Esmeron

Package leaflet: Information for the user

Esmeron, 50 mg/5 ml, solution for injection
Esmeron, 100 mg/10 ml, solution for injection
Rocuronium bromide
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific person. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Esmeron is and what it is used for
2. What you need to know before you use Esmeron
3. How to use Esmeron
4. Possible side effects
5. How to store Esmeron
6. Contents of the pack and other information

1. What Esmeron is and what it is used for

Esmeron belongs to a group of medicines called muscle relaxants. Muscle relaxants are used during surgery as part of general anaesthesia.
Esmeron is used in adult patients as an adjunct to general anaesthesia to facilitate tracheal intubation during routine and rapid induction of anaesthesia, and to provide skeletal muscle relaxation during surgical procedures. Esmeron is also indicated as an adjunctive agent in intensive care units (ICU) to facilitate intubation and mechanical ventilation.
Children and adolescents: Esmeron is indicated as an adjunct to general anaesthesia to facilitate tracheal intubation during routine anaesthesia and to provide skeletal muscle relaxation during surgical procedures in term neonates, children and adolescents (aged 0 to < 18 years).

2. Important information before using Esmeron

When not to use Esmeron
If the patient is allergic to rocuronium, bromide ion, or any of the other ingredients
of this medicine (listed in section 6).

Warnings and precautions
Information about the patient's health condition may be important when deciding on the administration of Esmeron.
Please inform the anaesthetist if any of the following symptoms have ever occurred:

• allergy to muscle relaxants
• kidney function disorders or kidney disease
• heart disease
• oedema (e.g. swelling around the ankles)
• liver or biliary tract disease or liver function disorders
• nerve or muscle disorders
• malignant hyperthermia in the past (sudden fever with rapid heartbeat, rapid breathing, and muscle stiffness, pain and/or weakness)

Certain medical conditions may affect the action of Esmeron, such as:

• low potassium levels in the blood
• high magnesium levels in the blood
• low calcium levels in the blood
• low protein levels in the blood
• dehydration
• acidosis
• high carbon dioxide levels in the blood (hypercapnia)
• general poor health condition
• obesity
• burns

If any of the above conditions are present, the doctor will determine the appropriate Esmeron dosage individually for the patient.

Children and elderly patients
Esmeron may be used in the paediatric population (including term newborns, children, and adolescents) and in elderly patients, but the doctor should first assess the patient's health condition.

Esmeron and other medicines
Inform the doctor about all medicines currently or recently taken, as well as any medicines the patient plans to take.

The following medicines may affect the action of Esmeron:

Medicines that enhance the effect of Esmeron:

• certain anaesthetics used during surgical procedures
• long-term concomitant use of corticosteroids (anti-inflammatory agents) and Esmeron in intensive care units
• certain antibiotics used for bacterial infections
• certain medicines used in the treatment of bipolar affective disorders (e.g. lithium salts)
• medicines used for cardiovascular disorders (quinidine, calcium channel blockers) or medicines that increase blood pressure
• medicines used in the treatment of malaria, e.g. quinine
• diuretics
• magnesium salts
• local anaesthetics (lidocaine, bupivacaine)
• anticonvulsants used during surgery (phenytoin)

Medicines that reduce the effect of Esmeron:

• long-term use of anticonvulsants (phenytoin, carbamazepine)
• medicines used in pancreatitis, blood coagulation disorders, or acute blood loss (protease inhibitors; gabexate, ulinastatin)

Medicines with variable effects on Esmeron:

• other muscle relaxants

Esmeron may affect the action of the following medicines:

• accelerates the effect of local anaesthetics (lidocaine)

Children and adolescents
Formal interaction studies have not been conducted. The above-mentioned interactions should be considered in children and adolescents.

Pregnancy and breastfeeding
Before using any medicine, consult a doctor or pharmacist.
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this medicine.
Breastfeeding should be avoided for 6 hours after administration of this medicine.

Driving and operating machinery
This medicine affects the ability to drive motor vehicles and operate machinery.
The doctor will inform the patient whether it is safe to drive or operate potentially dangerous machinery after receiving Esmeron.

Esmeron contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per vial, meaning the medicine is considered "sodium-free".

3. How to use Esmeron

Dosage
Your doctor will determine the appropriate dose of the medicine. Esmeron will be administered before and/or during surgical procedure.
The usual dose is 0.6 mg/kg body weight of rocuronium bromide, which lasts for 30 to 40 minutes.
The effect of Esmeron should be monitored during the procedure.
If necessary, an additional dose may be administered. The required dose depends on several factors,
including possible interactions with other medicines given simultaneously, duration of the surgical procedure, age and health status of the patient.

Method and route of administration
Esmeron is not intended for self-administration by the patient. Esmeron is administered as an intravenous solution, either as a single injection or by continuous infusion.
The medicine should be administered only by a physician or nurse.

Overdose of Esmeron
Medical personnel monitor the effect of the medicine, therefore overdose is unlikely. However, if an overdose occurs, artificial ventilation will be continued until the patient regains spontaneous respiration.
The duration of action of Esmeron can be shortened by administering a reversal agent.

