MIVACRON INJECTION 2MG/ML

Active substance: MIVACURIUM CHLORIDE

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.
. .

1
10000000124844
GSK-ITA-Parma-ITPAR

10000000124844

The following information is intended for medical or
healthcare professionals only

Mivacron
1

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D00055LEA

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Product Summary
1. Trade Name of the Medicinal Product
Mivacron® Injection 2mg/ml
2. Qualitative and Quantitative Composition
Mivacurium chloride 2.14mg in each 1ml of product
For a full list of excipients, see section 6.1.
3. Pharmaceutical Form
Liquid for injection
Clinical Particulars
4.1 Therapeutic Indications
Mivacron is a highly selective, short-acting, non-depolarising neuromuscular blocking
agent with a fast recovery profile. Mivacron is used as an adjunct to general
anaesthesia to relax skeletal muscles and to facilitate tracheal intubation and
mechanical ventilation in adults, children and infants 2 months and over.
This formulation contains no antimicrobial preservative and is intended for single
patient use.
4.2 Posology and Method of Administration
Use By Injection In Adults
Mivacron is administered by intravenous injection. The mean dose required to
produce 95% suppression of the adductor pollicis single twitch response to ulnar
nerve stimulations (ED95) is 0.07 mg/kg (range 0.06 to 0.09) in adults receiving
narcotic anaesthesia.
The recommended bolus dose range for healthy adults is 0.07-0.25 mg/kg. The
duration of neuromuscular blockade is related to the dose. Doses of 0.07, 0.15, 0.20
and 0.25 mg/kg produce clinically effective block for approximately 13, 16, 20 and
23 minutes respectively.
Doses of up to 0.15 mg/kg may be administered over 5 to 15 seconds. Higher doses
should be administered over 30 seconds in order to minimise the possibility of
occurrence of cardiovascular effects.
The following dose regimens are recommended for tracheal intubation:
I A dose of 0.2 mg/kg, administered over 30 seconds, produces good to excellent
conditions for tracheal intubation within 2 to 2.5 minutes.
II A dose of 0.25 mg/kg administered as a divided dose (0.15 mg/kg followed 30
seconds later by 0.1 mg/kg) produces good to excellent conditions for tracheal
intubation within 1.5 to 2.0 minutes of completion of administration of the first
dose portion.
With Mivacron, significant train-of-four fade is not seen during onset. It is often
possible to intubate the trachea before complete abolition of the train-of-four
response of the adductor pollicis muscle has occurred.
Full block can be prolonged by maintenance doses of Mivacron. Doses of 0.1 mg/kg
administered during narcotic anaesthesia each provide approximately 15 minutes of
additional clinically effective block. Successive supplementary doses do not give rise
to accumulation of neuromuscular blocking effect.
The neuromuscular blocking action of Mivacron is potentiated by isoflurane or
enflurane anaesthesia. If steady-state anaesthesia with isoflurane or enflurane has
been established, the recommended initial Mivacron dose should be reduced by up to
25%. Halothane appears to have only a minimal potentiating effect on Mivacron and
dose reduction of Mivacron is probably not necessary.
Once spontaneous recovery is underway it is complete in approximately 15 minutes
and is independent of the dose of Mivacron administered.
The neuromuscular block produced by Mivacron can be reversed with standard doses
of anticholinesterase agents. However, because spontaneous recovery after Mivacron
is rapid, a reversal may not be routinely required as it shortens recovery time by only
5-6 minutes.
Use as an Infusion in Adults
Continuous infusion of Mivacron may be used to maintain neuromuscular block. Upon
early evidence of spontaneous recovery from an initial Mivacron dose, an infusion
rate of 8 to 10 micrograms/kg/min (0.5 to 0.6 mg/kg/hr) is recommended.
The initial infusion rate should be adjusted according to the patient’s response to
peripheral nerve stimulation and clinical criteria. Adjustments of the infusion rate
should be made and should be increments of approximately 1 microgram/kg/min
(0.06 mg/kg/hr). In general, a given rate should be maintained for at least
3 minutes before a rate change is made. On average, an infusion rate of 6 to
7 micrograms/kg/minute will maintain neuromuscular block within the range of
89% to 99% for extended periods in adults receiving narcotic anaesthesia. During
steady-state isoflurane or enflurane anaesthesia, reduction in the infusion rate by
up to 40% should be considered. A study has shown that the mivacurium infusion
rate requirement should be reduced by up to 50% with sevoflurane. With halothane,
smaller reductions in infusion rate may be required.
Spontaneous recovery after Mivacron infusion is independent of the duration of
infusion and comparable to recovery reported for single doses.
Continuous infusion of Mivacron has not been associated with the development of
tachyphylaxis or cumulative neuromuscular blockade.
Mivacron (2 mg/ml) may be used undiluted for infusion.
Mivacron is compatible with the following infusion fluids.
Sodium chloride intravenous infusion (0.9% w/v)
Glucose intravenous infusion (5% w/v)
Sodium chloride (0.18% w/v) and glucose (4% w/v) intravenous infusion
Lactated Ringer’s Injection United States Pharmacopoeia (USP)
When diluted with the listed infusion solutions in the proportion of 1 plus 3 (i.e. to
give 0.5 mg/ml) Mivacron injection has been shown to be chemically and physically
stable for at least 48 hours at 30oC. However, since the product contains no
antimicrobial preservative, dilution should be carried out immediately prior to use,
administration should commence as soon as possible thereafter, and any remaining
solution should be discarded.
Doses in Infants and Children Aged 2 Months - 12 Years
Mivacron has a faster onset, shorter clinically effective duration of action and more
rapid spontaneous recovery profile in infants and children than in adults.
The ED95 in infants aged 2 to 6 months is approximately 0.07 mg/kg; and in infants
and children aged 7 months to 12 years is approximately 0.1 mg/kg.
Pharmacodynamic data for recommended initial doses in infants and children are
summarised in the following table:

