REMIFENTANIL KERN PHARMA 1 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INJECTION AND INFUSION

2. What you need to know before you take Remifentanilo Kern Pharma

Do not take Remifentanilo Kern Pharma

• if you are allergic (hypersensitive) to remifentanilo or any of the other ingredients,
• if you are allergic (hypersensitive) to other opioid medicines, such as morphine,
• if it is used as the only drug to induce anaesthesia.

Because the formulation includes glycine, remifentanilo must not be given for epidural or intrathecal use (injection into the area around the spine or into the cerebrospinal fluid).

Be careful with Remifentanilo Kern Pharma

Before starting treatment with Remifentanilo Kern Pharma, tell your doctor:

• you or someone in your family has ever abused or been dependent on alcohol, prescription medicines 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.

• if you have had any breathing problems (respiratory problems),
• if you have severe heart problems (heart failure),
• if you have been told you have low blood pressure (hypotension),
• if you have had severe liver problems (liver failure),
• if you feel weak or have suffered a decrease in blood volume (hypovolemia). You should also be careful if you are an elderly person.

While you are being treated with Remifentanilo Kern Pharma:

• As with other morphine-like medicines, you may experience:

• breathing problems (breathing that is too shallow or too slow),
• muscle stiffness. This effect depends on the dose and speed of administration. For this reason, when administered in a vein as a single slow injection (in a single bolus), Remifentanilo Kern Pharma should not be administered in less than 30 seconds.
• low blood pressure (hypotension) or a decrease in heart rate (bradycardia).

If this happens, your doctor will give you specific and appropriate treatment. Your doctor will adjust the dose you are being given and the speed of administration.

Your doctor will make sure you have recovered satisfactorily before allowing you to leave the recovery room.

• Remifentanilo has a rapid offset of action. There will be no residual analgesic activity within 5 to 10 minutes after stopping administration. During operations that are known to be painful, analgesics should be administered before stopping remifentanilo administration. Enough time should be allowed to ensure that longer-acting analgesics are effective. These analgesics should be chosen based on the type of surgery and the level of postoperative monitoring.

This medicine contains remifentanilo which is an opioid. Repeated use of opioids can make the medicine less effective (you 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 remifentanilo, it is important that you consult your doctor.

Ocasional reports of withdrawal reactions (e.g. rapid heartbeat, high blood pressure and agitation) have been reported after sudden stop 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 restart treatment with the medicine and gradually reduce the dose.

Using other medicines

Tell your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription.

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

In particular, tell your doctor or pharmacist if you are taking medicines for your heart or blood pressure, such as beta-blockers or calcium channel blockers, or medicines to induce sleep, reduce anxiety or relax muscles, belonging to a group of agents called benzodiazepines or 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 remifentanilo, as they may increase the risk of serotonin syndrome, a potentially fatal disease.

The concomitant use of remifentanilo and sedative medicines such as benzodiazepines or related medicines increases the risk of drowsiness, breathing difficulties (respiratory depression), coma and can be fatal. Therefore, concomitant use should only be considered when no other treatment options are 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 remifentanilo with sedative medicines, the dose and duration of concomitant treatment should be limited by your doctor.

Tell your doctor about all sedative medicines you are taking and follow your doctor's recommendations regarding the dose carefully. It may be useful to inform friends or family members so they are aware of the signs and symptoms mentioned above. Contact your doctor when you experience such symptoms.

Pregnancy and breastfeeding

Tell your doctor if you are pregnant or planning to become pregnant or breastfeed.

Generally, this medicine should not be used during pregnancy, unless your doctor tells you to.

You should not breastfeed during the 24 hours following administration of remifentanilo.

There is not enough data to recommend the use of remifentanilo during labour and delivery.

Ask your doctor or pharmacist for advice before taking any medicine.

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

Driving and using machines

Do not drive or use tools or machines after receiving this medicine, as it may affect your ability to react. Your doctor will tell you how long you should wait before driving or using machines again.

Athletes

Athletes should be careful as this medicine contains an active substance that may give a positive result in doping control.

3. How to take Remifentanilo Kern Pharma

You will never give yourself this medicine. This medicine will always be given by qualified people and under carefully controlled conditions.

Dose

The dose you receive will depend on:

• the operation,
• how much pain relief you need.

Doses vary from one patient to another. It depends on your age, body weight and general condition.

Your doctor will decide the dose that is right for you. He/she will adjust it according to the effect obtained during anaesthesia.

Method of administration

This medicine will be given to you by injection into a vein.

Remifentanilo can be given:

• as a single injection into your vein (injection in bolus),
• as a continuous infusion into your vein. This is when the medicine is given slowly over a long period of time.

Special care should be taken to avoid any accidental administration, especially at the end of anaesthesia.

Duration of treatment

Your doctor will decide the duration of therapy that is right for you and your operation.

