Last Updated on eMC 12-01-2018 View medicine  | Merck Sharp & Dohme Limited Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:23-11-2017

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Date of approval changed only.

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text
  • Change to section 4.8 - Undesirable effects - how to report a side effect

Date of revision of text on the SPC:20-12-2017

Legal Category:POM

Black Triangle (CHM): NO

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  • Section 4.4 Special warnings and precautions for use: In depth information added about the risks of malignant hyperthermia during anaesthesia.
  • Section 4.6 Pregnancy and lactation: Instructions about post administration of a single dose of Esmeron for lactating women.
  • Section 4.8 Undesirable effects: The adverse event of ‘malignant hyperthermia’ has been removed from the SOC of ‘general disorders and administration site conditions’. Reporting of suspected adverse reactions statement for the UK has been updated to reference downloading the yellow card App.

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects
  • Improved presentation of SPC

Date of revision of text on the SPC:09-09-2015

Legal Category:POM

Black Triangle (CHM): NO

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The principal change made to the SmPC is:

·        Section 4.8 – Undesirable effects:
o   Addition of ‘Malignant hyperthermia’ as an adverse reaction with a very rare frequency. This has been added following post-marketing surveillance.

 
Other changes in line with the latest QRD have been made.

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.1 - List of excipients

Date of revision of text on the SPC:21-10-2014

Legal Category:POM

Black Triangle (CHM): NO

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The changes made to the SmPC are as follows:

Sections 4.2 Posology and method of administration

·        Addition of cross-reference to section 4.4 in subsection Geriatric patients and patients with hepatic and/or biliary tract disease and/or renal failure.

Section 4.4 Special warnings and precautions for use

·        addition of the statement “Geriatric patients (65 years or older) may be at increased risk for residual neuromuscular block.” To align the SmPC with the CCDS. This was added based upon literature and Postmarketing Adverse Experience Report Data

“…. 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.  ….”

Section 4.8 Undesirable effects

·        Addition of country Reporting details for reporting of suspected adverse reactions

Section 5.1 Pharmacodynamic properties

·        Addition of cross-reference to section 4.2 in subsection Geriatric patients and patients with hepatic and/or biliary tract disease and/or renal failure.

Section 5.2 Pharmacokinetic properties

·        Addition of cross-reference to section 4.2 in subsections Geriatric patients and patients with hepatic and/or biliary tract disease and/or renal failure and Intensive Care unit.

Section 6.1 List of excipients

·        addition of the wording “(for pH adjustment)” after acetic acid. This change is made to align SmPC text with the CCDS.

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for use

Date of revision of text on the SPC:11-12-2012

Legal Category:POM

Black Triangle (CHM): NO

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A sentence in the first paragraph of section 4.4 was not approved text and has been deleted:

In case of intubation difficulties resulting in a clinical need for immediate reversal of a rocuronium induced neuromuscular block, the use of sugammadex should be considered.’

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.9 - Overdose
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:11-12-2012

Legal Category:POM

Black Triangle (CHM): NO

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4.4  Special warnings and precautions for use

Sugammadex or acetylcholinesterase inhibitors have been added to this section in brackets as an example of possible reversal agents that should be considered.


4.9  
Overdose

There are now 2 options available in this section for reversal of NMB (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. 

The additions are underlined.

 

9 Date of first authorisation/renewal of the authorisation, the correct dates have been added.

 

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable Effects
  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 5.2 - Pharmacokinetic Properties
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:23-08-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



The changes made to the SmPC are as follows:

4.1 Therapeutic indications now includes use of Esmeron in '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.

4.2 Posology and method of administration. Pediatric patients subheading.
'Neonates (0-27 days)' has been added and 'infants (28 days – 23 months)' has been split into 'infants (28 days – 2 months)' and 'toddlers (2 months – 23 months)', with an additional statement advising that 'the duration of action of the single intubating dose will be longer in neonates and infants than in children (see section 5.1)'

Children has been defined in all occurrences as 2-11 years.

The following sentence has been deleted 'There are insufficient data to support dose recommendations for the use of rocuronium bromide in neonates (0-1 month).'

