TRACRIUM SOLUTION FOR INJECT 25MG/2.5ML 50MG/5ML 250MG/25ML

Active substance: ATRACURIUM BESILATE

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10000000123979

2

Package Leaflet: Information for Healthcare Professions

10000000123979
GSK-ITA-Parma-ITPAR
United Kingdom-GBR
Tracrium
1

.
. .

Tracrium® 10 mg/ml Injection

atracurium besilate
Please refer to the Summary of Product Characteristics
for complete prescribing information.

Presentation
Tracrium Injection is a clear, faintly yellow, sterile aqueous solution
in a glass ampoule or vial containing 10 mg atracurium besilate per
ml. Each 2.5 ml ampoule contains 25 mg atracurium besilate, each
5 ml ampoule contains 50 mg atracurium besilate and each 25 ml vial
contains 250 mg atracurium besilate.
Uses
Tracrium is a highly selective, competitive or non-depolarising
neuromuscular blocking agent. It is used as an adjunct to general
anaesthesia or sedation in the Intensive Care Unit (ICU), to relax
skeletal muscles, and to facilitate tracheal intubation and mechanical
ventilation.

K

D00055LEA

Dosage and administration
Use by injection in adults: Tracrium is administered by intravenous
injection.
The dosage range recommended for adults is 0.3 to 0.6 mg/kg
(depending on the duration of full block required) and will provide
adequate relaxation for about 15 to 35 minutes.
Endotracheal intubation can usually be accomplished within 90 seconds
from the intravenous injection of 0.5 to 0.6 mg/kg.
Full block can be prolonged with supplementary doses of 0.1 to
0.2 mg/kg as required. Successive supplementary dosing does not give
rise to accumulation of neuromuscular blocking effect.
Spontaneous recovery from the end of full block occurs in about 35
minutes as measured by the restoration of the tetanic response to 95%
of normal neuromuscular function.
The neuromuscular block produced by Tracrium can be rapidly reversed
by standard doses of anticholinesterase agents, such as neostigmine
and edrophonium, accompanied or preceded by atropine, with no
evidence of recurarisation.
Use as an infusion in adults: After an initial bolus dose of 0.3 to
0.6 mg/kg, Tracrium can be used to maintain neuromuscular block
during long surgical procedures by administration as a continuous
infusion at rates of 0.3 to 0.6 mg/kg/hour.
Tracrium can be administered by infusion during cardiopulmonary
bypass surgery at the recommended infusion rates. Induced
hypothermia to a body temperature of 25° to 26°C reduces the rate of
inactivation of atracurium, therefore full neuromuscular block may be
maintained by approximately half the original infusion rate at these
low temperatures.
Tracrium is compatible with the following infusion solutions for the
times stated below:

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Infusion Solution
Period of Stability
Sodium Chloride Intravenous
24 hours
Infusion BP (0.9% w/v)
Glucose Intravenous
8 hours
Infusion BP (5% w/v)
Ringer’s Injection USP
8 hours
Sodium Chloride (0.18% w/v) and
8 hours
Glucose (4% w/v) Intravenous Infusion BP
Compound Sodium Lactate Intravenous
4 hours
Infusion BP (Hartmann’s Solution for Injection)
When diluted in these solutions to give atracurium concentrations of
0.5 mg/ml and above, the resultant solutions will be stable in daylight
for the stated periods at temperatures of up to 30°C.
Use in children: The dosage in children over the age of one month is
similar to that in adults on a body weight basis.
Use in neonates: The use of Tracrium is not recommended in neonates
since there are insufficient data available (see section 5.1 Summary of
Product Characteristics).
Use in the elderly: Tracrium may be used at standard dosage in elderly
patients. It is recommended, however, that the initial dose be at the
lower end of the range and that it be administered slowly.
Use in patients with reduced renal and/or hepatic function: Tracrium
may be used at standard dosage at all levels of renal or hepatic
function, including end stage failure.
Use in patients with cardiovascular disease: In patients with clinically
significant cardiovascular disease, the initial dose of Tracrium should be
administered over a period of 60 seconds.