Missed dose of Esmeron
Not applicable.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.

Uncommon or rare (observed in 0.01%–1% of patients):

• increased heart rate (tachycardia)
• decreased blood pressure (hypotension)
• reduced or enhanced effect of Esmeron
• pain at the injection site
• prolonged muscle-relaxing effect of Esmeron

Very rare (observed in less than 0.01% of patients):

• hypersensitivity reactions, such as changes in blood pressure or heart rate, and shock due to insufficient circulating blood volume
• chest tightness caused by bronchial muscle spasm (bronchospasm)
• skin disorders (e.g. angioedema, redness, rash, or blisters)
• muscle weakness or paralysis
• prolonged muscle function disorders, usually observed in critically ill patients (steroid myopathy), when Esmeron and corticosteroids (anti-inflammatory medicines) are administered simultaneously in intensive care units

Frequency unknown (frequency cannot be determined from available data):

• severe allergic coronary artery spasm (Kounis syndrome) causing chest pain (angina pectoris) or heart attack (myocardial infarction)
• pupil dilation (mydriasis) or fixed pupils that do not change size in response to light or other stimuli

Children and adolescents
Clinical studies in children and adolescents using rocuronium bromide (up to 1 mg/kg body weight) showed increased heart rate in 1.4% of patients.

Reporting suspected adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, Phone: +48 22 4921301, Fax: +48 22 4921309,
Website: https://smz.ezdrowie.gov.pl
Adverse reactions may also be reported to the marketing authorization holder.
Reporting suspected adverse reactions contributes to improving the safety of the medicine.

5. How to store the medicine Esmeron

Keep the medicine out of the sight and reach of children.
Esmeron should only be stored in a hospital pharmacy.
Store in a refrigerator (2°C - 8°C).
The medicine may be stored outside the refrigerator at a temperature below 30°C for a maximum period of 3 months.
The medicine may be placed in and removed from the refrigerator at any time during the 3-year shelf life, but the total duration of storage outside the refrigerator must not exceed 3 months.
The storage period must not exceed the expiry date indicated on the carton and vial after "EXP".
Do not use this medicine after the expiry date stated on the carton and vial after "EXP".
Do not use this medicine if visible particles are observed or if the solution is not clear.

6. Contents of the packaging and other information

What Esmeron contains

• The active substance is rocuronium bromide.
• The other components are: sodium acetate, sodium chloride, glacial acetic acid to pH 4, and water for injections. 1 ml of solution contains 1.64 mg of sodium. The medicine does not contain preservatives.

What Esmeron looks like and contents of the pack
Esmeron is a colourless to slightly yellowish-brown solution for injection or continuous infusion, containing 10 mg/ml rocuronium bromide.
Available pack sizes:

• Vials containing 50 mg rocuronium bromide in 5 ml solution (10 vials per pack)
• Vials containing 100 mg rocuronium bromide in 10 ml solution (10 vials per pack)

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
MSD Polska Sp. z o.o.
ul. Chłodna 51
00-867 Warsaw
Tel. (+48) 22 54 95 100
[email protected]
Manufacturer
N.V. Organon, Kloosterstraat 6, 5349 AB, Oss, Netherlands
Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, Netherlands

Information intended exclusively for medical professionals:

An intravenous medicinal product.
Like other neuromuscular blocking agents, Esmeron must be administered only by (or under the supervision of) experienced clinicians familiar with the actions and use of such medicinal products.
As with other neuromuscular blocking agents, the dose of Esmeron must be individualized for each patient. When determining the dose, the type of anaesthesia, expected duration of surgery, method of anaesthesia, anticipated duration of mechanical ventilation, possible interactions with other medicinal products administered before or during anaesthesia, and the patient's clinical condition should be taken into account.
Appropriate monitoring of neuromuscular transmission is recommended to assess the degree of neuromuscular block and its recovery.
Inhalational anaesthetic agents enhance the neuromuscular blocking effect of rocuronium bromide. This effect becomes clinically significant with prolonged anaesthesia, when volatile agents reach tissue concentrations sufficient to interact with rocuronium bromide. Therefore, during prolonged anaesthesia (longer than 1 hour) using inhalational agents, the dosing of Esmeron should be adjusted by administering smaller maintenance doses less frequently or by reducing the infusion rate (see section 4.5 of the Summary of Product Characteristics).
The recommended doses of Esmeron provided below serve as general guidelines for tracheal intubation and muscle relaxation during short- and long-term surgical procedures, as well as for use in Intensive Care Units in adult patients.

Dosing
Surgical procedures
Tracheal intubation
The standard dose for intubation during routine anaesthesia is 0.6 mg/kg body weight of rocuronium bromide. Adequate intubating conditions are achieved within 60 seconds after administration in most patients. In rapid sequence induction of anaesthesia, a dose of 1.0 mg/kg body weight of rocuronium bromide is recommended, providing adequate intubating conditions within 60 seconds in nearly all patients. When using a dose of 0.6 mg/kg body weight of rocuronium bromide during rapid sequence induction, tracheal intubation should be performed 90 seconds after administration.
Section 4.6 of the Summary of Product Characteristics refers to the use of rocuronium bromide during rapid sequence induction of anaesthesia in patients undergoing caesarean section.

