Prospect: information for the user

Remifentanilo Kern Pharma 5 mg powder for concentrate for injectable solution and for

perfusion EFG

Remifentanilo

Read this prospect carefully before starting to take the medicine.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed to you and should not be given to other people, even if they have the same symptoms, as it may harm them.
• If you consider that any of the adverse effects you are experiencing is severe or if you notice any adverse effect not mentioned in this prospect, inform your doctor or pharmacist.

1. What isRemifentanilo Kern Pharmaand for what it is used

2. What you need to know before starting to takeRemifentanilo Kern Pharma

3. How to takeRemifentanilo Kern Pharma

4. Possible adverse effects

5. Conservation ofRemifentanilo Kern Pharma

6. Contents of the package and additional information

Remifentanilo is an anesthetic that belongs to a group of medications known as opioids (substances that have an action similar to morphine in the body).

This medication is used:

• to help you sleep before a surgery,
• to keep you asleep and prevent you from feeling pain during the surgery,
• to stop you from feeling pain while receiving treatment in the Intensive Care Unit.

Do not take Remifentanilo Kern Pharma

• if you are allergic (hypersensitive) to remifentanilo or to any of the other components,
• if you are allergic (hypersensitive) to other opioid medications, such as morphine,
• if it is used as the only medication to induce anesthesia.

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

Be especially careful with Remifentanilo Kern Pharma

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

• if you or someone in your family has ever abused or had dependence on alcohol, prescription medications, or illegal drugs (“addiction”).
• if you are a smoker.
• if 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 respiratory problems (breathing difficulties),
• if you have severe heart problems (cardiac failure),
• if you have been told that your blood pressure is low (hypotension),
• if you have had severe liver problems (hepatic failure),
• if you feel weak or have experienced a decrease in blood volume (hypovolemia). You should also be cautious if you are an older person.

While you are being treated with Remifentanilo Kern Pharma:

• Like other morphine derivatives, you may experience:

• respiratory alterations (too shallow or too slow breathing),
• muscle rigidity. This effect depends on the dose and the rate of administration. For this reason, when administered intravenously as a single slow bolus, Remifentanilo Kern Pharma should not be administered in less than 30 seconds.
• low blood pressure (hypotension) or decreased heart rate (bradycardia).

If this happens, your doctor will administer a specific and appropriate treatment. Your doctor will adjust the dose you are receiving and the rate of administration.

Your doctor will ensure that you have recovered satisfactorily before allowing you to leave the recovery room.

• Remifentanilo has a rapid neutralization of its action. There will be no residual analgesic activity within 5 to 10 minutes after interrupting administration. During operations that are known to be painful, upon awakening, or during use in an Intensive Care Unit, analgesics should be administered before stopping remifentanilo administration.

Allow sufficient time 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 medication contains remifentanilo, which is an opioid. Repeated use of opioids can make the medication less effective (become accustomed 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.

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

Use of other medications

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

This is because remifentanilo may interact with other medications and cause adverse effects.

Particularly, inform your doctor or pharmacist if you are taking medications for the heart or blood pressure, such as beta-blockers or calcium channel blockers, or medications to induce sleep, reduce anxiety, or relax muscles, belonging to a group of agents called benzodiazepines or medications to treat depression, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs).

It is not recommended to use these medications at the same time as remifentanilo, as they may increase the risk of serotonin syndrome, a potentially fatal condition.

The concomitant use of remifentanilo and sedatives, such as benzodiazepines or related medications, increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and can be fatal. Therefore, concomitant use should only be considered when other treatment options are not possible. The concomitant use of opioids and other medications 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 along with sedatives, the dose and duration of concomitant treatment should be limited by your doctor.

Inform your doctor about all sedatives you are taking and follow your doctor's recommendations regarding the dose. It may be helpful to inform friends or family members about the signs and symptoms mentioned above. Contact your doctor when you experience these symptoms.

Pregnancy and breastfeeding

Inform your doctor if you are pregnant or plan to become pregnant or breastfeed.

Generally, this medication should not be used during pregnancy, unless your doctor tells you otherwise.

Do not breastfeed for 24 hours after receiving remifentanilo.

There is not enough data to recommend the use of remifentanilo during childbirth and cesarean section.

Consult your doctor or pharmacist before using any medication.

If you receive this medication 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 breathing difficulties.

Driving and operating machinery

Do not drive or operate tools or machinery after receiving this medication, as it may affect your reaction time. Your doctor will tell you how long to wait before driving or operating machinery.

Athletes

Athletes should be cautious as this medication contains an active ingredient that may result in a positive test in doping control.

You will never administer this medication to yourself. This medication will always be administered by qualified individuals and under carefully controlled conditions.

Dosage

The dose you will receive will depend on:

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

Doses vary from patient to patient. They depend on your age, body weight, and overall condition.

Your doctor will decide on the appropriate dose for you. They will adjust it based on the effect obtained during anesthesia.

