ROCURONIUM NORIDERM 10 mg/ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Rocuronium Noridem 10mg/ml solution for injection and infusion EFG

Rocuronium bromide

Read all of this leaflet carefully before you start 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, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

This medicine is a muscle relaxant.Muscle relaxants are used in general anesthesia for surgical operations, so that the muscles relax completely. This makes the operation easier for the surgeon. Normally, nerves send messages to muscles through impulses. Rocuronium Noridem works by temporarily blocking these impulses, so that the muscles relax. Since the muscles needed for breathing also relax, you will need help breathing (artificial respiration) untilyou can breathe on your own. The effect of the muscle relaxant is regularly checked during the operation, and if necessary, more Rocuronium Noridem will be administered. The effects of Rocuronium Noridem disappear at the end of the operation, and then you can start breathing on your own. Sometimes, another medicine is given to speed up this process. This medicine can also be used in the Intensive Care Unit.

2. What you need to know before you use Rocuronium Noridem

Do not use Rocuronium Noridem:

• If you are allergicto rocuronium or any of the other ingredients of this medicine (listed in section 6).

Tell your doctor if this applies to you.

Warnings and precautions

• Your medical history may affect how Rocuronium Noridem is administered to you. Tell your doctor if you have had or currently have any of the following diseases:

• allergy to muscle relaxants
• kidney failure or kidney disease
• heart disease
• edema (fluid retention, e.g., in the ankles)
• liver disease, gallbladder disease, or bile duct disease, or liver function disorders
• diseases that affect the nerves and muscles
• history of malignant hyperthermia (sudden fever with palpitations, rapid breathing, and muscle stiffness, pain, and/or weakness).

• Some medical conditions may affect how Rocuronium Noridem works.

For example:

• low potassium levels in the blood (hypokalemia)
• high magnesium levels in the blood (hypermagnesemia), e.g., when treating pregnancy toxemia with magnesium salts.
• low calcium levels in the blood (hypocalcemia)
• low protein levels in the blood (hypoproteinemia)
• dehydration
• too much acid in the blood (acidosis)
• too much carbon dioxide in the blood (hypercapnia)
• poor overall health
• overweight
• burns,

If you have any of these conditions, your doctor will take them into account when deciding the correct dose of Rocuronium Noridem.

Children/elderly patients

Rocuronium Noridem can be used in children (newborns to puberty) and elderly patients.

Other medicines and Rocuronium Noridem

Tell your doctor if you are using, have recently used, or might use any other medicines. This will help your doctor decide the correct dose of Rocuronium Noridem.

The following medicines may affect the effects of Rocuronium Noridem:

• Medicines that may increase the effect of Rocuronium Noridem:

• some anesthetics
• prolonged use of corticosteroids(anti-inflammatory medicines) with Rocuronium Noridem in the Intensive Care Unit
• some medicines for treating bacterial infections (antibiotics)
• some medicines for treating bipolar disorder (e.g., lithium)
• some medicines for heart disease or high blood pressure (quinidine, calcium antagonists, beta-blockers)
• some medicines for treating malaria (quinine)
• medicines that increase urine production (diuretics)
• magnesium salts
• local anesthetics (lidocaine and bupivacaine)
• short-term use of medicines for epilepsy (phenytoin), e.g., during an operation.

• Medicines that may decrease the effect of Rocuronium Noridem:

• prolonged use of corticosteroids(anti-inflammatory medicines) or medicines for treating epilepsy(phenytoin and carbamazepine)
• medicines for treating pancreatitis, blood coagulation disorders, or acute blood loss (protease inhibitors:gabexate, ulinastatin).

• Medicines that have a variable effect onRocuronium Noridem:

• other muscle relaxants.

Rocuronium Noridem may affect the effects of the following medicines:

• may increase the effect of local anesthetics (such as lidocaine).

Pregnancy, breastfeedingand fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before you are given this medicine.

Pregnancy

No harmful effects have been observed in animal studies, but there are no clinical data on rocuronium bromide in pregnant women. Therefore, rocuronium bromide should be used with caution in pregnant women.

Cesarean section

A doctor will decide whether rocuronium bromide can be used during a cesarean section. It has been shown that a dose of 0.6 mg of rocuronium bromide per kilogram of body weight can be used safely during a cesarean section and does not have harmful effects on the baby.

Breastfeeding

Breastfeeding should be postponed for 6 hours after administration of this medicine.

Driving and using machines

Your doctor will inform you when you can drive or use hazardous machines after administration of this medicine.

