Active ingredients: Sufentanil
Sufentanil-hameln 50 micrograms / ml solution for injection
Why is Sufentanil used? What is it for?
Sufentanil-hameln belongs to a group of medicines called opioid anesthetics that relieve or prevent pain during or after general anesthesia. Sufentanil-hameln is administered intravenously during and after major surgery that requires mechanical ventilation.
Sufentanil-hameln administered intravenously is used in / in:
Adults
- to prevent pain during induction and maintenance of anesthesia in combination with other anesthetic medicinal products
- as a medicine to induce and maintain anesthesia during major surgery
Children
Intravenous sufentanil is indicated as an analgesic during the induction and / or maintenance of balanced general anesthesia in children over 1 month of age.
Sufentanil-hameln administered epidurally is used in:
Adults
- to prevent pain after surgery and a caesarean section
- for the treatment of pain during labor and delivery
Children:
Epidural Sufentanil is indicated in children over 1 year of age for the control of post-surgical pain following general surgery, chest or orthopedic procedures.
Contraindications When Sufentanil should not be used
Do not use Sufentanil-hameln
- intravenously if:
- you are allergic to Sufentanil, other medicines similar to morphine or any of the other ingredients of this medicine.
- suffer from any disease that causes breathing difficulties, for example asthma or chronic bronchitis.
- you are taking antidepressant medicines known as monoamine oxidase inhibitors (MAOIs). MAOI therapy should be discontinued 2 weeks prior to surgery.
- suffer from a liver disease known as acute hepatic porphyria.
- you are taking or have recently taken other strong painkillers such as nalbuphine, buprenorphine, pentazocine.
- is in labor or before umbilical cord clamping during a cesarean delivery.
- epidural if:
- suffer from severe bleeding or shock.
- suffer from severe infection.
- suffer from impaired wound healing.
- infection at the injection site.
- have changes in the number of blood cells or if you are taking other medicines that prevent blood clots (anticoagulant medicines).
Precautions for use What you need to know before taking Sufentanil
Talk to your doctor or pharmacist before using Sufentanil-hameln.
- Sufentanil-hameln should only be administered by experienced anesthetists and in hospitals or other facilities where mechanical ventilation and post-operative monitoring are available.
- As with all strong pain relievers of this type, dose-dependent lowering of the respiratory rate may occur. This can last until the awakening phase or happen again during that time. For this reason, careful post-operative monitoring of patients is essential.
- Sufentanil-hameln should be used with extreme caution in patients with lung, liver, kidney and thyroid disease and in alcoholic patients.
- Prolonged medical use or previous abuse of this type of medicine may reduce its effectiveness and a dose increase may be necessary.
- Sufentanil-hameln should be administered with caution in patients with elevated intracranial pressure and cranio-cerebral trauma.
- In patients with low blood volume (hypotension) the administration of Sufentanil-hameln may cause a drop in blood pressure and slow heart rate.
- Prolonged administration of Sufentanil-hameln can be addictive.
- Involuntary muscle contractions can occur.
Newborns / infants
- Newborns are susceptible to breathing difficulties after sufentanil administration, as is the case with other opioids. For infants, only limited data are available on the use of intravenous sufentanil. For this reason, the physician will carefully evaluate the risks and benefits before administering Sufentanil-hameln to newborns and infants.
- Due to the risk of over- or underdose, the use of intravenous Sufentanil-hameln is not recommended during the neonatal period.
- The use of epidural Sufentanil-hameln is not recommended in children less than 1 year of age.
Interactions Which drugs or foods can modify the effect of Sufentanil
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Tell your doctor if you are taking any of the following medicines:
- strong pain medications such as opioids
- sedatives and anxiolytics such as barbiturates, tranquilizers, or benzodiazepines (e.g. diazepam, midazolam)
- muscle relaxants (e.g. vecuronium, suxamethonium)
- general narcotics (eg thiopental, etomidate, nitric oxide)
- neuroleptic drugs (antipsychotics)
- antibiotics to treat bacterial infections (erythromycin)
- medicines used to treat fungal infections (e.g. ketoconazole, itraconazole)
- medicines used to treat viral infections (e.g. ritonavir to treat HIVAIDS)
Warnings It is important to know that:
Warnings for doping in sport
For those who carry out sporting activities: the use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests and health risks.
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Sufentanil-hameln should not be given intravenously during labor because it crosses the placenta and can affect the baby's breathing.
Sufentanil passes into breast milk. Care should be taken when Sufentanil is administered to a nursing woman.
Sufentanil-hameln can be administered epidurally during delivery.
Driving and using machines
After you have been given Sufentanil-hameln, you should not drive or operate machinery for the next 24 hours.
Sufentanil-hameln contains sodium
Sufentanil-hameln contains 0.15 mmol (3.54 mg) of sodium for each milliliter of solution. This should be taken into consideration for patients on a controlled sodium diet.