Use in Intensive Care Unit (ICU) patients: After an optional initial
bolus dose of Tracrium of 0.3 to 0.6 mg/kg, Tracrium can be used
to maintain neuromuscular block by administering a continuous
infusion at rates of between 11 and 13 micrograms/kg/min (0.65 to
0.78 mg/kg/hr). There may be wide inter-patient variability in dosage
requirements and these may increase or decrease with time. Infusion
rates as low as 4.5 microgram/kg/min (0.27 mg/kg/hr) or as high as
29.5 microgram/kg/min (1.77 mg/kg/hr) are required in some patients.
The rate of spontaneous recovery from neuromuscular block after
infusion of Tracrium in ICU patients is independent of the duration of
administration. Spontaneous recovery to a train-of-four ratio >0.75 (the
ratio of the height of the fourth to the first twitch in a train-of-four)
can be expected to occur in approximately 60 minutes. A range of 32 to
108 minutes has been observed in clinical trials.
Monitoring: In common with all neuromuscular blocking agents,
monitoring of neuromuscular function is recommended during the use
of Tracrium in order to individualise dosage requirements.
Contraindications
Tracrium is contraindicated in patients known to be hypersensitive to
atracurium, cisatracurium or benzene sulfonic acid.
Special warnings and precautions for use
Precautions: In common with all the other neuromuscular blocking
agents, Tracrium paralyses the respiratory muscles as well as other
skeletal muscles but has no effect on consciousness. Tracrium should
be administered only with adequate general anaesthesia and only
by or under the close supervision of an experienced anaesthetist
with adequate facilities for endotracheal intubation and artificial
ventilation.
The potential for histamine release exists in susceptible patients during
Tracrium administration. Caution should be exercised in administering
Tracrium to patients with a history suggestive of an increased sensitivity
to the effects of histamine. In particular, bronchospasm may occur in
patients with a history of allergy and asthma.
High rates of cross-sensitivity between neuromuscular blocking agents
have been reported. Therefore, where possible, before administering
atracurium, hypersensitivity to other neuromuscular blocking
agents should be excluded. Atracurium should only be used when
absolutely essential in susceptible patients. Patients who experience a
hypersensitivity reaction under general anaesthesia should be tested
subsequently for hypersensitivity to other neuromuscular blockers.
Monitoring of serial creatinine phosphate (cpk) values should be
considered in asthmatic patients receiving high dose corticosteroids and
neuromuscular blocking agents in ICU.
Tracrium does not have significant vagal or ganglionic blocking
properties in the recommended dosage range. Consequently, Tracrium
has no clinically significant effects on heart rate in the recommended
dosage range and it will not counteract the bradycardia produced by
many anaesthetic agents or by vagal stimulation during surgery.
In common with other non-depolarising neuromuscular blocking
agents, increased sensitivity to atracurium may be expected in patients
with myasthenia gravis and other forms of neuromuscular disease.
As with other neuromuscular blocking agents severe acid-base and/or
serum electrolyte abnormalities may increase or decrease the sensitivity
of patients to atracrium.
As with other non-depolarising neuromuscular blockers
hypophosphataemia may prolong recovery. Recovery may be hastened
by correcting this condition.
Tracrium should be administered over a period of 60 seconds to
patients who may be unusually sensitive to falls in arterial blood
pressure, for example those who are hypovolaemic.
Tracrium is inactivated by high pH and so must not be mixed in the
same syringe with thiopental or any alkaline agent.
When a small vein is selected as the injection site, Tracrium should be
flushed through the vein with physiological saline after injection. When
other anaesthetic drugs are administered through the same in-dwelling
needle or cannula as Tracrium it is important that each drug is flushed
through with an adequate volume of physiological saline.
Atracurium is hypotonic and must not be administered into the infusion
line of a blood transfusion.
Studies in malignant hyperthermia in susceptible animals (swine) and
clinical studies in patients susceptible to malignant hyperthermia
indicate that Tracrium does not trigger this syndrome.
In common with other non-depolarising neuromuscular blocking
agents, resistance may develop in patients suffering from burns. Such
patients may require increased doses dependent on the time elapsed
since the burn injury and the extent of the burn.
Intensive Care Unit (ICU) patients: When administered to laboratory
animals, in high doses, laudanosine, a metabolite of atracurium has
been associated with transient hypotension and, in some species,
cerebral excitatory effects. Although seizures have been seen in ICU
patients receiving atracurium, a causal relationship to laudanosine has
not been established (see Undesirable effects).
Drug interactions
The neuromuscular block produced by Tracrium may be increased by
the concomitant use of inhalational anaesthetics such as halothane,
isoflurane and enflurane.

