Rocuronium bromide Noridem

PACKAGE LEAFLET

Package leaflet: Information for the user

Rocuronium Bromide Noridem 10 mg/mL Injection Solution for Injection or Infusion

rocuronium bromide
Generic Medicine
Please read this leaflet carefully before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

1. What Rocuronium Bromide Noridem is and what it is used for
2. What you need to know before using Rocuronium Bromide Noridem
3. How to use Rocuronium Bromide Noridem
4. Possible side effects
5. How to store Rocuronium Bromide Noridem
6. Package contents and other information

1. What Rocuronium bromide Noridem is and what it is used for

Rocuronium bromide Noridem is a muscle relaxant. Muscle relaxants are used during surgical procedures to facilitate general anaesthesia. During surgery, muscles must be completely relaxed. This makes it easier for the surgeon to perform the procedure. Normally, nerves send signals to muscles. Rocuronium bromide Noridem temporarily blocks these signals, thereby causing muscle relaxation. Since the respiratory muscles will also be relaxed, artificial ventilation will be initiated until natural breathing is restored. During surgery, the effect of the muscle relaxant is continuously monitored and, if necessary, additional doses of Rocuronium bromide Noridem are administered. At the end of the procedure, the effects of Rocuronium bromide Noridem are allowed to wear off to promote the return of natural breathing. In certain cases, another medicine may be given to speed up recovery. Rocuronium bromide Noridem may also be used in intensive care therapy.

2. What you need to know before using Rocuronium bromide Noridem

Do not use Rocuronium bromide Noridem

• if you are allergic to rocuronium or to any of the other ingredients of this medicine (listed in section 6). Inform your doctor if this applies to you.

Warnings and precautions

• Your medical history may affect how you receive Rocuronium bromide Noridem. Please consult your doctor if you have or have had any of the following conditions:

• allergy to muscle relaxant medicines

• impaired kidney function (renal failure) or kidney disease

• cardiovascular disease

• fluid retention (edema, e.g. in the ankles)

• liver, gallbladder or biliary tract disease or impaired liver function

• neuromuscular disorders

• history of malignant hyperthermia (sudden fever with rapid heartbeat, fast breathing, and muscle stiffness, pain and/or weakness)

• Certain medical conditions may affect how Rocuronium bromide Noridem works. For example:

• low potassium levels in the blood (hypokalaemia)

• high magnesium levels in the blood (hypermagnesaemia), e.g. when pre-eclampsia in pregnancy is treated with magnesium salts

• low calcium levels in the blood (hypocalcaemia)

• low protein levels in the blood (hypoproteinaemia)

• dehydration (lack of fluids)

• increased acidity in the blood (acidosis)

• increased carbon dioxide levels in the blood (hypercapnia)

• conditions causing general weakness

• obesity

• burns. If you have any of the above conditions, your doctor will take them into account when determining the most appropriate dose of Rocuronium bromide Noridem for you.

Children/elderly
Rocuronium bromide Noridem may be used in children (from newborns up to puberty) and in elderly patients.
Other medicines and Rocuronium bromide Noridem
Inform your doctor if you are taking, have recently taken, or might take any other medicines. This will help your doctor determine the most appropriate dose of Rocuronium bromide Noridem for you.
The following medicines may affect the effect of Rocuronium bromide Noridem:

• Medicines that increase the effect of Rocuronium bromide Noridem:

• certain anaesthetics

• concomitant use of corticosteroids (anti-inflammatory medicines) with Rocuronium bromide Noridem in intensive care therapy

• certain medicines used to treat bacterial infections (antibiotics)

• certain medicines used for bipolar disorder (lithium)

• certain medicines for heart conditions or high blood pressure (quinidine, calcium channel blockers, beta-blockers)

• certain medicines used to treat malaria (quinine)

• diuretics

• magnesium salts

• local anaesthetics (lidocaine and bupivacaine)

• short-term use of medicines for epilepsy (phenytoin), e.g. during surgical procedures.

• Medicines that decrease the effect of Rocuronium bromide Noridem:

• long-term use of corticosteroids (anti-inflammatory medicines) or medicines for epilepsy (phenytoin and carbamazepine)

• medicines for pancreatitis, blood coagulation disorders and acute bleeding (protease inhibitors: gabexate, ulinastatin).

• Medicines with variable effects on Rocuronium bromide Noridem:

• other muscle relaxants.

