Package leaflet: Information for the user

Sufentanil Chiesi, 5 micrograms/ml, solution for injection
Please read all of this leaflet carefully before use, as it contains important information for the patient.

Keep this leaflet, so that you can read it again if necessary.
If you have any questions, please consult your doctor, pharmacist, or nurse.
This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm someone else, even if their symptoms are the same.
If the patient experiences any adverse reactions, including any not listed in this leaflet, inform a doctor, pharmacist, or nurse. See section 4.

Leaflet contents:

What Sufentanil Chiesi is and what it is used for
What you need to know before using Sufentanil Chiesi
How to use Sufentanil Chiesi
Possible side effects
How to store Sufentanil Chiesi
Contents of the pack and other information

1. What Sufentanil Chiesi is and what it is used for

Sufentanil Chiesi is a narcotic analgesic belonging to the opioid group, containing the active substance sufentanil. It is used during surgical procedures as an anaesthetic and analgesic agent, and administered epidurally for the treatment of postoperative pain and pain during childbirth.
Sufentanil Chiesi is intended for hospital use only.

2. Important information before using Sufentanil Chiesi

When not to use Sufentanil Chiesi:

If the patient has a known allergy (hypersensitivity) to sufentanil or any of the other components of Sufentanil Chiesi.
If the patient has a known allergy to other painkillers belonging to the morphine-like derivatives group.
If the patient has intolerance to any of the components of the medicine or other drugs similar to morphine.
Intravenously during childbirth or before clamping the umbilical cord during caesarean section.
If the patient should avoid drugs that depress the respiratory centre.
If the patient has acute hepatic porphyria.
If the patient is currently being treated or has been treated within the last 14 days with a medicine from the MAO inhibitor group (used in the treatment of depression).
When the medicine is administered epidurally:
- if the patient has severe haemorrhage or shock,
- if the patient has sepsis,
- if the patient has an infection at the site of administration,
- if the patient has coagulation disorders (e.g. thrombocytopenia, coagulopathy), or is taking other anticoagulant medicines,
- if the patient has medical conditions which, in the opinion of the physician, may contraindicate the use of epidural anaesthesia.

Warnings and precautions
Before starting treatment, discuss the following with your doctor or nurse:

if the patient has a lung disease or has difficulty breathing;
if the patient has hypothyroidism;
if the patient has heart disorders;
if the patient has hypotension or reduced circulating blood volume, e.g. due to bleeding;
if the patient has liver or kidney disorders;
if the patient has abnormally slowed intestinal peristalsis;
if the patient has gallbladder or pancreatic diseases;
if the patient develops headaches or has a history of head injury;
if the patient has been using opioids long-term.

DURING treatment with Sufentanil Chiesi, consult your doctor:

if the patient experiences pain or increased sensitivity to pain (hyperalgesia) and does not respond to a higher dose of the medicine prescribed by the doctor.

Before starting treatment with Sufentanil Chiesi, discuss the following with your doctor or pharmacist:

if the patient or any of their relatives have ever misused alcohol, prescription medicines, or narcotics ("addiction");
if the patient smokes tobacco;
if the patient has ever had mood problems (depression, anxiety or personality disorder) or has been treated by a psychiatrist for other mental illnesses.

This medicine contains sufentanil, which is an opioid medicine. Repeated use of opioid painkillers may result in reduced effectiveness of the medicine (the patient may become tolerant to it). This may also lead to dependence and misuse of the medicine, which may result in life-threatening overdose. If the patient has concerns about the possibility of becoming addicted to Sufentanil Chiesi, it is important to consult a doctor.
Sufentanil may significantly depress the patient's respiratory function. Therefore, medical personnel should closely monitor the patient, ensure immediate access to resuscitation equipment, and, if necessary, administer a drug that counteracts the effects of opioids (naloxone).
Sleep-related breathing disorders
Sufentanil Chiesi may cause sleep-related breathing disorders such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxaemia (low oxygen levels in the blood). Symptoms of these disorders may include pauses in breathing during sleep, waking up at night due to breathlessness, difficulty maintaining sleep, or excessive daytime sleepiness. If these symptoms are observed, contact a doctor. The doctor may consider reducing the dose.
Administration of sufentanil may cause slowing or arrest of the heartbeat and may cause increased muscle tone. To prevent these effects, the doctor will use appropriate preventive measures, and if they occur, will initiate appropriate treatment.
Rapidly successive muscle spasms may occur.
In elderly and debilitated patients, a reduced dose of Sufentanil Chiesi is recommended, as they may exhibit increased sensitivity to the effects of the medicine.
Data on intravenous administration of sufentanil in small children are limited; therefore, before administering this medicine to newborns and young children, the expected benefits should be carefully weighed against the possible risks. The safety and efficacy of epidurally administered sufentanil in children under 1 year of age have not yet been established.
Due to its morphine-like properties, sufentanil may cause dependence. Dependence will not develop if sufentanil is used only for surgery as an anaesthetic agent. However, it may occur after prolonged use in intensive care units for pain relief.

