Active ingredients: Fentanyl
FENTANEST 0.1 mg / 2 ml solution for injection
Why is Fentanest used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
General opioid anesthetic.
THERAPEUTIC INDICATIONS
Due to its characteristics, Fentanest is more suitable than any other known analgesic for use in anesthesiology.
It can be used both in premedication for any type of anesthesia (even local) and in the postoperative course as during the operation itself. We recommend the association of Fentanest with nitrous oxide and with a neuroleptic, in particular with droperidol which it improves its analgesic activity and reduces its side effects (especially respiratory depression and vomiting), thus achieving neuroleptoanalgesia. Fentanest can also be associated, at suitably reduced doses, with barbiturates and common volatile anesthetics (halothane, isoflurane, etc.).
No cases of interference between the action of Fentanest and muscle relaxants have been described.
Contraindications When Fentanest should not be used
Hypersensitivity to the active substance, to morphine mimetics or to any of the excipients.
Not to be used in case of confirmed or presumed pregnancy.
Not to be used in the child in the first two years of life.
Precautions for use What you need to know before taking Fentanest
It is recommended in the elderly and in debilitated subjects to reduce the initial dose of Fentanest; subsequent doses should be based on the effect induced by the starting dose. Adjustment of opioid dosage should be made with caution in patients with any of the following conditions: uncontrolled hypothyroidism; lung pathologies; reduced lung reserve; alcoholism or impaired liver or kidney function due to the importance of these organs in the metabolism and excretion of the drug. Furthermore, these patients require prolonged monitoring in the postoperative period. Fentanest-induced profound analgesia is accompanied by profound respiratory depression, which may persist longer than the analgesic effect or recur in the postoperative period.
As with all potent opioids, respiratory depression is dose proportional. Therefore, if other narcotic analgesics are used together with Fentanest, the doctor will need to take into account the total dose of all these substances before prescribing them for analgesic purposes in the postoperative period. It is recommended that narcotics, in these cases, are initially prescribed in reduced doses, equal to 1/4 - 1/3 of the usual doses.
Certain forms of conduction anesthesia, such as spinal anesthesia, and some epidural anesthetics can impair respiratory function through an intercostal nerve block.
Therefore, in using Fentanest as a supplement to the aforementioned anesthesia, it will be necessary that the anesthetist is familiar with the functional alterations involved in these circumstances and is well prepared to deal with them.
You will also need to carry out routine monitoring of vital signs.
Fentanest should be used with caution in patients with chronic obstructive pulmonary disease, or with reduced respiratory reserve or with potentially compromised ventilation.
In such patients, in fact, narcotics can further reduce respiratory energy and increase airway resistance. During anesthesia this possibility can be dealt with by assisted or controlled breathing.
Like all powerful opioids:
Respiratory depression is dose related and can be counteracted with the use of specific narcotic antagonists such as naloxone, but additional doses of the latter may be necessary because respiratory depression may last longer than the antagonist's duration of action. opioid. Deep analgesia is accompanied by marked respiratory depression which may persist or recur in the postoperative period. Therefore patients should remain under adequate surveillance.
Resuscitation equipment and a narcotic antagonist should be available for immediate use. Hyperventilation during anesthesia can alter the patient's response to CO2, thus affecting respiration in the postoperative period.
Bradycardia, and possibly cardiac arrest, may occur if the patient has received an insufficient dose of anticholinergics or when fentanyl is used in combination with non-vagolytic muscle relaxants. Bradycardia can be treated with atropine. However, Fentanest should be used with caution in patients with cardiac bradyarrhythmia.
Opioids can induce hypotension, especially in hypovolaemic patients. Appropriate measures should be taken to maintain stable blood pressure. If hypotension occurs, it will be necessary to consider the possibility of a hypovolemia to be corrected with appropriate measures to maintain stable blood pressure or with adequate therapy with fluids by parenteral route. Operating conditions allowing this, the patient's posture must also be modified so as to improve venous return When moving patients, care must be taken not to provoke orthostatic hypotension.In the event that the hypervolemic treatment with intravenous fluids, together with the other countermeasures, fails to modify the hypotension, it will be necessary to consider the opportunity of administering drugs that increase blood pressure, other than adrenaline which could, paradoxically, further reduce blood pressure due to the alpha-adrenergic blocking effect of droperidol. When Fentanest is administered with a neuroleptic (such as droperidol) the physician must know the properties of each drug and in particular their different duration of action. When this combination is used, there is a higher incidence of hypotension. using this combination, fluids for infusion and other countermeasures to combat any hypotension should be available (see Interactions section). Neuroleptics can induce extrapyramidal symptoms that can be controlled with antiparkinsonian drugs.
