,
hypotension, electrolyte imbalance, hypokalemia and hypochloremic alkalosis, and
are extensions of the 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 fluid associated with toxicity or death is
not known.

Treatment
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.

Drug Registration Nos

020 20 20472 00, 020 20 20472 11.

Storage
Store in a dry place, below 25C.

Manufacturer
Teva Pharmaceutical Industries Ltd
P.O.Box 3190, Petach Tikva.

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