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Active substance(s): ROCURONIUM BROMIDE

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For Position Only

Information for the doctor

10 mg/ml
solution for injection


Esmeron® 10 mg/ml solution for injection
Each ml Esmeron contains 10 mg rocuronium bromide.
For the full list of excipients, see section 6.1.
Solution for injection.
pH: 3.8-4.2
4.1 Therapeutic indications
Esmeron is indicated in adult and paediatric patients (from term
neonates to adolescents [0 to <18 years]) as an adjunct to general
anaesthesia to facilitate tracheal intubation during routine sequence
induction and to provide skeletal muscle relaxation during surgery.
In adults Esmeron is also indicated to facilitate tracheal intubation
during rapid sequence induction and as an adjunct in the intensive
care unit (ICU) to facilitate intubation and mechanical ventilation.
4.2 Posology and method of administration
Like other neuromuscular blocking agents, Esmeron should only be
administered by, or under supervision of, experienced clinicians
who are familiar with the action and use of these drugs.
As with other neuromuscular blocking agents, the dosage of
Esmeron should be individualised in each patient. The method of
anaesthesia and the expected duration of surgery, the method
of sedation and the expected duration of mechanical ventilation,
the possible interaction with other drugs that are administered
concomitantly, and the condition of the patient should be taken into
account when determining the dose.
The use of an appropriate neuromuscular monitoring technique
is recommended for the evaluation of neuromuscular block and
Inhalational anaesthetics do potentiate the neuromuscular blocking
effects of Esmeron. This potentiation however, becomes clinically
relevant in the course of anaesthesia, when the volatile agents have
reached the tissue concentrations required for this interaction.
Consequently, adjustments with Esmeron should be made by
administering smaller maintenance doses at less frequent intervals
or by using lower infusion rates of Esmeron during long lasting
procedures (longer than 1 hour) under inhalational anaesthesia
(see section 4.5).
In adult patients the following dosage recommendations may serve
as a general guideline for tracheal intubation and muscle relaxation
for short to long lasting surgical procedures and for use in the
intensive care unit.
Surgical Procedures
Tracheal intubation
The standard intubating dose during routine anaesthesia is 0.6 mg/kg
rocuronium bromide, after which adequate intubation conditions
are established within 60 seconds in nearly all patients. A dose
of 1.0 mg/kg rocuronium bromide is recommended for facilitating
tracheal intubation conditions during rapid sequence induction
of anaesthesia, after which adequate intubation conditions are
established within 60 seconds in nearly all patients. If a dose of
0.6 mg/kg rocuronium bromide is used for rapid sequence induction
of anaesthesia, it is recommended to intubate the patient 90 seconds
after administration of rocuronium bromide.
For use of rocuronium bromide during rapid sequence induction of
anaesthesia in patients undergoing Caesarean section reference is
made to section 4.6.