Dosage and method of use How to use Sufentanil: Dosage
Sufentanil-hameln will be injected by an experienced physician into a vein (intravenously) or the space surrounding the spine (epidurally) before the operation begins. It will help you fall asleep and prevent you from experiencing pain during and after the operation.
During treatment with Sufentanil-hameln you will be closely monitored by trained healthcare personnel and emergency equipment will be available.
Use in children over one month of age and adolescents
Intravenous administration
Sufentanil is slowly injected into a vein by an anesthetist. The dosage depends on the dose of concomitant anesthetics, the type and duration of the surgery and will be determined by the anesthetist.
Use in children over 1 year of age and adolescents
Epidural administration
Sufentanil-hameln is slowly injected into the epidural space (part of the spine) by an anesthetist experienced in pediatric anesthesia techniques. Dosage depends on the concomitant use of local anesthetics and the required duration of analgesia.
Pediatric patients will be monitored for signs of slowed breathing for at least 2 hours after epidural administration of Sufentanil-hameln.
Dosage
Your doctor will decide at what dosage and for how long you should be given Sufentanilhameln.
The dosage depends on your age, body weight and physical condition, the type of surgical procedure and the level of anesthesia.
- The suggested dose should be carefully adjusted in patients with hypothyroidism (underactive thyroid gland), renal impairment, obesity and alcoholism. After surgery, it is recommended that such patients' vital signs be monitored for an extended period.
- For induction and maintenance of anesthesia, your doctor will carefully decide which dose is suitable for your child.
- Patients with liver or kidney damage require lower doses.
- Elderly and debilitated patients need lower doses.
Overdose What to do if you have taken too much Sufentanil
If you are given more Sufentanil-hameln than you should or if you miss a dose
Since Sufentanil-hameln is normally given by a doctor under carefully controlled conditions, it is unlikely that you will be given too much or that a dose will be missed.
In the very rare case that you accidentally get an overdose of Sufentanil-hameln, you may have difficulty breathing. In this case, you must inform your doctor or medical staff immediately so that the specialist team can act promptly.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Sufentanil
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The most common side effects are sedation, itching, nausea and vomiting. If you have difficulty breathing, tell your doctor immediately or get medical help.
Very common (affects more than 1 in 10 patients)
- sedation
- itch
Common (affects 1 to 10 users in 100)
- high pressure
- low pressure
- nausea
- vomiting • fast heartbeat • paleness • bluish discoloration of the skin in the newborn due to low oxygen levels in the blood • skin discoloration • muscle twitching • difficulty holding urine or urinating • fever • headache • dizziness • involuntary muscle contractions in the newborn
Uncommon (affects 1 to 10 users in 1000)
- irregular heartbeat
- decreased muscle tone in the newborn
- lower back pain
- hypersensitivity
- rhinitis
- apathy
- nervousness
- lack of voluntary coordination of muscle movements
- sustained muscle contractions that cause twitching and repetitive movements
- overactive reflexes
- abnormal increase in muscle tension
- decreased voluntary movements in the newborn
- dizziness
- visual disturbances
- allergic skin reaction
- abnormal sweating
- dry skin
- rash
- muscle twitching (intraoperative muscle movements)
- cold strokes
- breathing difficulties
- bronchospasm
- slow heartbeat
- cough
- hiccup
- alteration of the voice
- bluish discoloration of the skin due to low oxygen levels in the blood
- abnormal electrocardiogram
- muscle stiffness including chest wall stiffness, possibly resulting in impaired breathing
- injection site reaction or pain at the injection site
- increase or decrease in body temperature
- rash in the newborn
Not known (frequency cannot be estimated from the available data)
- narrowing of the pupils
- difficulty in breathing
- severe allergic reactions including skin rash, difficulty breathing and shock
- overwhelming sense of well-being (euphoria)
- involuntary movements
- heartbeat stops (the doctor has drugs to reverse this effect.)
- spasms of the throat muscles
- difficulty standing upright (dizziness)
- coma
- convulsions
- respiratory arrest
- water in the lungs
- skin redness
- muscle spasms
Side effects in children and adolescents
The frequency, type and severity of adverse reactions in children are expected to be the same as in adults.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Italian Medicines Agency, Website: www.agenziafarmaco.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and carton after "EXP:". The expiry date refers to the last day of that month.
Do not store above 25 ° C.
Keep the ampoules in the outer carton to protect the medicine from light.
The product should be used immediately after opening. For the shelf life of the diluted solution see "Information for healthcare professionals" below.
Do not use this medicine if you notice that the solution is not clear and free of particles, or if the container is damaged.
Your doctor and pharmacist are responsible for the proper storage, use and disposal of Sufentanil-hameln.
Other information
What Sufentanil-hameln contains
The active substance is sufentanil. 1 ml of solution contains 50 micrograms of sufentanil (equivalent to 75 micrograms of sufentanil citrate).
