Roqurum

Patient Information Leaflet

Roqurum, 10 mg/ml, solution for injection
Rocuronium bromide
Please read this leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same as yours.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

Table of Contents

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

1. What Roqurum is and what it is used for

The active substance in Roqurum is rocuronium bromide, which belongs to a group of medicines called muscle relaxants.
These medicines are used during surgical procedures as part of general anaesthesia and other medical interventions.
Roqurum is intended for use in adult patients:

• as an adjunct to general anaesthesia to facilitate tracheal intubation during routine and rapid induction of anaesthesia (tracheal intubation involves inserting a flexible plastic tube through the mouth into the trachea to provide mechanical ventilation),
• to achieve skeletal muscle relaxation during surgical procedures,
• as an adjunct in intensive care units (ICU) to facilitate intubation and mechanical ventilation.

Children and adolescents:
Roqurum is intended for use as an adjunct to general anaesthesia to facilitate tracheal intubation during routine anaesthesia and to achieve skeletal muscle relaxation during surgical procedures in full-term neonates, children and adolescents (0<18 years).

2. Important information before using Roqurum

When not to use Roqurum

• if the patient is allergic (hypersensitive) to rocuronium, bromide ion, or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with Roqurum, discuss this with your doctor, preferably an anaesthesiologist:

• if the patient is allergic to any muscle relaxant medicine
• if the patient has kidney, liver or biliary tract disease
• if the patient has heart disease or a condition associated with reduced blood flow
• if the patient has oedema (swelling), e.g. around the ankles
• if the patient has neuromuscular disorders (e.g. anterior poliomyelitis, myasthenia gravis, or Eaton-Lambert syndrome)
• if the patient has or has had the following symptoms: a rare tumour of the adrenal glands (pheochromocytoma) – this may increase the risk of a significant rise in blood pressure

Certain medical conditions/parameters may influence the effect of Roqurum, such as:

• low levels of calcium (hypocalcaemia), potassium (hypokalaemia) or protein in the blood
• high levels of magnesium (hypermagnesaemia) or carbon dioxide (hypercapnia) in the blood
• dehydration, e.g. due to severe vomiting, diarrhoea or excessive sweating
• obesity
• burns
• acidosis
• cachexia (severe wasting of the body).

If any of the above conditions apply, the doctor will take this into account when determining the appropriate dose of Roqurum for the patient.
Children and elderly patients
Roqurum can be used in children [in full-term newborns (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)] and in elderly patients, but the doctor should first assess the patient's health status.
Roqurum and other medicines
Tell your doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including those available without a prescription. Some medicines may affect the action of Roqurum.
Medicines that enhance the effect of Roqurum:

• certain anaesthetics used during surgical procedures
• prolonged, concomitant use of corticosteroids (anti-inflammatory and anti-allergic medicines) in intensive care units
• certain antibiotics (aminoglycosides, lincosamides, polypeptides, acylaminopenicillins) used to treat bacterial infections
• diuretics (medicines that increase urine excretion)
• medicines used to treat cardiovascular disorders (quinidine, calcium channel blockers, beta-adrenergic receptor blockers)
• medicines used for local anaesthesia (lidocaine, bupivacaine)
• an anticonvulsant used during surgery (phenytoin)
• medicines used to treat bipolar affective disorders (lithium salts)
• magnesium salts
• medicines used to treat malaria (quinine).

Medicines that reduce the effect of Roqurum:

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

Medicines that have variable effects on Roqurum:

• other muscle relaxants.

Roqurum may affect the action of the following medicines:

• accelerates the effect of local anaesthetics (lidocaine).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
Rocuronium bromide may be used prior to caesarean section.
Rocuronium bromide may be used in breastfeeding women only if the doctor considers that the potential benefits outweigh the risks.
Driving and operating machinery
Roqurum affects the ability to drive and operate machinery.
The doctor should inform the patient when it will be safe to drive or operate machinery.
Roqurum contains sodium
Roqurum contains less than 1 mmol (23 mg) of sodium per vial (10 ml), therefore the medicine is considered "sodium-free".

3. How to use Roqurum

Dosage
Roqurum should be administered only by, or under the supervision of, an experienced anaesthesiologist.
The doctor will determine the appropriate dose. Roqurum is given before or during a surgical procedure or other medical intervention. The usual dose is 0.6 mg/kg body weight of rocuronium bromide, which lasts for 30 to 40 minutes. The effect of Roqurum should be continuously monitored throughout the procedure.
If necessary, an additional dose may be administered. The dose of the drug depends on several factors, including possible interactions with other concomitantly administered medicines, the duration of the procedure, and the patient's age and clinical condition.

