Safentil 5 micrograms/ml solution for injection and for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Safentil 5 micrograms/ml injection and infusion solution EFG

Safentil 50 micrograms/ml injection and infusion solution EFG

sufentanil

Read the entire leaflet carefully before you are administered this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Safentil is and what it is used for
2. What you need to know before you are administered Safentil
3. How Safentil is administered
4. Possible adverse effects
5. How to store Safentil
6. Contents of the pack and other information

1. What Safentil is and what it is used for

Safentil belongs to a group of medicines called anaesthetics 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 balanced anaesthesia, or as an anaesthetic agent for the induction and maintenance of anaesthesia as part of major surgery.

Safentil may also be administered epidurally (into the spinal canal) to relieve pain after surgery or to treat pain during normal childbirth and delivery (vaginal birth).

Your doctor will decide whether this medicine is suitable for you.

Your doctor may prescribe Safentil for other indications. Please consult your doctor.

Use in children

Intravenous route: Safentil is used as an analgesic (for pain relief) to initiate and/or maintain general anaesthesia (balanced general anaesthesia) in children from 1 month of age.

Epidural route: Safentil is used in children from 1 year of age to treat pain after certain surgeries: abdominal surgery, thoracic surgery (heart and lung), or orthopaedic surgery (arms, legs, and back).

2. What you need to know before you are given Safentil

Your doctor will carry out the necessary investigations before administering this medicine to you.

Do not be given Safentil if:

• You are allergic to sufentanil, to other opioid compounds, or to any of the other components of this medicine (listed in section 6),
• You have difficulty expectorating secretions, pre-existing respiratory problems caused by treatment with other medicines, or a medical condition for which avoiding respiratory complications is important.
• For epidural injection: if you have severe bleeding or shock, severe blood infection (sepsis), or an infection at the injection site. You must also not be given Safentil as an epidural injection if you have impaired wound healing, are receiving anticoagulant therapy, or have other medical conditions that contraindicate epidural treatment.
• For intravenous injection during childbirth or caesarean section before clamping of the umbilical cord, as it may cause respiratory problems in the newborn.

Warnings and precautions

Talk to your doctor before you are given Safentil:

• If you experience pain or increased sensitivity to pain (hyperalgesia) that does not respond to a higher dose of the medicine as prescribed by your doctor.
• For intravenous injection: if you have increased pressure in the brain, uncontrolled low metabolism (hypothyroidism), lung diseases, reduced lung capacity, are alcoholic, or have hepatic or renal dysfunction, are elderly, or feel weakened.
• During epidural injection: if you have respiratory dysfunction or reduced lung capacity, or if the fetus shows signs of oxygen deficiency (fetal distress).
• If you have myasthenia gravis (a chronic muscle disease).
• If you are taking MAO inhibitors (a medicine for depression; see section "Other medicines and Safentil").
• If you are using other opioid-type medicines (e.g. strong painkillers), or if you have previously used or been dependent on such substances.
• If you have abnormally slow intestinal movements.
• If you have a disease of the gallbladder or pancreas.
• If you or any family member has ever abused or been dependent on alcohol, prescription medicines, or illegal drugs ("addiction").
• If you are a smoker.
• If you have ever had mood-related problems (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.

This medicine contains sufentanil, which is an opioid. Repeated use of opioid analgesics may lead to reduced effectiveness of the drug (the body becomes accustomed to it). It may also lead to dependence and abuse, which could result in potentially fatal overdose. It is important that you consult your doctor if you are concerned about developing dependence on Safentil.

Sleep-related breathing disorders

Safentil may cause sleep-related breathing disorders such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxemia (low blood oxygen levels during sleep). Symptoms may include pauses in breathing during sleep, waking up at night due to difficulty breathing, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else notices these symptoms, contact your doctor. Your doctor may consider reducing the dose.

Children and adolescents

Intravenous administration must not be used in neonates due to the risk of overdose or underdose of Safentil.

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

Using Safentil with other medicines

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

Tell your doctor if you are taking any of the following medicines:

• Sleeping pills, sedatives, medicines for mental disorders, or substances affecting the central nervous system (e.g. alcohol), as these may further impair breathing. In such cases, your doctor may consider reducing the dose of Safentil.
• Medicines to treat fungal infections (e.g. ketoconazole and itraconazole) and antiviral medicines (e.g. ritonavir), as these drugs may inhibit the metabolism of sufentanil. Your doctor may consider reducing the dose of Safentil.
• Medicines for depression known as monoamine oxidase inhibitors (MAOIs). These medicines must not be taken within 2 weeks before, or concurrently with, administration of Safentil.
• Medicines for depression known as selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs). Concomitant use of these medicines with Safentil is not recommended.
• Strong analgesics affecting the central nervous system (CNS inhibitors), alcohol, and certain illegal substances – if you are taking strong analgesics or other medicines affecting the central nervous system (e.g. sleeping pills, tranquilizers, medicines for mental disorders, alcohol, or certain illicit/illegal substances), inform your doctor, as it may be necessary to reduce the dose of Safentil. If you take strong analgesics or other substances affecting the central nervous system after receiving Safentil during surgery, the dose of the analgesic or CNS-affecting substance may also need to be reduced to lower the risk of serious adverse effects such as difficulty breathing, slow or shallow breathing, severe drowsiness, reduced level of consciousness, coma, and death.
• Concomitant use of opioids and medicines used to treat epilepsy, neurological pain, or anxiety (gabapentin and pregabalin), as this increases the risk of opioid overdose and respiratory depression, which may be life-threatening.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before you are given this medicine.