Caution is advised when Fentanest is co-administered with drugs affecting the serotonergic transmission systems.
The development of a potentially life-threatening serotonin syndrome may occur with the concomitant use of serotonergic medicinal products such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and certain metabolism-altering drugs serotonin (including MAO monoamine oxidase inhibitors). This can occur within the recommended dose range.
Serotonin syndrome can include changes in mental status (e.g. agitation, hallucinations, coma), autonomic hyperactivity (e.g. tachycardia, unstable blood pressure, hyperthermia), neuromuscular abnormalities (e.g. hyperreflexia, lack of coordination, rigidity and / or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea).
If serotonin syndrome is suspected, treatment with Fentanest should be promptly discontinued
As with other opioids due to their anticholinergic effect, administration of Fentanest can lead to increases in bile duct pressure and, in isolated cases, spasms of the Sphincter of Oddi may be observed.
The use of certain anticholinergic agents and neuromuscular blocking agents should be carefully considered in patients with myasthenia gravis before and during intravenous administration of Fentanest under general anesthesia.
Interactions Which drugs or foods can change the effect of Fentanest
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Effects of other medicinal products on Fentanest
When using high dosages of Fentanest, even relatively low doses of diazepam can cause cardiovascular depression.
Drugs such as barbiturates, benzodiazepines, neuroleptics, halogenated gases and other non-selective CNS depressants (e.g. alcohol) can potentiate the respiratory depression of narcotics.
In patients who have taken these drugs, the required dose of Fentanest will be lower than usual. Similarly, after administration of Fentanest, the dose of other CNS depressants should be reduced.
Fentanyl, a high clearance drug, is rapidly and extensively metabolised primarily by CYP3A4. Itraconazole (a potent CYP 3A4 inhibitor), administered orally at a dose of 200 mg / day for 4 days, did not significantly affect the pharmacokinetics of intravenously administered fentanyl.
However, in individual subjects, increases in plasma concentrations were observed.
Concomitant administration of fluconazole or voriconazole and fentanyl may result in increased exposure to fentanyl.
Administration of oral ritonavir, one of the strongest inhibitors of CYP3A4, reduced the clearance of intravenous fentanyl by two thirds; however, peak plasma concentrations following a single intravenous fentanyl dose did not change. Patients receiving single dose fentanyl together with potent CYP3A4 inhibitors, such as ritonavir, require special care and careful observation.
During prolonged treatment, a reduction in the dosage of fentanyl may be necessary to avoid its accumulation which may increase the risk of prolonged or delayed respiratory depression. Severe and unpredictable potentiation by MAOinhibitors has been reported for narcotic analgesics. to discontinue the use of MAO inhibitors 2 weeks before any surgical or anesthetic procedure. However, in several reports, the use of fentanyl during surgical or anesthetic procedures in patients treated with MAO inhibitors is harmless.
The association with other psychotropic drugs requires particular caution and vigilance on the part of the physician to avoid unexpected undesirable effects from interaction.
When Fentanest is used with a neuroleptic such as droperidol it can cause a decrease in pulmonary arterial pressure.
This must be taken into account during diagnostic or surgical procedures in which the patient's ultimate treatment may depend on the interpretation of the pulmonary artery pressure values. Furthermore, when Fentanest is used with droperidol and EEG is used as a postoperative monitoring, it will be observed that after the use of the combination, the electroencephalographic trace returns to normal more slowly than usual.
Serotonergic medicines
Co-administration of fentanyl with serotonergic agents such as a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) or a monoamine oxidase inhibitor (MAOI) may increase the risk of serotonin syndrome, a potentially life-threatening condition.
Effects of Fentanest on other medicinal products
Following administration of fentanyl, the dose of other CNS depressant medicinal products should be reduced.
Plasma concentrations of etomidate are significantly increased (factor 2 to 3) when administered with fentanyl. Total plasma clearance and volume of distribution of etomidate are reduced by a factor of 2 to 3, with no change in half-life, when administered with fentanyl. Co-administration of intravenous fentanyl and midazolam results in an increase in the terminal plasma half-life and a decrease in plasma clearance of midazolam. When these medicinal products are co-administered with fentanyl their dosage may need to be reduced.
Warnings It is important to know that:
The product should only be used in hospitals, clinics and nursing homes and only by the surgeon or anesthetist. As with other CNS depressants, patients treated with Fentanest should be kept under adequate surveillance.
