Sufentanil Hiesi

Leaflet accompanying the packaging: information for the user

Sufentanil Chiesi, 5 micrograms/ml, solution for injection

Read the leaflet carefully before using the medicine, as it contains

important information for the patient.

• The leaflet should be kept in case it needs to be read again.
• In case of any doubts, the doctor, pharmacist, or nurse should be consulted.
• This medicine has been prescribed specifically for one person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is Sufentanil Chiesi and what is it used for
• 2. Important information before using Sufentanil Chiesi
• 3. How to use Sufentanil Chiesi
• 4. Possible side effects
• 5. How to store Sufentanil Chiesi
• 6. Contents of the packaging and other information

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

Sufentanil Chiesi is a narcotic analgesic from the opioid group, containing sufentanil as the active ingredient. It is used in surgical procedures as an anesthetic and analgesic, and epidurally for the treatment of postoperative pain and during labor. Sufentanil Chiesi is intended for use only in a hospital setting.

2. Important information before using Sufentanil Chiesi

When not to use Sufentanil Chiesi:

• If the patient has been found to be allergic (hypersensitive) to sufentanil or any of the other ingredients of Sufentanil Chiesi.
• If the patient has been found to be allergic to other painkillers from the group of morphine derivatives.
• If the patient has a known intolerance to any of the ingredients of the medicine or other medicines similar to morphine.
• Intravenously during labor or before clamping the umbilical cord during a cesarean section.
• If the patient should avoid the use of drugs that act depressingly on the respiratory center.
• 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 drug from the group of MAO inhibitors (used in the treatment of depression).
• In the case where the medicine is administered epidurally:
• if the patient has severe bleeding or shock,
• if the patient has sepsis,
• if the patient has an infection at the injection site,
• if the patient has blood coagulation problems (e.g., thrombocytopenia, coagulopathy), or is taking other anticoagulant drugs,
• if the patient has medical conditions that, in the doctor's opinion, may exclude the use of epidural anesthesia techniques.

Warnings and precautions

Before starting treatment, the following should be discussed with the doctor or nurse:

• if the patient has lung disease or experiences breathing difficulties;
• if the patient has hypothyroidism;
• if the patient has heart rhythm disorders;
• if the patient has low blood pressure or too little blood circulating, e.g., due to bleeding;
• if the patient has liver or kidney problems;
• if the patient has abnormal intestinal peristalsis;
• if the patient has gallbladder or pancreas diseases;
• if the patient experiences headaches or has had a head injury;
• if the patient has been taking opioids for a long time.

DURING the use of Sufentanil Chiesi, the doctor should be consulted:

• 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 the use of Sufentanil Chiesi, the following should be discussed with the doctor or pharmacist:

• if the patient or any of their relatives have ever abused alcohol, prescription drugs, or narcotics ("addiction");
• if the patient smokes;
• 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 can lead to the medicine becoming less effective (the patient becomes accustomed to it). This can also lead to addiction and abuse of the medicine, which can result in life-threatening overdose. If the patient has concerns about the possibility of becoming addicted to Sufentanil Chiesi, it is essential to consult a doctor. Sufentanil can significantly depress the patient's respiratory function. Therefore, medical staff should closely monitor the patient and ensure easy access to life-support equipment, and possibly administer a medicine with an opposite effect to opioids (naloxone). Respiratory disorders associated with sleep Sufentanil Chiesi may cause respiratory disorders associated with sleep, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms of these disorders may include pauses in breathing during sleep, nighttime awakenings due to shortness of breath, difficulty maintaining sleep, or excessive daytime sleepiness. If these symptoms are observed, the doctor should be contacted. The doctor may consider reducing the dose. Administration of sufentanil may cause cardiac arrest or increased muscle tension. To prevent these symptoms, the doctor will take appropriate measures, and if they occur, will provide appropriate treatment. Rapidly recurring muscle spasms may occur. In elderly and debilitated patients, it is recommended to reduce the dose of Sufentanil Chiesi, as they may experience increased sensitivity to the medicine. Data on the intravenous administration of sufentanil in small children are limited; therefore, before using this medicine in newborns and small children, the ratio of expected benefits to potential risks should be carefully considered. The safety and efficacy of sufentanil administered epidurally in children under one year of age have not been established.

