FUROSEMIDE 10 MG/ ML ORAL SOLUTION

Active substance: FUROSEMIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Furosemide 10 mg/ml Oral Solution

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 1 ml of solution contains 10 mg of Furosemide.
Each 1 ml of solution also contains 98.5 mg Ethanol and 350 mg Sorbitol

For a full list of excipients, see section 6.1

3

PHARMACEUTICAL FORM
Oral Solution

Clear solution with a characteristic orange odor.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Furosemide is indicated in all conditions requiring prompt diuresis in patients
who are unable to take solid dose forms. Indications include cardiac,
pulmonary, hepatic and renal oedema, peripheral oedema due to mechanical
obstruction or venous insufficiency and hypertension.

4.2

Posology and method of administration

This liquid should only be taken orally.
The medication should be administered in the morning to avoid nocturnal
diuresis.
Adults (more than 18 years of age): The usual initial daily dose is 40mg. This
may be adjusted until an effective dose is achieved.
Elderly: in the elderly, Furosemide is generally eliminated more slowly.
Dosage should be titrated until the required response is achieved.
This product is not recommended to use in children below 18 years of age.

4.3

Contraindications

Hypovolaemia or dehydration. Anuria. Renal failure with anuria not
responding to furosemide, or as a result of poisoning by nephrotoxic or
hepatotoxic agents, or associated with hepatic coma. Severe hyperokalaemia,
hyperkalaemia and severe hyponatraemia. Pre-comatose and comatose states
associated with hepatic encephalopathy. Breast feeding.
Contra-indicated in hypersensitivity to Furosemide, sulphonamides or any of
the excipients listed.
Patients allergic to sulphonamides may show cross-sensitivity to furosemide.

4.4

Special warnings and precautions for use

This product should not be given to children because its ethanol content may
affect their CNS.
Caution is required in patients liable to electrolyte deficiency. Regular
monitoring of serum sodium, potassium and creatinine is generally
recommended during furosemide therapy; particularly close monitoring is
required in patients at high risk of developing electrolyte imbalances or in case

of significant additional fluid loss. Hypovolaemia or dehydration as well as
any significant electrolyte and acid-base disturbances must be corrected. This
may require temporary discontinuation of furosemide. Where indicated, steps
should be taken to correct hypotension or hypovolaemia before commencing
therapy.
Urinary output must be secured. Patients with partial obstructions of urinary
outflow for example patients with prostatic hypertrophy or impairment of
micturition have an increased risk of developing acute urinary retention and
require careful monitoring.
Particularly careful monitoring is necessary in:
• Patients with hypotension
• Patients who are at risk from a pronounced fall in blood pressure
• Patients with gout
• Patients with hepatorenal syndrome
• Patients with hypoproteinaemia, e.g. associated with nephrotic syndrome (the
effect of furosemide may be weakened and its ototoxicity potentiated).
Cautious dose titration is required


Patients that might manifest latent diabetes



Diabetic patients who might show increased insulin requirements

• Premature infants (possible development nephrocalcinosus/nephrolithiasis;
renal function must be monitored and renal ultrasonography performed).
The use of some diuretics is considered to be unsafe in acute porphyria
therefore caution should be exercised.
Excipient Warnings
This product contains:
Ethanol (alcohol) 11.7 vol %, i.e. up to 369.6mg per dose, equivalent to 9.4 ml
beer, 3.9 ml wine per dose. Harmful for those suffering from alcoholism. To
be taken into account in pregnant or breast-feeding women, children and highrisk groups such as patients with liver disease, epilepsy.

Sorbitol
It may cause flatulence, abdominal distension or diarrhoea if given in large
quantities to adults who are unable to take solid oral dose forms of furosemide.
Patients with rare hereditary problems of fructose intolerance, should not take
this medicine.