Each vial with 1 ml of solution contains 50 micrograms of sufentanil (equivalent to 75 micrograms of sufentanil citrate).
Each vial with 5 ml of solution contains 250 micrograms of sufentanil (equivalent to 375 micrograms of sufentanil citrate).
Each vial with 20 ml of solution contains 1000 micrograms of sufentanil (equivalent to 1500 micrograms of sufentanil citrate).
The other ingredients are water for injections, sodium chloride, citric acid monohydrate.
What Sufentanil-hameln looks like and contents of the pack
Solution for injection or concentrate for solution for infusion.
Sufentanil-hameln is a clear and colorless solution.
Sufentanil-hameln 50 micrograms / ml is supplied in colorless glass ampoules.
Original pack containing 5 ampoules of 1, 5 or 20 ml of solution.
Not all pack sizes may be marketed.
The following information is intended for medical or healthcare professionals only
Sufentanil-hameln 50 micrograms / ml solution for injection
Special precautions for use, handling and disposal
Sufentanil should only be administered by or under their supervision by anesthetists or other physicians experienced in its use and effects. Epidural administration should be performed by a physician with the necessary experience in the application of the epidural technique. Before administration, it is necessary to ascertain the correct position of the needle or catheter.
Sufentanil citrate is physically incompatible with diazepam, lorazepam, phenobarbital sodium, phenytoin sodium and thiopental sodium.
The product can be mixed with Ringer's solution, 0.9% sodium chloride or 5% glucose solution for infusion. For epidural administration the product can be mixed with a 0.9% solution of NaCl and / or bupivacaine.
The chemical and physical stability of the dilutions is guaranteed for 72 hours at 20 - 25 ° C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2 - 8 ° C, unless the dilution has been prepared under controlled aseptic conditions and validate.
Before administration, check the solution for particles or other signs of deterioration and that the package is intact. The solution must be discarded when such defects are observed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
SUFENTANIL HAMELN 50 mcg / ML SOLUTION FOR INJECTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml of solution contains
50 mcg of sufentanil (equivalent to 75 mcg of sufentanil citrate)
Each vial with 1 ml of solution contains 50 mcg of sufentanil (equivalent to 75 mcg of sufentanil citrate).
Each vial with 5 ml of solution contains 250 mcg of sufentanil (equivalent to 375 mcg of sufentanil citrate).
Each vial with 20 ml of solution contains 1000 mcg of sufentanil (equivalent to 1500 mcg of sufentanil citrate).
Sufentanil-hameln solution for injection contains 0.15 mmol (or 3.54 mg) of sodium per milliliter of solution.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Solution for injection or concentrate for solution for infusion
The solution is clear and colorless.
(pH: 3.5 - 5.0)
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Use in adults
Intravenous administration of sufentanil is indicated for use under anesthesia during any surgical procedure in patients undergoing endotracheal intubation with mechanical ventilation:
• as an analgesic component during the induction and maintenance of mixed anesthesia.
• as an anesthetic agent for induction and maintenance of anesthesia.
Epidural administration of sufentanil is indicated as an additional analgesic in addition to epidurally administered bupivacaine:
• for the postoperative treatment of pain due to general, thoracic and orthopedic surgery and Caesarean section.
• for the treatment of pain during labor and vaginal delivery.
Use in children
Intravenous sufentanil is indicated as an analgesic during the induction and / or maintenance of balanced general anesthesia in children over 1 month of age.
Epidural Sufentanil is indicated in children aged 1 year or older for the control of post-surgical pain during general surgery, chest or orthopedic procedures.
04.2 Posology and method of administration
Sufentanil should only be administered by, or under the supervision of, anesthetists or other physicians experienced in its use and effects. Epidural administration should be performed by a physician with the necessary experience in the application of the epidural technique. Before administration, it is necessary to ascertain the correct position of the needle or catheter.
The dosage should be established on a case-by-case basis based on the age, body weight and clinical picture of the patient (clinical diagnosis, concomitant administration of other medicinal products, anesthetic procedure, duration and type of surgery). The effect of the initial dose should be taken into account for the determination of additional doses.
In order to minimize the risk of bradycardia, it is recommended that a small dose of an anticholinergic be injected immediately prior to induction of anesthesia. Nausea and vomiting can be prevented by administering an antiemetic. The route of administration and dosage are shown below, according to the different indications:
Intravenous administration:
• Dosage in adults and adolescents:
• As an analgesic component during a mixed anesthesia induced and maintained by multiple anesthetics
Initial dose - i.v. bolus slow or infusion lasting 2 - 10 minutes: 0.5 - 2 mcg of sufentanil / kg body weight.
The duration of the effect depends on the dose. A dose of 0.5 mcg of sufentanil / kg body weight remains effective for approximately 50 minutes.
