Remifentanil Kern Pharma 5 mg powder for concentrate for solution for injection and for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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

injection EFG

Remifentanil

Read all of this leaflet carefully before you start taking this medicine.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to other people, even if they have the same symptoms as you, because it may harm them.
• If you think any of the side effects you experience are serious, or if you notice any side effects not listed in this leaflet, tell your doctor or pharmacist.

Leaflet contents:

1. What Remifentanilo Kern Pharma is and what it is used for
2. What you need to know before you take Remifentanilo Kern Pharma
3. How to take Remifentanilo Kern Pharma
4. Possible side effects
5. How to store Remifentanilo Kern Pharma
6. Contents of the pack and other information

1. What Remifentanilo Kern Pharma is and what it is used for

Remifentanil is an anesthetic that belongs to a group of medicines called opioids (substances that have an action similar to morphine in the body).

This medicine is used:

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

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

Do not take Remifentanilo Kern Pharma

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

Due to the presence of glycine in the formulation, remifentanil must not be administered epidurally or intrathecally (injection into the area around the spine or into the cerebrospinal fluid).

Take special care with Remifentanilo Kern Pharma

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

• if you or a family member have ever abused or been dependent on alcohol, prescription medicines, or illegal drugs (“addiction”),
• if you are a smoker,
• if you have ever had mood disorders (depression, anxiety, or personality disorder) or have been treated by a psychiatrist for other mental illnesses,
• if you have ever had respiratory problems (breathing difficulties),
• if you have severe heart problems (heart failure),
• if you have been told that your blood pressure is low (hypotension),
• if you have had severe liver problems (liver failure),
• if you feel weak or have experienced a reduction in blood volume (hypovolemia). You should also exercise caution if you are elderly.

While being treated with Remifentanilo Kern Pharma:

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

• respiratory disturbances (breathing too shallow or too slow),

• muscle rigidity. This effect depends on the dose and rate of administration. Therefore, when administered intravenously as a single slow injection (slow bolus), Remifentanilo Kern Pharma must not be given in less than 30 seconds.

• low blood pressure (hypotension) or decreased heart rate (bradycardia).

If this occurs, your doctor will administer appropriate and specific treatment. Your doctor will adjust the dose and rate of administration.

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

• Remifentanil has a rapid offset of action. There will be no residual analgesic activity within 5 to 10 minutes after stopping administration. During procedures known to be painful, upon awakening, or during use in an Intensive Care Unit, analgesics should be administered before discontinuing remifentanil.

Sufficient time must be allowed to ensure that longer-acting analgesics become effective. These analgesics should be selected based on the type of surgery and the level of postoperative monitoring.

This medicine contains remifentanil, which is an opioid. Repeated use of opioids may lead to reduced effectiveness of the medicine (tolerance). It may also cause dependence and abuse, which in turn may lead to potentially fatal overdose. If you are concerned about becoming dependent on remifentanil, it is important to consult your doctor.

Occasionally, withdrawal reactions (e.g., rapid heartbeat, high blood pressure, and agitation) have been reported after abrupt discontinuation of treatment with this medicine, especially when treatment has been 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.

Use of other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

This is because remifentanil may interact with other medicines and cause adverse effects.

In particular, inform your doctor or pharmacist if you are taking medicines for heart conditions 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 used to treat depression, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors (MAOIs). The concomitant use of these medicines with remifentanil is not recommended, as it may increase the risk of serotonin syndrome, a potentially life-threatening condition. The concomitant use of remifentanil and sedative medicines such as benzodiazepines or related drugs increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be fatal. Therefore, concomitant use should only be considered when no other treatment options are available. 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 may be potentially fatal.

However, if your doctor prescribes remifentanil together with sedative medicines, the dose and duration of concomitant treatment must be limited by your doctor.

Inform your doctor about all sedative medicines you are taking and follow your doctor’s instructions regarding dosage carefully. It may be helpful to inform friends or family members so they are aware of the symptoms mentioned above. Contact your doctor if you experience such symptoms.

Pregnancy and breastfeeding

Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding.

Generally, this medicine should not be used during pregnancy unless your doctor specifically instructs otherwise.

You must not breastfeed for 24 hours following administration of remifentanil.

There are insufficient data to recommend the use of remifentanil during labour and caesarean section.

Consult your doctor or pharmacist before using 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 drowsiness or breathing difficulties.

Driving and using machines

Do not drive or operate tools or machinery after receiving this medicine, as it may affect your reaction ability. Your doctor will advise you how long you should wait before resuming driving or using machines.