Rocuronium Noridem contains sodium

Each ampoule or vial contains 8.2 mg (0.36 mmol) of sodium.

This medicine contains less than 1 mmol of sodium (23 mg) per vial or ampoule; i.e., it is essentially “sodium-free”.

3. How to use Rocuronium Noridem

Dose

Your doctor will decide the dose of Rocuronium Noridem based on:

• the type of anesthetic used,
• the expected duration of the operation,
• other medicines you are taking,
• your age and health status.

You will be given Rocuronium Noridem before or during the operation. The recommended dose is 0.6 mg of rocuronium bromide per kilogram of body weight, and the effect lasts for 30 to 40 minutes. During the operation, the activity of Rocuronium Noridem will be checked. If necessary, more doses will be administered.

How Rocuronium Noridem is administered

Rocuronium Noridem is not intended for self-administration. Rocuronium Noridem will be administered intravenously (into a vein) with a single injection or through an infusion.

Injections should be administered by a doctor or nurse.

If you use more Rocuronium Noridem than you should

Medical staff will be monitoring your condition, and it is unlikely that you will be given too much Rocuronium Noridem. However, if this happens, artificial respiration will be maintained until you can breathe on your own. The effects of too much Rocuronium Noridem can be counteracted, and recovery can be accelerated by administering a medicine that counteracts the effects of Rocuronium Noridem.

In case of overdose or accidental ingestion, contact the Toxicology Information Service, phone 91 562 04 20.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If these side effects occur while you are under anesthesia, your anesthetist will see them and treat them.

The following side effects may occur:

Common (may affect up to 1 in 10 people)

• increased heart rate (tachycardia) in children (newborns to adolescents).

Uncommon or rare (may affect up to 1 in 100/1000 people)

• increased heart rate (tachycardia) in adults
• decreased blood pressure (hypotension)
• Rocuronium Noridem has no effect, is too effective, or is not effective enough
• pain at the injection site
• redness or itching at the injection site
• prolonged muscle relaxant effect of Rocuronium Noridem
• delayed recovery from anesthesia.

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

• allergic reactions such as difficulty breathing, changes in blood pressure and heart rate, shock (sudden drop in blood pressure) due to low blood circulation or skin changes (e.g., fluid retention, redness, or rash)
• chest pressure due to muscle spasms in the airways (bronchospasm)
• muscle weakness or paralysis
• chronic muscle disorder, usually observed after concurrent administration of Rocuronium Noridem and corticosteroids (anti-inflammatory medicines) in critically ill patients in the Intensive Care Unit (steroid myopathy)
• sudden fluid retention in the skin and mucous membranes (e.g., the throat or tongue), difficulty breathing, and/or itching or rash, often as an allergic reaction (angioedema)
• fluid retention (edema) in the face
• respiratory problems due to anesthesia
• rash, sometimes with intense itching and hives (urticaria)
• redness
• flushing.

Frequency not known (cannot be estimated from the available data)

• allergic spasm and severe coronary artery spasms (Kounis syndrome) that cause chest pain (angina) or

heart attack (myocardial infarction)

• dilated pupils (mydriasis) or fixed pupils that do not change size with light or other stimuli.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Rocuronium Noridem

Keep this medicine out of the sight and reach of children.

Store in a refrigerator (between 2°C and 8°C).

After opening the vial or ampoule, Rocuronium Noridem should be used immediately.

Chemical and physical stability of the diluted product has been demonstrated for 72 hours between 28°C and 32°C or for 72 hours between 2°C and 8°C. From a microbiological point of view, the diluted product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and normally should not exceed 24 hours at 2°C–8°C, unless the dilution has been made in controlled and validated aseptic conditions.

Do not use this medicine after the expiry date which is stated on the carton, label, and vial after EXP. The expiry date is the last day of the month stated.

The medicine should be inspected before use. The solution should only be used if it is clear, practically free of particles, and the container is not damaged.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition ofRocuronium Noridem

• The active ingredient is rocuronium bromide.

Each ml of solution contains 10 mg of rocuronium bromide.

• The other components are sodium acetate trihydrate, sodium chloride, glacial acetic acid, and water for injectable preparations.

Appearance of the Product and Container Content

Rocuronium Noridem is a clear, colorless to pale yellow injectable or infusion solution containing 10 mg/ml of rocuronium bromide.