4.5

Interaction with other medicinal products and other forms of interaction
ACE Inhibitors: Enhanced hypotensive effect when given with diuretics. A
marked fall in blood pressure and deterioration in renal function may be seen
when ACE inhibitors are added to furosemide therapy. The dose of furosemide
should be reduced for at least three days, or the drug stopped, before initiating
the ACE inhibitor or increasing the dose of an ACE inhibitor.
Alpha-blockers: Enhanced hypotensive effect when diuretics are given with
alpha-blockers, also increased risk of first dose hypotension with post-synaptic
alpha-blockers such as prazosin.
Analgesics: Diuretics can increase the risk of nephrotoxicity of NSAIDs, also
antagonism of diuretic effect. Antagonism of diuretic effect (especially with
indomethacin and ketorolac). Salicylic toxicity may be increased by
furosemide.
Angiotensin –II Receptor Antagonists: Enhanced hypotensive effect when
diuretics given with angiotensin-II receptor antagonists.
Anti-arrhythmics: Hypokalaemia caused by loop diuretics increases cardiac
toxicity with amiodarone, disopyramide, flecainide, and antagonises the action
of lidocaine and mexiletine.
Antibacterials: Avoid the use of diuretics in lymecycline treatment. There is
an increased risk of ototoxicity when loop diuretics are given with
aminoglycosides, polymyxins or vancomycin. Since this may lead to
irreversible damage, these drugs must only be used with furosemide if there
are compelling medical reasons. Impairment of renal function may develop in
patients receiving concurrent treatment with furosemide and high doses of
certain cephalosporins.
Antidepressants: Possible increase of hypokalaemia when loop diuretics are
given with reboxetine. There is an enhanced hypotensive effect when diuretics
are given with MAOIs. There is an increased risk of postural hypotension
when diuretics are given with tricyclic antidepressants.
Antiepileptics: There is an increased risk of hyponatraemia when diuretics are
given with carbemazepine. The effects of furosemide are antagonised by
phenytoin.
Antifungals: There is an increased risk of hypokalaemia when loop diuretics
are given with amphotericin.

Antipsychotics: Hypokalaemia caused by diuretics increase the risk of
ventricular arrhythmias with amisulpiride or sertindole. An enhanced
hypotensive effect may be seen when diuretics are given with phenothiazines.
Hypokalaemia caused by diuretics increases risk of ventricular arrhythmias
with pimozide (avoid concomitant use).
Antivirals: Plasma concentration of diuretics may be increased by nelfinavir,
ritonavir or saquinavir.
Atomoxetine: Hypokalaemia caused by diuretics increases the risk of
ventricular arrhythmias with atomoxetine.
Barbiturates: Plasma concentrations of diuretics may be decreased. There may
be an increased risk of osteomalacia when diuretics are taken in combination
with Phenobarbital.
Beta-blockers: There is an enhanced hypotensive effect when diuretics are
given with beta-blockers. Hypokalaemia caused by loop diuretics increases the
risk of ventricular arrhythmias with sotalol.
Cardiac glycosides: Hypokalaemia caused by loop diuretics increases cardiac
toxicity with cardiac glycosides.
Ciclosporin: there is an increased risk of nephrotoxicity and possibly
hypermagnesaemia when diuretics are given with ciclosporin.
Cisplatin: There is a risk of increased ototoxic effects if cisplatin and
furosemide are given concomitantly. In addition, nephrotoxicity of cisplatin
may be enhanced if furosemide is not given in low doses (e.g. 40mg in
patients with normal renal function) and with positive fluid balance when used
to achieve forced diuresis during cisplatin treatment.
Corticosteroids: The diuretic effect of diuretics is antagonized by
corticosteroids. There is an increased risk of hypokalaemia when loop
diuretics are given with corticosteroids.
Other Diuretics: There is an increased risk of hypokalaemia when loop
diuretics are given with acetazolamide. Profound diuresis is possible when
metolazone is given with furosemide. There is an increased risk of
hypokalaemia when loop diuretics are given with thiazides and related
diuretics.
Lithium: Loop diuretics reduce the excretion of lithium, which may lead to
increased plasma concentrations and a risk of toxicity. Therefore, it is
recommended that lithium levels are carefully monitored and where necessary
the lithium dosage is adjusted in patients receiving this combination.
Potassium salts: There is an increased risk of hypokalaemia when given with
potassium salts.

Sucralfate: Furosemide and sucralfate must not be taken within 2 hours of
each other as sucralfate decreases the absorption of furosemide from the
intestine and so reduces its effect.
Sympathomimetics, Beta 2: There is an increased risk of hypokalameia when
loop diuretics are given with high doses of beta2 synpathomimetics.
Tacrolimus: There is an increased risk of hypokalaemia when given with
tacrolimus.
Theophylline: There is an increased risk of hypokalaemia when loop diuretics
are given with theophylline.
Carbenoxolone, prolonged use of laxatives, liquorice: May increase the risk of
developing hypokalaemia.
Warfarin and clofibrate: Warfarin and clofibrate compete with furosemide in
the binding to serum albumin. This may have clinical significance in patients
with low serum albumin levels (e.g. in nephrotic syndrome). Furosemide does
not change the pharmacokinetics of warfarin to a significant extent, but a
strong diuresis with associated dehydration may weaken the antithrombotic
effect of warfarin.
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.