Method and route of administration
Roqurum is not intended for self-administration by the patient. Roqurum is administered intravenously as an injection or by continuous infusion.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although they do not occur in everyone.
Uncommon (may occur in no more than 1 in 100 people) or rare adverse effects
(may occur in no more than 1 in 1000 people):

• increased heart rate (tachycardia)
• decreased blood pressure
• weakness, increased intensity, or lack of effect of Roqurum
• pain or reaction at the injection site
• prolonged muscle-relaxing effect of the medicine, delayed emergence from anaesthesia.

Very rare adverse effects (may occur in no more than 1 in 10,000 people):

• hypersensitivity reactions, including life-threatening anaphylactic shock
• pseudoallergic reactions (anaphylactoid), including anaphylactoid shock
• chest tightness caused by bronchial muscle spasm (bronchospasm)
• skin reactions: urticaria, redness, rash
• angioedema
• facial swelling
• weakness* or paralysis of muscles
• prolonged muscle function disorders, usually observed in critically ill patients (steroid-induced myopathy*), when Roqurum and corticosteroids (anti-inflammatory medicines) are used simultaneously in intensive care units
• complications related to the airways resulting from the anaesthesia administered.

Frequency unknown (frequency cannot be estimated from the available data):

• severe allergic coronary artery spasm (Kounis syndrome) causing chest pain (angina pectoris) or heart attack (myocardial infarction).

Children and adolescents
Clinical studies in children and adolescents using rocuronium bromide (up to 1 mg/kg body weight) showed an increased heart rate in 1.4% of patients.
Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Roqurum

Store in a refrigerator (2 °C - 8 °C).
Keep the medicine out of the sight and reach of children.
Do not use Roqurum after the expiry date stated on the outer carton and
vial. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask
your pharmacist how to dispose of medicines no longer required. Following this advice helps protect the environment.

6. Contents of the pack and other information

What Roqurum contains

• The active substance is rocuronium bromide. 1 ml of solution contains 10 mg of rocuronium bromide.
• Other ingredients are: sodium chloride, sodium acetate trihydrate, glacial acetic acid (50% solution), water for injections.

What Roqurum looks like and contents of the pack
Roqurum is a clear solution.
Available pack sizes are:
10 vials of 2.5 ml in a cardboard box
10 vials of 5 ml in a cardboard box
10 vials of 10 ml in a cardboard box

Marketing Authorisation Holder
Bausch Health Ireland Limited
3013 Lake Drive
Citywest Business Campus
Dublin 24, D24PPT3
Ireland

Manufacturer
Siegfried Hameln GmbH
Langes Feld 13
31789 Hameln, Germany

The following information is intended for healthcare professionals only

An intravenous medicinal product.
Like other neuromuscular blocking agents, rocuronium bromide
should be administered only by, or under the supervision of, experienced clinicians
familiar with the action and use of such medicinal products.
As with other neuromuscular blocking agents, the dose of rocuronium bromide
should be individualized for each patient.
When determining the dose, the anaesthetic technique, 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 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 during 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 rocuronium bromide should be adjusted by administering smaller maintenance doses less frequently or by reducing the infusion rate of the medicinal product (see section 4.5 of the Summary of Product Characteristics).

Dosing
Appropriate monitoring of neuromuscular transmission is recommended to assess the degree of neuromuscular block and its recovery.
The recommended doses of Roqurum for adults described below may serve as general guidelines for endotracheal intubation and muscle relaxation during short- and long-term surgical procedures, as well as for use in Intensive Care Units.

Surgical procedures
Endotracheal intubation
The standard dose for intubation during routine anaesthesia is 0.6 mg/kg body weight of rocuronium bromide. Adequate conditions for intubation are achieved within 60 seconds after administration in nearly all patients. During rapid sequence induction in emergency situations, a dose of 1.0 mg/kg body weight of rocuronium bromide is recommended, which also provides adequate intubating conditions within 60 seconds in almost all patients. When using a dose of 0.6 mg/kg body weight of rocuronium bromide, intubation should be performed 90 seconds after administration.

Higher doses
If higher doses are required in individual patients, initial doses up to 2 mg/kg body weight of rocuronium bromide may be used, with no reported cardiovascular or vascular adverse effects. The use of higher doses of rocuronium bromide shortens the onset time of action and prolongs the duration of therapeutic effect.

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 a train-of-four stimulus.

Continuous infusion
If rocuronium bromide is administered as a continuous intravenous infusion, a loading 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 a train-of-four stimulus. 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/hour. In patients receiving inhalational anaesthesia, the infusion rate ranges from 0.3 to 0.4 mg/kg body weight/hour. Continuous monitoring of neuromuscular blockade is recommended due to individual requirements for infusion rate and the type of general anaesthesia used.

