REMIFENTANIL SALA 2 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INJECTION OR INFUSION

2. What you need to know before you are given Remifentanil Sala

Do not use Remifentanil Sala

• if you are allergic to remifentanil or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to fentanyl analogues (pain-relieving medicines similar to fentanyl and belonging to the class of medicines known as opioids)
• as an injection into the spinal canal
• as the only medicine to start anesthesia.

Warnings and precautions

Talk to your doctor before you start using Remifentanil Sala

• if you are allergic to any other opioid medicine, such as morphine or codeine
• if you have lung problems (you may be more sensitive to having difficulty breathing)
• if you are over 65 years old, weak or have low blood volume and/or low blood pressure (you are more sensitive to suffering cardiac disorders).

Talk to your doctor before you start taking remifentanil if:

• You or someone in your family has ever abused or been dependent on alcohol, prescription drugs, or illegal drugs ("addiction").
• You are a smoker.
• You have ever had mood problems (depression, anxiety, or personality disorder) or have been treated by a psychiatrist for other mental illnesses.

This medicine contains remifentanil which is an opioid. Repeated use of opioids can make the medicine lose its effectiveness (get used to its effect). It can also cause dependence and abuse, which can lead to a potentially fatal overdose. If you are concerned that you may become dependent on remifentanil, it is important that you consult your doctor.

Occasionally, withdrawal reactions (e.g., rapid heartbeat, high blood pressure, and agitation) have been reported after sudden discontinuation of treatment with this medicine, especially when treatment was administered for more than 3 days (see also section 4. Possible side effects). If you experience these symptoms, your doctor may resume treatment with the medicine and gradually reduce the dose.

If you are not sure if any of the above applies to you, consult your doctor or nurse before you are given Remifentanil Sala.

Other medicines and Remifentanil Sala

Tell your doctor if you are using, have recently used, or might use any other medicines, including those obtained without a prescription. This includes herbal medicines.

This is because remifentanil can interact with other medicines and cause side effects.

In particular, tell your doctor or pharmacist if you are taking:

• medicines for the heart or blood pressure, such as beta-blockers (this includes atenolol, metoprolol, carvedilol, propranolol, and bisoprolol) or calcium channel blockers (these include amlodipine, diltiazem, and nifedipine).
• medicines to treat depression, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors (MAOIs). It is not recommended to use these medicines at the same time as remifentanil, as they may increase the risk of serotonin syndrome, a potentially fatal disease.

The concomitant use of Remifentanil Sala and sedative medicines, such as benzodiazepines or other related medicines, increases the risk of drowsiness, difficulty breathing (respiratory depression), coma, and can put the patient's life at risk. Due to this, concomitant use with these medicines should only be considered when other treatment options are not possible. The concomitant use of opioids and other medicines used to treat epilepsy, nerve pain, or anxiety (gabapentin and pregabalin) increases the risk of opioid overdose and respiratory depression, and can be potentially fatal.

However, if your doctor prescribes Remifentanil Sala along with sedative medicines, they will limit the dose and duration of treatment.

Tell your doctor about all sedative medicines you are taking and closely follow the recommended dosage provided by your doctor. It may be useful for you to inform a family member or close friend of the signs and symptoms indicated above. Contact your doctor when you experience these symptoms.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine. Your doctor will weigh the benefit to you against the risk to your baby of receiving this medicine while pregnant.

You must stop breastfeeding your baby for 24 hours after receiving this medicine. If you express breast milk during this period, you must discard it and not give it to your baby.

If you receive this medicine during childbirth or shortly before delivery, it may affect your baby's breathing. You and your baby will be monitored for signs of excessive sleepiness or difficulty breathing.

Driving and using machines

If you are only in the hospital during the day, your doctor will tell you how long you should wait before leaving the hospital or driving. It may be dangerous to drive too soon after an operation.

After receiving Remifentanil Sala, you should not drink alcohol until you have fully recovered.

3. How Remifentanil Sala is given

This medicine should never be self-administered. This medicine will always be administered by qualified personnel.

Remifentanil can be administered:

• as a single injection into a vein
• as a continuous infusion into a vein. This is when the medicine is administered slowly over a longer period of time.

The way you are given the medicine and the dose you receive will depend on:

• the procedure or treatment you are having in the Intensive Care Unit
• how much pain you have.

The dose varies from patient to patient. No dose adjustment is required in patients with kidney and liver problems.

If you are given too much Remifentanil Sala

The effects of Remifentanil Sala are closely monitored throughout the operation and in intensive care, and appropriate measures will be taken immediately if you receive too much.

After your operation

Tell your doctor or nurse if you have pain. If you have pain after your procedure, you may be given other pain-relieving medicines.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following side effects may occur with this medicine.

Allergic reactions including anaphylaxis: These are rare (may affect up to 1 in 1,000 people who use Remifentanil Sala). The signs include:

• sudden attacks of sneezing and pain or feeling of pressure in the chest
• swelling of the eyelids, face, lips, mouth, or tongue
• hives with lumps or rash on any part of your body
• a faint

› If you experience any of these symptoms, contact a doctor urgently.

Tell your doctor as soon as possible if you feel any of the following effects:

Very common (may affect more than 1 in 10 people)

• muscle stiffness
• low blood pressure
• nausea or vomiting

Common (may affect up to 1 in 10 people)

• slow heart rate
• shallow or temporary stop in breathing
• itching
• coughing

Uncommon (may affect up to 1 in 100 people)

• lack of oxygen
• constipation

Rare (may affect up to 1 in 1,000 people)

• in patients receiving Remifentanil Sala along with other anesthetic medicines, cardiac arrest has been detected, usually preceded by a decrease in heart rate.

