)‫בטיחות‬
)‫מידע בטיחות‬
‫החמרה (( מידע‬
‫על החמרה‬
‫הודעה על‬
‫הודעה‬
__ 5/08_____________________ ‫תאריך‬
_____FUSID Injection _________‫שם תכשיר באנגלית‬
____052 74 24464 00____________‫מספר רישום‬
Teva Pharmaceutical Industries Ltd.,P.O.Box 3190, Petach Tikva ‫שם בעל הרישום‬
‫השינויים בעלון מסומנים על רקע צהוב‬
‫רופא‬
‫בעלון ללרופא‬
‫בעלון‬
‫ים‬/‫ים המבוקש‬/‫פרטים על השינוי‬
‫טקסט חדש‬
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, 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.
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.
Careful monitoring is also necessary in:
-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.
- 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.
‫טקסט נוכחי‬
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.
Serum cholesterol and triglyceride levels
may rise during furosemide treatment.
As with many other drugs, patients should
be observed regularly for the possible
occurrence of blood dyscrasias, liver
damage, or other idiosyncratic reactions.
‫פרק בעלון‬
Precautions
In patients who are at high risk for radiocontrast
nephropathy, furosemide is not recommended to
be used for duiresis as part of the preventative
measures against radiocontrast-induced
nephropathy.
Known hypersensitivity to furosemide or
sulfonamides.
Electrolyte deficiency(e.g: Severe hypokalaemia,
Known hypersensitivity to furosemide or
sulfonamides.
Electrolyte deficiency
Contraindications
severe hyponatraemia).
Hypovolaemia, dehydration
Renal failure due to nephrotoxic or hepatotoxic
agents.
Renal failure associated with hepatic coma.
Pre-comatose states associated with liver cirrhosis.
Anuria.
Renal failure due to nephrotoxic or
hepatotoxic agents.
Renal failure associated with hepatic coma.
Pre-comatose states associated with liver
cirrhosis.
Anuria.
Adverse reactions are categorized below by
organ system and listed by decreasing severity.
Gastrointestinal System Reactions
(1) pancreatitis, (2) jaundice (intrahepatic
cholestatic jaundice), (3) anorexia, (4) oral and
gastric irritation, (5) cramping, (6) diarrhea, (7)
constipation, (8) nausea, (9) vomiting
Systemic Hypersensitivity Reactions
(1) systemic vasculitis, (2) interstitial nephritis, (3)
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 (rare), (2) thrombocytopenia,
(3) agranulocytosis (rare), (4) hemolytic anemia,
(5) leucopenia, (6) anemia.
Dermatologic-Hypersensitivity Reactions
(1) exfoliative dermatitis, (2) erythema
multiforme, (3) purpura, (4) photosensitivity,
(5) urticaria, (6) rash, (7) pruritus.
Cardiovascular Reaction
Orthostatic hypotension may occur and may be
aggravated by alcohol, barbiturates, or narcotics.
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.
Gastrointestinal
Anorexia, oral and gastric irritation, nausea,
vomiting, cramping, diarrhea, constipation,
intrahepatic cholestatic jaundice, pancreatitis.
Hypersensitivity Reactions
Systemic vasculitis, interstitial
necrotizing angiitis.
nephritis,
Central Nervous System
Dizziness, vertigo, paresthesias, headache,
xanthopsia, blurred vision, tinnitus and hearing
loss.
Hematological
Anemia, leukopenia,
thrombocytopenia,
Gastrointestinal
Anorexia, oral and gastric irritation,
nausea, vomiting, cramping, diarrhea,
constipation,
intrahepatic
cholestatic
jaundice, pancreatitis.
Hypersensitivity Reactions
Systemic vasculitis, interstitial nephritis,
necrotizing angiitis.
Central Nervous System
Dizziness, vertigo, paresthesias, headache,
xanthopsia, blurred vision, tinnitus and
hearing loss.
Hematological
Anemia, leukopenia, thrombocytopenia,
agranulocytosis (rare), aplastic anemia
(rare), hemolytic anemia.
Dermatological
Purpura, photosensitivity, rash, urticaria.
exfoliative dermatitis, erythema multiforme,
pruritus.
Cardiovascular:
Thrombophlebitis,
hypotension.
orthostatic
Miscellaneous
Hyperglycemia,
glycosuria,
hyperuricemia, muscle spasm, weakness,
restlessness, urinary bladder spasm, fever,
transient pain at the injection site following
IM injection. Blood urea nitrogen (BUN)
levels may be increased. Serum calcium,
magnesium, potassium and sodium levels
may be decreased.
Adverse events
agranulocytosis (rare), aplastic anemia (rare),
hemolytic anemia.
Dermatological
Purpura, photosensitivity, rash, urticaria.
exfoliative dermatitis, erythema multiforme,
pruritus.
Cardiovascular:
Thrombophlebitis, orthostatic hypotension.
Miscellaneous
Hyperglycemia, glycosuria, hyperuricemia,
muscle spasm, weakness, restlessness, urinary
bladder spasm, fever, transient pain at the injection
site following IM injection. Blood urea nitrogen
(BUN) levels may be increased. Serum calcium,
magnesium, potassium and sodium levels may be
decreased.
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,
and
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/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/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 may intensify electrolyte imbalance,
particularly 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
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, and cisplatin, should be
avoided because of the potential for these
toxicities being increased. This is especially
important in patients presenting with renal
function impairment.
Drug Interactions
Furosemide/Corticosteroids
or
Corticotropin
(ACTH)/Carbenoxolone/Liquorice
may
intensify electrolyte imbalance, particularly
hypokalemia.
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.
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
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 overthe-counter products for appetite suppression and
cold symptoms.
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).
Others
Urine and blood glucose should be
checked periodically in diabetics receiving
furosemide, even in those suspected of
latent diabetes
Diagnostic
Interference
Manifestations
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 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.
Manifestations
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 the diuretic action.
Overdosage