Caesarean section
In patients undergoing caesarean section, rocuronium bromide may be used as part of rapid sequence induction provided that difficult intubation is not anticipated and an adequate dose of anaesthetic agent has been administered. Rocuronium bromide may also be used after intubation with succinylcholine. It has been shown that rocuronium bromide can be safely used at a dose of 0.6 mg/kg body weight in patients undergoing caesarean section.

Note 1: Doses of 1.0 mg/kg body weight have been studied during rapid sequence induction in emergency situations, but not in patients undergoing caesarean section. Therefore, in this patient group, only a dose of 0.6 mg/kg body weight is recommended.
Note 2: Reversal of neuromuscular blockade induced by neuromuscular blocking agents may be inhibited or insufficient in patients receiving magnesium salts due to pre-eclampsia, as magnesium enhances neuromuscular blockade. Therefore, in these patients, the dose of Roqurum should be reduced and individually adjusted to patient needs.

Children and adolescents
In neonates (0–27 days), infants (28 days to 2 months), toddlers (3 to 23 months), children (2 to 11 years), and adolescents (12 to 18 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 rates in adolescents are the same as in adults, whereas in children (2 to 11 years) an increased infusion rate may be required. In children (2 to 11 years), the same initial infusion rates as in adults are recommended, which should then be adjusted to maintain a twitch response of 10% of control or one or two responses in a train-of-four stimulus during the procedure.
Experience with the use of rocuronium bromide for rapid sequence induction in children and adolescents is limited. Therefore, the use of rocuronium bromide to facilitate endotracheal intubation during rapid sequence induction in children and adolescents is not recommended.

Dosing in elderly patients and patients with hepatic and/or biliary dysfunction and/or renal impairment
The standard intubation dose in elderly patients and patients with hepatic and/or biliary dysfunction and/or renal impairment is 0.6 mg/kg body weight of rocuronium bromide. In cases of rapid sequence induction in patients in whom prolonged duration of action is 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 0.3–0.4 mg/kg body weight/hour (see also "Continuous infusion").

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

Procedures performed in Intensive Care Units
Endotracheal intubation
The same doses as described above for surgical procedures are used for endotracheal intubation.

Dosing to facilitate mechanical ventilation
An initial loading dose of 0.6 mg/kg body weight of rocuronium bromide is recommended. When the twitch response returns to 10% of baseline or one to two responses are observed in a train-of-four stimulus, continuous intravenous infusion should be initiated. Dosing should always be adjusted to individual patient needs. The recommended initial infusion rate to maintain neuromuscular blockade at 80–90% (1–2 responses in a train-of-four) in adult patients is 0.3–0.6 mg/kg body weight/hour during the first hour of administration. Over the next 6 to 12 hours, the infusion rate should be reduced according to individual patient requirements. Thereafter, individual requirements remain relatively constant.
In controlled clinical trials, considerable variability in infusion rates among individual patients was observed, with a mean infusion rate ranging from 0.2 to 0.5 mg/kg body weight/hour, depending on the type and severity of organ dysfunction, concomitant medications, and individual patient characteristics. To achieve optimal patient control, neuromuscular transmission monitoring is recommended. Administration has been studied for up to seven days.

Special patient groups
The use of rocuronium bromide to facilitate mechanical ventilation in intensive care units is not recommended in children, adolescents, and elderly patients due to lack of data on efficacy and safety.

Method of administration
Roqurum is administered intravenously as a rapid bolus injection or by continuous infusion.
Compatibility studies have been conducted with the following intravenous infusion fluids.
Rocuronium bromide has been found compatible with: 0.9% sodium chloride solution and 5% glucose solution for infusion.
The intravenous infusion of rocuronium bromide should be started immediately after preparation and completed within 24 hours. Unused solutions should be discarded.

Use of higher than recommended doses of Roqurum
In cases of overdose and prolonged neuromuscular blockade, assisted ventilation and sedation should be continued.
Two methods of reversing neuromuscular blockade are known:
(1) Sugammadex may be administered to adult patients to reverse profound and deep neuromuscular block. The dose of sugammadex administered depends on the level of neuromuscular blockade.
(2) During spontaneous recovery of neuromuscular transmission, an appropriate dose of acetylcholinesterase inhibitor (e.g. neostigmine, edrophonium, pyridostigmine) or sugammadex should be administered. If administration of acetylcholinesterase inhibitor does not reverse neuromuscular blockade, ventilation should be continued until spontaneous respiration returns. Repeated administration of acetylcholinesterase inhibitors may be hazardous.