Rocuronium bromide Noridem may affect the effect of the following medicines:

• the effect of certain local anaesthetics (lidocaine) may be increased.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, please consult your doctor before this medicine is administered.
Pregnancy
Animal studies have not shown harmful effects; however, clinical data on the use of rocuronium bromide during pregnancy are not available. Therefore, rocuronium bromide should be used with caution in pregnant women.
Caesarean section
A doctor will decide whether rocuronium bromide can be used during a caesarean section. It has been shown that a dose of 0.6 mg of rocuronium bromide per kilogram of body weight can be safely used during caesarean section, without any harmful effects on the newborn.
Breastfeeding
Breastfeeding should be discontinued for 6 hours after administration of this medicine.
Driving and using machines
Your doctor will advise you when it is safe to resume driving or operating machinery after receiving Rocuronium bromide Noridem.
Rocuronium bromide Noridem contains sodium
Each vial contains 8.2 mg (0.36 mmol) of sodium.
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. essentially “sodium-free”.

3. How to use Rocuronium bromide Noridem

Dosage
Your doctor will determine the dose of Rocuronium bromide Noridem based on:

• type of anaesthetic used
• expected duration of the surgical procedure
• other medicines being used
• age and general health status.

Rocuronium bromide Noridem will be administered before and/or during a surgical procedure. The
usual dose is 0.6 mg of rocuronium bromide per kilogram of body weight, and the effect lasts between 30 and 40 minutes.
During the procedure, it will be verified that Rocuronium bromide Noridem is still effective.
Additional doses will be administered if necessary.

How Rocuronium bromide Noridem is administered
Rocuronium bromide Noridem is not intended for self-administration. Rocuronium bromide
Noridem will be given as a solution into a vein, either as a single injection or as an infusion.
Injections must be administered by a doctor or nurse.

If you are given more Rocuronium bromide Noridem than you should
The medical staff will closely monitor you, so it is unlikely that you will receive too much Rocuronium bromide Noridem. However, if this does happen, artificial ventilation will be continued until you are able to breathe on your own again. The effects of (excess) Rocuronium bromide Noridem can be reversed and recovery accelerated by using a medicine that antagonizes the effects of Rocuronium bromide Noridem.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If these side effects occur during anaesthesia, they will be observed and treated by the doctor.

The following side effects may occur:

Common (may affect less than 1 in 10 people)

• Increased heart rate (tachycardia) in children (from newborns to adolescents)

Uncommon/Rare (may affect less than 1 in 100/1,000 people)

• Increased heart rate (tachycardia) in adults
• Low blood pressure (hypotension)
• Absent effect, increased effect, or insufficient effect of Rocuronium bromide Noridem
• Pain at the injection site
• Redness or itching at the injection site
• Prolonged muscle-relaxing effect of Rocuronium bromide Noridem
• Delayed awakening from anaesthesia

Very rare (may affect less than 1 in 10,000 people)

• Allergic reactions, such as breathing difficulties, changes in blood pressure or heart rate, shock (marked decrease in blood pressure) due to inadequate blood circulation, or skin changes (e.g. fluid accumulation, redness, or skin rash)
• Laboured breathing due to spasms of the airway muscles (bronchospasm)
• Muscle weakness or paralysis
• Long-term muscle disorders when Rocuronium bromide Noridem is used in combination with corticosteroids (anti-inflammatory medicines) in intensive therapy for critically ill patients (steroid myopathy)
• Sudden accumulation of fluid in the skin or mucous membranes (e.g. throat or tongue), breathing difficulties and/or itching or skin rash, often resembling an allergic reaction (angioedema)
• Fluid accumulation (edema) in the face
• Airway problems due to anaesthesia
• Skin rash, sometimes with itching and severe hives (urticaria)
• Skin redness
• Flushing

Not known (frequency cannot be estimated from the available data)

• Severe allergic spasm of the coronary blood vessels (Kounis syndrome), causing chest pain (angina) or heart attack (myocardial infarction)
• Dilated pupils (mydriasis) or fixed pupils that do not change size in response to light or other stimuli

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse. You can also report side effects directly via the website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Rocuronium bromide Noridem

Keep this medicine out of the sight and reach of children.
Store in a refrigerator (2 °C – 8 °C).
Rocuronium bromide Noridem must be used immediately after opening the vial or bottle.
The diluted product is physically and chemically stable for 72 hours at 28°C – 32°C or for 72 hours at 2°C – 8°C.
From a microbiological standpoint, the product should be used immediately after dilution. If not used immediately, the storage duration and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2°C – 8°C, unless dilution has taken place under controlled and validated aseptic conditions.

Do not use this medicine after the expiry date stated on the carton, label of the vial or bottle after EXP. The expiry date refers to the last day of that month.
The medicine should be inspected visually before use. The solution should only be used if it is clear, practically free from particles, and contained in an undamaged container.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Rocuronium bromide Noridem contains

• The active substance is rocuronium bromide. 1 mL of solution contains 10 mg of rocuronium bromide.
• The other components are sodium acetate trihydrate, sodium chloride, glacial acetic acid, and water for injections.