Safentil should only be administered during pregnancy if the benefits outweigh the potential risks. Safentil may be administered via epidural route during childbirth.

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

Driving and using machines

Sufentanil may cause side effects that could seriously affect safety and your ability to drive safely.

Safentil may impair your ability to drive and operate machinery. You must not drive or operate machinery until sufficient time has passed after administration of Safentil. When returning home, you should be accompanied by a responsible adult, and you are advised to avoid alcohol.

Safentil contains sodium

This medicine contains 9 mg of sodium per ml of injectable solution. This corresponds to 0.45% of the maximum daily recommended dietary intake of sodium for an adult.

3. How Safentil is administered

Your doctor will inform you about the dose to be administered and how often. If you have any doubts, consult your doctor. Only the doctor may adjust the dose.

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

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

Safentil may also be administered epidurally (into the space around the spinal cord) to relieve pain in certain parts of the body, for example during childbirth or after surgery.

Usually, a doctor or nurse will administer the injection.

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

If you think you have been given too much Safentil

Contact your doctor if you think you have been given more Safentil than you should and you do not feel well.

If you are given more Safentil than you should, you may experience an increase in its effects, particularly in the form of breathing problems. In such cases, your doctor will take necessary measures such as providing oxygen and assisted ventilation, and will closely monitor your body temperature and fluid intake.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The doctor will manage any adverse effects that occur, especially during surgery. However, some may appear shortly afterwards; therefore, you will be kept under observation for some time after the operation.

Contact your doctor or go to the emergency room immediately if you experience any of the following serious adverse effects.

Uncommon adverse effects (may affect up to 1 in 100 people):

• Very slow pulse, tendency to faint
• Shortness of breath (dyspnea)/difficulty breathing/asthma-like attack (bronchospasm)
• Low body temperature
• Involuntary body movements that do not disappear when treatment is stopped

Adverse effects with frequency not known (cannot be estimated from available data):

• Sudden rash, breathing problems and fainting (within minutes or hours) caused by hypersensitivity (anaphylactic shock/reaction)
• Deep unconscious state (coma)
• Cardiac arrest
• Weak breathing or respiratory arrest, blue lips and nails
• Cramps
• Shock (in case of acute and severe illness)
• Shortness of breath, rapid breathing, wheezing, chest pain or discomfort, along with cough producing secretions or bloody sputum due to pulmonary congestion
• Throat spasms with difficulty breathing

Other side effects

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

• Drowsiness
• Itching

Common adverse 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 bleeding
• Vomiting and nausea
• Skin color changes
• Muscle jerks
• Involuntary urination
• Fever

Uncommon adverse effects (may affect up to 1 in 100 people):

• Slow or irregular pulse
• Nasal discharge
• Hypersensitivity
• Indifference, nervousness
• Unsteady movements, exaggerated reflexes, increased muscle tension, drowsiness
• Visual disturbances
• Blue lips, skin, mucous membranes or nails
• Abnormal results in heart electrical activity (ECG)
• Respiratory depression (hypoventilation), difficulty speaking, cough, hiccups, breathing problems
• Allergic eczema, excessive sweating, rash, dry skin
• Back pain, muscle spasms
• Increased body temperature, chills, reaction at injection site, pain at injection site, pain

Frequency not known (cannot be estimated from available data):

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

Other adverse effects in children and adolescents

In children, the frequency, nature, and severity of adverse reactions are expected to be the same as in adults.

Additionally, the following adverse effects may occur in newborns:

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

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

Uncommon adverse effects (may affect up to 1 in 100 people):

• Involuntary body movements
• Slow movements
• Rash
• Muscle weakness

Reporting of adverse effects

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

5. Storage of Safentil

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

Do not use this medicine after the expiry date stated on the label and the carton following EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage temperature conditions. Store in the original packaging to protect from light.

This medicine should be used immediately after opening. For more information regarding the shelf life after dilution, refer to the section for healthcare professionals below.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. These measures are intended to protect the environment.

6. Contents of the container and other information

Composition of Safentil

• The active substance is sufentanil (as citrate).

Safentil 5 micrograms/ml: Each ml of solution contains 5 micrograms of sufentanil as sufentanil citrate.