Sufentanil Chiesi and other medicines
Tell your doctor or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Some medicines may affect the way Sufentanil Chiesi works or increase the likelihood of adverse effects.
Inform your doctor or nurse if the patient is taking:

Medicines that may cause drowsiness, such as: barbiturates, benzodiazepines, neuroleptics, halogenated general anaesthetics, and other medicines acting on the central nervous system (e.g. alcohol), as they may intensify breathing difficulties caused by opioids, and benzodiazepines together with Sufentanil Chiesi may cause a drop in blood pressure.
Antidepressant medicines called monoamine oxidase inhibitors (MAOIs); these medicines must not be taken within 2 weeks before or concurrently with Sufentanil Chiesi.
Antidepressant medicines known as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Concurrent use of these medicines with Sufentanil Chiesi is not recommended.
Medicines used to treat epilepsy, neuropathic pain, or anxiety (gabapentin and pregabalin), as they may increase the risk of opioid overdose and respiratory depression, which may be life-threatening.
Ketoconazole and fluconazole (medicines used to prevent and treat skin and fungal infections), as well as ritonavir (a medicine used to treat HIV infection). These medicines may inhibit the breakdown of Sufentanil Chiesi.

Concurrent use of sufentanil and muscle relaxants: vecuronium or suxamethonium may cause a decrease in heart rate, especially if the heart rate was already slow (e.g. in patients receiving medicines used for heart diseases: calcium channel blockers or beta-blockers).
Concurrent use of high doses of sufentanil and nitrous oxide may lead to a drop in blood pressure and disturbances in heart rhythm, including a decrease in heart rate.

Sufentanil Chiesi with food, drink or alcohol
Avoid consuming alcohol, as it may intensify the adverse effects of the medicine.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine. The doctor will consider the possible risks and potential benefits of using Sufentanil Chiesi during pregnancy.
Intravenous administration of sufentanil during childbirth, as well as before clamping the umbilical cord during caesarean section, is contraindicated, as it may cause respiratory depression in the newborn. Epidurally administered sufentanil, as an analgesic, at doses up to 30 micrograms, has not shown any adverse effects on the condition of the labouring woman or the newborn.
Sufentanil passes into human milk. Consult your doctor before starting breastfeeding.

Driving and using machines
After administration of Sufentanil Chiesi, do not drive or operate machinery after leaving the hospital for the period specified by the doctor, as this medicine may cause dizziness and drowsiness.

Sodium content of Sufentanil Chiesi
Sufentanil Chiesi contains 3.54 mg of sodium (the main component of table salt) per millilitre of solution.
The medicine contains 35.4 mg of sodium in a 10 ml ampoule. This corresponds to 1.77% of the maximum recommended daily sodium intake in the diet for adults.
This should be taken into account when large volumes of the solution are administered to patients with reduced kidney function and to patients controlling sodium intake in their diet (e.g. more than 6.5 ml, corresponding to more than 1 mmol of sodium).
The medicine may be diluted in 0.9% NaCl solution. The sodium content from the diluent should be considered when calculating the total sodium content in the prepared diluted solution. For accurate information on the sodium content of the solution used to dilute the medicine, refer to the patient leaflet of the diluent used.