The use of Remifentanilo is not recommended in intensive care patients with mechanical ventilation for a period of more than 3 days.

If you take more Remifentanilo Kern Pharma than you should

Your doctor will take immediate action.

If you stop treatment with Remifentanilo Kern Pharma

Like other morphine-like medicines, this medicine can cause dependence.

Ask your doctor or pharmacist if you have any questions about the use of this medicine.

4. Possible side effects

Like all medicines, Remifentanilo Kern Pharma can cause side effects, although not everybody gets them.

Very common side effects (affect more than 1 in 10 people)

• muscle stiffness – please also see section 2,
• low blood pressure (hypotension) - please also see section 2,
• nausea, vomiting.

Common side effects (affect 1 to 10 people in 100)

• decrease in heart rate (bradycardia) - please also see section 2,
• increase in blood pressure after operation (hypertension),
• breathing problems (breathing that is too shallow or too slow) - please also see section 2, pauses in breathing (apnea),
• itching (pruritus),
• postoperative shivering.
• cough

Uncommon side effects (affect 1 to 10 people in 1,000)

• lack of oxygen in the blood (hypoxia),
• constipation,
• postoperative pain.

Rare side effects (affect 1 to 10 people in 10,000)

• in patients receiving remifentanilo together with one or more anaesthetic medicines, allergic reactions have been detected, including acute allergic hypersensitivity reaction (anaphylaxis),
• feeling sleepy (sedation) during recovery from general anaesthesia,
• in patients receiving remifentanilo together with other anaesthetic medicines, cardiac arrest/cardiac standstill has been detected, usually preceded by a decrease in heart rate (bradycardia).

Side effects of unknown frequency

• withdrawal syndrome (may manifest with the following side effects: increased heart rate, high blood pressure, feeling of agitation or restlessness, nausea, vomiting, diarrhoea, anxiety, chills, shivering and sweating)
• irregular heartbeat (arrhythmia)

If you experience any of the side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

Reporting of side effects

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

5. Storing Remifentanilo Kern Pharma

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

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

Do not store above 25°C.

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

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 are normally not more than 24 hours at 2-8°C, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

Do not use Remifentanilo Kern Pharma if you notice any signs of deterioration after reconstitution.

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

6. Container contents and additional information

Composition of Remifentanilo Kern Pharma

• The active ingredient is remifentanil. Each vial contains 1 mg of remifentanil (as hydrochloride).

After reconstitution, the solution contains 1 mg/ml of remifentanil (as hydrochloride), if prepared as recommended.

• The other components are: glycine and hydrochloric acid 37% (for pH adjustment).

Appearance of Remifentanilo Kern Pharma and container contents

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

Packaging of 5 vials.

Marketing authorization holder

Kern Pharma, S.L.

Venus, 72 - Pol. Ind. Colón II

08228 Terrassa - Barcelona

Spain

Manufacturer

Laboratorio Reig Jofré, S.A.

Gran Capitán 10

08970 Sant Joan Despí (Barcelona)

Spain

This leaflet was last revised in May 2022

Detailed and updated 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 exclusively for healthcare professionals:

Remifentanilo Kern Pharma 1 mg powder for concentrate for solution for injection and infusion

Handling and use instructions

This medicinal product must be reconstituted by adding 1 ml of solution for injection 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 further diluted.

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 aged 1 year or older).

For administration via Target-Controlled Infusion (TCI), the recommended dilution of remifentanil is 20 to 50 micrograms/ml.

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

• water for injectable preparations,
• injectable glucose solution 50 mg/ml (5%),
• injectable glucose solution 50 mg/ml (5%) and sodium chloride 9 mg/ml (0.9%),
• injectable sodium chloride solution 9 mg/ml (0.9%),
• injectable sodium chloride solution 4.5 mg/ml (0.45%).

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

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

Posology

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

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

Overdose treatment

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

In case of overdose or suspected overdose, the following protocol should be followed:

• discontinue administration of the medicinal product,
• maintain an open airway,
• initiate assisted ventilation with oxygen,
• and establish hemodynamic stability.

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

To maintain vascular filling, administration of certain medicinal products (vasopressors) may be useful to correct hypotension, as well as other supportive measures.

A morphine antidote such as naloxone can be administered intravenously to treat severe respiratory depression and muscle rigidity. It is unlikely that the duration of respiratory depression after overdose will be longer than the duration of the antidote.

Stability and storage conditions

Remifentanilo Kern Pharma is preservative-free and for single use only. Any unused material should be discarded.

Medicinal products should not be disposed of via wastewater or household waste.

Incompatibilities

Remifentanilo Kern Pharma should be reconstituted or diluted only with the recommended solutions for injection.

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

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

It is not recommended to administer this medicinal product in the same intravenous administration line as blood, serum, or plasma.

This medicinal product should not be mixed with other medicinal products prior to administration.