0.15 mg/kg

Time to
Maximum
Neuromuscular
Block (min)
1.4

Duration of
Clinically
Effective
Block (min)
9

0.2 mg/kg

1.7

9

Age

Dose for
Tracheal
Intubation

2 - 6 monthsA
7 months - 12 yearsB
AData
BData

obtained during halothane anaesthesia.
obtained during halothane or narcotic anaesthesia.

Package Leaflet: Information for the
Patient

Mivacron®
Injection 2 mg/ml
mivacurium
Read all of this leaflet carefully before
you are given this medicine because it
contains important information for you.
• eep this leaflet. You may need to read it again.
K
• f you have any further questions about your
I
illness or your medicine, ask your doctor,
nurse or pharmacist. This includes any
possible side effects not listed in this leaflet.
See section 4.
• f any of the side effects get serious, or if
I
you notice any side effects not listed in
this leaflet, please tell your doctor, nurse or
pharmacist.
What is in this leaflet:
1. What Mivacron is and what it is used for
2. What you need to know before you are
given Mivacron
3. How Mivacron is given
4. Possible side effects
5. How to store Mivacron
6. Contents of the pack and other
information

1. What Mivacron is and what it is
used for
Mivacron contains a medicine called mivacurium.
This belongs to a group of medicines called
muscle relaxants.
Mivacron is used:
• o relax muscles during operations on adults
t
and children over 2 months of age, including
heart surgery

Age

Maintenance
Dose

Duration of
Clinically
Effective
Block (min)

2 months - 12 yearsA

Mivacron®
Injection 2 mg/ml
mivacurium

United Kingdom-GBR

Since maximum block is usually achieved within 2 minutes following administration
of these doses, tracheal intubation should be possible within this time.
Infants and children generally require more frequent maintenance doses and
higher infusion rate than adults. Pharmacodynamic data for maintenance doses are
summarised in the table below together with recommended infusion rates:

0.1 mg/kg

6-9

Average Infusion
Rate Required to
Maintain 89-99%
Neuromuscular
Block
11 – 14 mcg/kg/min
(0.7 - 0.9 mg/kg/hr)