Description of the appearance of Rocuronium bromide Noridem and contents of the pack
Rocuronium bromide Noridem is a clear, colourless to pale yellow injection or infusion solution containing 10 mg of rocuronium bromide per millilitre.
Rocuronium bromide Noridem is available in 3 presentations:

• Glass vials containing 50 mg of rocuronium bromide (10 or 50 vials per pack)
• Glass ampoules containing 50 mg of rocuronium bromide (10 or 50 ampoules per pack)
• Plastic ampoules containing 50 mg of rocuronium bromide (10 or 50 ampoules per pack)

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Noridem Enterprises Ltd.
Evagorou & Makariou,
Mitsi Building 3, Office 115,
Nicosia 1065, Cyprus

Manufacturer
DEMO S.A. PHARMACEUTICAL INDUSTRY
21st Km National Road Athens-Lamia
14568 Greece
T: +30 210 8161802, F: +30 210816158

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

<[To be completed at national level]>

The following information is intended exclusively for healthcare professionals:

Preparation and handling
Incompatibilities
Physical incompatibility has been documented when Rocuronium bromide Noridem is added to solutions
containing the following medicinal products: amphotericin, amoxicillin, azathioprine, cefazolin, cloxacillin, dexamethasone,
diazepam, enoximone, erythromycin, famotidine, furosemide, hydrocortisone sodium succinate, insulin, methohexital,
methylprednisolone, prednisolone sodium succinate, thiopental, trimethoprim, and vancomycin. Rocuronium bromide
Noridem is also incompatible with soybean oil.
This medicinal product must not be mixed with other medicinal products except those mentioned in the
section “Method of administration”.
If Rocuronium bromide Noridem is administered through the same infusion line used for other medicinal products,
it is important that the infusion line be adequately flushed (e.g., with 0.9% NaCl) between the administration of Rocuronium bromide Noridem and any medicinal product whose incompatibility with Rocuronium bromide Noridem has been demonstrated or whose compatibility has not yet been established.

Dosage and method of administration
In adults, the following recommended doses may be used as a general guide for endotracheal intubation, muscle relaxation during short to long surgical procedures, and use in intensive care settings.

Surgical procedures
Endotracheal intubation
The standard dose for intubation during standard induction is 0.6 mg/kg of rocuronium bromide, which is sufficient in nearly all patients to achieve adequate conditions for intubation within 60 seconds. To facilitate endotracheal intubation during rapid sequence induction, a dose of 1.0 mg/kg of rocuronium bromide is recommended, which is sufficient in nearly all patients to achieve adequate conditions for intubation within 60 seconds. If rocuronium bromide is administered at a dose of 0.6 mg/kg for rapid sequence induction, it is recommended to wait 90 seconds after administration before intubating the patient.

Caesarean section
Doses of rocuronium bromide of 0.6 mg/kg do not affect Apgar scores, fetal muscle tone, or cardiorespiratory adaptation. Umbilical cord blood analysis indicates that rocuronium bromide crosses the placenta only minimally and does not result in observable adverse clinical effects in the neonate.
Doses of 1.0 mg/kg have been studied during rapid sequence induction, but not in patients undergoing caesarean section.

High doses
If higher doses are required, initial doses up to 2 mg/kg of rocuronium bromide have been administered without observed cardiovascular adverse effects. The use of higher doses reduces onset time and prolongs duration of action.

Maintenance doses
The recommended maintenance dose is 0.15 mg/kg of rocuronium bromide; in prolonged inhalational anaesthesia, the dose should be reduced to 0.075–0.1 mg/kg of rocuronium bromide. Maintenance doses should preferably be administered when the amplitude of the response to neuromuscular stimulation has returned to 25% of the control value, or when 2 or 3 responses are present to train-of-four stimulation (TOF).

Continuous infusion
If rocuronium bromide is administered by continuous infusion, it is recommended to start with a loading dose of 0.6 mg/kg. Continuous infusion may be initiated when the amplitude of the neuromuscular response begins to return. The infusion rate should be adjusted to maintain the neuromuscular response amplitude at 10% of the control value and to maintain 1 or 2 responses to TOF stimulation. In adults undergoing intravenous anaesthesia, this corresponds to an infusion rate of 0.3–0.6 mg/kg·h, while in those undergoing inhalational anaesthesia, it corresponds to an infusion rate of 0.3–0.4 mg/kg·h. Continuous monitoring of neuromuscular blockade is recommended, as requirements vary between patients and according to the anaesthetic technique used.

