Prospect: Information for the User

Safentil 5 micrograms/ml injectable solution and for EFG perfusion

Safentil 50 micrograms/ml injectable solution and for EFG perfusion

sufentanilo

Read this prospect carefully before this medication is administered to you, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse
• If you experience adverse effects, consult your doctor, pharmacist or nurse, even if they are not listed in this prospect. See section4.

1.What is Safentil and for what it is used

2.What you need to know before Safentil is started

3.How Safentil is administered

4.Possible adverse effects

5.Storage of Safentil

6.Contents of the package and additional information

Safentil belongs to the group of medications known as anesthetics and analgesics. It is a potent analgesic used in hospitals. Safentil can be administered intravenously (into a vein) to prevent pain during the induction and maintenance of combined anesthesia or as an anesthetic for the induction and maintenance of anesthesia, as part of major surgery.

Safentil can also be administered epidurally (into the spinal column) to alleviate pain after an intervention or to treat pain during normal childbirth (vaginal delivery).

The doctor will decide if this medication is suitable for you.

The doctor may administer Safentil for other indications. Consult your doctor.

Use in children

Intravenous route: Safentil is used as an analgesic (pain reliever) to initiate and/or maintain general anesthesia (balanced general anesthesia) in children aged one month and above.

Epidural route: Safentil is used in children aged one year and above to treat pain after some operations: abdominal surgery, thoracic surgery (heart and lung) or orthopedic surgery (arms, legs, and back).

Your doctor will perform the necessary investigations before administering this medication to you.

Do not administer Safentil:

• If you are allergic to sufentanil, other opioid compounds, or any of the other components of this medication (listed in section 6),
• If you have difficulty expectorating secretions, previous respiratory problems caused by treatment with other medications or any disease for which it is important to avoid respiratory problems.
• In epidural injection form, if you have severe bleeding or shock, severe blood infection or infection at the injection site. Do not administer Safentil in epidural injection form if you have wound healing problems, if you are receiving anticoagulant treatment, or if you have other medical conditions that contraindicate epidural treatment.
• In intravenous injection form during delivery or cesarean section before umbilical cord clamping, as it may cause respiratory problems in the newborn.

Warnings and precautions

Consult your doctor before Safentil is administered to you:

• If you experience pain or increased sensitivity to pain (hyperalgesia) that does not respond to a higher dose of the medication as prescribed by your doctor.
• For intravenous injection, if you experience increased intracranial pressure, uncontrolled low metabolism (hypothyroidism), respiratory diseases, reduced lung capacity, are an alcoholic or have liver or kidney dysfunction, are an elderly person or feel weakened.
• During epidural injection, if you experience respiratory dysfunction or reduced lung capacity and if the fetus shows signs of oxygen deficiency (fetal distress).
• If you have myasthenia gravis (chronic muscle disease).
• If you are taking monoamine oxidase inhibitors (a medication for depression, see section "Other medications and Safentil").
• If you are using other opioid-type medications (for example, strong pain medications), or if you have previously consumed or suffered dependence on this type of substance.
• If you have abnormally slow bowel movements.
• If you have gallbladder or pancreas disease.
• If you or any family member has ever abused or had dependence on alcohol, prescription medications, or illegal substances ("addiction").
• If you are a smoker.
• If you have ever had mood-related problems (depression, anxiety, or personality disorder) or have been treated by a psychiatrist for other mental health conditions.

This medication contains sufentanil, which is an opioid. Repeated use of opioid analgesics can make the medication less effective (the body becomes accustomed to them). It can also produce dependence and abuse, which can lead to a potentially fatal overdose. It is essential to consult your doctor if you are concerned about developing dependence on Safentil.

Sleep-related respiratory disorders

Safentil may cause sleep-related respiratory disorders such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). These symptoms may include pauses in breathing during sleep, nocturnal awakening due to difficulty breathing, difficulty maintaining sleep, or excessive daytime somnolence. If you or someone else observes these symptoms, contact your doctor. Your doctor may consider reducing the dose.