Sufentanil Chiesi and other medicines

The doctor or nurse should be informed 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 risk of side effects. The doctor or nurse should be informed about the use of:

• Medicines that may cause drowsiness, such as barbiturates, benzodiazepines, neuroleptics, halogenated general anesthetics, and other medicines that act on the central nervous system (e.g., alcohol), as they may enhance the respiratory depression caused by narcotics, and benzodiazepines may cause a drop in blood pressure when used with Sufentanil Chiesi.
• Antidepressant medicines called monoamine oxidase inhibitors (MAOIs); these medicines should not be taken within 2 weeks before or at the same time as Sufentanil Chiesi.
• Antidepressant medicines known as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). It is not recommended to use these medicines with Sufentanil Chiesi.
• Medicines used to treat epilepsy, neuralgia, or anxiety (gabapentin and pregabalin), as they may increase the risk of opioid overdose and respiratory depression, which can 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.

Concomitant 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 taking heart medications: calcium channel blockers or beta-adrenergic blockers). Concomitant use of high doses of sufentanil and nitrous oxide may lead to a drop in blood pressure and cardiac disorders, including a decrease in heart rate.

Sufentanil Chiesi with food, drink, or alcohol

Alcohol consumption should be avoided, as it may enhance the side effects of the medicine.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before using this medicine. The doctor will weigh the potential risks and benefits of using Sufentanil Chiesi during pregnancy. Intravenous administration of sufentanil during labor, as well as before clamping the umbilical cord during a cesarean section, is contraindicated, as it may cause respiratory depression in the newborn. Sufentanil administered epidurally, as an analgesic, in doses up to 30 micrograms, does not have an adverse effect on the mother or the newborn. Sufentanil passes into breast milk. Before starting breastfeeding, the patient should consult their doctor.

Driving and using machines

After administration of Sufentanil Chiesi, the patient should not drive vehicles or operate machines after leaving the hospital for a period determined by the doctor, as the medicine may cause dizziness and drowsiness.

Sufentanil Chiesi contains sodium

Sufentanil Chiesi contains 3.54 mg of sodium (the main component of table salt) per milliliter 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 intake of sodium in the diet for adults. This should be taken into account when administering large volumes of the solution (e.g., more than 6.5 ml, which corresponds to more than 1 mmol of sodium) to patients with reduced kidney function and to patients controlling their sodium intake. The medicine can be diluted in a 0.9% NaCl solution. The sodium content from the diluent should be considered when calculating the total sodium content in the prepared dilution of the medicine. To obtain accurate information about the sodium content in the solution used for dilution, the patient information leaflet of the diluent should be consulted.

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 qualified and authorized person. The medicine is administered by slow intravenous injection or continuous intravenous infusion. It can also be administered through a catheter inserted into the spine (into the epidural space) by a doctor who is familiar with the actions and uses of the medicine, or under their supervision. The doctor will decide on the amount and frequency of administration of the medicine to the patient, depending on the patient's health condition and response to treatment. The doctor may decide to interrupt the infusion in case of a mechanical obstruction (e.g., blockage of the tube, needle, or catheter). It is essential to always use this medicine according to the recommendations. Using Sufentanil Chiesi may lead to addiction. The medicine should not be administered more frequently or for a longer period than recommended by the doctor.

Using a higher dose of Sufentanil Chiesi than recommended

Sufentanil is used exclusively in strictly controlled conditions, ensuring its proper use. However, in case of overdose, excessive slowing or complete cessation of respiratory function may occur.

4. Possible side effects

Like all medicines, Sufentanil Chiesi can cause side effects, although not everybody gets them. The following side effects are related to the use of sufentanil, including side effects reported during clinical trials and after the medicine was placed on the market. Very common side effects (occurring in at least 1 in 10 people):

• excessive sedation,
• itching.

Common side effects (occurring in 1 to 10 in 100 people):

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

Uncommon side effects (occurring in 1 to 10 in 1,000 people):

• rhinitis,
• allergic reactions (hypersensitivity),
• apathy, nervousness,
• coordination disorders (ataxia), involuntary movements of limbs or the whole body (dyskinesia) in newborns, excessive reaction to external stimuli (hyperreflexia), increased muscle tone, immobility in newborns (hypokinesia), drowsiness,
• vision disorders,
• heart rhythm disorders (atrioventricular block, bradycardia, arrhythmia, ECG abnormalities),
• bronchospasm, respiratory depression, voice disorders, cough, hiccups, breathing disorders,
• allergic skin inflammation, 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 the available data):

• anaphylactic shock, anaphylactic reaction, pseudoanaphylactic reaction,
• coma, seizures, involuntary muscle spasms,
• pupil constriction,
• cardiac arrest,
• shock,
• respiratory arrest, apnea, respiratory depression, pulmonary edema, laryngospasm,
• skin redness (flushing),
• muscle spasms.