Fentanest can only be administered in suitable facilities where the respiratory tract can be controlled and by respiratory health care personnel.
Induction of muscle stiffness may also occur in the respiratory muscles. The phenomenon depends on the speed of the injection; it can, in fact, reduce the incidence by proceeding with a slow intravenous injection (normally sufficient for the lowest doses) or through premedication with benzodiazepines and the use of muscle relaxants. With the phenomenon now underway, it is essential to resort to assisted or controlled breathing as well as, if necessary, to a curarising agent compatible with the patient's conditions.
Non-epileptic myoclonic / clonic movements may occur. Neuroleptics can induce extrapyramidal symptoms which can be controlled with anti-parkinsonian agents
Head injuries and intracranial hypertension - Fentanest should be used with caution in patients particularly sensitive to depression of the respiratory centers, and in comatose patients suffering from head trauma or brain tumor. Keep in mind that Fentanest can mask the course of head injuries. Rapid bolus injections of opioids should be avoided in patients with impaired intracerebral function; in these patients, the transient reduction in mean arterial pressure was occasionally associated with a short-term reduction in cerebral perfusion pressure.
Drug addiction - Fentanyl can cause morphine drug addiction and is therefore susceptible to abuse. Patients on chronic opioid therapy or those with a history of opioid abuse may require higher dosages.
Fentanest should not be mixed with alkaline or buffered solutions.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Not to be used in cases of confirmed or presumed pregnancy and in the child in the first two years of life. There is insufficient information on the use of fentanyl in pregnancy. Fentanyl can cross the placenta in early pregnancy. Animal studies have shown reproductive toxicity. The potential risk to humans is unknown.
Administration (i.m. or i.v.) during delivery, (including caesarean delivery), is not recommended, because fentanyl crosses the placenta and the respiratory centers of the fetus are particularly sensitive to opioids. If fentanyl is nevertheless administered, an antidote for the child should always be at hand.
Since fentanyl is excreted in breast milk, breastfeeding within 24 hours following administration of the medicinal product is not recommended. The benefit / risk of breastfeeding following administration of fentanyl should be considered.
Use in children:
Analgesia during surgery, enhancement of anesthesia in spontaneous breathing
Analgesic techniques in spontaneously breathing children should be used only as part of the anesthetic technique or as part of sedation / analgesia techniques by trained personnel and in an environment where sudden stiffness of the chest walls requiring intubation or apnea can be managed. requiring airway support (see Dose, method and time of administration).
Effects on driving and using machines:
Fentanyl may impair the ability to drive and use machines. Patients should only drive or operate machinery if sufficient time has elapsed following the administration of fentanyl.
For those who play sports:
The use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
Important information about some of the ingredients:
FENTANEST 0.1 mg / 2 ml solution for injection contains methyl parahydroxybenzoate and propyl parahydroxybenzoate. It can cause allergic reactions (even delayed) and, exceptionally, bronchospasm.
Dosage and method of use How to use Fentanest: Dosage
Route of administration
Fentanest can only be administered in suitable facilities where the respiratory tract can be controlled and by respiratory health care personnel. Fentanest can be administered intramuscularly or intravenously. The intramuscular route is preferred in premedication, for analgesia in the postoperative course and for pain therapy in general; the intravenous route (direct or by perfusion) during surgery.
Even when administered undiluted, the preparation does not cause local irritative manifestations.
Dosages refer to normal adults.
Intramuscularly - on average 0.1-0.2 mg (2-4 ml) of Fentanest per dose.
Intravenously - to perform a neurolepto-analgesic anesthesia, the total doses of Fentanest are of the order of 0.4-0.8 mg.
While maintaining an anesthesia performed with the usual techniques, the dosage should be adjusted according to the analgesic depth to be obtained, the type of intervention, the sensitivity of the subject and the quantity of other drugs administered, bearing in mind that among these (barbiturates, ether, flux, etc.) and the Fentanest exists enhancement.
Neuroleptoanalgesia - for this type of anesthesia the association of Fentanest with the neuroleptic droperidol can be extemporaneous, in the proportions deemed suitable by the anesthetist.
Neuroleptoanalgesia is practically implemented according to these schemes:
Preanesthesia - 0.1 mg of Fentanest and 5 mg of droperidol intramuscularly, 30 "-60" before surgery.
The simultaneous use of atropine at a dose of 0.25 mg is optional. The same administration is used, pro / dose, for the treatment of postoperative pain.