4.6

Pregnancy and lactation

Pregnancy:
Results of animal work, in general, show no hazardous effect of furosemide in
pregnancy. There is clinical evidence of safety of the drug in the third
trimester of human pregnancy; however, furosemide crosses the placental
barrier. It must not be given during pregnancy unless there are compelling
medical reasons.
Lactation:

Furosemide passes into breast milk and may inhibit lactation. Breastfeeding
must be avoided during treatment with furosemide.

4.7

Effects on ability to drive and use machines
Mental alertness may be reduced and the ability to drive or operate machinery
may be impaired.

4.8

Undesirable effects
The frequencies of adverse events are ranked according to the following:
Very common(≥1/10),
Common (≥1/100 to <1/10),
Uncommon (≥1/1,000 to <1/100),
Rare (≥1/10,000 to <1/1,000),
Very Rare (< 1/10,000),
Not known (cannot be estimated from the available data)

System Organ
Class

Very common
(≥1/10)

Common (≥1/100
to <1/10)

Uncommon
(≥1/1,000 to
<1/100)

Cardiac
disorders
Congenital,
familial and
genetic
disorders
Ear and
labyrinth
disorders

Very rare
(<1/10,000)

bone marrow
depression,
(necessitates
withdrawal of
treatment),
leucopenia,
eosinophilia

Blood and
lymphatic
system
disorders

Rare (≥1/10,000 to
<1/1,000)

agranulocyt
osis,
aplastic
anaemia,
haemolytic
anaemia

Patent ductus
arteriosus

Patent
ductus
arteriosus

Tinnitus,
reversible or
irreversible loss of
hearing (although
usually transitory,
particularly in
patients with renal
failure,
hypoproteinaemia
(e.g. in nephritic
syndrome) and/or
when intravenous

Tinnitus,
reversible
or
irreversible
loss of
hearing
(although
usually
transitory,
particularly
in patients
with renal

Cardiac
arrhythmias

Not known
(cannot be
estimated from
the available
data)
thrombocytopeni
a

furosemide has
been given too
rapidly)

visual
disturbance
dry mouth,
thirst, nausea,
bowel motility
disturbances,
vomiting,
diarrhea,
constipation
Fatigue

Gastrointestina
l disorders

General
disorders and
administration
site conditions
Hepato-biliary
disorders

Investigations

Metabolism
and nutrition
disorders

Musculoskeleta
land connective
tissue disorders
Nervous system
disorders
Psychiatric

creatinine
increased, blood
urea increased
dehydration,
hyponatraemia
, pre –existing
hypochloremic
metabolic
alkalosis may
be agravated,
hypokalaemia,
hypocalcaemia
,
hypomagnese
mia
(incidences of
the last three
are reduced by
triamterene)

dehydration,
hyponatraemia,
pre –existing
hypochloremic
metabolic
alkalosis may be
agravated,
hypokalaemia,
hypocalcaemia,
hypomagnesemia
(incidences of the
last three are
reduced by
triamterene)

Acute Pancreatitis

Acute
Pancreatitis

Malaise, Fever

Malaise,
Fever

Pure Intrahepatic
Cholestasis,
Hepatic function
abnormal,
Jaundice

Eye disorders

failure,
hypoprotein
aemia (e.g.
in nephritic
syndrome)
and/or
when
intravenous
furosemide
has been
given too
rapidly)

Pure
Intrahepati
c
Cholestasis,
Hepatic
function
abnormal,
Jaundice
Transamina
ses
increased,
blood
tetany

Transaminases
increased, blood

impaired
glucose
tolerance (by
hypokalaemia),
hyperuricaemi
a, gout,
reduction of
serum HDLcholesterol,
elevation of
serum LDLcholesterol,
elevation of
serum
triglycerides,
metabolic
acidosis
muscle cramps,
muscle
weakness
Paraesthesia,
confusion
Psychiatric

disorder
Renal and
urinary
disorders

Reduced
diuresis,
urinary
incontinence,
urinary
obstruction (in
patients with
hyperplasia of
the prostate,
bladder
inability to
empty,
urethral
stricture
unspecified)

Skin and
subcutaneous
tissue disorders

Vascular
disorders

disorder NOC
nephrocalcinosis
(in pre-term
infants treated
with Furosemide),
interstitial
nephritis, acute
renal failure

nephrocalci
nosis (in
pre-term
infants
treated with
Furosemide
), interstitial
nephritis,
acute renal
failure