Maintenance dose - administered i.v. at the onset of signs of anesthesia attenuation: 10 - 50 mcg of sufentanil (approximately 0.15 - 0.7 mcg / kg body weight).
Weaning phase - during this phase, the dose should be reduced very slowly.
• As an anesthetic for induction / maintenance of anesthesia
Initial dose - slow i.v. injection or short infusion lasting 2 - 10 minutes: 7 - 20 mcg of sufentanil / kg body weight.
Maintenance dose - administered i.v. upon onset of signs of anesthesia attenuation: 25 - 50 mcg of sufentanil (approximately 0.36 - 0.7 mcg / kg body weight).
Maintenance doses in the range of 25 - 50 mcg of sufentanil are generally sufficient to maintain a stable cardiovascular situation during the course of anesthesia.
Note: Maintenance doses should be tailored to the needs of the individual patient and to the expected residual duration of surgery.
• Dosage in children over 1 month of age:
Due to the wide variability of pharmacokinetic parameters in neonates, no precise dose recommendations can be made. See also sections 4.4 and 5.2.
Premedication with an anticholinergic such as atropine is recommended for all doses, unless this is contraindicated.
• Induction of anesthesia:
Sufentanil can be administered as a slow bolus injection of 0.2-0.5 mcg / kg over 30 seconds or more, in combination with an anesthesia induction agent. For major surgery (eg surgery cardiac) doses up to 1 mcg / kg can be administered.
• Maintenance of anesthesia in ventilated patients
Sufentanil can be administered as part of a balanced anesthesia. The dosage depends on the dose of the concomitant anesthetic agents, the type and duration of the surgery. In cardiac surgery, an initial dose of 0.3-2 mcg / kg administered by slow bolus injection lasting at least 30 seconds may be followed by additional boluses of 0.1-1 mcg / kg as needed, for a maximum total of 5 mcg / kg.
Note:
Maintenance doses should be tailored to the individual patient's needs and to the expected remaining duration of surgery. Due to the higher clearance rate in children, these patients may need to administer higher doses or at shorter intervals.
Sufentanil as a single bolus anesthetic did not provide a reliable level of anesthesia and required concomitant administration of other anesthetics.
Epidural administration:
• Dosage in adults:
Epidural administration as an additional analgesic in addition to epidurally administered bupivacaine:
• For the postoperative treatment of pain due to general, thoracic and orthopedic surgery, and Caesarean section
An epidural loading dose may be administered intraoperatively: 10 - 15 ml of 0.25% bupivacaine plus 1 μg of sufentanil / ml.
In the postoperative phase, a continuous epidural infusion of 0.175% bupivacaine plus 1 μg of sufentanil / ml should be administered as a background analgesic infusion, with initial administration of 5 ml per hour and individual maintenance doses of 4 - 14 ml per hour. At the request of the patient, 2 ml bolus injections can be administered. A block time of 20 minutes is recommended.
• For the treatment of pain during labor and vaginal delivery
The addition of 10 mcg of sufentanil in combination with epidural bupivacaine (0.125% - 0.25%) allows for a more lasting and deeper analgesia. Injection of a volume of 10 ml has been shown to be optimal. In order to obtain a better mixture, bupivacaine should be added to the sufentanil, at the desired concentration. If necessary, the optimal total volume of 10 ml can be achieved by dilution with a saline solution. 0.9% sodium chloride. If necessary, two additional injections of the mixture can be administered. The total dose of 30 mcg of sufentanil should not be exceeded.
• Dosage in children:
Sufentanil should be administered epidurally to children only by anesthetists specifically trained in pediatric epidural anesthesia and in the control of the respiratory depressant effects of opioids. Appropriate resuscitation equipment, including devices to protect the airways, should be readily available. and an opioid "antagonist".
Pediatric patients should be monitored for signs of respiratory depression for at least 2 hours after epidural administration of sufentanil.
The use of epidural sufentanil in pediatric patients has only been documented in a limited number of cases.
• Children older than 1 year:
A single bolus dose of 0.25-0.75 mcg / kg of sufentanil administered during the operation provides pain relief for a period of 1 to 12 hours. The duration of effective analgesia is affected by the surgical procedure and by the concomitant use of local amide epidural anesthetic.
• Children under the age of 1 year:
The safety and efficacy of sufentanil in children less than 1 year of age have not been established (see also sections 4.4 and 5.1).
Currently available data for children over 3 months of age are described in section 5.1 but no recommendation on a posology can be established.
There are no data available for newborns and infants less than 3 months of age.
Specific dosage precautions:
As a general rule, elderly and debilitated patients require lower doses. In the elderly, the elimination half-life of sufentanil is not prolonged, but there is an increased risk of developing cardiovascular changes.
The total planned dose should be carefully individualized in patients with any of the following disorders: decompensated hypothyroidism, lung disease, especially if vital capacity is reduced, obesity and alcoholism. It is also advisable to subject these patients to prolonged postoperative monitoring.