Athletes

Athletes should be cautious, as this medicine contains an active substance that may result in a positive doping test.

3. How to take Remifentanilo Kern Pharma

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

Dosage

The dose you will receive depends on:

• the type of surgery,
• how much pain relief you need.

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

Your doctor will decide the dose suitable for you. He/she will adjust it according to the effect achieved during anesthesia.

Method of administration

This medicine will be administered to you intravenously.

Remifentanil may be given:

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

Special care must be taken to avoid any accidental administration, particularly at the end of anesthesia.

Duration of treatment

Your doctor will decide the duration of therapy appropriate for you and your surgery.

The use of Remifentanil in mechanically ventilated intensive care patients is not recommended for periods longer than 3 days.

If you take more Remifentanilo Kern Pharma than you should

Your doctor will promptly take the necessary actions.

If you interrupt treatment with Remifentanilo Kern Pharma

Like other morphine derivatives, this medicine may lead to dependence.

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

4. Possible adverse effects

Like all medicines, Remifentanil Kern Pharma can cause adverse effects, although not everyone will experience them.

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

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

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

• decreased heart rate (bradycardia) – please also see section 2,
• postoperative increase in blood pressure (hypertension),
• respiratory disturbances (breathing too shallow or too slow) – please also see section 2, breathing pauses (apnea),
• itching (pruritus),
• postoperative tremors,
• cough.

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

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

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

• in patients receiving remifentanil together with one or more anesthetic drugs, allergic reactions including acute allergic hypersensitivity reaction (anaphylaxis) have been reported,
• feeling drowsy (sedation) during recovery from general anesthesia,
• in patients receiving remifentanil together with other anesthetic drugs, cardiac arrest/asystole has been reported, usually preceded by a decreased heart rate (bradycardia).

Adverse effects of unknown frequency

• withdrawal syndrome (may present with the following adverse effects: increased heart rate, arterial hypertension, feeling agitated or restless, nausea, vomiting, diarrhea, anxiety, chills, tremors, and sweating),
• irregular heartbeat (arrhythmia).

If you consider any of the adverse effects you experience to be severe, or if you notice any adverse effect not mentioned in this leaflet, inform your doctor or pharmacist.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Remifentanil Kern Pharma

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

Do not use remifentanil after the expiry date stated on the carton and vial. The expiry date refers to the last day of the month indicated.

Do not store above 30°C.

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

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

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

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

Medicines must not be disposed of via wastewater or household waste. Unused medicines and their containers should be returned to a pharmacy’s SIGRE collection point. If you are unsure, ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Remifentanil Kern Pharma

• The active substance is remifentanil. Each vial contains 5 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% (to adjust pH).

Appearance of Remifentanil Kern Pharma and Contents of the Package

Remifentanil is a white or almost white powder for concentrate for injectable solution and for infusion.

Packaging: 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 reviewed in May 2022

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

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This information is intended exclusively for healthcare professionals:

Remifentanil Kern Pharma 5 mg powder for concentrate for injectable solution 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 remifentanil concentration of approximately 1 mg/ml.

After reconstitution, the solution must not be administered undiluted but should be further diluted.

For manually administered infusions, remifentanil may 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 (target-controlled infusion), the recommended dilution of remifentanil is 20 to 50 micrograms/ml.

Reconstitution and dilution of remifentanil solution may be performed using one of the following injection solutions:

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

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

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

Dosage

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

Depending on the indication, dosage recommendations are provided for adults and/or children (aged 1 to 12 years), with dose adjustments suggested for special populations.

Overdose Management

Due to the very short duration of action, the potential for harmful effects following overdose is limited to the immediate period after administration. Discontinuation of the drug results in a rapid response, with return to baseline status within 10 minutes.

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

• discontinue administration of the medicine,
• maintain a patent 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 drugs (vasopressors) may be useful to correct hypotension, along with other supportive measures.

An opioid antagonist such as naloxone may be administered intravenously to treat severe respiratory depression and muscle rigidity. It is unlikely that the duration of respiratory depression after overdose will exceed the duration of action of the antidote.

Stability and Storage Conditions

Remifentanil Kern Pharma is preservative-free and intended for single use only. Any unused material must be discarded.

Medicines must not be disposed of via wastewater or household waste.

Incompatibilities

Remifentanil Kern Pharma must only be reconstituted or diluted with the recommended injection solutions.

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

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

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

This medicine must not be mixed with other medicinal products prior to administration.