Children and adolescents

It should not be administered intravenously to neonates due to the risk of overdose or administering too small a dose of Safentil.

Epidural administration of Safentil is not indicated in children under 1 year.

Use of Safentil with other medications

Inform your doctor if you are using, have used recently, or may need to use any other medication.

Inform your doctor if you are taking any of the following medications:

• Somnifacients, sedatives, medications for mental disorders or substances affecting the central nervous system (for example, alcohol) as they may further impair breathing. In this case, your doctor may consider reducing the Safentil dose.
• Medications for treating fungal infections (for example, ketoconazole and itraconazole) and antiviral medications (for example, ritonavir), as these medications may inhibit sufentanil circulation. Your doctor may consider reducing the Safentil dose.
• Medications for treating depression, known as monoamine oxidase inhibitors (MAOIs). These medications should not be taken in the 2 weeks prior to or concurrently with Safentil administration.
• Medications for treating depression known as selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs). It is not recommended to use these medications concurrently with Safentil.
• Strong analgesics affecting the central nervous system (CNS inhibitors), alcohol, and some illicit substances - if you are taking strong analgesics or other medications affecting the CNS (for example, somnifacients, tranquilizers, medications for mental disorders, alcohol, or some illicit substances/illicit drugs), inform your doctor as it may be necessary to reduce the Safentil dose. If you take strong analgesics or other substances affecting the CNS after Safentil administration during surgery, it may also be necessary to reduce the analgesic or CNS-affecting substance dose to reduce the risk of severe adverse effects such as difficulty breathing with slow or shallow breathing, intense somnolence, and decreased level of consciousness, coma, and death.
• The concurrent use of opioids and medications for treating epilepsy, neurological pain, or anxiety (gabapentin and pregabalin), as they increase the risk of opioid overdose and respiratory depression and may put the patient's life at risk.

Pregnancy and lactation

If you are pregnant or breastfeeding, or if you think you may be pregnant or plan to become pregnant, consult your doctor before this medication is administered to you.

Safentil should only be administered during pregnancy if the benefits outweigh the potential risks. Safentil may be administered epidurally during delivery.

Sufentanil is excreted in breast milk. Your doctor will assess whether you should breastfeed.

Driving and operating machinery

Sufentanil may cause side effects that could severely affect your ability to drive safely.

Safentil may affect your ability to drive and operate machinery. Do not drive or operate machinery until a sufficient amount of time has passed since Safentil administration. When returning home, you should be accompanied by a responsible adult and it is recommended that you avoid alcohol.

Safentil contains sodium

This medication contains 9 mg of sodium per ml of injectable solution. This is equivalent to 0.45% of the maximum daily recommended sodium intake in an adult diet.

Your doctor will inform you about the dose they will administer and the frequency. If you have any doubts, consult your doctor. Only your doctor can modify the dose.

The dose is adjusted according to your age, weight, general condition, diseases, use of other medications, type of intervention, and need for analgesia.

Safentil can be administered intravenously (into a vein) to relieve pain throughout the body (or as anesthesia) during surgical interventions.

Safentil can also be administered epidurally (in the area of the spinal column) to relieve pain in some parts of the body, for example during childbirth or after an intervention.

Usually, a doctor or nurse will administer the injection.

For more instructions on how to administer Safentil (including administration in children), consult the section "The following information is intended exclusively for healthcare professionals" at the end of the prospectus.

If you believe you have been administered too much Safentil

Contact your doctor if you believe you have been administered too much Safentil and you do not feel well.

If you are administered too much Safentil, you will notice an increase in the effect, especially in the form of respiratory problems. In these cases, your doctor will take the necessary measures such as oxygen supply and assisted breathing and will closely monitor your body temperature and the amount of fluid you take.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

The doctor will treat any side effects that occur, especially during the operation. However, some may occur shortly after and, therefore, you will be kept under observation for some time after the operation.