Induction - rapid intravenous infusion (1000 drops / minute equal to 50 ml of solution / minute) of 50-100 ml of a solution prepared by diluting the contents of 10 ampoules (equal to 1 mg) of Fentanest and 2 bottles ( equal to 50 mg) of droperidol in 500 ml of 5% glucose solution.
At the same time, a mixture of N2O / O2 in the ratio of 3/1 is administered in a semi-closed circuit. After intravenous injection of 25-50 mg of succinylcholine (and manual hyperventilation), tracheal intubation is carried out, while the infusion is slowed down to about 50 drops / minute and the administration of the mixture of N2 O / O2, reduced to the ratio 2/1, at the rate of 12-15 liters / minute.
Maintenance - the average infusion rate is between 15-30 drops / minute and must be adjusted to the operating times and individual sensitivity, accelerating it if the patient moves, if blood pressure, heart and respiratory rate increase and if sweating appears ; decreasing it if the patient is calm, with stability of blood pressure, pulse and breathing rate and if the skin is dry.
If surgical needs require it, muscle relaxation is carried out with divided doses of 25 mg of succinylcholine. The administration of N2 O / O2 is continued in the ratio 2/1.
End of the intervention, awakening - about 15 minutes before the end of the intervention, perfusion is further slowed down (10 drops / minute), while at the same time the administration of N2O is decreased. At the end of the skin suture, the infusion is interrupted; the patient is hyperventilated with air for 2 "-3", then extubation is carried out. Usually the patient is in a position to be immediately sent to the ward.
Instead of continuous perfusion, Fentanest and droperidol can be administered intravenously directly at the following doses:
Induction - Fentanest 0.4 mg (8 ml); droperidol 20 mg (8 ml).
Initiation of incision and maintenance - as needed (based on clinical signs above) Fentanest 0.025 mg.
Further administrations, if necessary, at even lower doses, in this case diluting the Fentanest. For long-term interventions 10-15 mg of droperidol will also be reinjected.
The methods of administering the nitrous oxide and the curarizer remain identical to those of the continuous perfusion technique.
Pediatric patients
Children aged 12-17 years: follow the adult dosage
Children aged 2 to 11 years: the usual dose in children should be as follows:
Age
Use in children:
Analgesia during surgery, enhancement of spontaneously breathing anesthesia Techniques with analgesia in spontaneously breathing children should only be used as part of the anesthetic technique or as part of sedation / analgesia techniques by trained personnel and in an environment where it is possible to manage sudden stiffness of the chest walls requiring intubation, or apnea requiring airway support (see Special Warnings)
The dosage of Fentanest should be individualized according to age, body weight, physical status, existing medical conditions, use of other medicines and the type of surgery and anesthesia. In the elderly and other patients at risk, the starting dose of Fentanest should be reduced; for subsequent doses, the effect induced by the starting dose should be based.
Overdose What to do if you have taken too much Fentanest
In case of accidental ingestion / intake of an overdose of Fentanest, notify your doctor immediately or go to the nearest hospital.
Signs and symptoms - the manifestations of an overdose of Fentanest are nothing more than an extension of its pharmacological actions. Depending on the individual sensitivity, the clinical picture is mainly determined by the degree of respiratory depression which can vary from bradypnea to apnea.
Treatment - in the presence of hypoventilation or apnea, oxygen should be given and assisted or controlled breathing should be used, as indicated. The airways must be kept open and for this purpose it may be appropriate to use an oropharyngeal cannula and an endotracheal tube.
As indicated, a specific narcotic antagonist, such as naloxone, should be kept ready for use to address the respiratory depression induced by fentanyl.
However, this does not preclude the use of more immediate countermeasures.
It should be noted that the duration of respiratory depression following an overdose of fentanyl may exceed the duration of action of the antagonist, therefore an additional dose of the latter may be required.
If respiratory depression is associated with muscle stiffness, the use of an intravenous neuromuscular blocking agent may be necessary to facilitate assisted or controlled breathing.
Patients must be carefully monitored, body heat and proper fluid intake must be maintained. In case of severe or persistent hypotension, the presence of hypovolemia should be suspected, to be addressed with appropriate parenteral fluid therapy.
Side Effects What are the side effects of Fentanest
Based on pooled safety data from clinical trials, the most common adverse reactions (incidence ≥ 5%) were (% incidence): nausea, vomiting, muscle stiffness, hypotension, hypertension, bradycardia and sedation.
The table below lists undesirable effects, including those mentioned above, associated with the use of IV fentanyl evaluated in both clinical trials and post-marketing.