AData obtained during halothane or narcotic anaesthesia.
The neuromuscular blocking action of mivacurium is potentiated by inhalational
agents. A study has shown that the mivacurium infusion rate requirement should be
reduced by up to 70% with sevoflurane in children aged 2 – 12 years.
Once spontaneous recovery is underway, it is complete in approximately 10 minutes.
Dose in Neonates and Infants < 2 Months of Age
The safety and efficacy of Mivacron in neonates and infants < 2 months has not
yet been established. Currently available data are described in section 5.1, but no
recommendation on posology can be made.
Dose in the Elderly
In elderly patients receiving single bolus doses of Mivacron, the onset time, duration
of action and recovery rate may be extended relative to younger patients by 20 to
30%. Elderly patients may also require decreased infusion rates or smaller or less
frequent maintenance bolus doses.
Dose in Patients with Cardiovascular Disease
In patients with clinically significant cardiovascular disease, the initial dose of
Mivacron should be administered over 60 seconds. Mivacron has been administered
in this way with minimal haemodynamic effects to patients undergoing cardiac
surgery.
Dose in Patients with Reduced Renal Function
In patients with end-stage renal failure the clinically effective duration of block
produced by 0.15 mg/kg is approximately 1.5 times longer than in patients with
normal renal function. Subsequently, dosage should be adjusted according to
individual clinical response.
Prolonged and intensified neuromuscular blockade may also occur in patients with
acute or chronic renal failure as a result of reduced levels of plasma cholinesterase
(see section 4.4 Special Warnings and Precautions for Use).
Dose in Patients with Reduced Hepatic Function
In patients with end-stage liver failure the clinically effective duration of block
produced by 0.15 mg/kg is approximately three times longer than in patients with
normal hepatic function. This prolongation is related to the markedly reduced plasma
cholinesterase activity seen in these patients. Subsequently, dosage should be
adjusted according to individual clinical response.
Dose in Patients with Reduced Plasma Cholinesterase Activity
Mivacurium is metabolised by plasma cholinesterase. Plasma cholinesterase activity
may be diminished in the presence of genetic abnormalities of plasma cholinesterase
(e.g. patients heterozygous or homozygous for the atypical plasma cholinesterase
gene), in various pathological conditions (see section 4.4 Special
Warnings and Precautions for Use) and by the administration of certain drugs (see
interactions with other medicaments). The possibility of prolonged neuromuscular
block following administration of Mivacron must be considered in patients with
reduced plasma cholinesterase activity. Mild reductions (i.e. within 20% of the lower
limit of the normal range) are not associated with clinically significant effects on
duration (See Contra-indications and Special Warnings and
Precautions for information about use in patients who are homozygous or
heterozygous for the plasma cholinesterase gene).
Dose in Obese Patients
In obese patients (those weighing 30% or more above their ideal bodyweight for
height), the initial dose of Mivacron should be based upon ideal bodyweight and not
actual bodyweight.
Instructions to open the ampoule
See Section 6.6 Special precautions for disposal and other handling for further
information.
Monitoring
In common with all neuromuscular blocking agents, monitoring of
neuromuscular function is recommended during the use of Mivacron in order
to individualise dosage requirements.

4.3 Contraindications
Mivacron should not be administered to patients known to have allergic hypersensitivity
to the drug.
Mivacron is contraindicated in pregnancy since there is no information on the use of
Mivacron in pregnant women.
Mivacron is contraindicated in patients known or suspected of being homozygous
for the atypical plasma cholinesterase gene (see section 4.4 Special warnings and
precautions for use).
4.4 Special Warnings and Precautions for Use
In common with all the other neuromuscular blocking agents, Mivacron paralyses
the respiratory muscles as well as the other skeletal muscles but has no effect on
consciousness. Mivacron should be administered only by or under close supervision of
an experienced anaesthetist with adequate facilities for endotracheal intubation and
artificial ventilation.
Prolonged and intensified neuromuscular blockade following mivacurium may
occur secondary to reduced plasma cholinesterase activity in the following states or
pathological conditions:
• Physiological variation as in pregnancy and the puerperium (see Pregnancy and
Lactation).
• Genetically determined abnormalities of plasma cholinesterase (see below and
Contraindications).
• Severe generalised tetanus, tuberculosis and other severe or chronic infections.
• Chronic debilitating disease, malignancy, chronic anaemia and malnutrition.
• Myxoedema and collagen diseases.
• Decompensated heart disease.
• Peptic ulcer.
• Burns (see below).
• End-stage hepatic failure, (see Dosage and Administration).
• Acute, chronic or end-stage renal failure (see Dosage and Administration).
• Iatrogenic: following plasma exchange, plasmapheresis, cardiopulmonary bypass,
and as a result of concomitant drug therapy (see Interactions).
In common with suxamethonium/succinylcholine, adult and paediatric patients
homozygous for the atypical plasma cholinesterase gene (1 in 2500 patients) are
extremely sensitive to the neuromuscular blocking effect of Mivacurium. In three
such adults patients, a small dose of 0.03 mg/kg (approximately the ED10-20 in
genotypically normal patients) produced complete neuromuscular block for 26 to
128 minutes.
In patients heterozygous for the atypical plasma cholinesterase gene, the clinically
effective duration of block of mivacurium 0.15 mg/kg is approximately 10 min
longer than in control patients.
Once spontaneous recovery had begun, neuromuscular block in these patients was
antagonised with conventional doses of neostigmine.
Patients with burns may develop resistance to non-depolarising neuromuscular
blocking agents and require increased doses. However such patients may also
have reduced plasma cholinesterase activity, requiring dose reduction.
Consequently burn patients should be given a test dose of 0.015-0.020 mg/kg