Immediately contact your doctor or go to the emergency room if you observe the following severe side effects.

Less common side effects(may affect up to 1 in 100 people):

• Very slow pulse, tendency to faint
• Lack of air (dyspnea)/difficulty breathing/asthmatic crisis (bronchospasm)
• Low body temperature
• Involuntary body movements that do not disappear when treatment is interrupted

Side effects of unknown frequency(cannot be estimated from available data):

• Sudden rash, respiratory problems, and fainting (in minutes or hours) caused by hypersensitivity (anaphylactic shock)
• Deep unconsciousness (coma)
• Cardiac arrest
• Weak or stopped breathing, blue lips and nails
• Cramps
• Shock (in case of acute and severe disease)
• Lack of air, rapid shallow breathing, chest pain, and cough with bloody sputum due to lung congestion
• Cramps in the throat with difficulty breathing

Other side effects

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

• Drowsiness
• Itching

Common side effects(may affect up to 1 in 10 people):

• Difficulty urinating or absence of urine excretion
• Fast pulse
• Dizziness and headache
• High blood pressure
• Dizziness caused by low blood pressure or hemorrhage
• Vomiting and nausea
• Change in skin color
• Muscle spasms
• Involuntary urination
• Fever

Less common side effects(may affect up to 1 in 100 people)

• Slow or irregular pulse
• Nasal secretion
• Hypersensitivity
• Indifference, nervousness
• Unstable movements, powerful reflexes, increased muscle tension, drowsiness
• Visual disturbances
• Blue lips, skin, mucous membranes, or nails
• Abnormal heart activity (ECG) results
• Depressed respiration (hyperventilation), difficulty speaking, cough, hiccups, respiratory problems
• Allergic eczema, intense sweating, rash, dry skin
• Back pain, muscle spasms
• Increased body temperature, chills, reaction at the injection site, pain at the injection site, pain

Unknown frequency(cannot be estimated from available data)

• Involuntary muscle contractions
• Constricted pupils
• Skin redness
• Muscle spasms

Other side effects in children and adolescents

In children, it is predictable that the frequency, nature, and severity of adverse reactions will be the same as in adults.

Additionally, in newborns, the following side effects may occur:

Common side effects(may affect up to 1 in 10 people)

-Trembling

-Blue lips, skin, mucous membranes, or nails (neonatal cyanosis)

Less common side effects(may affect up to 1 in 100 people)

-Involuntary body movements

-Slow movements

-Rash

-Muscle weakness

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://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 this medication after the expiration date that appears on the label and the box after CAD. The expiration date refers to the last day of the month indicated.

This medication does not require special temperature storage conditions.Store in the original packaging to protect itfrom light.

This medication must be used immediately after opening. If you want more information on the validity period after dilution, consult the section for healthcare professionals later on.

Medicines should not be thrown down the drain or in the trash. Ask your pharmacist how to dispose of the containers and the medication that you no longer need. These measures are intended to protect the environment.

Composition of Safentil

• The active principle is sufentanil (in the form of citrate).

Safentil 5 micrograms/ml: Each ml of solution contains 5 micrograms of sufentanil in the form of sufentanil citrate.

Safentil 50 micrograms/ml: Each ml of solution contains 50 micrograms of sufentanil in the form of sufentanil citrate. The other components are: sodium chloride, sodium hydroxide "to adjust the pH", hydrochloric acid "to adjust the pH" and water for injection preparations.

Aspect of the product and content of the package

The solution is transparent and colorless, free of visible particles, with a pH of 4.0 to 6.0 and an osmolality of 250 to 310 mOsmol/kg.

10 ml and 5 ml capacity glass ampoules, type I. The ampoules are presented with a adhesive label and in preformed PVC trays (each tray contains 5 ampoules) as secondary packaging, sealed with PE film. The removable membrane of the PVC blisters is only used in the case of 5 ml capacity ampoules.

Only some sizes of packaging may be commercially available.