As with other analgesics, the most commonly reported side effects of some importance after Fentanest injection are: respiratory depression, apnea, muscle stiffness and bradycardia; in the absence of corrective measures these phenomena can lead to respiratory arrest, circulatory depression, cardiac arrest. Also observed: hypotension, dizziness, blurred vision, nausea and vomiting, laryngospasm, sweating
It has also been reported that a resurgence of respiratory depression may occur in the postoperative period. With this in mind, patients should be carefully observed and, if necessary, appropriate countermeasures should be taken. When a neuroleptic such as droperidol is used with Fentanest The following side reactions may occur: chills and / or tremors, restlessness and postoperative hallucinatory episodes (sometimes associated with transient periods of mental depression); extrapyramidal symptoms (dystonia, akathisia, oculogyric crisis), have been observed up to 24 hours later the intervention (see Warnings). Any extrapyramidal symptoms can usually be reduced or controlled with antiparkinsonian drugs. Postoperative somnolence is frequently reported following use of droperidol. After use of Fentanest in combination with droperidol, increases in blood pressure with or without pre-existing hypertension have also been reported. This could depend on an alteration, still unexplained, of the sympathetic activity, secondary to high doses of the two drugs, but the phenomenon is often attributed to sympathetic stimulation of anesthetic or surgical origin during the light stage of anesthesia.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects. Like all medicines, FENTANEST can cause side effects, although not everybody gets them.
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. Undesirable effects can also be reported directly through the national reporting system at the address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
See the expiration date indicated on the package
The expiry date of the product shown on the package refers to the product in intact packaging, correctly stored.
Warning: Do not use the product after the expiry date shown on the package
The medicinal product does not require any special storage precautions
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the reach and sight of children
COMPOSITION
1 vial of 2ml contains: active ingredient: 0.157 mg fentanyl citrate equal to 0.100 mg fentanyl.
Excipients: methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, water for injections.
PHARMACEUTICAL FORM AND CONTENT
Injectable solution. Pack of 5 ampoules each containing 0.1 mg of fentanyl in 2 ml of solution.
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
FENTANEST 0.1 MG / 2 ML SOLUTION FOR INJECTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ampoule of 2 ml contains:
0.157 mg fentanyl citrate equal to 0.100 mg fentanyl
03.0 PHARMACEUTICAL FORM
Injectable solution
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Due to its characteristics, Fentanest is more suitable than any other known analgesic for use in anesthesiology.
It can be used both in premedication for any type of anesthesia (even local) and in the postoperative course as during the operation itself. We recommend the association of Fentanest with nitrous oxide and with a neuroleptic, in particular with droperidol which it improves its analgesic activity and reduces its side effects (especially respiratory depression and vomiting), thus achieving neuroleptoanalgesia. Fentanest can also be associated, at suitably reduced doses, with barbiturates and common volatile anesthetics (halothane, isoflurane, etc.).
No cases of interference between the action of Fentanest and muscle relaxants have been described.
04.2 Posology and method of administration
Route of administration
Fentanest can only be administered in suitable facilities by respiratory health care personnel (see section 4.4).
Fentanest can be administered intramuscularly or intravenously. The intramuscular route is preferred in premedication, for analgesia in the postoperative course and for pain therapy in general; the intravenous route (direct or by perfusion) during surgery.
Even when administered undiluted, the preparation does not cause local irritative manifestations.
Dosages refer to normal adults.
Intramuscularly - on average 0.1-0.2 mg (2-4 ml) of Fentanest per dose.
Intravenously - to perform a neurolepto-analgesic anesthesia, the total doses of Fentanest are of the order of 0.4-0.8 mg.
While maintaining an anesthesia performed with the usual techniques, the dosage should be adjusted according to the analgesic depth to be obtained, the type of intervention, the sensitivity of the subject and the quantity of other drugs administered, bearing in mind that among these (barbiturates, ether, flux, etc.) and the Fentanest exists enhancement.
Neuroleptoanalgesia - for this type of anesthesia, the association of Fentanest with the neuroleptic droperidol can be extemporaneous, in the proportions considered suitable by the anesthetist; or the ready-to-use preparation available under the name of Leptofen can be used.
In the latter, the two components are present in the proportion of 1:50, ie 1 ml of Leptofen contains 0.05 mg of Fentanest and 2.5 mg of droperidol.
Neuroleptoanalgesia is practically implemented according to these schemes:
Preanesthesia - 0.1 mg of Fentanest and 5 mg of droperidol intramuscularly, 30 "-60" before surgery.