4.5 Interaction with other medicinal products and other forms of interaction
Effects of other drugs on Esmeron: 'Reversal of the block with anticholinesterase inhibitors…..' now reads 'Reversal of the block with acetylcholinesterase inhibitors…..'

The following new paragraphs on paediatric patients has been added.

'Paediatric patients
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.'

4.8 Undesirable effects

The following new paragraphs on paediatric patients has been added.

'Paediatric patients
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%.'

5.1 Pharmacodynamic properties
The paediatric population section now reads:

Paediatric patients

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 block **

(min)

Time to reappearance of T3 **

(min)

Neonates (0-27 days)

n=10

0.98 (0.62)

56.69 (37.04)

n=9

Infants (28 days-2 months)

n=11

0.44 (0.19)

n=10

60.71 (16.52)

 

Toddler (3 months-23 months)

n=28

0.59 (0.27)

 

45.46 (12.94)

n=27

Children (2-11 years)

n=34

0.84 (0.29)

 

37.58 (11.82)

Adolescents (12-17 years)

n=31

0.98 (0.38)

42.90 (15.83)

n=30

* Dose of rocuronium administered within 5 seconds.

** Calculated from the end of administration of the rocuronium intubating dose

The paragraph referring to 'Geriatric patients and patients with hepatic and/or biliary tract disease and/or renal failure'  has been given its own heading.  

5.2 Pharmacokinetic Properties
The following new information has been added:

Paediatric patients
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 (l.hr-1.kg-1). The volume of distribution (l.kg-1) 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 oxyde (induction) and isoflurane/nitrous oxide (maintenance anaesthesia)

 

 

PK Parameters

Patient age range

Term newborn infants

(0-27 days)

Infants


(28 days to 2 months)

Toddlers


(3-23 months)

Children


(2-11 years)

Adolescents


(12-17 years)

 

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 (L/kg)

 

0.42 (0.06)

 

0.31 (0.03)

 

0.23 (0.03)

 

0.18 (0.02)

 

0.18 (0.01)

 

t ½ β (hr)

 

1.1 (0.2)

 

0.9 (0.3)

 

0.8 (0.2)

 

0.7 (0.2)

 

0.8 (0.3)

 As a result the following paragraph has been deleted: 'In infants (28 days to 23 months), the apparent volume of distribution at steady state conditions is increased compared to adults and children (2-11 years).  In older children (3-8 yr), a trend is seen towards higher clearance and shorter elimination half-life (approximately 20 minutes) compared to adults, younger children and infants.'

 There are also other minor changes to headings to bring the SmPC into line with QRD 8.0 (the standard text for SmPCs).

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:13-09-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.4 of the SmPC was updated to include wording on cross rectivity:
"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."

 

Reasons for adding or updating:

  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 4.7 - Effects on Ability to Drive and Use Machines
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 5.2 - Pharmacokinetic Properties
  • Change to section 6.1 - List of Excipients
  • Change to section 6.2 - Incompatibilities
  • Change to section 6. 4 - Special Precautions for Storage
  • Change to section 6. 5 - Nature and Contents of Container
  • Change to section 7 - Marketing Authorisation Holder
  • Change to section 10 date of revision of the text
  • Change to section 1 -Name of the Medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable Effects
  • Change to section 5.3 - Preclinical Safety Data
  • Change to section 6. 3 - Shelf Life
  • Change to section 6. 6 - Instructions for use, handling and disposal
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use

Date of revision of text on the SPC:01-03-2008

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

text in bold are added and text striked out is deleted

SUMMARY OF PRODUCT CHARACTERISTICS                                                                                                                        

 

1.             NAME OF THE MEDICINAL PRODUCT

 

ESMERONEsmeron® 10mg/ml solution for injection

 

 

2.             QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each ml Esmeron contains 10 mg rocuronium bromide. 

For a full list of excipients, see 6.1.

 

               

3.             PHARMACEUTICAL FORM

 

Esmeron is supplied as a sSolution for intravenous injection.

pH:  3.8-4.2

 

4.             CLINICAL PARTICULARS

 

4.1           Therapeutic indications

Esmeron is indicated as an adjunct to general anaesthesia to facilitate tracheal intubation during routine and rapid sequence induction, and to provide skeletal muscle relaxation, during surgery. Esmeron is also indicated as an adjunct in the intensive care unit (ICU) to facilitate intubation and mechanical ventilation.