3. How to use Sufentanil Chiesi

This medicine is not intended for self-administration by the patient. The medicine will always be administered to the patient by a suitably qualified and authorized person.
This medicine is given as a slow intravenous injection or as a continuous intravenous infusion. It may also be administered via a catheter inserted into the spine (into the epidural space) by a physician familiar with the drug's actions and uses, or under such a physician's supervision.
The physician will decide the amount and frequency of administration based on the patient's health condition and response to treatment.
The physician may decide to interrupt the infusion in case of a mechanical obstruction (e.g. blockage of tubing, needle, or catheter).
It is very important always to use this medicine exactly as recommended. Use of Sufentanil Chiesi may lead to dependence. Do not administer it more frequently or for a longer duration than prescribed by the physician.
Administration of a higher than recommended dose of Sufentanil Chiesi
Sufentanil is used exclusively under strictly controlled conditions, which ensures its proper use. However, in case of overdose, excessive respiratory depression or complete respiratory arrest may occur.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Below are the adverse reactions associated with the use of sufentanil, including those reported during clinical trials and after the medicine was placed on the market.

Very common adverse reactions (occur in at least 1 in 10 people):

excessive sedation,
itching.

Common adverse reactions (occur in 1 to 10 in 100 people):

seizures in infants, dizziness, headache,
increased heart rate,
elevated or decreased blood pressure, pallor,
cyanosis in newborns,
vomiting, nausea,
skin discoloration,
muscle tremors,
problems with urination (urinary retention, urinary incontinence),
fever.

Uncommon adverse reactions (occur in 1 to 10 in 1,000 people):

rhinitis,
allergic reactions (hypersensitivity),
apathy, nervousness,
movement coordination disorders (ataxia), involuntary movements of limbs or the whole body (dyskinesia) in newborns, exaggerated response to external stimuli (hyperreflexia), increased muscle tone, reduced motor activity in newborns (hypokinesia), somnolence,
visual disturbances,
heart rhythm disorders (atrioventricular block, bradycardia, arrhythmia, ECG abnormalities),
bronchospasm, respiratory depression, voice disturbances, cough, hiccough, breathing difficulties,
allergic dermatitis, excessive sweating, rash, infantile rash, dry skin,
back pain, decreased muscle tone in infants, muscle stiffness,
decreased body temperature, increased body temperature, chills, reaction or pain at the injection site, pain.

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

anaphylactic shock, anaphylactic reaction, pseudoanaphylactic reaction,
coma, convulsions, involuntary muscle contractions,
miosis (pupillary constriction),
cardiac arrest,
shock,
respiratory arrest, apnoea, respiratory depression, pulmonary oedema, laryngospasm,
skin redness (flushing),
muscle spasms.

Adverse reactions very commonly occurring after epidural administration include:
itching, sedation, and nausea (all reported more frequently than adverse reactions occurring after intravenous administration). In addition, early respiratory depression may occur.
Sufentanil administered epidurally may very rarely cause delayed respiratory depression.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website: https://smz.ezdrowie.gov.pl.
Adverse reactions can also be reported to the responsible entity.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Sufentanil Chiesi

Keep the medicine out of the sight and reach of children.
Do not use Sufentanil Chiesi after the expiry date stated on the carton.
The expiry date refers to the last day of the specified month.
Do not store above 25°C. Protect from light.
Do not use Sufentanil Chiesi if a change in colour is observed, if the solution contains visible particles, or if the packaging is damaged or leaking.

6. Contents of the pack and other information

What Sufentanil Chiesi contains

The active substance is sufentanil. One millilitre contains 5 micrograms of sufentanil in the form of 7.5 micrograms of sufentanil citrate. One 10 ml ampoule contains 50 micrograms of sufentanil.
The other ingredients are: sodium chloride, citric acid, and water for injections.

What Sufentanil Chiesi looks like and contents of the pack
Sufentanil Chiesi is available in 10 ml ampoules made of colourless glass, with green-yellow-yellow
rings, containing a colourless solution free from visible particles. Each pack contains 5 ampoules of 10 ml solution.
Marketing Authorisation Holder and Manufacturer
For further information, please contact the local representative of the Marketing Authorisation Holder:
Fax: +48221004038
{Logo Chiesi}

Information intended exclusively for medical professionals:

Dosage and administration
Route of administration:
Sufentanil should be administered only by anaesthesiologists or other physicians familiar with the drug's actions and uses, or under their supervision. Epidural administration must be performed exclusively by a physician experienced in epidural techniques. Prior to administration, correct placement of the needle or catheter must be verified.