Higher doses
Should there be reason for selection of larger doses in individual patients,
there is no indication from clinical studies that the use of initial doses up
to 2 mg/kg rocuronium bromide is associated with an increased frequency
or severity of cardiovascular effects. The use of these high dosages of
rocuronium bromide decreases the onset time and increases the duration
of action (see section 5.1).
Maintenance dosing
The recommended maintenance dose is 0.15 mg/kg rocuronium bromide;
in the case of long-term inhalational anaesthesia this should be reduced to
0.075-0.1 mg/kg rocuronium bromide. The maintenance doses should best
be given when twitch height has recovered to 25% of control twitch height,
or when 2 to 3 responses to train of four stimulation are present.
Continuous infusion
If rocuronium bromide is administered by continuous infusion, it is
recommended to give a loading dose of 0.6 mg/kg rocuronium bromide
and, when neuromuscular block starts to recover, to start administration by
infusion. The infusion rate should be adjusted to maintain twitch response
at 10% of control twitch height or to maintain 1 to 2 responses to train of
four stimulation. In adults under intravenous anaesthesia, the infusion
rate required to maintain neuromuscular block at this level ranges from
0.3-0.6 mg/kg/h (300-600 micrograms/kg/h) and under inhalational anaesthesia
the infusion rate ranges from 0.3-0.4 mg/kg/h. Continuous monitoring of
neuromuscular block is essential since infusion rate requirements vary from
patient to patient and with the anaesthetic method used.
Paediatric population
For neonates (0-27 days), infants (28 days-2 months), toddlers (3-23 months),
children (2-11 years) and adolescents (12-17 years) the recommended
intubation dose during routine anaesthesia and maintenance dose are
similar to those in adults.
However, the duration of action of the single intubating dose will be longer
in neonates and infants than in children (see section 5.1)
For continuous infusion in paediatrics, the infusion rates, with the exception
of children (2-11 years), are the same as for adults. For children aged
2-11 years higher infusion rates might be necessary.
Thus, for children (2-11 years) the same initial infusion rates as for adults
are recommended and then this should be adjusted to maintain twitch
response at 10% of control twitch height or to maintain 1 or 2 responses to
train of four stimulation during the procedure.
The experience with rocuronium bromide in rapid sequence induction
in paediatric patients is limited. Rocuronium bromide is therefore not
recommended for facilitating tracheal intubation conditions during rapid
sequence induction in paediatric patients.
Geriatric patients and patients with hepatic and/or biliary tract disease
and/or renal failure
The standard intubation dose for geriatric patients and patients with
hepatic and/or biliary tract disease and/or renal failure during routine
anaesthesia is 0.6 mg/kg rocuronium bromide. A dose of 0.6 mg/kg should be
considered for rapid sequence induction of anaesthesia in patients in which
a prolonged duration of action is expected. Regardless of the anaesthetic
technique used, the recommended maintenance dose for these patients is
0.075-0.1 mg/kg rocuronium bromide, and the recommended infusion rate is
0.3-0.4 mg/kg/h (see Continuous infusion). (See also section 4.4.)
Overweight and obese patients
When used in overweight or obese patients (defined as patients with a
body weight of 30% or more above ideal body weight) doses should be
reduced taking into account ideal body weight.
Intensive Care Procedures
Tracheal intubation
For tracheal intubation, the same doses should be used as described above
under surgical procedures.
Maintenance dosing
The use of an initial loading dose of 0.6 mg/kg rocuronium bromide is
recommended, followed by a continuous infusion as soon as twitch height
recovers to 10% or upon reappearance of 1 to 2 twitches to train of four
stimulation. Dosage should always be titrated to effect in the individual
patient. The recommended initial infusion rate for the maintenance of a
neuromuscular block of 80-90% (1 to 2 twitches to TOF stimulation) in adult
patients is 0.3-0.6 mg/kg/h during the first hour of administration, which
will need to be decreased during the following 6-12 hours, according to
the individual response. Thereafter, individual dose requirements remain
relatively constant.
A large between patient variability in hourly infusion rates has been found
in controlled clinical studies, with mean hourly infusion rates ranging
from 0.2-0.5 mg/kg/h depending on nature and extent of organ failure(s),
concomitant medication and individual patient characteristics. To provide
optimal individual patient control, monitoring of neuromuscular transmission
is strongly recommended. Administration up to 7 days has been investigated.
Special populations
Esmeron is not recommended for the facilitation of mechanical ventilation
in the intensive care in paediatric and geriatric patients due to a lack of
data on safety and efficacy.
Method of administration
Esmeron is administered intravenously either as a bolus injection or as a
continuous infusion (see section 6.6).
4.3 Contraindications
Hypersensitivity to rocuronium or to the bromide ion or to any of the
4.4 Special warnings and precautions for use
Since Esmeron causes paralysis of the respiratory muscles, ventilatory
support is mandatory for patients treated with this drug until adequate

spontaneous respiration is restored. As with all neuromuscular blocking
agents, it is important to anticipate intubation difficulties, particularly when
used as part of a rapid sequence induction technique.
As with other neuromuscular blocking agents, residual neuromuscular
blockade has been reported for Esmeron. In order to prevent complications
resulting from residual neuromuscular blockade, it is recommended
to extubate only after the patient has recovered sufficiently from
neuromuscular block. Geriatric patients (65 years or older) may be at
increased risk for residual neuromuscular block. Other factors which
could cause residual neuromuscular blockade after extubation in the
post-operative phase (such as drug interactions or patient condition)
should also be considered. If not used as part of standard clinical practice,
the use of a reversal agent (such as sugammadex or acetylcholinesterase
inhibitors) should be considered, especially in those cases where residual
neuromuscular blockade is more likely to occur.
High rates of cross-sensitivity between neuromuscular blocking agents
have been reported. Therefore, where possible, before administering
Esmeron, hypersensitivity to other neuromuscular blocking agents should
be excluded. Esmeron 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.
Rocuronium may increase the heart rate.
In general, following long term use of neuromuscular blocking agents in
the ICU, prolonged paralysis and/or skeletal muscle weakness has been
noted. In order to help preclude possible prolongation of neuromuscular
block and/or overdosage it is strongly recommended that neuromuscular
transmission is monitored throughout the use of neuromuscular blocking
agents. In addition, patients should receive adequate analgesia and
sedation. Furthermore, neuromuscular blocking agents should be titrated
to effect in the individual patients by or under supervision of experienced
clinicians who are familiar with their actions and with appropriate
neuromuscular monitoring techniques.
Myopathy after long term administration of other non-depolarising
neuromuscular blocking agents in the ICU in combination with corticosteroid
therapy has been reported regularly. Therefore, for patients receiving both
neuromuscular blocking agents and corticosteroids, the period of use of the
neuromuscular blocking agent should be limited as much as possible.
If suxamethonium is used for intubation, the administration of Esmeron
should be delayed until the patient has clinically recovered from the
neuromuscular block induced by suxamethonium.
The following conditions may influence the pharmacokinetics and/or
pharmacodynamics of Esmeron:
Hepatic and/or biliary tract disease and renal failure
Because rocuronium is excreted in urine and bile, it should be used with
caution in patients with clinically significant hepatic and/or biliary diseases
and/or renal failure. In these patient groups prolongation of action has been
observed with doses of 0.6 mg/kg rocuronium bromide.
Prolonged circulation time
Conditions associated with prolonged circulation time such as
cardiovascular disease, old age and oedematous state resulting in an
increased volume of distribution, may contribute to a slower onset of
action. The duration of action may also be prolonged due to a reduced
plasma clearance.
Neuromuscular disease
Like other neuromuscular blocking agents, Esmeron should be used
with extreme caution in patients with a neuromuscular disease or after
poliomyelitis since the response to neuromuscular blocking agents may be
considerably altered in these cases. The magnitude and direction of this
alteration may vary widely. In patients with myasthenia gravis or with the
myasthenic (Eaton-Lambert) syndrome, small doses of Esmeron may have
profound effects and Esmeron should be titrated to the response.
In surgery under hypothermic conditions, the neuromuscular blocking
effect of Esmeron is increased and the duration prolonged.
Like other neuromuscular blocking agents, Esmeron may exhibit a prolonged
duration and a prolonged spontaneous recovery in obese patients when the
administered doses are calculated on actual body weight.
Patients with burns are known to develop resistance to non-depolarising
neuromuscular blocking agents. It is recommended that the dose is titrated
to response.
Conditions which may increase the effects of Esmeron
Hypokalaemia (e.g. after severe vomiting, diarrhoea and diuretic therapy),
hypermagnesaemia, hypocalcaemia (after massive transfusions),
hypoproteinaemia, dehydration, acidosis, hypercapnia, cachexia.
Severe electrolyte disturbances, altered blood pH or dehydration should
therefore be corrected when possible.
4.5 Interaction with other medicinal products and other forms of interaction
The following drugs have been shown to influence the magnitude and/or
duration of action of non-depolarising neuromuscular blocking agents.
Effect of other drugs on Esmeron
Increased effect:
• Halogenated volatile anaesthetics potentiate the neuromuscular
block of Esmeron. The effect only becomes apparent with
maintenance dosing (see section 4.2). Reversal of the block with
acetylcholinesterase inhibitors could also be inhibited.
• After intubation with suxamethonium (see section 4.4).
• Long-term concomitant use of corticosteroids and Esmeron in the
ICU may result in prolonged duration of neuromuscular block or
myopathy (see section 4.4 and 4.8).