Among the very common side effects after epidural administration are itching, sedation, and nausea (all reported more frequently than side effects after intravenous administration). Additionally, early respiratory depression may occur. Sufentanil administered epidurally may very rarely cause late respiratory depression.

Reporting side effects

If any side effects occur, including any side effects not listed in the leaflet, the doctor, pharmacist, or nurse should be informed. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of 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. Side effects can also be reported to the marketing authorization holder. Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Sufentanil Chiesi

The medicine should be stored out of sight and reach of children. Sufentanil Chiesi should not be used after the expiry date stated on the packaging. The expiry date refers to the last day of the given month. The medicine should not be stored at temperatures above 25°C. It should be protected from light. Sufentanil Chiesi should not be used if a change in color is observed, if the solution contains visible particles, or if the packaging is damaged.

6. Contents of the packaging and other information

What Sufentanil Chiesi contains

• The active substance of the medicine is sufentanil. One milliliter 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 what the packaging contains

Sufentanil Chiesi is available in ampoules made of colorless glass, with green-yellow-yellow rings, containing a colorless solution without visible particles. One packaging contains 5 ampoules of 10 ml of solution.

Marketing authorization holder and manufacturer

For more detailed information, please contact the local representative of the marketing authorization holder:

Fax: +48221004038

Date of the last update of the leaflet:

{Logo Chiesi}
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Information intended only for healthcare professionals:

Dosage and administration

Method of administration: Sufentanil should be administered only by anesthesiologists or other doctors who are familiar with the actions and uses of the medicine, or under their supervision. Epidural administration must be performed only by a doctor with experience in the technique of epidural administration of the medicine. Before administration, the correct placement of the needle or catheter should be checked. The dose should be determined individually for each patient, depending on their age, weight, and clinical condition (clinical diagnosis, concomitant treatment, type of general anesthesia, duration and type of surgical procedure). During the administration of supplementary 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 one of the anticholinergic drugs immediately before inducing general anesthesia. Nausea and vomiting can be prevented by administering antiemetic drugs. Dosage: INTRAVENOUS ADMINISTRATION Adults and adolescents: As an analgesic in general anesthesia induced and maintained with several anesthetics: Initial dose: 0.5 to 2 micrograms/kg of body weight - administered in slow intravenous injection or continuous intravenous infusion over 2 to 10 minutes. The duration of action of the medicine depends on the dose. A dose of 0.5 micrograms/kg of body weight acts for approximately 50 minutes. Maintenance dose: 10 to 50 micrograms (approximately 0.15 to 0.7 micrograms/kg of body weight) - administered intravenously when clinical signs of anesthesia wear-off appear. The infusion phase - in this phase, the dose should be reduced very slowly. As an anesthetic for induction and maintenance of general anesthesia: Initial dose: 7 to 20 micrograms/kg of body weight - administered in 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 of body weight) - administered intravenously when clinical signs of anesthesia wear-off appear. Maintenance doses of 25 to 50 micrograms of sufentanil are usually sufficient to maintain cardiovascular stability during general anesthesia. Note: Maintenance doses should be selected individually, depending on the patient's condition and the expected time remaining until the end of the operation. Children: The efficacy and safety of sufentanil administered intravenously in children under 2 years of age have been documented only in a limited number of cases.

• For induction and maintenance of general anesthesia during cardiac surgery or general surgery, in combination with 100% oxygen, the following doses are recommended:
• newborns and children up to 3 years: 5 to 15 micrograms/kg of body weight,
• children up to 12 years: 5 to 20 micrograms/kg of body weight.

Note: Maintenance doses should be selected individually, depending on the patient's condition and the expected time remaining until the end of the operation. Due to the higher clearance of the medicine in children, they may require higher doses or more frequent administration. Sufentanil administered to patients as monotherapy in injection did not provide sufficient general anesthesia, and patients required additional anesthetics. EPIDURAL ADMINISTRATION as a supplementary analgesic in epidural anesthesia with bupivacaine:

• In the treatment of postoperative pain after general surgery, thoracic surgery, orthopedic surgery, and cesarean section: Intraoperatively, an epidural loading dose can be administered: 10 to 15 ml of 0.25% bupivacaine solution together with 1 microgram of sufentanil per milliliter. In the postoperative period, 0.175% bupivacaine solution can be administered in continuous epidural infusion together with 1 microgram of sufentanil per milliliter as a supplementary infusion to achieve an analgesic effect, with an initial rate of 5 ml/h, and to maintain the effect - with an individually adjusted rate of 4 to 14 ml/h. On demand, additional bolus injections of 2 ml can be administered. It is recommended to maintain a 20-minute lockout interval.