Dosage should be individualized for each patient depending on age, body weight, and clinical condition (clinical diagnosis, concomitant therapy, type of general anaesthesia, duration and type of surgical procedure). When administering supplemental doses, the effect of the initial dose should be taken into account.

To reduce the risk of bradycardia, it is recommended to administer a small dose of an anticholinergic agent intravenously immediately before induction of anaesthesia. Nausea and vomiting may be prevented by administering antiemetic agents.

Dosage:
INTRAVENOUS ADMINISTRATION
Adults and adolescents:

As an analgesic in balanced general anaesthesia maintained with multiple agents:
Initial dose: 0.5 to 2 micrograms/kg body weight – administered as a slow intravenous injection or continuous intravenous infusion over 2 to 10 minutes. Duration of action depends on the dose. A dose of 0.5 micrograms/kg body weight provides an effect lasting approximately 50 minutes.
Maintenance dose: 10 to 50 micrograms (approximately 0.15 to 0.7 micrograms/kg body weight) – administered intravenously when clinical signs of waning anaesthesia occur. During the recovery phase, the dose should be tapered very gradually.
As an anaesthetic agent for induction and maintenance of general anaesthesia:
Initial dose: 7 to 20 micrograms/kg body weight – administered as a slow intravenous injection or short-term intravenous infusion over 2 to 10 minutes.
Maintenance dose: 25 to 50 micrograms (approximately 0.36 to 0.7 micrograms/kg body weight) – administered intravenously when clinical signs of waning general anaesthesia occur. Maintenance doses of 25 to 50 micrograms of sufentanil are usually sufficient to maintain cardiovascular stability during general anaesthesia.
Note: Maintenance doses should be individually adjusted based on the patient's condition and the anticipated time remaining until the end of surgery.

Children:
The efficacy and safety of intravenous sufentanil in children under 2 years of age have been documented only in a limited number of cases.

For induction and maintenance of anaesthesia during cardiac and vascular surgery or general surgical procedures, with administration of 100% oxygen, the following doses are recommended:
- Neonates and children up to 3 years: 5 to 15 micrograms/kg body weight
- Children up to 12 years: 5 to 20 micrograms/kg body weight

Note: Maintenance doses should be individually adjusted based on the patient's condition and the anticipated time remaining until the end of surgery. Due to higher drug clearance in children, higher doses or more frequent dosing may be required.
Sufentanil administered as monotherapy via intravenous injection has not been sufficient to achieve adequate general anaesthesia, and additional anaesthetic agents were required.

EPIDURAL ADMINISTRATION
as an adjunct analgesic in epidural anaesthesia with bupivacaine:

For postoperative pain relief following general surgery, thoracic surgery, orthopaedic procedures, and caesarean section: An intraoperative loading dose may be administered epidurally: 10 to 15 mL of 0.25% bupivacaine solution with 1 microgram of sufentanil/mL. In the postoperative period, 0.175% bupivacaine solution with 1 microgram of sufentanil/mL should be administered as a continuous epidural infusion for analgesia, initially at a rate of 5 mL/h, and subsequently adjusted individually between 4 and 14 mL/h to maintain analgesia. On-demand bolus injections of 2 mL may be administered. A 20-minute lockout interval is recommended.
For pain relief during labour and vaginal delivery: The simultaneous addition of 10 micrograms of sufentanil to bupivacaine (0.125% - 0.25% solution) enhances and prolongs analgesic effect. An optimal injection volume of 10 mL has been demonstrated. To ensure proper mixing, sufentanil should be drawn first, followed by bupivacaine in the required proportions. The final volume of 10 mL may be achieved by diluting the mixture with 0.9% sodium chloride solution. If necessary, two additional injections of the combined solution may be administered. The total dose of sufentanil should not exceed 30 micrograms.
Note: The efficacy and safety of epidurally administered sufentanil in children have been documented only in a limited number of cases.