Other drugs:
• antibiotics: aminoglycoside, lincosamide and polypeptide
antibiotics, acylamino-penicillin antibiotics.
• diuretics, quinidine and its isomer quinine, magnesium
salts, calcium channel blocking agents, lithium salts, local
(lidocaine i.v, bupivacaine epidural) and acute
administration of phenytoin or ß-blocking agents.
Recurarisation has been reported after post-operative administration
of: aminoglycoside, lincosamide, polypeptide and acylamino-penicillin
antibiotics, quinidine, quinine and magnesium salts (see section 4.4).
Decreased effect:
• Prior chronic administration of phenytoin or carbamazepine.
• Calcium chloride, potassium chloride.
• Protease inhibitors (gabexate, ulinastatin).
Variable effect:
• Administration of other non-depolarising neuromuscular
blocking agents in combination with Esmeron may
produce attenuation or potentiation of the neuromuscular
block, depending on the order of administration and the
neuromuscular blocking agent used.
• Suxamethonium given after the administration of
Esmeron may produce potentiation or attenuation of the
neuromuscular blocking effect of Esmeron.
Effect of Esmeron on other drugs
Esmeron combined with lidocaine may result in a quicker onset of
action of lidocaine.
Paediatric population
No formal interaction studies have been performed. The above
mentioned interactions for adults and their special warnings and
precautions for use (see section 4.4) should be taken into account
for paediatric patients.
4.6 Pregnancy and lactation
For rocuronium bromide, no clinical data on exposed pregnancies
are available. Animal studies do not indicate direct or indirect
harmful effects with respect to pregnancy, embryonal/foetal
development, parturition or postnatal development. Caution should
be exercised when prescribing Esmeron to pregnant women.
Caesarean section
In patients undergoing Caesarean section, Esmeron can be used as
part of a rapid sequence induction technique, provided no intubation
difficulties are anticipated and a sufficient dose of anaesthetic agent
is administered or following suxamethonium facilitated intubation.
However, Esmeron, administered in doses of 0.6 mg/kg may not
produce adequate conditions for intubation until 90 seconds after
administration. This dose has been shown to be safe in parturients
undergoing Caesarean section. Esmeron does not affect Apgar
score, foetal muscle tone or cardiorespiratory adaptation. From
umbilical cord blood sampling it is apparent that only limited
placental transfer of rocuronium bromide occurs which does not
lead to the observation of clinical adverse effects in the newborn.
Note 1: doses of 1.0 mg/kg have been investigated during rapid
sequence induction of anaesthesia, but not in Caesarean section
patients. Therefore, only a dose of 0.6 mg/kg is recommended in
this patient group.
Note 2: Reversal of neuromuscular block induced by neuromuscular
blocking agents may be inhibited or unsatisfactory in patients
receiving magnesium salts for toxemia of pregnancy because
magnesium salts enhance neuromuscular blockade. Therefore, in
these patients the dosage of Esmeron should be reduced and be
titrated to twitch response.
It is unknown whether rocuronium bromide is excreted in human
breast milk. Animal studies have shown insignificant levels of
rocuronium bromide in breast milk.
Insignificant levels of rocuronium bromide were found in the milk
of lactating rats. There are no human data on the use of Esmeron
during lactation. Esmeron should be given to lactating women only
when the attending physician decides that the benefits outweigh
the risks.
4.7 Effects on ability to drive and use machines
Since Esmeron is used as an adjunct to general anaesthesia, the
usual precautionary measures after a general anaesthesia should
be taken for ambulatory patients.
4.8 Undesirable effects
Summary of the safety profile
The most commonly occurring adverse drug reactions include
injection site pain/reaction, changes in vital signs and prolonged
neuromuscular block. The most frequently reported serious adverse
drug reactions during post-marketing surveillance is ‘anaphylactic
and anaphylactoid reactions’ and associated symptoms. See also
the explanations below the table.
Tabulated list of adverse reactions
Preferred term1
Uncommon/rare2 Very rare (<1/10 000)
(<1/100, >1/10 000)
Immune system
Anaphylactic reaction
Anaphylactoid reaction
Anaphylactic shock
Anaphylactoid shock