 

4.2           Posology and method of administration

 

Dosage

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 individualized in each patient.  The anaesthetic method of anaesthesiaused, 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 routine use of an appropriate neuromuscular monitoring technique is recommended for the evaluation of neuromuscular block and recovery.

 

Inhalational anaesthetics do potentiate the neuromuscular blocking effects of Esmeron.  This potentiation however, only 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 Interaction with other medicaments and other forms of interaction 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 per kg body weight rocuronium bromide, after which adequate intubation conditions are established within 60 seconds in nearly all patients. A dose of 1.0 mg/kg of rocuronium bromide per kg of body weight 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 Iin patients undergoing Caesarean section a 1.0mg/kg dose has not been investigated.  (See Section 4.6 Pregnancy and Lactation).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 Esmeron per kg body weight rocuronium bromide; in the case of long-term inhalational anaesthesia this should be reduced to 0.075-0.1 mg/kg of rocuronium bromide. per kg body weight. 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 Esmeron rocuronium bromide is administered by continuous infusion, it is recommended to give a loading dose of 0.6 mg/kg Esmeron per kg rocuronium bromide body weight 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.kg1 hour1 mg/kg/h (300-600 micrograms/kg/h kg1 hour-1) and under inhalational anaesthesia the infusion rate ranges from 0.3-0.4mg.kg1 h1 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.

 

Dosing in pPaediatric patients

For infants (28 days–23 months), Children children (1-142-11 years) and infants (1-12 months) and adolescents (12–18 years) under halothane anaesthesia manifest similar sensitivity to Esmeron as adults.the recommended intubation dose during routine anaesthesia and maintenance dose are similar to those in adults.  Onset of action is faster in infants and children than in adults.

 

For continuous infusion in paediatrics, the infusion rates, with the exception of children, are the same as for adults.  For children higher infusion rates might be necessary.  For children the same initial infusion rates as for adults are recommended and 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.

 

Clinical duration is shorter in children than in adults.  There are no insufficient data to support dose recommendations for the use of Esmeron rocuronium bromide in neonates (0-1 month).

 

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.

 

Dosing in gGeriatric 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 per kg body weight.  A dose of 0.6 mg/kg per kg body weight should be considered for rapid sequence induction of anaesthesia in patients in which a prolonged duration of action is expected, but adequate conditions for intubation may not be established until 90 seconds after administration of rocuronium bromide. Regardless of the anaesthetic technique used, the recommended maintenance dose for these patients is 0.075-0.1 mg/kg rocuronium bromide per kg body weight, and the recommended infusion rate is 0.3-0.4 mg.kg-1.h-1mg/kg/h (see also Continuous infusion).

 

Dosing in oOverweight 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 a lean body mass.ideal body weight.

 

Intensive Care Procedures

 

Tracheal intubation

For tracheal intubation, the same doses should be used as described above under surgical procedures.

 

Dosing to facilitate mechanical ventilation :Maintenance dosing

The use of an initial loading dose of 0.6 mg/kg rocuronium bromide per kg body weight 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-1.h-1 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  0.20 - 0.50 mg.kg-1.h-1mg/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

There are no data to support dose recommendations for the facilitation of mechanical ventilation in paediatric and geriatric patients.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.

 

Administration

Esmeron is administered intravenously either as a bolus injection or as a continuous infusion (see also Instructions for use/handling section 6.6).

 

4.3           Contraindications

 

Former anaphylactic reactions Hypersensitivity to rocuronium or to the bromide ion or to any of the excipients.

 

4.4           Special warnings and special 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. 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 should be considered, especially in those cases where residual neuromuscular blockade is more likely to occur.

 

Anaphylactic reactions can occur following the administration of neuromuscular blocking agents.  Precautions for treating such reactions should always be taken.  Particularly in the case of previous anaphylactic reactions to neuromuscular blocking agents, special precautions should be taken since allergic cross-reactivity to neuromuscular blocking agents has been reported.