In patients with hepatic or renal insufficiency the possibility of reduced elimination should be considered and the dosage should be reduced accordingly.
Patients receiving long-term opioid therapy or patients who have abused opioids in the past may need higher doses.
The duration of administration depends on the expected duration of the intervention.
The injection of sufentanil can be given as a single dose or in repeated doses.
Rapid bolus injections should be avoided. When given in combination with a sedative agent, both drugs must be administered using two different syringes.
The duration of epidural administration depends on clinical evolution. There are insufficient clinical data on its use for a period longer than five days after surgery.
04.3 Contraindications
The use of sufentanil is contraindicated in patients:
• with hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to other morphinomimetics.
• suffering from ailments where depression of the respiratory centers must be avoided,
• suffering from acute hepatic porphyria,
• who are receiving MAO inhibitors at the same time or who have received them within the last 14 days (see section 4.5),
• in the presence of simultaneous treatment with a mixture of morphine agonist-antagonists (eg nalbuphine, buprenorphine, pentazocine),
• who are breastfeeding; 24 hours after the anesthesia, it is possible to start breastfeeding again.
Intravenous use is not recommended during labor or prior to umbilical cord clamping during caesarean section due to the possibility of respiratory depression in the newborn. This does not occur if use is epidural in labor, during which time sufentanil, in doses up to 30 micrograms, does not affect the condition of the mother or the newborn (see section 4.6).
As with other epidurally administered opioids, sufentanil should not be given in the presence of severe bleeding or shock, septicemia, injection site infection, alterations in homeostasis, such as thrombocytopenia and coagulopathy, or in the presence of anticoagulant therapy or other concomitant drug therapy or medical conditions for which epidural administration technique is contraindicated.
04.4 Special warnings and appropriate precautions for use
As with all potent opioids:
Respiratory depression is dose related and can be reversed by specific narcotic antagonist drugs (naloxone), but repeat dosing of the latter may be required as respiratory depression may last longer than the opioid antagonist's action. profound anesthesia is accompanied by marked respiratory depression, which may persist in the postoperative phase and, if sufentanil has been administered intravenously, may reappear. Close monitoring of patients is therefore essential and it is also necessary to ensure that adequate equipment is available. for resuscitation and narcotic antagonist drugs. Hyperventilation during anesthesia can alter the patient's response to CO2 and therefore lead to post-operative breathing changes.
Intravenous sufentanil should only be given to patients undergoing endotracheal intubation with mechanical ventilation.
Non-epileptic (myo) clinical movements may occur
With epidural administration, caution should be exercised in the presence of respiratory depression or in the presence of compromised respiratory function and in the presence of fetal distress. The patient should be closely monitored for at least 1 hour after each dose, as early respiratory depression may occur.
The use of rapid bolus injections of opioids should be avoided in patients with impaired intracerebral function, in such patients the transient decrease in mean arterial pressure was sometimes accompanied by a short-term decrease in cerebral perfusion pressure.
It is recommended to reduce the dosage in the elderly and debilitated patients. Opioids should be titrated with caution in patients with any of the following conditions: uncontrolled hypothyroidism, lung disease, reduced respiratory reserve, alcoholism, liver or kidney dysfunction. Such patients also require prolonged postoperative monitoring.
It is not recommended to administer intravenous sufentanil during delivery or during caesarean section prior to omphalotomy, as there is a risk of inducing respiratory depression in the newborn. However, controlled studies have shown that epidural administered sufentanil in addition to bupivacaine at doses not exceeding 30 mcg does not compromise the health of the parturient and the newborn during labor.
As with the administration of other opioids, particular sensitivity to the respiratory depression effects of sufentanil is expected in neonates. In infants, only limited data are reported on sufentanil following intravenous administration. Due to the wide variability of pharmacokinetic parameters in neonates, there is a risk of over- or underdose of intravenous sufentanil in the neonatal period. See also sections 4.2 and 5.2. The safety and efficacy of epidural sufentanil in infants of age less than 1 year has not yet been established (see also sections 4.2 and 5.1).
Therefore, the risk / benefit ratio should be carefully considered before using sufentanil in newborns and infants.
Induction of muscle stiffness may occur which may also affect the respiratory chest muscles but can be avoided by the following precautions: slow intravenous injection (usually sufficient for lower doses), premedication with benzodiazepine and use of muscle relaxants.
Bradycardia and possibly cardiac arrest may occur if the patient has received an insufficient amount of anticholinergic or when sufentanil is combined with non-vagolytic muscle relaxants.Bradycardia can be treated with atropine.
Tachycardia induced by pancuronium administration may mask the bradycardic effect.
Opioids can induce hypotension, especially in hypovolaemic patients. Appropriate measures must be taken to maintain stable blood pressure.