----------------!---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Information for the user

5. How Esmeron is stored
6. Contents of the pack and other information

10 mg/ml
solution for injection


Read all of this leaflet carefully before you are given 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 anaesthetist or other
• If you get any side effects, talk to your anaesthetist or other
doctor. This includes any possible side effects not listed in this
leaflet. See section 4.
What is in this leaflet
1. What Esmeron is and what it is used for
2. What you need to know before Esmeron is given
3. How Esmeron is given
4. Possible side effects

1. What Esmeron is and what it is used for
Esmeron is one of a group of drugs called muscle relaxants.
Muscle relaxants are used during an operation as part of a general
anaesthetic. When you have an operation your muscles must be completely
relaxed. This makes it easier for the surgeon to perform the operation.
Normally, your nerves send messages called impulses to your muscles.
Esmeron acts by blocking these impulses so that your muscles relax.
Because your breathing muscles also relax, you will need help to breathe
(artificial ventilation) during and after your operation until you can breathe
on your own again.
During the operation your anaesthetist will keep a check on the effect of
the muscle relaxant, and if necessary will give you some more. At the end
of surgery, the effects of the drug are allowed to wear off and you will start
breathing on your own. Sometimes the anaesthetist will give you another
drug to help speed this up.
Esmeron can also be used in Intensive Care Units to keep your muscles
2. What you need to know before Esmeron is given
You should not receive Esmeron
if you are allergic (hypersensitive) to rocuronium, the bromide ion
or any of the other ingredients of this medicine (listed in section 6).
➔ Tell your anaesthetist if this applies to you.

Warnings and precautions
Talk to your anaesthetist before you receive this medicine:
• if you are allergic to muscle relaxants
• if you have had kidney, heart, liver or gall bladder disease
• if you have had diseases affecting nerves and muscles
• if you have fluid retention (oedema).
➔ Tell your anaesthetist if any of these applies to you.
Some conditions may influence the effects of Esmeron — for example:
• low calcium levels in the blood
• low potassium levels in the blood
• high magnesium levels in the blood
• low levels of protein in the blood
• too much carbon dioxide in the blood
• loss of too much water from the body, for example by being sick,
diarrhoea or sweating
• over-breathing leading to too little carbon dioxide in the blood
• general ill-health
• burns
• being very overweight (obesity)
• very low body temperature (hypothermia).
If you have any of these conditions, your anaesthetist will take it into
account when deciding the correct dose of Esmeron for you.
Children and Elderly
Esmeron can be used in children (newborns and adolescence) and elderly
but your anaesthetist should first assess your medical history.

Other medicines and Esmeron
➔ Tell your anaesthetist if you are taking other medicines or
have recently taken them. This includes medicines or herbal
products that you have bought without a prescription. Esmeron
may affect other medicines or be affected by them.
Medicines which increase the effect of Esmeron:
• certain antibiotics
• certain medicines for heart disease or high blood pressure
(water tablets, calcium channel blockers, beta-blockers and
• certain anti-inflammatory medicines (corticosteroids)
• medicines for manic depressive illness (bipolar disorder)
• magnesium salts
• certain medicines used to treat malaria.
Medicines which decrease the effect of Esmeron:
• certain medicines for epilepsy
• calcium chloride and potassium chloride
• certain protease inhibitors called gabexate and ulinastatin.
In addition, you may be given other medicines before or during
surgery which can alter the effects of Esmeron. These include
certain anaesthetics, other muscle relaxants, medicines such as
phenytoin and medicines which reverse the effects of Esmeron.
Esmeron may make certain anaesthetics work more quickly. Your
anaesthetist will take this into account when deciding the correct
dose of Esmeron for you.