Ask your doctor if you would like more
explanation about this medicine.

including herbal medicines. This is because
these medicines can affect how well
Tracrium works or can cause side effects.

Package Leaflet:
Information for the Patient

2. What you need to know before
you have Tracrium

Tracrium® 10 mg/ml Injection

Do not have Tracrium if:
• you are allergic to atracurium besilate,
any other muscle relaxant or any of the
other ingredients in Tracrium (listed in
section 6)
• you have reacted badly to an anaesthetic
before.
Do not have Tracrium if any of the above
apply to you. If you are not sure, talk to
your doctor, nurse or pharmacist before
you have Tracrium.

In particular tell your doctor, nurse or
pharmacist if you are taking any of the
following:
• anaesthetics (used to reduce sensation
and pain during surgical procedures)
• antibiotics (used to treat infections)
• medicines for heart conditions
• medicines for high blood pressure
• water tablets (diuretics), such as
furosemide
• medicines for fits (epilepsy), such as
phenytoin or carbamazepine
• medicines containing magnesium, such
as those to treat indigestion and heart
burn
• drugs for Alzheimer’s disease
(anticholinesterases e.g. donepezil)
• medicines for mental illness, such as
lithium
• medicines for inflammation of the joints,
such as chloroquine or D-penicillamine
• steroids.

atracurium besilate
Read all of this leaflet carefully
before you start having this
medicine because it contains
important information for you.
• Keep this leaflet. You may need to
read it again.
• If you have any further questions ask
your doctor, pharmacist or nurse.
• If you get any side effects, talk to
your doctor, pharmacist or nurse.
This includes any possible side
effects not listed in this leaflet.
See section 4.
What is in this leaflet:
1. What Tracrium is and what it is used
for
2. What you need to know before you
have Tracrium
3. How to have Tracrium
4. Possible side effects
5. How to store Tracrium
6. Contents of the pack and other
information
1. What Tracrium is and what it
is used for
Tracrium contains a medicine called
atracurium besilate. This belongs
to a group of medicines called
muscle relaxants.
Tracrium is used:
• to relax muscles during operations
on adults and children over 1 month
of age
• to help insert a tube into the
windpipe (tracheal intubation), if a
person needs help to breathe
• to relax the muscles of adults in
intensive care.

Warnings and precautions
Talk to your doctor, pharmacist or nurse
before having Tracrium if:
• you have muscle weakness, tiredness
or difficulty in co-ordinating your
movements (myasthenia gravis)
• you have a neuromuscular disease, such
as a muscle wasting disease, paralysis,
motor neurone disease or cerebral palsy
• you have a severe electrolyte imbalance
• you have a lower than normal volume of
blood (hypovolaemia)
• you have a burn which requires medical
treatment
• you have ever had an allergic reaction to
any muscle relaxant which was given as
part of an operation
• you have a history of sensitivity to
histamine. In particular, spasm of the
airways may occur if you have a history
of allergy or asthma.