• o help insert a tube into the windpipe (tracheal
t
intubation), if a person needs help to breathe
Ask your doctor if you would like more
explanation about this medicine.

2. What you need to know before you
are given Mivacron
Do not have Mivacron if:
• ou are allergic to mivacurium, any other
y
muscle relaxant or any of the other ingredients
in Mivacron (listed in Section 6)
• ou or your family have reacted badly to an
y
anaesthetic before.
Do not have Mivacron if any of the above apply
to you. If you are not sure, talk to your doctor,
nurse or pharmacist before you have Mivacron.
Warnings and precautions
Talk to your doctor, nurse or pharmacist before
having this medicine if:
• ou have muscle weakness, tiredness or
y
difficulty in co-ordinating your movements
(myasthenia gravis)
• ou have a neuromuscular disease, such as
y
a muscle wasting disease, paralysis, motor
neurone disease or cerebral palsy
• ou have a burn which requires medical
y
treatment
• ou have ever had an allergic reaction to any
y
muscle relaxant that was given as part of an
operation.
Talk to your doctor before having this medicine, if
you have or have ever had any of the following:
• Tetanus

• severe or long-standing infection such as
A
tuberculosis (TB)
• ny long-standing illness which has left you
A
weak
• Cancer
• Anaemia
• Malnutrition
• An under-active thyroid gland
• Heart disease
• Stomach ulcers

• Burns
• Liver or kidney disease
Tell your doctor if:
• ou are pregnant or have been pregnant
Y
recently or you have given birth in the last
6 months
• ou have been diagnosed as having
Y
a genetically determined abnormal
cholinesterase.
If you are not sure if any of the above apply to
you, talk to your doctor, nurse or pharmacist
before you are given Mivacron.
Other medicines and Mivacron
Tell your doctor, nurse or pharmacist if you
are taking or have recently taken any other
medicines. This includes medicines obtained
without a prescription, including herbal
medicines. This is because these medicines can
affect how well Mivacron works or can cause
side effects.
In particular tell your doctor, nurse or pharmacist
if you are taking any of the following:
• naesthetics (used to reduce sensation and
a
pain during surgical procedures)
• antibiotics (used to treat infections)
• edicines for uneven heart beats (anti-arrhythmics)
m
• medicines for high blood pressure
• water tablets (diuretics), such as frusemide
• edicines for inflammation of the joints, such
m
as chloroquine or d-penicillamine
• steroids
• edicines for fits (epilepsy), such as phenytoin
m
or carbamazepine
• edicines for mental illness, such as
m
lithium, monoamine oxidase inhibitors
(MAOIs) or chlorpromazine (which can
also be used for sickness)
• medicines containing magnesium.
• edicines used to treat depression and/or
m
anxiety SSRIs (selective serotonin reuptake
inhibitors) including fluoxetine, paroxetine,
sertraline, fluvoxamine, citalopram,
escitalopram
.
Pregnancy and breast-feeding
If you are pregnant, or are breast-feeding, . .
think you may be pregnant or are planning