For Position Only


Nervous system
Cardiac disorders
Vascular disorders

Preferred term1
(<1/100, >1/10 000)

Very rare (<1/10 000)
Flaccid paralysis


Respiratory, thoracic
and mediastinal
Skin and
subcutaneous tissue

Circulatory collapse
and shock
Angioneurotic oedema
Erythematous rash
Muscular weakness3
Steroid myopathy3

Musculoskeletal and
connective tissue
General disorders
Drug ineffective
Face oedema
and administration Drug effect/
site conditions
Drug effect/
response increased
Injection site pain
Injection site
Injury, poisoning
Airway complication of
and procedural
neuromuscular block anaesthesia
Delayed recovery
from anaesthesia
MedDRA version 8.1
Although very rare, severe anaphylactic reactions to neuromuscular
blocking agents, including Esmeron, have been reported.
Anaphylactic/anaphylactoid reactions are: bronchospasm,
cardiovascular changes (e.g. hypotension, tachycardia, circulatory
collapse – shock), and cutaneous changes (e.g. angioedema,
urticaria). These reactions have, in some cases, been fatal. Due to
the possible severity of these reactions, one should always assume
they may occur and take the necessary precautions.
Since neuromuscular blocking agents are known to be capable
of inducing histamine release both locally at the site of injection
and systemically, the possible occurrence of itching and
erythematous reaction at the site of injection and/or generalised
histaminoid (anaphylactoid) reactions (see also under anaphylactic
reactions above) should always be taken into consideration when
administering these drugs.
In clinical studies only a slight increase in mean plasma histamine
levels has been observed following rapid bolus administration of
0.3-0.9 mg/kg rocuronium bromide.
Prolonged neuromuscular block
The most frequent adverse reaction to nondepolarising blocking
agents as a class consists of an extension of the drug’s
pharmacological action beyond the time period needed. This may
vary from skeletal muscle weakness to profound and prolonged
skeletal muscle paralysis resulting in respiratory insufficiency or
Myopathy has been reported after the use of various
neuromuscular blocking agents in the ICU in combination with
corticosteroids (see section 4.4).
Local injection site reactions
During rapid sequence induction of anaesthesia, pain on injection
has been reported, especially when the patient has not yet
completely lost consciousness and particularly when propofol is
used as the induction agent. In clinical studies, pain on injection
has been noted in 16% of the patients who underwent rapid
sequence induction of anaesthesia with propofol and in less than
0.5% of the patients who underwent rapid sequence induction of
anaesthesia with fentanyl and thiopental.
Paediatric population
A meta-analysis of 11 clinical studies in paediatric patients (n=704)
with rocuronium bromide (up to 1 mg/kg) showed that tachycardia
was identified as adverse drug reaction with a frequency of 1.4%.
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
(see details below)
United Kingdom: Yellow Card Scheme at:
Malta: ADR Reporting at:


Frequencies are estimates derived from post-marketing
surveillance reports and data from the general literature.
Post-marketing surveillance data cannot give precise incidence
figures. For that reason, the reporting frequency was divided over
two rather than five categories.
after long-term use in the ICU