Pregnancy and breast-feeding
If you are pregnant or breast-feeding,
think you may be pregnant or are
planning to have a baby, ask your doctor
or pharmacist for advice before having this
medicine.
Driving and using machines
It can be dangerous to drive or operate
machinery too soon after having had an
operation. Your doctor will tell you how
long to wait before you can drive and use
machinery.
.
. .

If you are not sure if any of the above
apply to you, talk to your doctor, nurse or
pharmacist before you are given Tracrium.
Other medicines and Tracrium
Tell your doctor, nurse or pharmacist if you
are taking, have recently taken or might
take any other medicines. This includes
medicines obtained without a prescription,

3. How to have Tracrium
How your injection is given
You will never be expected to give yourself
this medicine. It will always be given to
you by a person who is qualified to do so.

10000000123979
GSK-ITA-Parma-ITPAR
United Kingdom-GBR
Tracrium
1

K

D00055LEA

Undesirable effects
The most commonly reported adverse reactions during treatment
are hypotension (mild, transient) and skin flushing, these events are
attributed to histamine release. Very rarely, severe anaphylactoid
or anaphylactic reactions have been reported in patients receiving
atracurium in conjunction with one or more anaesthetic agents.
Adverse reactions are listed below by system organ class and
frequency. Frequencies are defined as: very common > 1/10, common
>1/100 and < 1/10, uncommon >1/1,000 and < 1/100, rare >1/10,000
and < 1/1,000, very rare < 1/10,000.
Very common, common and uncommon frequencies were
determined from clinical trial data. Rare and very rare frequencies
were generally derived from spontaneous data. The frequency
classification “Not known” has been applied to those reactions where
a frequency could not be estimated from the available data.
Clinical Trial Data:
Vascular Disorders
Common
Hypotension (mild, transient)#, Skin flushing#
Respiratory, thoracic and mediastinal disorders
Uncommon
Bronchospasm#

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Post-Marketing Data:
Immune system disorders
Very rare
Anaphylactic reaction, anaphylactoid reaction
including shock, circulatory failure and cardiac arrest
Very rarely severe anaphylactoid or anaphylactic reactions have been
reported in patients receiving atracurium in conjunction with one or
more anaesthetic agents
Nervous system disorder
Not known
Seizures
There have been reports of seizures in ICU patients who have been
receiving atracurium concurrently with several other agents. These
patients usually had one or more medical conditions predisposing
to seizures (e.g. cranial trauma, cerebral oedema, viral encephalitis,
hypoxic encephalopathy, uraemia). A causal relationship to
laudanosine has not been established. In clinical trials, there appears to
be no correlation between plasma laudanosine concentration and the
occurrence of seizures.
Skin and subcutaneous tissue disorders
Rare
Urticaria

Musculoskeletal and connective tissue disorders
Not known
Myopathy, muscle weakness
There have been some reports of muscle weakness and/or myopathy
following prolonged use of muscle relaxants in severely ill patients
in the ICU. Most patients were receiving concomitant corticosteroids.
These events have been seen infrequently in association with
atracurium and a causal relationship has not been established.
Events which have been attributed to histamine release are indicated
by a hash (#)