Special dosage precautions
Elderly or debilitated patients generally require lower doses.
In elderly patients, the half-life of sufentanil is not prolonged, but there may be an increased risk of cardiovascular adverse effects.

The selected total dose should be administered cautiously in patients with any of the following conditions: uncorrected hypothyroidism, lung disease (particularly with reduced vital capacity), obesity, or alcoholism. In such cases, prolonged postoperative observation is indicated.

In cases of renal or hepatic insufficiency, reduced elimination of sufentanil should be considered, and the dose should be reduced accordingly.

Chronic pain patients receiving opioids or those with a history of opioid dependence may require higher doses.

The duration of sufentanil administration depends on the length of the surgical procedure.
The injection solution may be administered once or repeatedly. Avoid administering sufentanil as a single, rapidly injected bolus dose. If a sedative is co-administered with sufentanil, it should be given as a separate injection.

The duration of epidural administration depends on the patient's clinical course. There are insufficient clinical data on the use of the drug for more than five postoperative days.

Special warnings and precautions for use
Sufentanil must be used under conditions that include endotracheal intubation and mechanical ventilation.

As with all potent opioids:
Respiratory depression is dose-dependent and can be reversed by specific opioid antagonists (naloxone). Because respiratory depression may persist longer than the antagonist's effect, repeated doses of naloxone may be necessary. The dose and interval between antagonist doses depend on the previously administered dose of sufentanil and the time elapsed since administration.

Profound general anaesthesia may be associated with significant respiratory depression, which may persist into the postoperative period. When sufentanil is administered intravenously, respiratory depression may recur. Therefore, appropriate monitoring and care are essential. Resuscitation equipment and opioid antagonists must be readily available. Hyperventilation during anaesthesia may alter the patient's response to CO₂, affecting postoperative respiratory function.

Sleep-related breathing disorders
Opioids may cause sleep-related breathing disorders, including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent manner. In patients with CSA, consider reducing the total opioid dose.

Increased muscle tone, including of the chest wall muscles, may occur, but can be avoided by the following precautions: slow intravenous injection (often sufficient for smaller doses), premedication with benzodiazepines or muscle relaxants.

Opioid-induced hyperalgesia
As with other opioids, if pain control is inadequate despite increasing doses of sufentanil, opioid-induced hyperalgesia should be considered. It may be necessary to reduce the dose of sufentanil, discontinue treatment, or reassess the treatment regimen. Non-epileptic myoclonic movements may occur.

Insufficient anticholinergic premedication or the use of non-anticholinergic muscle relaxants in combination with sufentanil may lead to bradycardia or even cardiac arrest. Bradycardia can be treated with atropine. Tachycardia induced by pancuronium may mask bradycardia.

Opioids may cause hypotension, particularly in hypovolemic patients. Appropriate measures should be taken to maintain stable arterial blood pressure.

In patients with impaired intracranial pressure compensation mechanisms, avoid rapid intravenous injection of opioids. Transient decreases in mean arterial pressure have been associated with transient reductions in cerebral perfusion pressure in such patients.

Patients with a history of chronic opioid use or opioid dependence may require higher doses.

Dosage reduction is recommended in elderly or debilitated patients.

Increasing opioid doses to determine optimal dosing should be done cautiously in patients with uncorrected hypothyroidism, lung disease (especially reduced pulmonary reserve), alcoholism, or impaired liver or kidney function. These patients should be observed for a longer period postoperatively.

Gastrointestinal effects
Sufentanil, as a μ-opioid receptor agonist, may slow gastrointestinal motility. Therefore, caution is advised when administering sufentanil to patients at risk of intestinal obstruction.

Sufentanil, as a μ-opioid receptor agonist, may cause spasm of the sphincter of Oddi. Therefore, caution is advised in patients with biliary tract disorders, including acute pancreatitis.

When administering the drug epidurally, caution is required in cases of respiratory depression or dysfunction and in cases of fetal risk. The patient should be closely monitored for at least 1 hour after each dose due to the risk of early respiratory depression. Because of possible changes in fetal heart rate during epidural administration, fetal heart rate should be monitored and any disturbances treated as necessary.