 

Dose levels greater than 0.9 mg Esmeron per kg body weight may increase the heart rate; this effect could counteract the bradycardia produced by other anaesthetic agents or by vagal stimulation.Rocuronium may increase the heart rate.

In general, following long term use of muscle relaxantsneuromuscular 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 muscle relaxantsneuromuscular blocking agents.  In addition, patients should receive adequate analgesia and sedation.   Furthermore, muscle relaxants 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.Because Esmeron is always used with other agents and because the occurrence of malignant hyperthermia during anaesthesia is possible, even in the absence of known triggering agents, clinicians should be familiar with early signs, confirmatory diagnosis and treatment of malignant hyperthermia prior to the start of any anaesthesia.  In animal studies Esmeron was shown not to be a triggering factor for malignant hyperthermia

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, Esmeron 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. per kg body weight.

 

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.

 

Hypothermia

In surgery under hypothermic conditions, the neuromuscular blocking effect of Esmeron is increased and the duration prolonged.

 

Obesity

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.

 

Burns

Patients with burns are known to develop resistance to non-depolarizing 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 medicaments medicinal products and other forms of interaction

 

The following drugs have been shown to influence the magnitude and/or duration of action of non-depolarizing 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 anticholinesterase inhibitors could also be inhibited.

 

·            High doses of: thiopental, methohexital, ketamine, fentanyl, gammahydroxybutyrate, etomidate and propofol

*        Other non-depolarising neuromuscular blocking agents.

·          After intubation with Prior administration of 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 eg lincomycin and clindamycin and polypeptide antibiotics, acylamino-penicillin antibiotics. tetracycline, high doses of metronidazole.

·          diuretics, thiamine, MAO inhibiting agents, quinidine and its isomer quinine, magnesium salts, calcium channel blocking agents, lithium salts, local anaesthetics (lidocaine i.v, bupivacaine epidural) and acute administration of phenytoin or ß-blocking agents.

, protamine, -adrenergic blocking agents, magnesium salts, calcium channel blocking agents and lithium salts.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:

-     neostigmine, edrophonium, pyridostigmine, aminopyridine derivatives.

- Pprior chronic administration of corticosteroids phenytoin or carbamazepine

noradrenaline, azathioprine (only transient and limited effect), theophylline,cCalcium 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.

 

4.6          Pregnancy and lactation

In animal studies neither embryotoxicity nor teratogenicity was observed that could be attributed to treatment with rocuronium bromide.

There are no data on the use of Esmeron during human pregnancy to assess potential harm to the foetus.  Esmeron should be given to pregnant women only when the attending physician decides that the benefits outweigh the risks.  

Pregnancy

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 succinylcholine suxamethonium facilitated intubation.  However, Esmeron, administered in doses of 0.6 mg/kg per kg body weight 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 mg.kg1 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.

 

Lactation

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 decided that the benefits outweigh the risks.     

A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Esmeron should be made taking into account the benefit of breast-feeding to the child and the benefit of Esmeron therapy to the woman.

 

4.7          Effects on ability to drive and use of machines

 

It is not recommended to use potentially dangerous machinery or drive a car within 24 hours after the full recovery from the neuromuscular blocking action of Esmeron.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

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.




MedDRA SOC

Preferred term[1]

Uncommon/rare[2]
(<1/100, >1/10 000)

Very rare (<1/10 000)

Immune system disorders

 

Hypersensitivity

 

Anaphylactic reaction

 

Anaphylactoid reaction

 

Anaphylactic shock

 

Anaphylactoid shock

Nervous system disorders

 

Flaccid paralysis

Cardiac disorders

Tachycardia

 

Vascular disorders

Hypotension

Circulatory collapse and shock

 

 

 

 

Flushing

Respiratory, thoracic and mediastinal disorders

 

Bronchospasm

Skin and subcutaneous tissue disorders

 

Angioneurotic edema

 

Urticaria

 

Rash

 

Erythematous rash

Musculoskeletal and connective tissue disorders

 

Muscular weakness[3]

 

Steroid myopathy3

General disorders and administration site conditions

Drug ineffective

Face oedema

Drug effect/ therapeutic response decreased

 

Drug effect/ therapeutic response increased

 

Injection site pain

 

Injection site reaction

 

Injury, poisoning and procedural complications

Prolonged neuromuscular block

Airway complication of anaesthesia

Delayed recovery from anaesthesia

 

MedDRA version 8.1

1] Frequencies are estimates derived from post-marketing surveillance reports and data from the general literature.