Unknown(cannot be estimated from the available data)

• physical need for Remifentanil Sala (dependence) or need to increase doses over time to achieve the same effect (tolerance)
• seizures (convulsions)
• a type of irregular heartbeat (atrioventricular block)
• irregular heartbeat (arrhythmia)

Side effects that may occur after your operation:

Common

• chills
• increased blood pressure

Uncommon

• pain

Rare

• feeling of extreme calm or drowsiness (sedation)

Unknown

Withdrawal syndrome (may manifest with the appearance of the following side effects: increased heart rate, high blood pressure, feeling of agitation or restlessness, nausea, vomiting, diarrhea, anxiety, chills, tremors, and sweating).

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if it is possible that the side effects are 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 Remifentanil Sala

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

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

Do not store above 30°C.

The chemical and physical stability of the reconstituted solution has been demonstrated for 24 hours at 25°C.

The chemical and physical stability of the diluted solution has been demonstrated for 4 hours at 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times and conditions are the responsibility of the user and normally should not exceed 24 hours at 2-8°C, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

Do not use Remifentanil Sala if you notice any signs of deterioration after reconstitution.

Once reconstituted, Remifentanil Sala should be used immediately. Any unused diluted solution should be discarded. Medicines should not be disposed of via wastewater or household waste. Your doctor or nurse will dispose of any medicine that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Remifentanil Sala

• The active substance is remifentanil hydrochloride.
• The other ingredients are: glycine and hydrochloric acid 37% (for pH adjustment).

After reconstitution as indicated, each ml contains 1 mg of remifentanil.

Appearance and pack of the product

Remifentanil is a white or off-white powder for concentrate for solution for injection or infusion.

Packs of 5 vials.

Marketing authorization holder and manufacturer

Laboratorio Reig Jofré, S.A.

C/ Gran Capitán, 10

08970 Sant Joan Despí (Barcelona)

Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Denmark: Remifentanil Reig Jofre 2 mg powder for concentrate for solution for injection or infusion, solution

Norway: Remifentanil Reig Jofre 2 mg powder for concentrate for solution for injection or infusion, solution

Spain: Remifentanilo Sala 2 mg powder for concentrate for solution for injection or infusion EFG

Sweden: Remifentanil Reig Jofre 2 mg powder for concentrate for solution for injection or infusion, solution

Date of last revision of this leaflet:May 2022

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es/

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This information is intended only for healthcare professionals:

Remifentanil Sala 2 mg powder for concentrate for solution for injection or infusion

Handling and use instructions

This medicine should be reconstituted by adding 2 ml of injection solution to obtain a reconstituted solution with a remifentanil concentration of approximately 1 mg/ml. After reconstitution, the solution should not be administered as is, but should be diluted again.

Remifentanil Sala is for single use.

For manually performed infusions, remifentanil can be diluted to concentrations ranging from 20 to 250 micrograms/ml (the recommended dilution is 50 micrograms/ml in adults and 20 to 25 micrograms/ml in children over 1 year of age).

For administration via Target-Controlled Infusion (TCI), the recommended dilution of remifentanil is 25 to 50 micrograms/ml.

The dilution of the remifentanil solution can be performed with one of the following injection solutions:

• Water for injections
• Glucose 50 mg/ml (5%) injection solution
• Glucose 50 mg/ml (5%) and sodium chloride 0.9 mg/ml (0.9%) injection solution
• Sodium chloride 0.9 mg/ml (0.9%) injection solution
• Sodium chloride 0.45 mg/ml (0.45%) injection solution

The dilution depends on the technical capacity of the infusion device and the patient's expected requirements.

This medicine is compatible with lactated Ringer's injection solution, lactated Ringer's and glucose 50 mg/ml (5%) injection solution, as well as propofol when administered through an intravenous catheter.

Posology

Refer to the Summary of Product Characteristics for information on posology.

Depending on the indications, the recommended dosages are given for adults and/or children (from 1 to 12 years of age) and proposed adjustments for special populations are made.

Overdose treatment

Due to the very short duration of action, the potential for harmful effects due to an overdose is limited to the immediate period following administration. The response to discontinuation of the medicine is rapid, returning to the initial state within 10 minutes.

In case of overdose or suspected overdose, the protocol to follow is as follows:

• interrupt administration of the medicine,
• keep the airway open,
• start assisted ventilation with oxygen,
• and establish hemodynamic stability.

If respiratory depression is associated with muscle stiffness, a neuromuscular blocker may be required to facilitate ventilation.

To maintain vascular filling, it may be useful to administer certain medicines (vasopressors) to correct hypotension, as well as other supportive measures.

An opioid antagonist such as naloxone can be administered intravenously to treat severe respiratory depression and muscle stiffness. It is unlikely that the duration of respiratory depression after an overdose will be longer than the duration of the opioid antagonist.

Incompatibilities

Remifentanil Sala should only be reconstituted or diluted with the recommended injection solutions.

It should not be reconstituted or mixed with lactated Ringer's injection solution or lactated Ringer's and glucose 50 mg/ml (5%) injection solution.

This medicine should not be mixed with propofol in the same solution for intravenous administration.

This medicine should not be administered within the same intravenous administration line as blood, serum, or plasma.

This medicine should not be mixed with other medicines before administration.