As with other opioids, neonates may be particularly sensitive to the respiratory depressant effects of sufentanil. Data on intravenous sufentanil in young children are limited; therefore, the benefit-risk ratio should be carefully evaluated before using this drug in neonates and young children. Due to high variability in pharmacokinetic parameters in neonates, there is a risk of administering too high or too low a dose of sufentanil in the neonatal period. See also "Dosage and administration".

The safety and efficacy of epidurally administered sufentanil in children under 1 year of age have not been established (see "Dosage and administration").

Tolerance and opioid use disorder (abuse and dependence)
Due to its morphine-like properties, sufentanil may lead to dependence. Dependence will not develop if sufentanil is used only for surgery as an anaesthetic agent. However, dependence may occur after prolonged use in intensive care units, where increasingly higher doses of sufentanil are administered to achieve adequate analgesia. Withdrawal symptoms may appear after treatment lasting more than one week, and are likely after two weeks of treatment.

Therefore, the following recommendations are given:

Doses should not exceed what is necessary.
Dose reduction should be gradual over several days.
Clonidine may be used if necessary to manage withdrawal symptoms. Repeated opioid administration may lead to tolerance, physical and psychological dependence, and opioid use disorder (OUD). Abuse or intentional misuse of Sufentanil Chiesi may lead to overdose or death. The risk of OUD is increased in patients with a personal or family history (parents or siblings) of substance use disorders (including alcohol use disorders), active smokers, or patients with other psychiatric disorders (e.g., major depression, anxiety disorders, personality disorders). Patients should be monitored for drug-seeking behaviors (e.g., early requests for repeat prescriptions). This includes verifying concomitant use of opioids and psychoactive drugs (e.g., benzodiazepines). In patients with objective and subjective symptoms of OUD, consultation with an addiction specialist should be considered.

Discontinuation and withdrawal syndrome
Repeated administration over a prolonged period at short intervals may lead to withdrawal syndrome upon discontinuation. Rare cases of sufentanil withdrawal symptoms, including tachycardia, hypertension, and agitation, have been reported after abrupt discontinuation, particularly after prolonged administration exceeding three days. In reported cases, resumption of the drug and gradual tapering of the infusion dose were beneficial. Sufentanil Chiesi is not recommended for use in mechanically ventilated intensive care patients for treatment periods longer than three days.

Sufentanil Chiesi contains 0.15 mmol (3.54 mg) of sodium per mL of solution.
The 10 mL ampoule contains 35.4 mg of sodium, equivalent to 1.77% of the WHO-recommended maximum daily sodium intake of 2 g for adults. This should be considered when administering large volumes of solution (e.g., more than 6.5 mL, corresponding to more than 1 mmol of sodium) to patients with impaired renal function or those on sodium-restricted diets.

The drug may be diluted with 0.9% NaCl solution. The sodium content from the diluent should be considered when calculating the total sodium content of the prepared dilution. For accurate information on sodium content in the diluent solution, refer to the product characteristics of the diluent used.

Interactions with other medicinal products and other forms of interaction
Drugs such as barbiturates, etomidate, benzodiazepine derivatives, neuroleptics, opioids, halogenated anaesthetics, and other non-selective central nervous system depressants (e.g., alcohol) may potentiate respiratory depression caused by narcotic agents. When any of these drugs are used concomitantly with sufentanil, the doses of one or both drugs should be reduced.

Concomitant administration of sufentanil and benzodiazepines may cause a drop in arterial blood pressure.
If patients have received such drugs, the dose of sufentanil should be reduced. Similarly, after administration of sufentanil, the dose of other central nervous system depressants should be reduced.

Concomitant administration of sufentanil and vecuronium or succinylcholine may cause bradycardia, especially if heart rate is already reduced (e.g., in patients receiving calcium channel blockers or beta-blockers). Dose reduction of one or both drugs is recommended.

Concomitant use of high-dose sufentanil infusion and nitrous oxide may lead to decreased arterial blood pressure, reduced heart rate, and reduced cardiac output.