Rocuronium Noridem is available in three sizes:

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

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Noridem Enterprises Limited

Evagorou & Makariou

Mitsi Building 3, Office 115

1065 Nicosia, 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 authorized in the Member States of the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

Date of the last revision of this leaflet:September 2024

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)

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This information is intended only for healthcare professionals:

Preparation and Handling

Incompatibilities

Physical incompatibility of Rocuronium Noridem has been documented when added to solutions containing the following medicinal products: amphotericin, amoxicillin, azathioprine, cefazolin, cloxacillin, dexamethasone, diazepam, enoximone, erythromycin, famotidine, furosemide, sodium hydrocortisone succinate, insulin, methohexital, methylprednisolone, prednisolone sodium succinate, thiopental, trimethoprim, and vancomycin. Rocuronium Noridem is also incompatible with soybean oil.

It is not recommended to mix this medicinal product with other medicinal products except those mentioned in the "Method of Administration" section.

If Rocuronium Noridem is administered through the same infusion line previously used with other medicinal products, it is important that it be properly flushed (e.g., with NaCl 0.9%) between the administration of Rocuronium Noridem and medicinal products with demonstrated incompatibility or unestablished compatibility with Rocuronium Noridem.

Posology and Method of Administration

In adult patients, the following dosage recommendations can serve as a general guideline for tracheal intubation and muscle relaxation in surgical interventions of short to long duration, as well as for use in the intensive care unit.

Surgical Interventions

Tracheal Intubation

The standard intubation dose in routine anesthesia is 0.6 mg/kg-1 of rocuronium bromide, which provides adequate intubation conditions in almost all patients within 60 seconds. A dose of 1.0 mg/kg-1 of rocuronium bromide is recommended to facilitate tracheal intubation conditions during rapid sequence induction anesthesia, which provides adequate intubation conditions in almost all patients within 60 seconds. If a dose of 0.6 mg/kg-1 of rocuronium bromide is administered during rapid sequence induction anesthesia, it is recommended to intubate the patient 90 seconds after administration of rocuronium bromide.

Cesarean Section

Doses of 0.6 mg/kg-1 of rocuronium bromide do not affect the Apgar index, fetal muscle tone, or cardiopulmonary adaptation. Blood samples from the umbilical cord have shown limited placental transfer of rocuronium bromide with no adverse effects on the newborn.

Doses of 1.0 mg/kg-1 have been studied in rapid sequence induction anesthesia, but not in cesarean section patients.

High Doses

In case there is a reason to choose high doses in certain patients, it has been indicated that initial doses of up to 2 mg/kg-1 of rocuronium bromide have been used without detecting adverse cardiovascular effects. The use of these high doses reduces the onset time and increases the duration of action.

Maintenance Doses

The recommended maintenance dose is 0.15 mg/kg-1 of rocuronium bromide; in the case of prolonged use of inhalation anesthetics, the dose should be reduced to 0.075-0.1 mg/kg-1 of rocuronium bromide. Maintenance doses should be administered preferably when neuromuscular transmission reaches 25% recovery, or when 2 or 3 responses to stimulation appear in trains of four.

Continuous Infusion

If rocuronium bromide is administered by continuous infusion, it is recommended to administer a loading dose of 0.6 mg/kg-1 of rocuronium bromide and, when neuromuscular blockade begins to recover, start continuous infusion. The infusion rate should be adjusted to maintain neuromuscular transmission response at 10% of the control response height or to maintain 1 or 2 responses to stimulation in trains of four. In adults, the infusion rate is equivalent to 0.3-0.6 mg/kg-1/h-1 under intravenous anesthesia and 0.3-0.4 mg/kg-1/h-1 under inhalation anesthesia. Continuous monitoring of neuromuscular blockade is recommended, as the required infusion rates vary from patient to patient and with the anesthetic method used.

Pediatric Population

The recommended dose for intubation in routine anesthesia and the maintenance dose in newborns (0-27 days), infants (28 days-23 months), children (2-11 years), and adolescents (12-17 years) is similar to that of adults.

However, the duration of action of the single intubation dose will be longer in newborns and infants than in children.

In continuous infusion in pediatrics, the infusion rates are the same as those for adults, except in children (2-11 years). In children between 2 and 11 years, inclusive, higher infusion rates may be necessary.

Thus, in children (2-11 years), the same initial dose as for adults is recommended, and then it should be adjusted to maintain the neuromuscular transmission response at 10% of the control response height or to maintain one or two responses to stimulation in trains of four.

The experience with rocuronium bromide in rapid sequence induction in pediatric patients is limited. Therefore, rocuronium bromide is not recommended to facilitate tracheal intubation conditions during rapid sequence induction in pediatric patients.