[2] Post-marketing surveillance data cannot give precise incidence figures. For that reason, the reporting frequency was divided over two rather than five categories.

[3] after long-term use in the ICU

 

 

Anaphylactic reactionsAnaphylaxis

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 that they may occur and take the necessary precautions.

 

Histamine release and histaminoid reactions

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 such as bronchospasm and cardiovascular changes e.g. hypotension and tachycardia (see also under anaphylactic reactions above) should always be taken into consideration when administering these drugs. 

 

Rash, exanthema, urticaria, bronchospasm and hypotension have been reported very rarely in patients given rocuronium bromide.

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  per kg body weight

 

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 apnea.

 

Myopathy

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.

 

Prolonged neuromuscular block

Prolonged neuromuscular block has been reported very rarely in patients given rocuronium bromide (see section 4.4).

 

4.9          Overdosage

 

In the event of overdosage and prolonged neuromuscular block, the patient should continue to receive ventilatory support and sedation.  Upon start of spontaneous recovery an acetylcholinesterase inhibitor (e.g. neostigmine, edrophonium, pyridostigmine) 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 per kg body weight) was administered.

 

 

5.0          PHARMACOLOGICAL PROPERTIES

 

5.1          Pharmacodynamic properties

 

Pharmacotherapeutic group (ATC code)

Muscle relaxants, peripherally acting agents.  ATC code: M03AC09.

 

Mechanism of Action

Esmeron (rocuronium bromide) is a fast onset, intermediate acting non-depolarizing 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 balanced intravenous anaesthesia is approximately 0.3 mg/kg per kg body weight. rocuronium bromide.  The  ED95 in infants is lower than in adults and children (0.25, 0.35 and 0.40 mg/kg  respectively).

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 Esmeron per kg body weight (2 x ED90 under balancedintravenous 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. general muscle paralysis adequate for any type of procedure is established.  The clinical duration (the duration until spontaneous recovery to 25% of control twitch height) with this dose 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 Esmeron per kg body weight is 14 minutes.

 

With lower dosages of 0.3-0.45 mg Esmeron per kg body weight (1-1½ x ED90), onset of action is slower and duration of action is shorter (13-26 mins).  After administration of 0.45 mg/kg rocuronium bromide, Esmeron per kg body weight, 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 per kg body weight.  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 per kg body weight, 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.

With doses higher than 1.0mg rocuronium bromide per kg body weight the intubation conditions will not improve appreciably; the duration of action, however, will be prolonged.  Doses higher than 4 x ED90 have not been studied

Special populations

Mean onset time in infants and children at an intubation dose of 0.6 mg/kg is slightly shorter than in adults.  The duration of relaxation and the time to recovery tend to be shorter in children compared to infants and adults.  The duration of action of maintenance doses of 0.15 mg/kg rocuronium bromide Esmeron per kg body weight 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).  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 Esmeron per kg body weight 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, such as (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 ml.kg-1 and plasma clearance is 3.7 (3.5-3.9) ml/kg/min.ml.kg-1.min-1.

 

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. ml.kg-1.min-1. (See also Posology and method of administration).

 

In infants (28 days to 23 months), the apparent volume of distribution at steady state conditions is increased compared to adults and children (2-11 years).  In older children (3-8 yr), a trend is seen towards higher clearance and shorter elimination half-life (approximately 20 minutes) compared to adults, younger children and infants.

 

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 l.kg-1and a plasma clearance of 2.1 (± 0.8) ml/kg/minml.kg-1.min-1 were found. (See also Posology and method of administration).

 

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.

 

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.