Physical Dependence and Tolerance: Due to its morphine mimetic properties, sufentanil can lead to physical dependence. If sufentanil is used solely as an anesthetic during surgery, physical dependence does not occur.
After continuous long-term administration in the ICU, physical dependence may occur.
Withdrawal symptoms are possible after treatment for longer than one week and are likely if the treatment period is longer than two weeks. The following recommendations are provided:
1. The dose of sufentanil should not be higher than necessary.
2. Reduce the dose slowly over the days.
3. Administer clonidine as needed to suppress withdrawal symptoms.
Patients on chronic opioid therapy or with a history of opioid abuse may require higher doses.
Sufentanil-hameln contains 0.15 mmol (or 3.54 mg) of sodium per milliliter of solution. If large quantities of solution are applied (eg more than 6.5 ml corresponding to more than 1 mmol sodium) this fact should be taken into consideration by patients on a controlled sodium diet.
Sufentanil can induce a positive result in doping tests. Doping with sufentanil can cause health risks.
04.5 Interactions with other medicinal products and other forms of interaction
Drugs such as barbiturates, benzodiazepines, neuroleptics, halogen gases, and other non-selective central nervous system depressants (e.g. alcohol) may potentiate the respiratory depression of narcotics. When patients have taken such drugs, the required dose of sufentanil will be lower than usual. Likewise, following administration of sufentanil, the dose of other central nervous system depressants should be reduced.
Co-administration of benzodiazepines can cause a decrease in blood pressure.
Concomitant administration of high doses of sufentanil and nitrous oxide can cause a reduction in blood pressure, heart rate and cardiac output.
It is generally recommended to discontinue MAO inhibitors 2 weeks prior to surgery or anesthesia. However, several cases have been reported in which no complications have occurred following the use of fentanyl, an opioid analogue, in patients receiving MAO inhibitor therapy.
Co-administration of sufentanil and vecuronium or suxamethonium may induce bradycardia, especially if the heart rate is already low (eg, in patients receiving calcium channel blockers or beta blockers). Therefore, the dosage of one or both drugs should be appropriately reduced.
Sufentanil is mainly metabolised via the human cytochrome P450 3A4 enzyme. However, inhibition by erythromycin (a known inhibitor of the cytochrome P450 3A4 enzyme) has not been observed in vivo. Although clinical data is lacking, in vitro data suggest that other potent inhibitors of the cytochrome P450 3A4 enzyme (eg ketoconazole, itraconazole, ritonavir) may inhibit the metabolism of sufentanil. This may increase the risk of prolonged or delayed respiratory depression. The concomitant use of these drugs requires special care and observation of the patient, in particular it may be necessary to reduce the dose of sufentanil.
04.6 Pregnancy and breastfeeding
Pregnancy
The safety of intravenous sufentanil during human pregnancy has not been established, although studies in animals have not shown teratogenic effects.
Sufentanil should not be used intravenously during pregnancy.
Sufentanil rapidly crosses the human placenta and its concentration increases linearly as the concentration in the maternal blood increases.
A ratio of 0.81 was calculated between the concentration in the umbilical vein and the concentration in the maternal venous blood. Intravenous administration of sufentanil is not recommended during obstetric procedures (including caesarean section), since sufentanil, such as other opioids, can cross the placenta and cause respiratory failure.
As with other drugs, the risk must be weighed against the potential benefit to the patient.
Controlled clinical studies performed during labor have shown that sufentanil administered epidurally in addition to bupivacaine in doses up to 30 micrograms has no harmful effect on the parturient or neonate, but intravenous use is contraindicated during labor. Sufentanil crosses the placenta After epidural administration of a total dose not exceeding 30 micrograms, mean plasma concentrations of 0.016 ng / ml have been found in the umbilical vein An antidote for the child must always be available.
Feeding time
Sulfetanil is secreted in breast milk. Therefore, sufentanil is contraindicated during lactation. Taking into account the pharmacokinetic factors, lactation can be resumed 24 hours after anesthesia.
Caution should be exercised when sufentanil is administered to nursing mothers.
For data on laboratory animals, see section 5.3.
04.7 Effects on ability to drive and use machines
Patients should only drive or operate machinery if sufficient time has elapsed after administration of sufentanil. In addition, patients must go home accompanied, and must have been advised that alcohol consumption should be avoided.
04.8 Undesirable effects
The safety of sufentanil was evaluated in 650 sufentanil-treated subjects who participated in 6 clinical studies. Of these, 78 subjects participated in 2 studies where sufentanil was administered intravenously as an anesthetic agent for induction and maintenance of anesthesia in subjects undergoing major surgery (coronary artery bypass or open heart surgery). . The remaining 572 subjects participated in 4 studies where sufentanil was administered epidurally as a postoperative analgesic, or as an adjunct to epidural bupivacaine during labor and vaginal deliveries. These subjects received at least 1 dose of sufentanil and Safety data provided. Based on pooling of safety data from these clinical trials, the most commonly occurring adverse drug reactions (with% incidence ≥ 5%) were (with% incidence): sedation; pruritus ; nausea and vomit .