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10000000124844
GSK-ITA-Parma-ITPAR
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Mivacron
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Mivacron followed by appropriate dosing guided by monitoring of block with a
nerve stimulator.
Caution should be exercised in administering Mivacron to patients with a history
suggestive of an increased sensitivity to the effects of histamine e.g. asthma. If
Mivacron is used in this group of patients it should be administered over 60 seconds.
High rates of cross-sensitivity (greater than 50%) between neuromuscular blocking
agents have been reported. Therefore, where possible, before administering
mivacurium, hypersensitivity to other neuromuscular blocking agents should
be excluded. Mivacurium 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.
Mivacron 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.
In adults, doses of Mivacron > 0.2 mg/kg (>3 x ED95) have been associated with
histamine release when administered by rapid bolus injection. However, the
slower administration of the 0.2 mg/kg Mivacron dose and the divided
administration of the 0.25 mg/kg Mivacron dose minimised the cardiovascular
effects of these doses. Cardiovascular safety did not appear to be compromised in
children given a rapid bolus dose of 0.2 mg/kg in clinical studies.
The use in neonates and infants < 2 months is not recommended due to limited data.
(see also section 4.2 and 5.1)
Mivacron does not have significant vagal or ganglion blocking properties in the
recommended dosage range. Recommended doses of Mivacron consequently have
no clinically significant effects on heart rate and 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 mivacurium can be expected in patients with Myasthenia Gravis,
other forms of neuromuscular disease and cachectic patients. Severe acid base or
electrolyte abnormalities may increase or reduce sensitivity to mivacurium.
Mivacron solution is acidic (approximately pH 4.5) and should not be mixed in the
same syringe or administered simultaneously through the same needle as highly
alkaline solutions (e.g. barbiturate solutions). It has been shown to be compatible
with some commonly used peri-operative drugs supplied as acidic solutions e.g.
fentanyl, alfentanil, sufentanil, droperidol and midazolam. Where other anaesthetic
agents are administered through the same indwelling needle or cannula as used for
Mivacron, and compatibility has not been demonstrated, it is recommended that each
drug is flushed through with physiological saline.
Studies in malignant hyperthermia-susceptible pigs, indicated that Mivacron does not
trigger this syndrome. Mivacron has not been studied in malignant hyperthermia-susceptible
patients.
No data are available on the long-term use of Mivacron in patients undergoing
mechanical ventilation in the intensive care unit.
Reversal of Neuromuscular Block: as with other neuromuscular blocking agents,
evidence of spontaneous recovery should be observed prior to administration
of reversal agent (e.g. neostigmine). The use of a peripheral nerve stimulator to
evaluate recovery prior to and following reversal of neuromuscular block is strongly
recommended.
Pharmaceutical Precautions – see section 6.2 Incompatibilities and section 6.4 Special
precautions for disposal and other handling.
4.5 Interaction with Other Medicinal Products and Other Forms of Interaction
The neuromuscular block produced by Mivacron may be increased by the concomitant
use of inhalational anaesthetics such as enflurane, isoflurane, sevoflurane and
halothane.
Mivacron has been safely administered following succinylcholine facilitated
intubation. Evidence of spontaneous recovery from succinylcholine should be
observed prior to administration of Mivacron.
In common with all non-depolarising neuromuscular blocking agents, the magnitude
and/or duration of non-depolarising neuromuscular block may be increased and
infusion requirements may be reduced as a result of interaction with;
• antibiotics, including the aminoglycosides, polymyxins, spectinomycin, tetracyclines,
lincomycin and clindamycin
• anti-arrhythmic drugs: propranolol, calcium channel blockers, lidocaine
procainamide and quinidine
• diuretics: furosemide and possibly thiazides, mannitol and acetazolamide
• magnesium salts
• ketamine
• lithium salts
• ganglion blocking drugs: trimetaphan, hexamethonium
Drugs that may reduce plasma cholinesterase activity may also prolong the
neuromuscular blocking action of Mivacron. These include anti-mitotic drugs,
monoamine oxidase inhibitors, ecothiophate iodine, pancuronium, organophosphates,
anticholinesterases, certain hormones, bambuterol and selective serotonin reuptake
inhibitors.
Rarely, certain drugs may aggravate or unmask latent Myasthenia Gravis or
actually induce a Myasthenic syndrome: increased sensitivity to Mivacron would
be consequent on such a development. Such drugs include various antibiotics,
beta-blockers (propranolol, oxprenolol), antiarrhythmic drugs (procainamide,
quinidine), antirheumatic drugs (chloroquine, D-pencillamine), trimetaphan,
chlorpromazine, steroids, phenytoin and lithium.
The administration of combinations of non-depolarising neuromuscular blocking
agents in conjunction with Mivacron may produce a degree of neuromuscular
blockade in excess of that which might be expected from an equipotent total dose of
Mivacron. 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
agents, as this may result in a prolonged and complex block which can be difficult to
reverse with anticholinesterase drugs.
4.6. Fertility, Pregnancy and Lactation
Fertility studies have not been performed.
Animal studies have indicated that mivacurium has no adverse effect on foetal
development.
Mivacurium should not be used during pregnancy unless the expected clinical benefit
to the mother outweighs any potential risk to the foetus.
Plasma cholinesterase levels decrease during pregnancy. Mivacurium has been
used to maintain neuromuscular block during Caesarean section, but due to the
reduced levels of plasma cholinesterase, dosage adjustments to the infusion rate
were necessary. A further reduction in the infusion rate may also be required during
Caesarean section in patients pre-treated with magnesium sulfate, due to the
potentiating effects of magnesium.
It is not known whether mivacurium is excreted in human milk.
4.7 Effect on Ability to Drive and Use Machines
This precaution is not relevant to the use of mivacurium. Mivacurium will always be
used in combination with a general anaesthetic and therefore the usual precautions
relating to performance of tasks following general anaesthesia apply.
4.8 Undesirable Effects
Adverse events are listed below by system organ class and frequency. Frequencies are
defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000
to <1/100), rare (≥1/10000 to <1/1000) and very rare (<1/10,000) including isolated
reports.
Immune disorders
Very rare:
Severe anaphylactic or anaphylactoid reaction. Severe anaphylactic
or anaphylactoid reactions have been reported in patients receiving
mivacurium chloride in conjunction with one or more anaesthetic
agents.
Cardiac disorders
Uncommon: Transient tachycardia*