The simultaneous use of atropine at a dose of 0.25 mg is optional. The same administration is used, pro / dose, for the treatment of postoperative pain.
Induction - rapid intravenous infusion (1000 drops / minute equal to 50 ml of solution / minute) of 50-100 ml of a solution prepared by diluting the contents of 10 ampoules (equal to 1 mg) of Fentanest and 2 bottles (equal to to 50 mg) of droperidol in 500 ml of 5% glucose solution.
At the same time, a mixture of N2O / O2 in the ratio of 3/1 is administered in a semi-closed circuit.
After intravenous injection of 25-50 mg of succinylcholine (and manual hyperventilation), tracheal intubation is carried out, while the infusion is slowed down to about 50 drops / minute and the administration of the mixture of N2O / O2, reduced to the ratio 2, continues. / 1, at the rate of 12-15 liters / minute.
Maintenance - the average infusion rate is between 15-30 drops / minute and must be adapted to the operating times and individual sensitivity, accelerating it if the patient moves, if blood pressure, heart and respiratory rate increase and if sweating appears; decreasing it if the patient is calm, with stability of blood pressure, pulse and breathing rate and if the skin is dry.
If surgical needs require it, muscle relaxation is carried out with divided doses of 25 mg of succinylcholine.
The administration of N2O / O2 is continued in the ratio 2/1.
End of the intervention, awakening - about 15 minutes before the end of the operation, perfusion is further slowed down (10 drops / minute), while at the same time the administration of N2O is decreased. At the end of the cutaneous suture the infusion is interrupted; the patient is hyperventilated with air for 2 "-3", then extubation is carried out. Usually the patient is able to be immediately sent to the ward.
Instead of continuous perfusion, Fentanest and droperidol can be administered intravenously directly at the following doses:
Induction - Fentanest 0.4 mg (8 ml); droperidol 20 mg (8 ml).
Beginning of the incision and maintenance - as needed (based on the above clinical signs) Fentanest 0.025 mg.
Further administrations, if necessary, at even lower doses, in this case diluting the Fentanest. For long-term interventions 10-15 mg of droperidol will also be reinjected.
The methods of administering the nitrous oxide and the curarizer remain identical to those of the continuous perfusion technique.
Pediatric patients
Children aged 12-17 years: follow the adult dosage
Children aged 2 to 11 years: the usual dose in children should be as follows:
Use in children:
Analgesia during surgery, enhancement of anesthesia in spontaneous breathing
Analgesic techniques in spontaneously breathing children should only be used as part of the anesthetic technique or as part of sedation / analgesia techniques by trained personnel and in an environment where sudden stiffness of the chest walls requiring intubation, or apnea can be managed. requiring airway support (see section 4.4.)
04.3 Contraindications
Hypersensitivity to the active substance, to other morphinomimetics or to any of the excipients.
Not to be used in case of confirmed or presumed pregnancy.
Not to be used in the child in the first two years of life
04.4 Special warnings and appropriate precautions for use
The product should only be used in hospitals, clinics and nursing homes and only by the surgeon or anesthetist. As with other CNS depressants, patients treated with Fentanest should be kept under adequate surveillance.
Fentanest can only be administered in suitable facilities by healthcare personnel assigned to monitor the respiratory tract.
Fentanest-induced profound analgesia is accompanied by profound respiratory depression, which may persist longer than the analgesic effect or recur in the postoperative period. As with all potent opioids, respiratory depression is dose proportional. Therefore, if other narcotic analgesics are used together with Fentanest, the doctor will need to take into account the total dose of all these substances before prescribing them for analgesic purposes in the postoperative period. It is recommended that narcotics, in these cases, are initially prescribed in reduced doses, equal to 1/4 - 1/3 of the usual doses.
Certain forms of conduction anesthesia, such as spinal anesthesia, and some epidural anesthetics can alter respiratory function through a block of the intercostal nerves. Therefore, in using Fentanest as a supplement to the aforementioned anesthesia, it will be necessary that the anesthetist be familiar. with the functional alterations at play in these circumstances and are well prepared to deal with them.You will also need to carry out routine monitoring of vital signs.
Fentanest should be used with caution in patients with chronic obstructive pulmonary disease, or with reduced respiratory reserve or with potentially compromised ventilation.
In such patients, in fact, narcotics can further reduce respiratory energy and increase airway resistance. During anesthesia this possibility can be dealt with by assisted or controlled breathing.