Higher doses
Higher initial doses of up to 2 mg/kg of rocuronium bromide have been used in individual patients during surgical procedures, without adverse cardiovascular or vascular effects being observed. The use of higher doses of rocuronium bromide accelerates the onset of action and prolongs the duration of therapeutic effect (see section 5.1 of the Summary of Product Characteristics).

Maintenance doses
The recommended maintenance dose is 0.15 mg/kg body weight of rocuronium bromide. During prolonged anaesthesia with inhalational agents, the maintenance dose should be reduced to 0.075–0.1 mg/kg body weight of rocuronium bromide. Maintenance doses should be administered when the twitch response returns to 25% of control or when two or three responses are observed in response to four stimuli.

Continuous infusion
If rocuronium bromide is administered by continuous infusion, an initial dose of 0.6 mg/kg body weight of rocuronium bromide is recommended. When neuromuscular blockade begins to wear off, the infusion should be started. The infusion rate should be adjusted to maintain the twitch response at 10% of control or to maintain one or two responses in response to four stimuli. In adults, during intravenous anaesthesia, the infusion rate required to maintain neuromuscular blockade at this level ranges from 0.3 to 0.6 mg/kg body weight/h. During inhalational anaesthesia, the infusion rate ranges from 0.3 to 0.4 mg/kg body weight/h. Continuous monitoring of neuromuscular blockade is recommended due to individual variability and the anaesthetic agents and techniques used.

Children and adolescents
In neonates (0–27 days), infants (28 days to 2 months), young children (3 to 23 months), children (2 to 11 years), and adolescents (12 to 17 years), the recommended intubation dose during routine anaesthesia and the maintenance dose are similar to those in adults.
However, the duration of action of a single intubation dose is longer in neonates and infants than in older children (see section 5.1 of the Summary of Product Characteristics).
The infusion rate in adolescents is the same as in adults. In children aged 2 to 11 years, higher infusion rates may be required. Therefore, an initial infusion rate similar to that in adults is recommended, followed by adjustment to maintain the twitch response at 10% of control or one or two responses in response to four stimuli.
Experience with the use of rocuronium bromide in rapid sequence induction in children and adolescents is limited. Therefore, rocuronium bromide is not recommended to facilitate tracheal intubation during rapid sequence induction in children and adolescents.

Dosing in elderly patients, patients with hepatic and/or biliary dysfunction and/or renal insufficiency
The standard intubation dose in elderly patients and in patients with liver disease and/or biliary tract disorders and/or renal failure is 0.6 mg/kg body weight of rocuronium bromide.
In rapid sequence induction of anaesthesia in patients in whom prolonged duration of action may be expected, a dose of 0.6 mg/kg body weight should be considered. Regardless of the anaesthetic technique used, the recommended maintenance dose in these patients is 0.075–0.1 mg/kg body weight of rocuronium bromide, and the recommended infusion rate is 0.3 to 0.4 mg/kg body weight/h (see “Continuous infusion”) (see also section 4.4 of the Summary of Product Characteristics).

Dosing in overweight and obese patients
In overweight or obese patients (defined as those whose body weight is 30% or more above ideal body weight), Esmeron doses should be reduced, based on lean body mass.

Procedures performed in Intensive Care Units
Tracheal intubation
The same doses used for tracheal intubation as described above for surgical procedures are recommended.

Dosing to facilitate mechanical ventilation
An initial dose of 0.6 mg/kg body weight of rocuronium bromide is recommended. When the twitch response returns to 10% of baseline or when 1 to 2 responses are observed in response to four stimuli, continuous infusion should be initiated. Dosing must always be individualized according to the patient's needs. The recommended initial infusion rate to maintain neuromuscular blockade at 80 to 90% (1 to 2 responses in response to four stimuli) in adult patients is 0.3 to 0.6 mg/kg body weight/h during the first hour. During the subsequent 6 to 12 hours, the infusion rate should be reduced according to the individual patient's requirements. Thereafter, individual requirements remain relatively stable. In controlled clinical studies, considerable variability in infusion rates among patients has been observed, with mean hourly infusion rates ranging from 0.2 to 0.5 mg/kg body weight/h, depending on the type and severity of organ dysfunction, concomitant medications, and individual patient characteristics. Neuromuscular transmission monitoring is recommended to achieve optimal patient control. The drug has been administered for periods of up to seven days.

Special patient groups
The use of Esmeron to facilitate mechanical ventilation in Intensive Care Units is not recommended in children and adolescents or in elderly patients due to lack of data on efficacy and safety.

Method of administration
Esmeron is administered intravenously as a rapid bolus injection or by continuous infusion (see section 6.6 of the Summary of Product Characteristics).