 

Acute toxicity:

In acute toxicity studies rocuronium bromide was intravenously administered to cats and dogs up to a dose of 350 x ED90 and 750 x ED90 respectively.  This last dose was administered in 4 consecutive doses at intervals of 30 minutes (9, 18, 36 and 72 mg per kg body weight) and resulted in death due to cardiac collapse.

 

Subacute toxicity:

In subacute toxicity studies rocuronium bromide was intravenously administered to cats and dogs up to a dose of 37 x ED90 and 60 x ED90 respectively two times per week for a period of 4 weeks.  Unforeseen mortalities occurred in three out of seven dogs at the dose of 60 x ED90 (10.8 mg per kg body weight).  The cause of death could not be established, but was considered to be related to interactions between rocuronium treatment and experimental procedures and/or instrumentation and anaesthesia.

 

Chronic toxicity:

Chronic toxicity studies have not been performed with rocuronium bromide.

 

Mutagenicity and carcinogenicity:

In vivo and in vitro mutagenicity studies revealed no mutagenic potential of rocuronium bromide.

Carcinogenicity studies have not been performed with rocuronium bromide.

 

Reproductive toxicity:

Studies in rats with administration of rocuronium bromide during organogenesis using subpharmacological intravenous doses revealed no evidence of embryolethality, teratological changes or suppression of growth of the foetuses.

 

6.             PHARMACEUTICAL PARTICULARS

 

6.1          List of excipients

 

Esmeron contains the following excipients:

·          sSodium acetate (for pH adjustment)

·          sSodium chloride

·          aAcetic acid and

·          wWater for injections

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.

 

Except for those solutions with which Esmeron has shown to be compatible (see section 6.6), it is not recommended to mix Esmeron with solutions, or drugs in the same syringe or bag.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% NaCINaCl) 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 can be stored for threehas a shelf life of 3 years, provided it is stored under the prescribed conditions (see Special precautions for storage).  The date mentioned behind "exp.:" 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, it is recommended to discard any unused solution.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 30oc.  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 8oC, 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 between 8°-30°C outside of the refrigerator at a temperature of up to 30°C for a maximum 12 weeks,for up to 3 months, after which it should be discarded.  Once stored at 8°-30°C Esmeron should not be returned to the refrigerator. 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.

 

 

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 12 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.

Esmeron 250 mg in 25 ml (10mg/ml)

Packaging of 4 vials each containing 250 mg rocuronium bromide.

 

Not all presentations 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 batch number.

 

 

 

6.6          Instructions for use and handling (and disposal) 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 Haemaccel35. Administration should be begun immediately after mixing, and should be completed within 24 hours. after mixing  Unused solutions should be discarded.

Esmeron can be injected into the intravenous line of a running infusion containing most of the commonly used intravenous drugs, except those mentioned under Incompatibilities.

 

7.             NAME AND ADDRESS OF THE HOLDER OF THE MARKETING AUTGORISATION Marketing authorisation holder

 

NV Organon, Kloosterstraat 6,  PO Box 20, 5340 BH Oss, The Netherlands

 

8.             Marketing authorisation number

 

PL 05003/0041

 

9.             Date of first authorisation

 

4 August 2000

 

10.          Date of (partial) revision of the text

 

                August 2007 March 2008

 

 

REF: USEsVial17.0

 



Reasons for adding or updating:

  • Change from BAN to rINN
  • Change to section 10 (date of (partial) revision of the text

Date of revision of text on the SPC:01-01-2006

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Change from Ban to rINN - Amoxycillin to amoxicillin &  frusemide to furosemide
 
Change to section 10. -  December 2002 to January 2006

Reasons for adding or updating:

  • Change from BAN to rINN
  • Change to section 10 (date of (partial) revision of the text
  • Pending awaiting re-submission

Date of revision of text on the SPC:01-08-2005

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 6.2  Amoxycillin to amoxicillin & frusemide to furosemide 

Reasons for adding or updating:

  • Correction of spelling/typing errors

Reasons for adding or updating:

  • Improved Electronic Presentation

Reasons for adding or updating:

  • Change to section 6.2 - Incompatibilities

Reasons for adding or updating:

  • Improved Electronic Presentation

Reasons for adding or updating:

  • New SPC for eMC ie an SPC for an existing product, but one that is new for the eMC