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

Appearance of the product and contents of the container

The solution is clear, colourless, free from visible particles, with a pH of 4.0 to 6.0 and osmolality of 250 to 310 mOsmol/kg.

Clear glass ampoules with a capacity of 10 ml and 5 ml respectively, type I. The ampoules are supplied with an adhesive label and packed in pre-formed PVC trays (each tray contains 5 ampoules) as secondary packaging, sealed with a PE foil. The peelable membrane of the PVC blisters is used only for the 5 ml capacity ampoules.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Medochemie Ltd,
1-10 Constantinoupoleos Street
3011, Limassol
Cyprus

Manufacturer

Medochemie Ltd,
Ampoule Injectable Facility: 48 Iapetou Street,
Agios Athanassios Industrial Area,
Agios Athanassios
Cyprus

Further information on this medicinal product is available from the local representative of the Marketing Authorization Holder:

Saniproject, S.L.
C/ Retamas 11 – Urb. Puentelasierra
28210 Valdemorillo, Madrid
SPAIN

This medicinal product is authorized in the EEA Member States under the following names:

Denmark	SOFENTIL 5 mcg/ml and 50 mcg/ml solution for injection/infusion
Croatia	SOFENTIL 5 micrograms/ml solution for injection/infusion and Sofentil 50 micrograms/ml solution for injection/infusion
Cyprus	SOFENTIL 5 mcg/ml and 50 mcg/ml solution for injection/infusion
Czech Republic	SONTILEN
Latvia	SONTILEN 5 micrograms/ml and 50 micrograms/ml solution for injection/infusion
Lithuania	SONTILEN 5 micrograms/ml and 50 micrograms/ml concentrate for solution for injection/infusion
Malta	SOFENTIL 5 mcg/ml and 50 mcg/ml solution for injection/infusion
Portugal	SOFENTIL 5 mcg/ml and 50 mcg/ml solution for injection/infusion
Romania	SOFENTIL 5 mcg/ml and 50 mcg/ml solution for injection/infusion
Slovak Republic	SOFENTIL 5 micrograms/ml and 50 micrograms/ml solution for injection/infusion

Date of the latest approval of this leaflet: February 2023.

Detailed 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/).

This information is intended exclusively for healthcare professionals:

Dosage and method of administration

Adults

Combined anaesthesia and analgesia:

• Analgesia: 0.5 – 5 micrograms/kg intravenously (IV)
• Anaesthesia: 25 – 50 micrograms/kg IV

Epidural analgesia in postoperative pain management: 25 – 50 micrograms.

Analgesic supplement during childbirth: 5 – 20 micrograms epidurally.

Intravenous administration

To avoid bradycardia, it is recommended to administer a small intravenous dose of an anticholinergic agent immediately before induction.

Epidural administration

Correct placement of the needle or catheter in the epidural space must be confirmed before injecting Safentil.

Paediatric population

Intravenous administration

Children ≤1 month (neonates)

Due to the high variability of pharmacokinetic parameters in neonates, a reliable dose recommendation cannot be provided.

Children > 1 month

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

Induction of anaesthesia

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

Maintenance of anaesthesia in ventilated patients

Safentil may be administered as part of combined anaesthesia. The dose depends on the dose of concomitant anaesthetic agents, the type and duration of the procedure. 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 microgram/kg as required, up to a total maximum of 5 micrograms/kg for cardiac surgery.

Epidural administration

Safentil should only be administered epidurally to children by an anaesthesiologist experienced in paediatric epidural anaesthesia and in managing opioid-induced respiratory depression. Resuscitation equipment and opioid antagonists must be immediately available.

After epidural administration of Safentil, paediatric patients must be monitored for signs of respiratory depression for at least 2 hours. The use of epidurally administered sufentanil in paediatric patients has only been documented in a limited number of cases.

Children < 1 year:

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

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

Children > 1 year:

A single intraoperative bolus dose of 0.25–0.75 micrograms/kg body weight of sufentanil provides pain relief for a period of 1 to 12 hours. The duration of effective analgesia depends on the type of surgical procedure and concomitant epidural administration of amide-type local anaesthetics.

Elderly patients (aged 65 years and over) and debilitated patients:

As with other opioids, elderly and debilitated patients require lower doses.

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

• Uncompensated hypothyroidism
• Pulmonary disorders, especially if vital capacity is reduced
• Alcoholism or hepatic and renal impairment.

Prolonged postoperative monitoring is also recommended in these patients.

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

Special precautions for disposal and other handling

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

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

Shelf-life after opening:

After opening, the medicinal product should be used immediately.

Shelf-life after dilution:

Chemical and physical stability has been demonstrated for 24 hours when stored below 25°C and at 2–8°C.

From a microbiological standpoint, diluted solutions should be used immediately. If not used immediately, the duration and conditions of storage during use are the responsibility of the user and normally should not exceed 24 hours at 2–8°C, unless dilution has been carried out under controlled and validated aseptic conditions.