Including the adverse drug reactions (ADRs) mentioned above, the table below shows the ADRs that have been reported with the use of sufentanil in clinical trials or in post-marketing experience. The frequency categories shown are based on the following convention:
Pediatric population
The frequency, type and severity of adverse reactions in children are expected to be the same as in adults.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicine is important, as it allows for continuous monitoring of the benefit / risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the National Reporting System. address www.agenziafarmaco.gov.it/it/responsabili ".
04.9 Overdose
Signs and symptoms
An overdose of sufentanil is manifested by an increase in its pharmacological effects.
Depending on the individual sensitivity, the clinical picture is primarily determined by the degree of respiratory depression which varies from bradypnea to apnea. Due to the pharmacological properties of sufentanil, respiratory depression can occur already at therapeutic doses (i.v .: greater than 0.3 mcg / kg body weight). Since sufentanil is administered under controlled conditions, adequate control of these symptoms should be ensured.
Treatment
In the presence of hypoventilation or apnea, oxygen should be administered and breathing should be assisted or controlled as required. A specific narcotic antagonist, such as naloxone, should be used to control respiratory depression as indicated. This does not preclude the use of more immediate countermeasures. Respiratory depression may last longer than the effect of the antagonist; therefore additional doses of the latter may be required. If respiratory depression is associated with muscle stiffness, administration of an intravenous neuromuscular blocking agent may be required to facilitate assisted or controlled breathing.
The patient must be closely monitored, body temperature and fluid balance must be kept stable. If hypotension is severe or persists, the possibility of hypovolaemia should be considered and, if present, controlled by parenteral administration of appropriate fluids.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: anesthetics; opioid anesthetics
ATC code: N01AH03.
Sufentanil, a potent opioid analgesic, is a specific mc agonist, with 7-10 times greater affinity for mc receptors than fentanyl. Sufentanil has a much more marked analgesic action than fentanyl; hemodynamic stability and a good supply of oxygen to the myocardium are maintained in its presence. The maximum effects are reached within a few minutes of intravenous administration. Pharmacological tests have shown cardiovascular stability. and EEG appearance similar to those obtained with fentanyl. There were no immunosuppressive or haemolytic effects, nor induction of histamine release. As with other opioids, sufentanil can induce bradycardia through possible effects on the central vagus nucleus. The pancuronium-induced increase in heart rate is not reduced, or only partially reduced, by sufentanil.
Sufentanil has a high safety index (LD50 / ED50 for the lowest level of analgesia) in the rat; with a value of 25 211, the index is higher than that of fentanyl or morphine. The reduced accumulation and rapid elimination from the retention compartments allow for rapid recovery. The depth of analgesia is dose-dependent and can be adapted appropriately to the intensity of pain during surgery.
Several effects caused by sufentanil (particularly respiratory depression) can be reversed by the administration of an antagonist such as naloxone.
Pediatric population
Epidural administration
The mean onset and duration values of analgesia were 3.0 ± 0.3 and 198 ± 19 minutes after epidural administration of 0.75 μg / kg of sufentanil in 15 children aged 4 to 12 years, respectively.
Epidural sufentanil has only been administered to a limited number of children aged 3 months to 1 year as a single bolus dose of 0.25-0.75 mcg / kg for postoperative pain control.
In children over 3 months of age, an epidural bolus dose of 0.1 mcg / kg of sufentanil followed by an epidural "infusion of 0.03-0.3 mcg / kg / h in combination with an anesthetic local amide, provided effective postoperative analgesia for up to 72 hours in patients after umbilical surgery.
05.2 Pharmacokinetic properties
The results of studies conducted with intravenous doses of 250 - 1500 mcg of sufentanil, in cases where it was possible to collect blood samples and measure the serum concentration for prolonged periods, are as follows:
the half-lives in the distribution phase are 2.3 - 4.5 minutes and 35 - 73 minutes, the mean final elimination half-life is 784 (656 - 938) minutes, the volume of distribution in the central compartment is 14, 2 liters, steady-state volume of distribution 344 liters, clearance 917 ml / minute. Due to the limitations of the analytical methods, the elimination half-life of the 250 mcg dose is significantly shorter (240 minutes) than that of the dose of 500 - 1500 mcg (10 - 16 hours).
The half-life in the distribution phase, rather than the elimination half-life, is the determining factor for the fall in plasma concentration from a therapeutic to a subtherapeutic level. Sufentanil exhibits linear pharmacokinetics with regard to the dosages considered. The biotransformation of the substance occurs mainly in the liver and small intestine. Almost 80% of the administered dose is eliminated within 24 hours and only 2% in unchanged form. The plasma protein binding of sufentanil is 92.5%.