to have a baby, ask your doctor for advice before
being given 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.

3. How Mivacron is given
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.
Mivacron can be given:
• s a single injection into your vein (intravenous
a
bolus injection)
• s a continuous infusion into your vein. This is
a
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
• he amount and duration of muscle relaxation
t
required
• your expected response to the medicine.
Children under 2 months old should not have this
medicine.
If you receive more Mivacron than you
should
Mivacron 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.

Vascular disorders
.
Very common: Flushing*
. .
*
Uncommon: Hypotension
Respiratory, thoracic and mediastinal disorders
Uncommon: Bronchospasm*
Skin and subcutaneous tissue disorders
Uncommon: Erythema*, urticaria*
*Associated with the use of Mivacron there have been reports of skin flushing,
erythema, urticaria, hypotension, transient tachycardia or bronchospasm which
have been attributed to histamine release. These effects are dose related and more
common following initial doses of ≥0.2 mg/kg or more when given rapidly and are
reduced if Mivacron is injected over 30 to 60 seconds or in divided doses over
30 seconds.
The safety profile in children is similar to that in adults.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the 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.
4.9 Overdose
Prolonged muscle paralysis and its consequences are the main signs of overdosage
with neuromuscular blocking agents. However, the risk of haemodynamic side-effects
especially decreases in blood pressure may be increased.
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. Cardiovascular support may be provided
by proper positioning of the patient and administration of fluids or vasopressor
agents as required.
Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: Peripherally acting muscle relaxants, other quaternary
ammonium compounds, ATC code: M03AC10.
Mivacurium is a short-acting, non-depolarising skeletal muscle relaxant which is
hydrolysed by plasma cholinesterase. Mivacurium binds competitively with cholinergic
receptors on the motor end-plate to prevent the action of acetylcholine, resulting in a
blockade of neuromuscular transmission. This is rapidly reversed by the administration
of the cholinesterase inhibitors, neostigmine and edrophonium.
5.2 Pharmacokinetic Properties
Mivacurium chloride is a mixture of three stereoisomers, the trans-trans and cis-trans
stereoisomers comprise 92% to 96% of mivacurium chloride and when studied
in cats their neuromuscular blocking potencies are not significantly different from
each other or from mivacurium chloride. The cis-cis isomer has been estimated
from studies in cats to have one-tenth of the neuromuscular blocking potency of
the other two stereoisomers. Enzymatic hydrolysis by plasma cholinesterase is the
primary mechanism for inactivation of mivacurium and yields a quaternary alcohol
and a quaternary monoester metabolite. Pharmacological studies in cats and dogs
have shown that metabolites possess insignificant neuromuscular, autonomic or
cardiovascular activity at concentrations higher than seen in man.
5.3 Preclinical Safety Data
Mivacurium has been evaluated in four short term mutagenicity tests. Mivacurium
was non-mutagenic in the Ames salmonella assay, the mouse lymphoma assay, the
human lymphocyte assay and the in vivo rat bone marrow cytogenetic assay.
There is no information available on whether Mivacurium has carcinogenic potential.
Fertility studies have not been performed.
Animal studies have indicated that mivacurium has no adverse effect on foetal
development.
Pharmaceutical Particulars
6.1 List of Excipients
Hydrochloric Acid
EP
Water for Injections EP
6.2 Incompatibilities
Mivacurium is acidic (approximately pH 4.5) and should not be mixed with highly
alkaline solutions, e.g. barbiturates.
6.3 Shelf Life
18 months
6.4 Special Precautions for Storage
Store below 25°C. Do not freeze. Protect from light.
6.5 Nature and Contents of Container
Neutral glass ampoules containing 5ml or 10ml of product.
Not all pack sizes may be marketed.
6.6 Special Precautions for Disposal and Other Handling
Since no antimicrobial preservative is included, Mivacron must be used under full
aseptic conditions and any dilution carried out immediately before use.
Any unused solution in open ampoules should be disposed of in accordance with
local requirements.
Mivacron injection is acidic (approximately pH 4.5) and should not be mixed
with highly alkaline solutions (e.g. barbiturates). Mivacron has been shown to
be compatible with some commonly used peri-operative drugs supplied as acidic
solutions. Where such agents are administered through the same indwelling needle or
cannula as used for Mivacron injection, and compatibility has not been demonstrated,
it is recommended that each drug is flushed through with physiological saline.
Instructions to open the ampoule
Ampoules are equipped with the OPC (One Point Cut) opening system and must be
opened following the below instructions:
1. hold with the hand the bottom part of the
ampoule as indicated in picture 1
2. put the other hand on the top of the ampoule
positioning the thumb above the coloured point
and press as indicated in picture 2
Picture 1
Picture 2
Administrative Data
7. Marketing Authorisation Holder
The Wellcome Foundation Ltd, 980 Great West Road, Brentford, Middlesex TW8 9GS
Trading as GlaxoSmithKline UK, Stockley Park West, Uxbridge, Middlesex UB11 1BT
8. Marketing Authorisation Number
PL 00003/0325
9. Date of First Authorisation/Renewal of Authorisation
21st January 2009
This leaflet was last revised in March 2014