Respiratory depression from narcotic analgesics can be neutralized with the use of narcotic antagonists. However, the patient should be kept under appropriate surveillance because the respiratory depression exerted by the amount of fentanyl administered during the anesthesia could last longer than the action. antagonists of narcotics Before resorting to the latter, however, consult the instruction sheets of the individual agents (levallorfane, nalorphin and naloxone).
Resuscitation equipment and a narcotic antagonist should be available for immediate use. Hyperventilation during anesthesia can alter the patient's response to CO2, thus affecting respiration in the postoperative period.
Fentanest can cause muscle stiffness, including in the respiratory muscles. The phenomenon depends on the speed of the injection; it can, in fact, reduce the incidence by proceeding with a slow intravenous injection (normally sufficient for the lowest doses) or through premedication with benzodiazepines and the use of muscle relaxants. With the phenomenon now underway, it is essential to resort to assisted or controlled breathing as well as, if necessary, to a curarizer compatible with the patient's conditions.
Non-epileptic myoclonic / clonic movements may occur. Neuroleptics can induce extrapyramidal symptoms which can be controlled with anti-parkinsonian agents.
Bradycardia, and possibly cardiac arrest, may occur if the patient has received an insufficient dose of anticholinergics or when fentanyl is used in combination with non-vagolytic muscle relaxants. Bradycardia can be treated with atropine. However, Fentanest should be used with caution in patients with cardiac bradyarrhythmia.
Opioids can induce hypotension, especially in hypovolaemic patients.If hypotension occurs, it will be necessary to consider the possibility of a hypovolemia to be corrected with appropriate measures to maintain stable blood pressure or with adequate therapy with fluids by parenteral route. Operating conditions allowing this, the patient's posture must also be modified so as to improve venous return. When moving patients, care must be taken not to provoke orthostatic hypotension. In the event that the hypervolemic treatment with intravenous fluids, together with the other countermeasures, fails to modify the hypotension, the opportunity to administer drugs should be considered which increase blood pressure, other than adrenaline which could, paradoxically, further reduce blood pressure due to the alpha-adrenergic blocking effect exerted by droperidol.
When Fentanest is administered with a neuroleptic such as droperidol, hypotension may occur with a higher incidence; the physician must know the properties of each drug and in particular their different duration of action. Furthermore, when using this combination, fluids for infusion and other countermeasures to combat possible hypotension must be available (see section 4.5).
Head injuries and intracranial hypertension - Fentanest should be used with caution in patients particularly sensitive to depression of the respiratory centers, and in comatose patients suffering from head trauma or brain tumor. Keep in mind that Fentanest can mask the course of head injuries. Rapid bolus injections of opioids should be avoided in patients with impaired intracerebral function; in these patients, the transient reduction in mean arterial pressure was occasionally associated with a short-term reduction in cerebral perfusion pressure.
In the elderly, in debilitated subjects and in other patients at risk, the starting dose of Fentanest should be appropriately reduced; subsequent doses should be based on the effect induced by the starting dose. Adjustment of opioid dosage should be made with caution in patients with any of the following conditions: uncontrolled hypothyroidism; lung pathologies; reduced lung reserve; alcoholism or impaired liver or kidney function due to the importance of these organs in the metabolism and excretion of the drug. Furthermore, these patients require prolonged monitoring in the postoperative period.
Drug addiction - Fentanyl can cause the onset of a morphine-type drug addiction and is therefore susceptible to abuse.
Patients on chronic opioid therapy or those with a history of opioid abuse may require higher dosages.
Pediatric patients:
Analgesic techniques in spontaneously breathing children should be used only as part of the anesthetic technique or as part of sedation / analgesia techniques by trained personnel and in an environment where sudden stiffness of the chest walls requiring intubation or apnea can be managed. requiring airway support.
04.5 Interactions with other medicinal products and other forms of interaction
Effects of other medicinal products on Fentanest
When using high dosages of Fentanest, even relatively low doses of diazepam can cause cardiovascular depression.
Other CNS depressant drugs (e.g. barbiturates, benzodiazepines, narcotics, neuroleptics, general anesthetics and halogenated gases) show additive or potentiating effects towards Fentanest. In patients who have taken these drugs, the useful dose of Fentanest will be lower than the usual one. Similarly, after administration of Fentanest, the dose of other CNS depressants should be reduced.
Fentanyl is rapidly and extensively metabolised primarily by CYP3A4. Itraconazole, a potent inhibitor of CYP 3A4, administered at a dose of 200 mg / day orally for 4 days, did not significantly affect the pharmacokinetics of intravenously administered fentanyl.