Very low concentrations of sufentanil have been detected in plasma following epidural administration of doses ranging from 3 to 30 micrograms, in both healthy and parturient volunteers. Sufentanil has also been detected in umbilical blood.
Maximum plasma concentrations of epidurally administered sufentanil are reached within 10 minutes, and are 4 to 6 times lower than those obtained following intravenous administration. The addition of epinephrine (50 - 75 mcg) reduces the initial absorption rate of sufentanil by 25% - 50%.
Pediatric population
Pharmacokinetic information in children is limited.
Intravenous administration
Plasma protein binding in children is lower than in adults and increases with age. In neonates sufentanil is protein bound for approximately 80.5% compared to 88.5% in infants, 91.9% in infants. children and 92.5% in adults.
Following administration of an intravenous bolus of sufentanil of 10-15 micrograms / kg in pediatric patients undergoing cardiac surgery, the pharmacokinetics of sufentanil follow a tri-exponential curve as in adults (Table 1). Body weight normalized clearance was higher in infants and children than in adolescents, whose clearance rates were comparable to those in adults. In neonates, clearance was significantly reduced and showed a wide variability (range 1.2 to 8.8 ml / min / kg and an isolated value of 21.4 ml / min). In neonates, a greater volume of distribution was demonstrated. at steady-state and a longer elimination half-life. Pharmacodynamic differences, due to differences in pharmacokinetic parameters, may be greater considering the unbound fraction.
Table 1: Mean pharmacokinetic parameters of sufentanil in children after administration of 10-15 μg / kg of sufentanil as a single intravenous bolus (N = 28).
Cl = clearance, normalized with body weight; N = number of patients included in the analysis; SD = standard deviation; T½? = Elimination half-life; Vdss = volume of distribution at steady state. The age ranges listed are those of the children studied.
Epidural administration.
After epidural administration of 0.75 μg / kg of sufentanil in 15 children aged 4 to 12 years, plasma levels taken at 30, 60, 120, and 240 minutes post injection ranged from 0.08 ± 0.01 to 0.10 + 0.01 ng / ml.
In 6 children aged 5-12 years who received a bolus of 0.6 mcg / kg sufentanil followed by a continuous "epidural infusion containing 0.08 mcg / kg / h of sufentanil and bupivacaine 0.2 mg / kg / h for 48 h, maximum concentrations were reached approximately 20 minutes after bolus injection and ranged from values below the limit of quantification (
05.3 Preclinical safety data
Effects on reproduction (impaired fertility, embryotoxic and foetotoxic effects, neonatal mortality rate) were observed in rats and rabbits only following administration of toxic doses to the maternal animal (2.5 times the dose used for l " man for 10 - 30 days). No teratogenic effects were reported.
No studies have been published concerning the long-term analysis of the carcinogenic potential of sufentanil in animals.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Sodium chloride, citric acid monohydrate (for pH correction), water for injections.
06.2 Incompatibility
Sufentanil citrate is physically incompatible with diazepam, lorazepam, phenobarbital sodium, phenytoin sodium and thiopental sodium.
06.3 Period of validity
Shelf life before opening:
3 years.
Shelf life during use:
The product should be used immediately after opening.
Shelf life after dilution:
The chemical and physical stability of the dilutions (see section 6.6) is guaranteed for 72 hours at 20 - 25 ° C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2 - 8 ° C, unless the dilution has been prepared under controlled aseptic conditions and validate.
06.4 Special precautions for storage
Do not store above 25 ° C.
Keep the ampoules in the outer carton to protect from light. For storage conditions after dilution see section 6.3.
06.5 Nature of the immediate packaging and contents of the package
Vials (colorless glass, type I)
Original pack containing 5 ampoules of 1 ml each
Original pack containing 5 ampoules of 5 ml each
Original packaging containing 5 ampoules of 20 ml each
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Before administration, visually check that there are no particulate matter or other signs of deterioration and that the packaging is intact. The solution should be discarded when defects of this kind are observed.
The product can be mixed with Ringer's solution, 0.9% sodium chloride or 5% glucose solution for infusion.
For epidural administration the product can be mixed with a 0.9% solution of NaCl and / or bupivacaine.
07.0 MARKETING AUTHORIZATION HOLDER
hameln pharmaceuticals gmbh
Langes Feld 13
31789 Hameln
Germany
08.0 MARKETING AUTHORIZATION NUMBER
5 ampoules of 1 ml of solution for injection 50 mcg / ml - AIC 035629017
5 ampoules of 5 ml of solution for injection 50 mcg / ml - AIC 035629029
5 ampoules of 20 ml of solution for injection 50 mcg / ml - AIC 035629031
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 29/09/2003
Date of last renewal: 15/05/2010
10.0 DATE OF REVISION OF THE TEXT
22.08.2015
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