Paediatric population
For neonates (0–27 days), infants (28 days–2 months), toddlers (3–23 months), children (2–11 years), and adolescents (12–17 years), the recommended dose for intubation during standard anaesthesia and the maintenance dose are similar to those recommended for adults.
However, the duration of action of a single intubation dose will be longer in neonates and infants compared to older children.
For continuous infusion in paediatrics, infusion rates are the same as in adults, except in children (2–11 years), where higher infusion rates may be required.
Therefore, in children (2–11 years), it is recommended to start with the same initial infusion rate as in adults and then adjust it subsequently to maintain neuromuscular response amplitude at 10% of the control value or to maintain 1 or 2 responses to TOF stimulation.
Experience with rocuronium bromide for rapid sequence induction in paediatric patients is limited. Therefore, the use of rocuronium bromide to facilitate endotracheal intubation during rapid sequence induction is not recommended in this patient group.

Elderly patients and patients with hepatic and/or biliary disease and/or renal insufficiency
The standard dose for intubation in elderly patients and those with hepatic and/or biliary disease and/or renal insufficiency during routine anaesthesia is 0.6 mg/kg of rocuronium bromide. For rapid sequence induction in patients expected to have prolonged duration of action, a dose of 0.6 mg/kg of rocuronium bromide should be considered. Regardless of the anaesthetic technique used, the recommended maintenance dose for this patient group is 0.075–0.1 mg/kg body weight of rocuronium bromide, with an infusion rate of 0.3–0.4 mg/kg·h (see Continuous infusion).

Overweight and obese patients
When this medicinal product is used in overweight or obese patients (defined as patients with body weight more than 30% above ideal body weight), dosing should be reduced based on ideal body weight.

Short-term use in intensive care
Endotracheal intubation
For endotracheal intubation, refer to the same doses indicated above for surgical procedures.

Maintenance doses
An initial bolus dose of rocuronium bromide of 0.6 mg/kg body weight is recommended, followed by continuous infusion as soon as the response amplitude returns to 10% or upon reappearance of 1 or 2 responses to TOF stimulation. Dosing should always be titrated according to the observed effect in each individual patient. In adult patients, the recommended initial infusion rate to maintain 80–90% neuromuscular blockade (presence of 1 or 2 responses to TOF stimulation) is 0.3–0.6 mg/kg·h body weight for the first hour of administration. The infusion rate should then be reduced over the next 6–12 hours according to individual response. After this period, the individual dose required remains relatively constant in each patient. Rocuronium bromide Noridem should be used for short periods; however, total duration should not exceed 7 days due to insufficient data on long-term use.
Clinical studies have shown marked variability in infusion rates. The mean infusion rate ranged from 0.2 to 0.5 mg/kg·h body weight depending on the nature and extent of organ dysfunction, concomitant medications, and individual patient characteristics. To ensure optimal patient control, monitoring of neuromuscular transmission is strongly recommended. Administration for up to 7 days has been studied.

Special patient populations
Rocuronium bromide Noridem is not indicated to facilitate mechanical ventilation in intensive care settings in paediatric and elderly patients due to lack of data on safety and efficacy.

Method of administration
Rocuronium bromide Noridem is administered intravenously either as a bolus or by continuous infusion.
Compatibility studies have been performed with the following infusion fluids. At nominal concentrations of 0.5 mg/mL and 2.0 mg/mL, Rocuronium bromide Noridem was found compatible with: 0.9% NaCl, 5% glucose, 5% glucose in 0.9% NaCl, water for injections, Ringer's lactate solution, and Haemaccel. Administration should begin immediately after mixing and be completed within 24 hours.
Single-use.
Warm glass vials to room temperature before puncturing to reduce the risk of breakage. Unused solution must be discarded.

Special precautions for storage
Store in a refrigerator (2°C–8°C).
Rocuronium bromide Noridem does not contain preservatives; therefore, it should be used immediately after opening the vial or ampoule.
The diluted product is physically and chemically stable for 72 hours at 28°C–32°C or 72 hours at 2°C–8°C. From a microbiological standpoint, the product should be used immediately after dilution. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2°C–8°C, unless dilution has been performed under controlled and validated aseptic conditions.

Disposal and other handling
Unused medicine and waste materials derived from this medicine must be disposed of in accordance with local regulations.

Overdose
In cases of overdose and prolonged neuromuscular blockade, the patient must remain on controlled ventilation and sedation. In this situation, two options are available for reversal of neuromuscular blockade:

1. In adults, sugammadex may be used to reverse profound and deep blockade. The dose of sugammadex administered depends on the degree of neuromuscular blockade.
2. An acetylcholinesterase inhibitor (neostigmine, edrophonium, pyridostigmine) or sugammadex may be used at the first signs of spontaneous recovery at appropriate doses. If administration of anticholinesterase agents fails to antagonize the neuromuscular effects of rocuronium bromide, ventilation should be continued until spontaneous respiration returns. Repeated administration of acetylcholinesterase inhibitors may be dangerous.
   In animal studies, severe cardiovascular impairment leading to cardiac failure was observed only after administration of a cumulative dose of 750 x ED (135 mg/kg body weight of rocuronium bromide).