medicinal product is important. It allows continued monitoring of the
benefit/risk balance of the medicinal product. Healthcare professionals
are asked to report any suspected adverse reactions via the Yellow Card
Scheme at: www.mhra.gov.uk/yellowcard.
.
Fertility, pregnancy and lactation
. .
Fertility: Fertility studies have not been performed.
Pregnancy: Animal studies have indicated that Tracrium has no
significant effects on foetal development.
In common with all neuromuscular blocking agents, Tracrium should
be used during pregnancy only if the potential benefit to the mother
outweighs any potential risk to the foetus.
Tracrium is suitable for maintenance of muscle relaxation during
Caesarean section as it does not cross the placenta in clinically
significant amounts following recommended doses.
Breast-feeding: It is not known whether Tracrium is excreted in
human milk.
Ability to drive and use machines
This precaution is not relevant to the use of atracurium. Atracurium
will always be used in combination with a general anaesthetic and
therefore the usual precautions relating to performance of tasks
following general anaesthesia apply.
Toxicity and treatment of overdosage
Signs: Prolonged muscle paralysis and its consequences are the main
signs of overdosage.
Management: It is essential to maintain a patent airway together with
assisted positive pressure ventilation until spontaneous respiration
is adequate. Full sedation will be required since consciousness is
not impaired. Recovery may be hastened by the administration of
anticholinesterase agents accompanied by atropine or glycopyrrolate,
once evidence of spontaneous recovery is present.
Pharmaceutical precautions
Store at temperatures between 2° to 8°C. Do not freeze.
Keep container in the outer carton in order to protect from light.
Any unused Tracrium from opened ampoules should be discarded.
Legal category
POM
Package quantities
Box of 5 x 2.5 ml ampoules (each ampoule containing 25 mg atracurium
besilate).
Box of 5 x 5 ml ampoules (each ampoule containing 50 mg atracurium
besilate).
Box of 2 x 25 ml vials (each vial containing 250 mg atracurium besilate).
Further information
Tracrium is inactivated by Hofmann elimination, a non-enzymatic
process which occurs at physiological pH and temperature, and by ester
hydrolysis catalysed by non-specific esterases.
The termination of the neuromuscular blocking action of Tracrium
is not dependent on its hepatic or renal metabolism or excretion.
Its duration of action, therefore, is unlikely to be affected by impaired
renal, hepatic or circulatory function.
Tests with plasma from patients with low levels of
pseudochlolinesterase show that the inactivation of Tracrium proceeds
unaffected.
Tracrium has no direct effect on intra-ocular pressure, and is therefore
suitable for use in ophthalmic surgery.
Variations in the blood pH and body temperature of the patient within
the physiological range will not significantly alter the duration of
action of Tracrium.
Haemofiltration and haemodiafiltration have a minimal effect on
plasma levels of atracurium and its metabolites, including laudanosine.
The effects of haemodialysis and haemoperfusion on plasma levels of
atracurium and its metabolites are unknown.
Tracrium is made by GlaxoSmithKline Manufacturing S.p.A.,
San Polo di Torrile, Parma, Italy
Product licence number
PL 00003/0166
The Wellcome Foundation Ltd., Stockley Park West, Uxbridge,
Middlesex UB11 1BT
Tracrium is a registered trademark of the GlaxoSmithKline
group of companies
© 2013 GlaxoSmithKline group of companies. All rights reserved

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the

Tracrium can be given:
• as a single injection into your vein
(intravenous bolus injection)
• as a continuous infusion into your vein.
This is where the drug is slowly given to
you over a long period of time.
Your doctor will decide the way you are
given the drug and the dose you will
receive. It will depend on:
• your body weight
• the amount and duration of muscle
relaxation required
• your expected response to the medicine.
Children less than 1 month old should not
have this medicine.
If you receive more Tracrium than you
should
Tracrium will always be given under
carefully controlled conditions.
However, if you think that you have been
given more than you should tell your
doctor or nurse immediately.
4. Possible side effects
Like all medicines, Tracrium can cause side
effects, although not everybody gets them.
The following effects may happen with
this medicine:
Allergic reactions
If you have an allergic reaction, tell your
doctor or nurse straight away. The signs
may include:
Common side effects
(may affect up to 1 in 10 people)
• decrease in blood pressure
• reddening of your skin
Uncommon side effects
(may affect up to 1 in 100 people)
• wheezing or coughing
Rare side effects
(may affect up to 1 in 1,000 people)
• a lumpy skin rash or ‘hives’ anywhere on
your body