• welling of your eyelids, face, lips, mouth or tongue
s
• lumpy skin rash or ‘hives’ anywhere on your
a
body
• a collapse
Very Common (may affect more than 1 in 10
people)
• reddening of the skin
Uncommon (may affect up to 1 in 100 people)
• increase in heart rate
• decrease in blood pressure
• wheezing or coughing
• rash
Reporting of side effects
If you get any side effects, talk to your doctor,
nurse or pharmacist. 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 Mivacron
• Keep out of the sight and reach of children.
• o not use Mivacron after the expiry date
D
which is stated on the pack after ‘Exp’.
• Store below 25°C. Do not freeze.
• tore in the original package to protect from light.
S
• hen Mivacron is made up it should be
W
used straight away. Do not throw away any
medicines via wastewater or household waste.
Your doctor, nurse or pharmacist will throw
away any medicine that is no longer required.
This will help protect the environment.

4. Possible side effects

What Mivacron contains
• The active substance is mivacurium chloride.
• he other ingredients are hydrochloric acid and
T
Water for Injections.
What Mivacron looks like and contents of
the pack
• ivacron solution for injection comes in ampoules
M
containing 5 ml or 10 ml of the product.

0800 198 5000 (UK only).
Please be ready to give the following information:
Product name
Mivacron Injection 2 mg/ml
Reference number 00003/0325
This is a service provided by the Royal National
Institute of Blind People.
This leaflet was last revised in March 2014
Mivacron is a registered trademark of the
GlaxoSmithKline group of companies
© 2014 GlaxoSmithKline group of
companies. All rights reserved

6. Contents of the pack and other
information

Like all medicines, Mivacron can cause side
effects, although not everybody gets them.
Allergic reactions (may affect up to 1 in 10,000
people)
If you have an allergic reaction, tell your doctor
or nurse straight away. The signs may include:
• udden wheeziness, chest pain or chest
s
tightness

Marketing Authorisation Holder and
Manufacturer
Marketing Authorisation holder: The Wellcome
Foundation Limited, 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:

.
. .

10000000124844

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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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