Special precautions for dosage Elderly or debilitated patients usually require smaller doses. The half-life of sufentanil is not prolonged in elderly patients, but there may be an increased risk of cardiovascular disorders. The selected total dose should be administered cautiously in the presence of any of the following diseases: uncontrolled hypothyroidism, lung disease, especially with reduced vital capacity, obesity, alcoholism. In these cases, prolonged postoperative monitoring of the patient is recommended. In case of renal or hepatic impairment, the possibility of reduced sufentanil elimination should be considered, and the dose should be reduced accordingly. Patients who have been taking opioids for a long time or have a history of opioid addiction may require higher doses. The duration of sufentanil use depends on the duration of the operation. The solution for injection can be administered once or repeatedly. It is recommended to avoid administering sufentanil in a single rapid injection (bolus). If sufentanil is administered together with a sedative, it should be administered in a separate injection. The duration of epidural administration depends on the development of the patient's clinical condition. There are insufficient clinical data on the use of the medicine for more than five postoperative days.

Special warnings and precautions for use

The use of sufentanil is subject to the following conditions: endotracheal intubation and mechanical ventilation of the patient. Similarly, as with all strong opioids: Respiratory depression is dose-dependent and can be reversed by the administration of specific opioid antagonists (naloxone). Since respiratory depression may persist longer than the effect of the antagonist, it may be necessary to repeat the dose. The dose and interval between doses of the antagonist depend on the previously administered dose of sufentanil and the time of its administration. Deep general anesthesia may be accompanied by significant respiratory depression. It may persist in the postoperative period, and if sufentanil was administered intravenously, it may recur. Therefore, patients should be closely monitored. It is essential to ensure easy access to life-support equipment and the possibility of administering opioid antagonists. Hyperventilation during anesthesia may change the patient's response to CO2, affecting respiratory function in the postoperative period. Respiratory disorders associated with sleep Opioids may cause respiratory disorders associated with sleep, including central sleep apnea (CSA) and sleep-related hypoxemia. The use of opioids increases the risk of CSA in a dose-dependent manner. In patients with CSA, it is recommended to consider reducing the total dose of opioids. It is possible to experience increased muscle tension, including chest muscles, but this can be avoided by taking the following precautions: slow intravenous injection (for smaller doses, this is usually a sufficient precaution), prior administration of benzodiazepines or muscle relaxants. Opioid-induced hyperalgesia Similarly to other opioids, in case of insufficient pain control in response to an increased dose of sufentanil, the possibility of opioid-induced hyperalgesia should be considered. It may be necessary to reduce the dose of sufentanil, discontinue treatment, or verify treatment. Myoclonic movements may occur. Administration of too small a dose of an anticholinergic drug to the patient, or use of sufentanil in combination with muscle relaxants that do not have a vagolytic effect, may cause bradycardia, and even cardiac arrest. Bradycardia can be treated with atropine. Tachycardia caused by the administration of pancuronium may predominate over bradycardia. Opioids may cause hypotension, especially in patients with hypovolemia. Appropriate measures should be taken to maintain blood pressure at a stable level. In patients with impaired intracranial compensatory mechanisms, opioids should not be administered in rapid intravenous injection. In such patients, it has been observed that transient hypotension is accompanied by a short-term decrease in cerebral perfusion pressure. In patients who have been taking opioids for a long time or have a history of opioid addiction, higher doses may be necessary. It is recommended to reduce the dose in elderly or debilitated patients. When increasing the dose of opioids to determine the optimal dose, it should be done cautiously in patients with: uncontrolled hypothyroidism, lung disease, reduced vital capacity, alcoholism, impaired liver or kidney function. Such patients should be monitored for a longer period after the operation. Effect on the gastrointestinal tract Sufentanil, as a μ-opioid receptor agonist, may slow down gastrointestinal motility. Therefore, caution should be exercised when using sufentanil in patients at risk of intestinal obstruction. Sufentanil, as a μ-opioid receptor agonist, may cause spasm of the sphincter of Oddi. Therefore, caution should be exercised when using sufentanil in patients with biliary tract disease, including acute pancreatitis. When administering the medicine epidurally, caution should be exercised in case of respiratory depression or disorders, as well as in case of a risk to the fetus. The patient should be closely monitored for at least one hour after each dose due to the possibility of early respiratory depression. Considering the possible changes in fetal heart rate during epidural administration, fetal heart rate should be monitored, and any disorders should be treated. Similarly to other opioids, it can be expected that the newborn will be particularly sensitive to the respiratory depressant effect of sufentanil. Data on the intravenous administration of sufentanil in small children are limited; therefore, before using this medicine in newborns and small children, the ratio of expected benefits to potential risks should be carefully considered. Due to the significant variability of pharmacokinetic parameters in newborns, 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 sufentanil administered epidurally in children under one year of age have not been established (see "Dosage and administration"). Tolerance and substance use disorder (abuse and dependence) Due to its morphine-like properties, sufentanil may cause dependence. Dependence will not develop if sufentanil is used only for operations as an anesthetic. Dependence may occur after long-term use in intensive care units, where increasingly higher doses of sufentanil are administered to achieve a satisfactory analgesic effect. After treatment lasting more than a week, withdrawal symptoms may already occur, and after two weeks of treatment, this is likely. Therefore, the following recommendations are given:

• 1. Doses should not be higher than necessary.
• 2. Dose reduction should be gradual, over several days.
• 3. If necessary, to combat withdrawal symptoms, clonidine can be used. After repeated administration of opioids, tolerance, physical dependence, and opioid use disorder (OUD) may develop. Abuse or intentional misuse of Sufentanil Chiesi may lead to overdose or death. The risk of developing OUD is increased in patients with a history of substance use disorders (including alcohol use disorders), active smokers, or patients with other mental health disorders (e.g., major depression, anxiety disorders, and personality disorders). Patients will require monitoring for drug-seeking behavior (e.g., requesting prescriptions too early). This includes verifying concomitantly used opioids and psychoactive drugs (such as benzodiazepines). In patients with objective and subjective symptoms of OUD, consultation with an addiction therapy specialist should be considered.

Discontinuation of treatment and withdrawal syndrome Repeated administration of the medicine at short intervals over a long period may lead to the development of a withdrawal syndrome after discontinuation of treatment. In rare cases, after sudden discontinuation of treatment, especially after prolonged administration for more than three days, cases of sufentanil withdrawal syndrome have been reported, including tachycardia, hypertension, and agitation. In the reported cases, it was beneficial to resume administration of the medicine and gradually reduce the dose administered in the infusion. It is not recommended to use Sufentanil Chiesi in mechanically ventilated patients in intensive care units for a treatment period longer than three days. Sufentanil Chiesi contains 0.15 mmol (3.54 mg) of sodium per milliliter of solution. The medicine contains 35.4 mg of sodium in a 10 ml ampoule, which corresponds to 1.77% of the maximum recommended daily intake of sodium in the diet for adults. This should be taken into account when administering large volumes of the solution (e.g., more than 6.5 ml, which corresponds to more than 1 mmol of sodium) to patients with reduced kidney function and to patients controlling their sodium intake. The medicine can be diluted in a 0.9% NaCl solution. The sodium content from the diluent should be considered when calculating the total sodium content in the prepared dilution of the medicine. To obtain accurate information about the sodium content in the solution used for dilution, the patient information leaflet of the diluent should be consulted.