Geriatric Patients and Patients with Hepatic and/or Biliary and/or Renal Impairment

The standard intubation dose in geriatric patients and in patients with hepatic and/or biliary and/or renal impairment during routine anesthesia induction is 0.6 mg/kg-1 of rocuronium bromide. The use of a dose of 0.6 mg/kg-1 of rocuronium bromide in the rapid sequence induction technique should be considered in those patients where a prolongation of the duration of action is anticipated. Regardless of the anesthetic technique used, the recommended maintenance dose for these patients is 0.075-0.1 mg/kg-1 of rocuronium bromide, and the recommended infusion rate is 0.3-0.4 mg/kg-1/h-1 (see "Continuous Infusion").

Obese and Overweight Patients

When using rocuronium bromide in obese or overweight patients (defined as patients whose body weight exceeds 30% or more of their ideal body weight), the doses should be reduced and calculated based on the ideal body weight.

Short-term Use in Intensive Care

Tracheal Intubation

For tracheal intubation, the same doses as those described for surgical interventions should be used.

Maintenance Doses

A loading dose of 0.6 mg/kg-1 of rocuronium bromide is recommended, followed by continuous infusion when the level of neuromuscular transmission response reaches 10% of the control response height or until 1 or 2 responses to stimulation appear in trains of four. The doses should always be adjusted according to the observed effect in each patient. The initial infusion rate recommended to achieve an 80-90% neuromuscular blockade (1 or 2 responses to stimulation in trains of four) in adult patients is 0.3-0.6 mg/kg-1/h-1 during the first hour of administration. According to the patient's response, the infusion rate will be reduced in the following 6-12 hours. Afterward, the required individual dose remains relatively constant. The use of Rocuronium Noridem should be short-term. However, the total duration should not exceed 7 days due to the lack of long-term information.

A great variability in infusion rates has been observed in clinical studies. The average infusion rate ranges from 0.2-0.5 mg/kg-1/h-1, depending on the nature and degree of organic impairment, concomitant medication, and the individual patient's condition. To cover the needs of each patient, monitoring of neuromuscular transmission is recommended. Its administration has been studied for up to a total of 7 days.

Special Populations

We do not have data on the safety and efficacy of using Rocuronium Noridem to facilitate mechanical ventilation in pediatric or geriatric patients. Therefore, its use is not recommended in these patients.

Method of Administration

Rocuronium Noridem is administered intravenously, either by bolus injection or by continuous infusion.

Compatibility studies have been performed with the following infusion solutions. At concentrations of 0.5 mg/ml and 2.0 mg/ml, Rocuronium Noridem has been shown to be compatible with: NaCl 0.9%, dextrose 5%, dextrose 5% in NaCl 0.9%, sterile water for injections, Ringer's lactate solution, and Haemaccel. The solutions should be administered immediately after mixing and completed within 24 hours.

For single use.

The glass vials should be at room temperature before being punctured, to reduce the possibility of fragmentation. Unused solutions should be discarded.

Special Precautions for Storage

Store in a refrigerator (between 2 °C and 8 °C).

Since Rocuronium Noridem does not contain preservatives, it should be used immediately once the vial or ampoule is opened.

Chemical and physical stability has been demonstrated during use for 72 hours at 28-32 °C or for 72 hours at 2-8 °C of the diluted product. From a microbiological point of view, the diluted product should be used immediately. If not used immediately, the in-use storage times and conditions before use are the responsibility of the user and normally should not exceed 24 hours at 2-8 °C, unless the dilution has been performed under controlled and validated aseptic conditions.

Elimination and Other Handling

The elimination of unused medicinal products and all materials that have come into contact with them will be carried out in accordance with local regulations.

Overdose

In case of overdose and prolonged neuromuscular blockade, the patient should remain under mechanical ventilation and sedation. In this situation, there are two options to reverse the neuromuscular blockade: (1) In adults, sugammadex can be administered for the reversal of intense (complete) and profound blockade. The dose of sugammadex to be administered will depend on the degree of neuromuscular blockade.

(2) An acetylcholinesterase inhibitor (e.g., neostigmine, edrophonium, pyridostigmine) or sugammadex can be administered at adequate doses once spontaneous recovery has begun. When the administration of an acetylcholinesterase inhibitor ceases to reverse the neuromuscular effects of rocuronium bromide, mechanical ventilation should be continued until spontaneous respiration is restored. Repeated dosing of an acetylcholinesterase inhibitor can be hazardous.

In animal studies, severe depression of cardiovascular function, which eventually leads to cardiac collapse, did not occur until the administration of a cumulative dose of 750 x DE90 (135 mg/kg-1 of rocuronium bromide).