4.9 Overdose
In the event of overdosage and prolonged neuromuscular block, the
patient should continue to receive ventilatory support and sedation. There
are two options for the reversal of neuromuscular block: (1) In adults,
sugammadex can be used for reversal of intense (profound) and deep
block. The dose of sugammadex to be administered depends on the
level of neuromuscular block. (2) An acetylcholinesterase inhibitor
(e.g. neostigmine, edrophonium, pyridostigmine) or sugammadex can
be used once spontaneous recovery starts and should be administered
in adequate doses. When administration of an acetylcholinesterase
inhibiting agent fails to reverse the neuromuscular effects of Esmeron,
ventilation must be continued until spontaneous breathing is restored.
Repeated dosage of an acetylcholinesterase inhibitor can be dangerous.
In animal studies, severe depression of cardiovascular function, ultimately
leading to cardiac collapse did not occur until a cumulative dose of
750 x ED90 (135 mg/kg rocuronium bromide) was administered.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Muscle relaxants, peripherally acting agents,
ATC code: M03AC09.
Mechanism of Action
Esmeron (rocuronium bromide) is a fast onset, intermediate acting
non-depolarising neuromuscular blocking agent, possessing all of the
characteristic pharmacological actions of this class of drugs (curariform).
It acts by competing for nicotinic cholinoceptors at the motor end-plate.
This action is antagonised by acetylcholinesterase inhibitors such as
neostigmine, edrophonium and pyridostigmine.
Pharmacodynamic effects
The ED90 (dose required to produce 90% depression of the twitch response
of the thumb to stimulation of the ulnar nerve) during intravenous
anaesthesia is approximately 0.3 mg/kg rocuronium bromide. The ED95 in
infants is lower than in adults and children (0.25, 0.35 and 0.40 mg/kg
The clinical duration (the duration until spontaneous recovery to 25% of
control twitch height) with 0.6 mg/kg rocuronium bromide is 30–40 minutes.
The total duration (time until spontaneous recovery to 90% of control
twitch height) is 50 minutes. The mean time of spontaneous recovery
of twitch response from 25 to 75% (recovery index) after a bolus dose
of 0.6 mg/kg rocuronium bromide is 14 minutes. With lower dosages of
0.3-0.45 mg/kg rocuronium bromide (1 -1½ x ED90), onset of action is slower
and duration of action is shorter. With high doses of 2 mg/kg, clinical
duration is 110 minutes.
Intubation during routine anaesthesia
Within 60 seconds following intravenous administration of a dose of
0.6 mg/kg rocuronium bromide (2 x ED90 under intravenous anaesthesia),
adequate intubation conditions can be achieved in nearly all patients
of which in 80% intubation conditions are rated excellent. General
muscle paralysis adequate for any type of procedure is established
within 2 minutes. After administration of 0.45 mg/kg rocuronium bromide,
acceptable intubation conditions are present after 90 seconds.
Rapid Sequence Induction
During rapid sequence induction of anaesthesia under propofol or fentanyl/
thiopental anaesthesia, adequate intubation conditions are achieved
within 60 seconds in 93% and 96% of the patients respectively, following a
dose of 1.0 mg/kg rocuronium bromide. Of these, 70% are rated excellent.
The clinical duration with this dose approaches 1 hour, at which time the
neuromuscular block can be safely reversed. Following a dose of 0.6 mg/kg
rocuronium bromide, adequate intubation conditions are achieved within
60 seconds in 81% and 75% of the patients during a rapid sequence
induction technique with propofol or fentanyl/thiopental, respectively.
Paediatric population
Mean onset time in infants, toddlers and children at an intubation
dose of 0.6 mg/kg is slightly shorter than in adults. Comparison within
paediatric age groups showed that the mean onset time in neonates
and adolescents (1.0 min.) is slightly longer than in infants, toddlers and
children (0.4, 0.6 and 0.8 min., respectively). The duration of relaxation and
the time to recovery tend to be shorter in children compared to infants
and adults. Comparing within paediatric age groups demonstrated that
mean time to reappearance of T3 was prolonged in neonates and infants
(56.7 and 60.7 min., respectively) when compared to toddlers, children and
adolescents (45.4, 37.6 and 42.9 min., respectively).
Mean (SD) time to onset and clinical duration following 0.6 mg/kg
rocuronium initial intubating dose* during sevoflurane/nitrous oxide and
isoflurane/nitrous oxide (maintenance) anaesthesia (Paediatric patients)
PP group
Time to maximum Time to reappearance
of T3 **
block **
Neonates (0-27 days)
0.98 (0.62)
56.69 (37.04)
Infants (28 days-2 months)
0.44 (0.19)
60.71 (16.52)
Toddler (3 months-23 months)
0.59 (0.27)
45.46 (12.94)
Children (2-11 years)
0.84 (0.29)
37.58 (11.82)
Adolescents (12-17 years)
0.98 (0.38)
42.90 (15.83)
* Dose of rocuronium administered within 5 seconds.
** Calculated from the end of administration of the rocuronium intubating