Holder of the marketing authorization

Medochemie Ltd,

1-10 Constantinoupoleos Street

3011, Limassol

Cyprus

Manufacturer

Medochemie Ltd,

Ampoule Injectable Facility: 48 Iapetou Street,

Agios Athanassios Industrial Area,

Agios Athanassios

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Saniproject, S.L.

C/ Retamas 11 – Urb.Puentelasierra

28210 Valdemorillo, Madrid

SPAIN

This medicine is authorized in the EEA member states with the following names:

Last approval date of this leaflet: February 2023.

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

This information is intended solely for healthcare professionals:

Dosage and administration

Adults

Anesthesia and combined analgesia:

• Analgesia: 0.5 - 5 micrograms/kg by IV
• Anesthesia: 25 - 50 micrograms/kg by IV

Epidural analgesia in postoperative pain treatment: 25 - 50 micrograms.

Analgesic complement in childbirth: 5 - 20 micrograms by epidural.

IV administration

To avoid bradycardia, it is recommended to administer a small dose of anticholinergic intravenously just before induction.

Epidural administration

The correct placement of the needle or catheter in the epidural space must be checked before injecting Safentil.

Pediatric population

IV administration

Newborns (≤1 month)

Due to the high variability of pharmacokinetic parameters in newborns, it is not possible to make a reliable recommendation for the dose.

Children > 1 month

At all doses, to avoid bradycardia, premedication with an anticholinergic (such as atropine) is recommended, unless contraindicated.

Anesthesia induction

Safentil can be administered as a slow bolus of 0.2-0.5 micrograms/kg over 30 seconds or more in combination with an anesthetic induction agent. In major surgery (e.g. cardiac surgery), doses of up to 1 microgram/kg may be administered.

Maintenance of anesthesia in ventilated patients

Safentil can be administered as part of a combined anesthesia. The dose depends on the dose of concomitant anesthetic agents, the type and duration of the intervention. An initial dose of 0.3-2 micrograms/kg administered as a slow bolus over at least 30 seconds may be followed by additional boluses of 0.1-1 micrograms/kg as needed up to a maximum total dose of 5 micrograms/kg for cardiac surgery.

Epidural administration

Only an anesthesiologist familiar with pediatric epidural anesthesia and the management of opioid-induced respiratory depression should administer Safentil to children by epidural route. Equipment for resuscitation and opioid antagonists should be readily available.

After epidural administration of Safentil, pediatric patients should be monitored for signs of respiratory depression for at least 2 hours.

Children <1

The safety and efficacy of sufentanil in children under 1 year have not been established.

No data are available in neonates or infants under 3 months.

Children > 1 year:

A single intraoperative dose of 0.25-0.75 micrograms/kg of sufentanil administered as a bolus relieves pain for a period of 1-12 hours. The duration of effective analgesia depends on the surgical intervention and concomitant epidural administration of local anesthetics such as amide.

Geriatric patients (from 65 years) and debilitated patients

Like other opioids, geriatric patients and debilitated patients require lower doses.

The planned total dose should be carefully adjusted in patients with any of the following conditions:

Also, prolonged postoperative monitoring is recommended in these patients.

Patients on chronic opioid treatment or with a history of opioid abuse may require higher doses.

Special precautions for disposal and other manipulations

It can be mixed with isotonic sodium chloride solution for infusion, 5% glucose solution for infusion, and Ringer-lactate solution for infusion.

Use gloves when opening the vial. Accidental skin exposure should be treated by rinsing the affected area with water. Avoid using soap, alcohol, and other cleaning products that may cause chemical or physical damage to the skin.

Period of validity after opening:

After opening, the medicine should be used immediately.

Period of validity after dilution

Chemical and physical stability has been demonstrated during use for 24 hours below 25°C and at 2-8°C.

From a microbiological point of view, dilutions should be used immediately. If not used immediately, the time and conditions of conservation during use are the responsibility of the user and normally should not exceed 24 hours at 2-8°C, unless the dilution was prepared in controlled and validated aseptic conditions.