Rash,
photosensitivity

decreased
blood
pressure,
(which, if
pronounced
may cause
signs and
symptoms such
as impairment
of
concentration
and reactions,
lightheadedness,
sensations of
pressure in the
head,
headache,
dizziness,
drowsiness,
weakness,
disorders of
vision, dry
mouth,
orthostatic
intolerance)

decreased blood
pressure, (which,
if pronounced
may cause signs
and symptoms
such as
impairment of
concentration
and reactions,
light-headedness,
sensations of
pressure in the
head, headache,
dizziness,
drowsiness,
weakness,
disorders of
vision, dry
mouth,
orthostatic
intolerance)

Hypotension,
hypovolaemia

Rash,
photosensiti
vity

Vasculitis,
Thrombosis, shock

Urticaria,
purpura,
erythema
multiforme ,
exfoliative
dermatitis,
itching, bullous
lesions

Vasculitis,
Thrombosis
, shock

Severe
anaphylactic or
anaphylactoid
reactions

Immune
system
disorders

Premature infants
If furosemide is administered to premature infants during the first weeks of
life, it may increase the risk of persistence of patent ductus arteriosus. Risk of

nephrocalcinosis/nephroliathisis (see Tetany and reduced serum calcium and
section 4.4)

4.9

Overdose

Overdosing may lead to dehydration and electrolyte depletion through
excessive diuresis. Severe potassium loss may lead to serious cardiac
arrhythmias.
Treatment of overdose consists of fluid replacement and electrolyte imbalance
correction.
No specific antidote to furosemide is known. If ingestion has only just taken
place, attempts may be made to limit further systemic absorption of the active
ingredient by measures such as gastric lavage or those designated to reduce
absorption (e.g. activated charcoal).

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group:
High-Ceiling Diuretic Sulfonamide - CO3C A 01
Furosemide is a potent loop diuretic which inhibits sodium and chloride
reabsorption at the Loop of Henlé. The drug eliminates both positive and
negative free water production. Furosemide acts at the luminal face of the
epithelial cells by inhibiting co-transport mechanisms for the entry of sodium
and chloride. Furosemide gains access to its site of action by being transported
through the secretory pathway for organic acids in the proximal tubule. It
reduces the renal excretion of uric acid. Furosemide causes an increased loss
of potassium in the urine and also increases the excretion of ammonia by the
kidney.

5.2

Pharmacokinetic properties

Furosemide is a weak carboxylic acid which exists mainly in the dissociated
form in the gastro-intestinal tract. Furosemide is rapidly but incompletely
absorbed (60-70%) on oral administration and its effect is largely over within
four hours. The optimal absorption site is the upper duodenum at pH 5.0.
Regardless of route of administration, 69-97% of activity from a radio-labelled
dose is excreted in the first 4 hours after the drug is given. Furosemide is
mainly eliminated via the kidneys (80-90%); a small fraction of the dose
undergoes biliary elimination and 10-15% of the activity can be recovered
from the faeces.
When oral doses of Furosemide are given to normal subjects the mean
bioavailability of the drug is approximately 52% but the range is wide. In
plasma, Furosemide is extensively bound to proteins mainly to albumin. The
unbound fraction in plasma averages 2 - 4% at therapeutic concentrations. The
volume of distribution ranges between 170 - 270ml/Kg. The half life of the ß
phase ranges from 45 - 60 min. The total plasma clearance is about
200ml/min. Renal excretion of unchanged drug and elimination by metabolism
plus faecal excretion contribute almost equally to the total plasma clearance.
Furosemide is in part cleared by the kidneys in the form of the glucuronide
conjugate.

5.3

Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are
additional to that already included in other sections of the SPC.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Liquid sorbitol
Glycerol
Sodium dihydrogen phosphate dihydrate
Ethanol (96%)
Orange flavor
Sodium hydroxide (32% w/v)
Purified water.

6.2

Incompatibilities
Not applicable

6.3

Shelf life

30 months
3 months after opening

6.4

Special precautions for storage
Store in the original package in order to protect from light.

6.5

Nature and contents of container

Amber (Type III) glass bottle, with child-resistant, tamper-evident cap with
PEBD seal, along with a 5 ml metered syringe with 0.1 ml graduation.
Capacity: 150 ml

6.6

Special precautions for disposal
No special requirements.

7

MARKETING AUTHORISATION HOLDER

Alapis S.A.
2, Aftokratoros Nikolaou str.
17671, Athens, Greece

8

MARKETING AUTHORISATION NUMBER(S)
PL 35574/0001

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
17/05/2011

10

DATE OF REVISION OF THE TEXT
17/05/2011

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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