Geriatric patients and patients with hepatic and/or biliary tract disease
and/or renal failure
The duration of action of maintenance doses of 0.15 mg/kg rocuronium
bromide might be somewhat longer under enflurane and isoflurane
anaesthesia in geriatric patients and in patients with hepatic and/or renal
disease (approximately 20 minutes) than in patients without impairment of
excretory organ functions under intravenous anaesthesia (approximately
13 minutes) (see section 4.2). No accumulation of effect (progressive
increase in duration of action) with repetitive maintenance dosing at the
recommended level has been observed.
Intensive Care Unit
Following continuous infusion in the Intensive Care Unit, the time to
recovery of the train of four ratio to 0.7 depends on the level of block at
the end of the infusion. After a continuous infusion for 20 hours or more
the median (range) time between return of T2 to train of four stimulation
and recovery of the train of four ratio to 0.7 approximates 1.5 (1-5) hours in
patients without multiple organ failure and 4 (1-25) hours in patients with
multiple organ failure.
Cardiovascular surgery
In patients scheduled for cardiovascular surgery the most common
cardiovascular changes during the onset of maximum block following
0.6-0.9 mg/kg rocuronium bromide are a slight and clinically insignificant
increase in heart rate up to 9% and an increase in mean arterial blood
pressure up to 16% from the control values.
Reversal of muscle relaxation
Administration of acetylcholinesterase inhibitors, (neostigmine,
pyridostigmine or edrophonium) at reappearance of T2 or at the first signs
of clinical recovery, antagonises the action of Esmeron.
5.2 Pharmacokinetic Properties
After intravenous administration of a single bolus dose of rocuronium
bromide the plasma concentration time course runs in three
exponential phases. In normal adults, the mean (95% CI) elimination
half-life is 73 (66-80) minutes, the (apparent) volume of distribution at
steady state conditions is 203 (193-214) ml/kg and plasma clearance
is 3.7 (3.5-3.9) ml/kg/min.
Rocuronium is excreted in urine and bile. Excretion in urine approaches
40% within 12-24 hours. After injection of a radiolabeled dose of
rocuronium bromide, excretion of the radiolabel is on average 47% in urine
and 43% in faeces after 9 days. Approximately 50% is recovered as the
parent compound. No metabolites are detected in plasma.
Paediatric population
Pharmacokinetics of rocuronium bromide in paediatric patients (n=146)
with ages ranging from 0 to 17 years were evaluated using a population
analysis of the pooled pharmacokinetic datasets from two clinical trials
under sevoflurane (induction) and isoflurane/nitrous oxide (maintenance)
anesthesia. All pharmacokinetic parameters were found to be linearly
proportional to body weight illustrated by a similar clearance (
The volume of distribution ( and elimination half-life (h) decrease with
age (years). The pharmacokinetic parameters of typical paediatrics within
each age group are summarized below:
Estimated PK parameters (Mean [SD]) of rocuronium bromide in typical
paediatric patients during sevoflurane and nitrous oxide (induction) and
isoflurane/nitrous oxide (maintenance anaesthesia)
Patient age range
Children Adolescents
Parameters newborn
infants (28 days to (3-23 months) (2-11 years) (12-17 years)
(0-27 days) 2 months)
CL (L/kg/hr) 0.31 (0.07) 0.30 (0.08) 0.33 (0.10)
0.35 (0.09) 0.29 (0.14)
Volume of
distribution 0.42 (0.06) 0.31 (0.03) 0.23 (0.03)
0.18 (0.02) 0.18 (0.01)
1.1 (0.2)
0.9 (0.3)
0.8 (0.2)
0.7 (0.2)
0.8 (0.3)
t ½ β (hr)
Geriatric patients and patients with hepatic and/or biliary tract disease
and/or renal failure
In controlled studies the plasma clearance in geriatric patients and in
patients with renal dysfunction was reduced, in most studies however
without reaching the level of statistical significance. In patients
with hepatic disease, the mean elimination half-life is prolonged by
30 minutes and the mean plasma clearance is reduced by 1 ml/kg/min.
(See section 4.2.)
Intensive Care unit
When administered as a continuous infusion to facilitate mechanical
ventilation for 20 hours or more, the mean elimination half-life and the
mean (apparent) volume of distribution at steady state are increased.
A large between patient variability is found in controlled clinical studies,
related to nature and extent of (multiple) organ failure and individual
patient characteristics. In patients with multiple organ failure a mean
(± SD) elimination half-life of 21.5 (± 3.3) hours, a (apparent) volume of
distribution at steady state of 1.5 (± 0.8) l/kg and a plasma clearance of
2.1 (± 0.8) ml/kg/min were found. (See section 4.2.)
5.3 Preclinical safety data
Effects in non-clinical studies were observed only at exposures
considered sufficiently in excess of the maximum human exposure
indicating little relevance to clinical use.
There is no proper animal model to mimic the usually extremely complex
clinical situation of the ICU patient. Therefore the safety of Esmeron
when used to facilitate mechanical ventilation in the Intensive Care Unit
is mainly based on results obtained in clinical studies.

6.1 List of excipients
Esmeron contains the following excipients:
• Sodium acetate (E262) (for pH adjustment)
• Sodium chloride
• Acetic acid (E260) (for pH adjustment)
• Water
No preservative has been added
6.2 Incompatibilities
Physical incompatibility has been documented for Esmeron when
added to solutions containing the following drugs: amphotericin,
amoxicillin, azathioprine, cefazolin, cloxacillin, dexamethasone,
diazepam, enoximone, erythromycin, famotidine, furosemide,
hydrocortisone sodium succinate, insulin, intralipid, methohexital,
methylprednisolone, prednisolone sodium succinate, thiopental,
trimethoprim and vancomycin.
Esmeron must not be mixed with other medicinal products except
those mentioned in section 6.6.
If Esmeron is administered via the same infusion line that is
also used for other drugs, it is important that this infusion line is
adequately flushed (e.g. with 0.9% NaCl) between administration
of Esmeron and drugs for which incompatibility with Esmeron has
been demonstrated or for which compatibility with Esmeron has not
been established.
6.3 Shelf life
Esmeron has a shelf life of 3 years, provided it is stored under the
prescribed conditions (see Special precautions for storage). The
date mentioned on the carton and on the label of the vial is the
expiry date; this is the date up to which Esmeron may be used.
Since Esmeron does not contain a preservative, the solution should
be used immediately after opening the vial.
After dilution with infusion fluids (see section 6.6), chemical and
physical in-use stability has been demonstated for 72 hours at
30°C. From a microbiological point of view, the diluted product
should be used immediately. If not used immediately, in-use storage
times and conditions prior to use are the responsibility of the user/
administrator and would normally not be longer than 24 hours at
2 to 8°C, unless dilution has taken place in controlled and validated
aseptic conditions.
6.4 Special precautions for storage
Storage in the Refrigerator
Esmeron should be stored at 2°-8°C in the dark and used within the
expiry date given on the pack.
Storage out of the refrigerator
Esmeron may also be stored outside of the refrigerator at a
temperature of up to 30°C for a maximum 12 weeks, after which it
should be discarded. The product should not be placed back into
the refrigerator, once it has been kept outside. The storage period
must not exceed the shelf-life.
For storage conditions after first opening of the medicinal product,
see section 6.3.
6.5 Nature and contents of containers
Esmeron 25 mg in 2.5 ml (10mg/ml)
Packaging of 10 vials each containing 25 mg rocuronium bromide.
Esmeron 50 mg in 5 ml (10mg/ml)
Packaging of 10 vials each containing 50 mg rocuronium bromide.
Esmeron 100 mg in 10 ml (10mg/ml)
Packaging of 10 vials each containing 100 mg rocuronium bromide.
Not all pack sizes may be marketed.
Type 1 Ph.Eur., clear, colourless, glass vial with a rubber closure and
flip off cap. The rubber stopper of the vial does not contain latex.
In correspondence please quote lot number.
6.6 Special precautions for disposal and other handling
Compatibility studies with the following infusion fluids have been
performed: In nominal concentrations of 0.5 mg/ml and 2.0 mg/ml
Esmeron has been shown to be compatible with: 0.9% NaCl,
5% dextrose, 5% dextrose in saline, sterile water for injections,
Lactated Ringers and Haemaccel. Administration should be begun
immediately after mixing, and should be completed within 24 hours.
Any unused medicinal product or waste material should be
disposed of in accordance with local requirements.
7. Marketing authorisation holder
NV Organon, Kloosterstraat 6, PO Box 20, 5340 BH Oss,
The Netherlands
8. Marketing authorisation number
PL 05003/0041
MALTA: MA 031/00201
9. Date of first authorisation/renewal of the
Date of first authorisation: 15th July 1996
Date of latest renewal: 7th May 2002
10. Date of revision of the text
March 2015