Sufentanil is primarily metabolized by the cytochrome P450 3A4 isoenzyme. However, in vivo, erythromycin (a known inhibitor of cytochrome P450 3A4) did not inhibit its action. Despite the lack of clinical data, in vitro studies suggest that other strong inhibitors of cytochrome P450 3A4 (e.g., ketoconazole, itraconazole, ritonavir) may slow sufentanil metabolism, potentially increasing the risk of prolonged or delayed respiratory depression. Concomitant use of such drugs requires special care and close monitoring. A reduction in sufentanil dose may be necessary.

Concomitant administration of sufentanil with serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs), may increase the risk of serotonin syndrome, a potentially life-threatening condition. MAOIs must not be administered within 2 weeks before or during treatment with Sufentanil Chiesi.

Gabapentinoids
Concomitant use of opioids and gabapentinoids (gabapentin and pregabalin) increases the risk of opioid overdose, respiratory depression, and death.

Effects on fertility, pregnancy, and lactation
Pregnancy
The safety of intravenous sufentanil in pregnant women has not been established, although animal studies have not shown teratogenic effects. As with any drug, the risk should be weighed against the benefit for the patient. Sufentanil crosses the placenta. Intravenous administration during labour and before clamping the umbilical cord during caesarean section is contraindicated (see When not to use Sufentanil Chiesi).

Controlled clinical studies during labour have shown that epidural administration of sufentanil up to 30 micrograms as an adjunct to bupivacaine has no harmful effects on mother or neonate. However, intravenous administration is contraindicated during labour. After epidural administration of a total dose not exceeding 30 micrograms, the mean concentration in umbilical cord plasma was 0.016 ng/mL. An antidote should always be readily available for the neonate.

Breastfeeding
Sufentanil passes into human milk. Caution should be exercised when administering sufentanil to a breastfeeding woman.

Overdose
Subjective and objective symptoms
Symptoms of sufentanil overdose are exaggerated effects of its pharmacological action. Depending on individual sensitivity, the clinical picture is primarily determined by the degree of respiratory depression, ranging from slowed respiration to complete apnoea.

Pharmacological action of the drug may cause respiratory depression even after therapeutic doses (iv.: above 0.3 micrograms/kg body weight). Sufentanil is used exclusively under strictly controlled conditions, ensuring proper management of these symptoms.

Treatment
In case of reduced respiratory rate or apnoea, oxygen should be administered and assisted or controlled ventilation should be initiated as indicated. If appropriate, a specific opioid antagonist (e.g., naloxone) should be administered to reverse respiratory depression. This does not exclude the need for immediate supportive measures. Because respiratory depression may outlast the antagonist effect, repeated doses of the antagonist may be necessary. In cases of concomitant respiratory depression and muscle rigidity, intravenous administration of a depolarizing muscle relaxant may be required to facilitate assisted or controlled ventilation. The patient should be carefully monitored, with maintenance of normal body temperature and fluid balance. In cases of significant or persistent hypotension, hypovolemia should be considered and corrected with appropriate parenteral fluid administration.

Pharmaceutical incompatibilities
Sufentanil citrate is physically incompatible with diazepam, lorazepam, sodium phenobarbital, phenytoin, and thiopental.

Shelf life
Shelf life before first opening:
3 years.

Shelf life after dilution:
Diluted solutions have been shown to maintain chemical and physical stability for 72 hours at 25°C (see Special precautions for disposal and preparation for administration).

From a microbiological standpoint, diluted solutions should be used immediately.
If not used immediately, the user is responsible for storage conditions and duration, which should generally not exceed 24 hours at 2–8°C, unless dilution was performed under controlled, validated aseptic conditions.

Special precautions for disposal and preparation for administration
For infusions, Sufentanil Chiesi may be diluted with Ringer's solution, 0.9% sodium chloride solution, or 5% glucose solution. The diluted solution should be used within 72 hours of preparation.

For epidural administration, the drug may be mixed with 0.9% sodium chloride solution and/or bupivacaine solution.

Before administration, the contents of the ampoules should be carefully inspected for particulate matter, container damage, or any visible signs of deterioration.
If such defects are observed, the solution should be discarded.

Sufentanil chiesi