Method of administration

This medication will be administered intravenously.

Remifentanilo can be given:

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

Care should be taken to avoid any accidental administration, particularly at the end of anesthesia.

Treatment duration

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

Remifentanilo is not recommended for use 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 interrupt treatment with Remifentanilo Kern Pharma

Like other morphine derivatives, this medication can cause dependence.

Consult your doctor or pharmacist if you have any doubts about the use of this medication.

Like all medicines, Remifentanilo Kern Pharma may cause side effects, although not everyone will experience them.

Very common side effects (affect more than one person in every 10)

• Muscle stiffness – please see section 2, also,
• Low blood pressure (hypotension) - please see section 2, also,
• Nausea, vomiting.

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

• Decreased heart rate (bradycardia) - please see section 2, also,
• Postoperative increase in blood pressure (hypertension),
• Respiratory disturbances (too shallow or too slow breathing) - please see section 2, also, pauses in breathing (apnea),
• Itching (pruritus),
• Postoperative shivering.
• Coughing

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

• Lack of oxygen in the blood (hypoxia),
• Constipation,
• Postoperative pain.

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

• In patients receiving remifentanil along with one or more anesthetic drugs, anaphylactic hypersensitivity reactions have been detected, including acute allergic reaction (anaphylaxis),
• Feeling drowsy (sedation) during recovery from general anesthesia,
• In patients receiving remifentanil along with other anesthetic drugs, cardiac arrest/heart stoppage has been detected, usually preceded by a decrease in heart rate (bradycardia).

Side effects of unknown frequency

• Abstinence syndrome (may manifest with the following side effects: increased heart rate, hypertension, feeling agitated or restless, nausea, vomiting, diarrhea, anxiety, chills, shivering, and sweating)
• Irregular heartbeat (arrhythmia)

If you consider that any of the side effects you experience are severe or if you notice any side effect not mentioned in this prospectus, inform your doctor or pharmacist.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not appearing in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use remifentanilo after the expiration date that appears on the packaging and in the vial. The expiration date is the last day of the month indicated.

Do not store at a temperature above 30ºC.

Chemical and physical stability has been demonstrated during the use of the reconstituted solution for 24 hours at 25ºC.

Chemical and physical stability has been demonstrated during the use of the diluted solution for 4 hours at 25ºC.

From a microbiological point of view, the product must be used immediately. If it is not used immediately, storage times and conditions are the responsibility of the person using it and should normally not exceed 24 hours at 2-8ºC, unless reconstitution/dilution was performed in controlled and validated aseptic conditions.

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

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and unused medications at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and unused medications. This will help protect the environment.

Composition of Remifentanilo Kern Pharma

• The active ingredient is remifentanilo. Each vial contains 5 mg of remifentanilo (as hydrochloride).

After being reconstituted, the solution contains 1 mg/ml of remifentanilo (as hydrochloride), if it is prepared as recommended.

• The other components are: glycine and hydrochloric acid 37% (to adjust the pH).

Appearance of Remifentanilo Kern Pharma and contents of the package

Remifentanilo is a white or off-white powder for concentrated solution for injection and for infusion.

Packaging of 5 vials.

Marketing Authorization Holder

Kern Pharma, S.L.

Venus, 72 - Pol. Ind. Colón II

08228 Terrassa - Barcelona

Spain

Responsible for manufacturing

Laboratorio Reig Jofré, S.A.

Gran Capitán 10

08970 Sant Joan Despí (Barcelona)

Spain

This leaflet was revised in May 2022

The detailed and updated information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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This information is intended solely for doctors or healthcare professionals:

Remifentanilo Kern Pharma 5 mg powder for concentrated solution for injection and for infusion

Handling and use instructions

This medicine must be reconstituted by adding 5 ml of injection solution to obtain a reconstituted solution with a concentration of remifentanilo of approximately 1 mg/ml.

After reconstitution, the solution must not be administered as it is, but rather diluted again.

For manual infusions, remifentanilo 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 TCI, the recommended dilution of remifentanilo is 20 to 50 micrograms/ml.

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

- water for injection preparations,

- injection solution of glucose 50 mg/ml (5%),

- injection solution of glucose 50 mg/ml (5%) and sodium chloride 9 mg/ml (0.9%),

- injection solution of sodium chloride 9 mg/ml (0.9%),

- injection solution of sodium chloride 4.5 mg/ml (0.45%).

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

Dosage

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

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

Treatment of overdose

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

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

• interrupt the administration of the medication,
• keep a respiratory pathway open,
• start 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 active vascular filling, administration of certain drugs (vasopressors) to correct hypotension as well as other supportive measures may be useful.

Naloxone, an opioid antagonist, 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 antagonist.

Stability and storage conditions

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

Medicines should not be disposed of through the drains or in the trash.

Incompatibilities

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

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

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

It is not recommended to administer this medicine through the same intravenous route as blood, serum, or plasma.

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