----------------!---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Pregnancy and breast feeding
➔ Tell your anaesthetist if you are pregnant or might be
pregnant, or if you are breast feeding.
Your anaesthetist may still give you Esmeron, but you need
to discuss it first. If you are pregnant or breast-feeding, think
you may be pregnant or are planning to have a baby, ask your
anaesthetist or other doctor for advice before taking this
medicine. Esmeron may be given to you if you are having a
Caesarean section.
Driving and using machines
Do not drive or use machines until advised it is safe to
do so. Because Esmeron is given as part of a general
anaesthetic, you may feel tired, weak or dizzy for some
time afterwards. Your anaesthetist will be able to advise
you on how long the effects are likely to last.
3. How Esmeron is given
Your anaesthetist will work out the dose of Esmeron you need
based on:
• the type of anaesthetic
• the expected length of the operation
• other drugs you are taking
• your state of health.
The normal dose is 0.6 mg per kg body weight and the effect will
last 30–40 minutes.
For Position Only

How Esmeron is given
Esmeron will be given to you by your anaesthetist. Esmeron is given
intravenously (into a vein), either as single injections or as a continuous
infusion (a drip).
If you are given more Esmeron than you need
As your anaesthetist will be monitoring your condition carefully it is unlikely
that you will be given too much Esmeron. However, if this happens, your
anaesthetist will keep you breathing artificially (on a ventilator) until you
can breathe on your own. You will be kept asleep while this takes place.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not
everybody gets them. If these side effects occur while you are under
anaesthetic, they will be seen and treated by your anaesthetist.
Uncommon side effects
(may affect up to 1 in 100 people)
• the drug is too effective, or not effective enough
• the drug works for longer than expected
• lowering of blood pressure
• increase in heart rate
• pain near the site of injection.
Very rare side effects
(may affect up to 1 in 10,000 people)
• allergic (hypersensitivity) reactions (such as difficulty in breathing,
collapse of the circulation and shock)
• wheezing of the chest

muscle weakness
sudden fever with rapid heartbeat, rapid breathing and stiffness, pain
and/or weakness in your muscles
• swelling, a rash or redness of the skin.
If any of the side effects gets serious
Or if you notice any side effects not listed in this leaflet:
➔ Tell your anaesthetist or other doctor.
Reporting of side effects
If you get any side effects, talk to your anaesthetist or other doctor.
This includes any possible side effects not listed in this leaflet. You can
also report side effects directly (see details below). By reporting side
effects you can help provide more information on the safety of this
United Kingdom: Yellow Card Scheme at:
Malta: ADR Reporting at:
5. How Esmeron is stored
The hospital will keep Esmeron according to the correct storage conditions,
and will ensure that it's in its expiry date.
6. Contents of the pack and other information
What Esmeron contains
The active substance of Esmeron is rocuronium bromide 10 mg/ml.
The other ingredients are sodium acetate (E262), sodium chloride,
acetic acid (E260) and water for injections. Each millilitre (ml) of
Esmeron contains 1.72 mg of sodium. No preservative has been added.

What Esmeron looks like and contents of the pack
Esmeron is a colourless to slightly yellow/brown solution for
injection. It is available in vials containing 25 mg (10 vials per pack),
50 mg (10 vials per pack) or 100 mg (10 vials per pack) of rocuronium
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder: NV Organon, Kloosterstraat 6,
PO Box 20, 5340 BH Oss, The Netherlands.
Manufacturer: NV Organon, Kloosterstraat 6, PO Box 20, 5340 BH
Oss, The Netherlands.
Problems reading this leaflet?
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: Esmeron
Reference Number: PL 05003/0041
This is a service provided by the Royal National Institute of the
This leaflet was last revised in March 2015.

+ Expand Transcript

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.