Very Rare side effects
(may affect up to 1 in 10,000 people)
• sudden wheeziness, chest pain or chest
tightness
• swelling of your eyelids, face, lips, mouth
or tongue
• decrease in heart rate
• shock, circulatory failure, cardiac arrest
Very rarely a severe allergic reaction can
occur when given one or more anaesthetic
agent.
Other side effects (unknown frequency)
that you may experience are:
• seizures
• muscle disease (myopathy) or muscle
weakness
Reporting of side effects
If you get any side effects, talk to your
doctor, pharmacist or nurse. This includes
any possible side effects not listed in this
leaflet. You can also report side effects
directly via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard.
By reporting side effects you can help
provide more information on the safety of
this medicine.
5. How to store Tracrium
• Keep out of the sight and reach of
children
• Do not use Tracrium after the expiry
date which is stated on the pack after
EXP. The expiry date refers to the last
day of that month
• Store between 2 and 8°C. Do not freeze
• Keep in the outer carton in order to
protect from light
• When Tracrium is made up it should be
used straight away. Any unused solution
should be thrown away
6. Contents of the pack and other
information
What Tracrium contains
• The active substance is atracurium
besilate

• The other ingredients are benzene
sulfonic acid and Water for Injections.
What Tracrium looks like and contents of
the pack
Tracrium injection comes in boxes of 5 by
2.5 ml and 5 ml glass ampoules or 2 by
25 ml glass vials.
Each vial/ampoule contains 10 mg/ml of
the active ingredient atracurium besilate.
Marketing authorisation holder
and manufacturer
Marketing Authorisation Holder:
The Wellcome Foundation Ltd.,
Stockley Park West, Uxbridge,
Middlesex UB11 1BT
Manufacturer:
GlaxoSmithKline Manufacturing S.p.A.,
Strada Provinciale Asolana 90,
43056 San Polo di Torrile, Parma, Italy.
Other formats
To listen to or request a copy of this leaflet
in Braille, large print or audio please call,
free of charge:

0800 198 5000 (UK only)
Please be ready to give the following
information:
Product name
Reference number

Tracrium Injection
00003/0166

This is a service provided by the
Royal National Institute of Blind People
This leaflet was revised in October 2013
Tracrium is a registered trademark
of the GlaxoSmithKline group of
companies
© 2013 GlaxoSmithKline group of
companies. All rights reserved

.
. .

10000000123979

2

In common with all non-depolarising neuromuscular blocking
agents the magnitude and/or duration of a non-depolarising
neuromuscular block may be increased as a result of interaction with:
antibiotics, including the aminoglycosides, polymyxins, spectinomycin,
tetracyclines, lincomycin and clindamycin; antiarrhythmic drugs:
propranolol, calcium channel blockers, lidocaine, procainamide and
quinidine; diuretics: furosemide and possibly mannitol, thiazide
diuretics and acetazolamide; magnesium sulphate; ketamine; lithium
salts; ganglion blocking agents: trimetaphan, hexamethonium.
Rarely, certain drugs may aggravate or unmask latent myasthenia
gravis or actually induce a myasthenic syndrome; increased sensitivity
to Tracrium would be consequent on such a development. Such drugs
include various antibiotics, beta-blockers (propranolol, oxprenolol),
antiarrhythmic drugs (procainamide, quinidine), antirheumatic drugs
(chloroquine, D-penicillamine), trimetaphan, chlorpromazine, steroids,
phenytoin and lithium.
The onset of non-depolarising neuromuscular block is likely to be
lengthened and the duration of block shortened in patients receiving
chronic anticonvulsant therapy.
The administration of combinations of non-depolarising neuromuscular
blocking agents in conjunction with Tracrium may produce a degree
of neuromuscular blockade in excess of that which might be expected
were an equipotent total dose of Tracrium administered. Any
synergistic effect may vary between different drug combinations.
A depolarising muscle relaxant such as suxamethonium chloride should
not be administered to prolong the neuromuscular blocking effects of
non-depolarising blocking agents such as atracurium, as this may result
in a prolonged and complex block which can be difficult to reverse with
anticholinesterase drugs.
Treatment with anticholinesterases, commonly used in the treatment
of Alzheimer’s disease e.g. donepezil, may shorten the duration and
diminish the magnitude of neuromuscular blockade with atracurium.

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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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