Interactions with other medicines and other types of interactions

Medicines such as barbiturates, etomidate, benzodiazepine derivatives, neuroleptics, opioids, halogenated anesthetics, and other substances that non-selectively depress the central nervous system (e.g., alcohol) may enhance the respiratory depression caused by narcotics. If any of these medicines are used concomitantly with sufentanil, the dose of one or both medicines should be reduced. Concomitant administration of sufentanil and benzodiazepines may cause a drop in blood pressure. If patients have taken such medicines, it will be necessary to reduce the dose of sufentanil. Similarly, after administration of sufentanil, the dose of other central nervous system depressants should be reduced. Concomitant use of sufentanil and vecuronium or suxamethonium may cause bradycardia, especially if the heart rate was already slow (e.g., in patients taking heart medications: calcium channel blockers or beta-adrenergic blockers). It is recommended to reduce the dose of one or both medicines. Concomitant use of high doses of sufentanil in injection solution and nitrous oxide may lead to a drop in blood pressure, cardiac disorders, including a decrease in heart rate. Sufentanil is metabolized mainly by the cytochrome P450 3A4 isoenzyme; however, in vivo, no inhibition of its action by erythromycin (a known inhibitor of cytochrome P450 3A4) has been observed. Despite the lack of clinical data, in vitro data suggest that the metabolism of sufentanil may be slowed down by other potent inhibitors of cytochrome P450 3A4 (e.g., ketoconazole, itraconazole, ritonavir). This could increase the risk of prolonged or delayed respiratory depression. Concomitant use of such medicines requires the patient to be under special care and close monitoring. In particular, it may be necessary to reduce the dose of sufentanil. Concomitant administration of sufentanil with a serotonergic medicine, such as a selective serotonin reuptake inhibitor (SSRI), a serotonin-norepinephrine reuptake inhibitor (SNRI), or a monoamine oxidase inhibitor (MAOI), may increase the risk of serotonin syndrome, a potentially life-threatening condition. Monoamine oxidase inhibitors should not be taken within 2 weeks before or at the same time as 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 sufentanil administered intravenously in pregnant women has not been established, although animal studies have not shown the development of severe birth defects. As with other medicines, the risk should be weighed against the benefits for the patient. Sufentanil crosses the placental barrier. Intravenous administration during labor, as well as before clamping the umbilical cord during a cesarean section, is contraindicated (see "When not to use Sufentanil Chiesi"). Controlled clinical trials conducted during labor have shown that sufentanil administered epidurally in doses up to 30 micrograms, as a supplementary analgesic to bupivacaine, did not have an adverse effect on either the mother or the newborn, while intravenous administration is contraindicated during labor. After epidural administration of a total dose not exceeding 30 micrograms, the mean concentration in umbilical cord blood was found to be 0.016 nanograms per milliliter. An antidote for the newborn should always be available. Breastfeeding Sufentanil passes into breast milk. Caution should be exercised when administering sufentanil to a breastfeeding woman.

Overdose

Objective and subjective symptoms Overdose of sufentanil is characterized by enhanced pharmacological effects. Depending on individual sensitivity, the clinical picture is mainly determined by the degree of respiratory depression, which can range from slowed breathing to complete apnea.

Pharmacological action of the drug may cause respiratory depression even at therapeutic doses (i.v.: over 0.3 micrograms/kg body weight). Sufentanil is used exclusively in strictly controlled conditions, which guarantees proper control of these

symptoms.
Treatment
In case of decreased respiratory rate or apnea, oxygen should be administered and assisted or controlled breathing should be used, according to indications. If indicated, a specific agent with antagonistic action, such as naloxone, should be administered to control respiratory depression. This does not exclude the immediate implementation of other remedial measures. Respiratory depression may persist longer than the effect of the antagonist, so it may be necessary to administer repeated doses. In case of simultaneous occurrence of respiratory depression and muscle stiffness, it may be necessary to administer an intravenous depolarizing muscle relaxant to facilitate assisted or controlled breathing. The patient should be carefully monitored; proper body temperature and fluid balance should be maintained. In case of significant or persistent decrease in arterial blood pressure, the possibility of hypovolemia should be considered, and if it is confirmed, it should be counteracted by administering an appropriate amount of fluids parenterally.

Pharmaceutical incompatibilities

Sufentanil citrate shows physical incompatibility with diazepam, lorazepam, sodium salt of phenobarbital, phenytoin, and thiopental.

Shelf life

Shelf life before first opening of the packaging
3 years.
Shelf life after dilution
It has been demonstrated that diluted solutions maintain chemical and physical stability for 72 hours at a temperature of 25 ° C (see Special precautions for disposal and preparation of the medicinal product for use).
From a microbiological point of view, diluted solutions should be used immediately.
If the solution is not used immediately, the user is responsible for the storage conditions and time, which should not normally exceed 24 hours at a temperature of 2 to 8 ° C, unless the dilution took place in controlled, approved aseptic conditions.

Special precautions for disposal and preparation of the medicinal product for use

For infusions, Sufentanil Chiesi can 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.
In case of epidural administration, the drug can be mixed with 0.9% sodium chloride solution and (or) bupivacaine solution.
Before administering Sufentanil Chiesi, the contents of the ampoules should be carefully examined to assess whether there has been any precipitation of particles, damage to the container, or any visible signs of deterioration.
If such defects are found, the solution should be discarded.