However, in individual subjects, increases in plasma concentrations were observed.
Administration of oral ritonavir, one of the strongest inhibitors of CYP3A4, reduced the clearance of intravenous fentanyl by two thirds; however, peak plasma concentrations following a single intravenous fentanyl dose were not affected. Patients receiving single dose fentanyl together with potent CYP3A4 inhibitors, such as ritonavir, require special care and careful observation.
Concomitant administration of fluconazole or voriconazole and fentanyl may result in increased exposure to fentanyl. During prolonged treatment, a reduction in the dosage of fentanyl may be necessary to avoid its accumulation which may increase the risk of prolonged or delayed respiratory depression .
Severe and unpredictable enhancement by MAO inhibitors has been reported for narcotic analgesics. It is recommended that the use of MAO inhibitors be discontinued 2 weeks prior to any surgical or anesthetic procedure.
The association with other psychotropic drugs requires particular caution and vigilance on the part of the physician to avoid unexpected undesirable effects from interaction.
When Fentanest is administered with a neuroleptic such as droperidol, hypotension may occur with a higher incidence; the physician must know the properties of each drug and in particular their different duration of action. In addition, when using this combination, fluids for infusion and other countermeasures to combat any hypotension must be available.
When Fentanest is used with a neuroleptic such as droperidol it can cause a decrease in pulmonary arterial pressure. This must be taken into account during diagnostic or surgical procedures in which the patient's ultimate treatment may depend on the interpretation of the pulmonary artery pressure values.
Furthermore, when Fentanest is used with droperidol and EEG is used as a postoperative monitoring, it will be observed that after the use of the combination, the electroencephalographic trace returns to normal more slowly than usual.
Effects of Fentanest on other medicinal products
Following administration of fentanyl, the dose of other CNS depressant medicinal products should be reduced.
Total plasma clearance and volume of distribution of etomidate are reduced by a factor of 2 to 3, with no change in half-life, when administered with fentanyl. Co-administration of intravenous fentanyl and midazolam results in an increase in the terminal plasma half-life and a decrease in plasma clearance of midazolam. When these medicinal products are co-administered with fentanyl their dosage may need to be reduced.
04.6 Pregnancy and lactation
Not to be used in case of confirmed or presumed pregnancy and in the child in the first two years of life.
There is insufficient information on the use of fentanyl in pregnancy. Fentanyl can cross the placenta in early pregnancy. Animal studies have shown reproductive toxicity. The potential risk to humans is unknown.
Non-administration (i.m. or i.v.) during delivery, even in caesarean section, because fentanyl crosses the placenta and the respiratory centers of the fetus are particularly sensitive to opioids.
Since fentanyl is excreted in breast milk, the benefit / risk ratio of breastfeeding following the administration of fentanyl must be carefully considered. In any case, do not breastfeed within 24 hours following administration of the medicinal product.
04.7 Effects on ability to drive and use machines
Patients should only drive or operate machinery if sufficient time has elapsed following the administration of fentanyl.
04.8 Undesirable effects
Data from clinical studies
The safety of IV fentanyl was evaluated in 376 subjects who participated in 20 clinical trials evaluating IV fentanyl as an anesthetic. These subjects were given at least one dose of fentanyl and then the safety data were evaluated. Based on the pooled safety data from these clinical trials, the most common adverse reactions (incidence ≥ 5%) were (% incidence): nausea, vomiting, muscle stiffness, hypotension, hypertension, bradycardia and sedation.
The table below lists undesirable effects, including those mentioned above, associated with the use of IV fentanyl evaluated in both clinical trials and post-marketing.
The frequency categories used correspond to the following convention: very common (≥1 / 10), common (≥1 / 100,
As with other analgesics, the most commonly reported side effects of some importance after Fentanest injection are: respiratory depression, apnea, muscle stiffness and bradycardia; in the absence of corrective measures these phenomena can lead to respiratory arrest, circulatory depression, cardiac arrest. Also observed: hypotension, dizziness, blurred vision, nausea and vomiting, laryngospasm, sweating.
It has also been reported that a resumption of respiratory depression may occur in the postoperative period. With this in mind, patients should be carefully observed and, if necessary, appropriate countermeasures should be adopted. When a neuroleptic such as droperidol is used with Fentanest the following side reactions may occur: chills and / or tremors, restlessness and post-operative hallucinatory episodes (sometimes associated with transient periods of mental depression); extrapyramidal symptoms (dystonia, akathisia, oculogyric crisis), were observed up to 24 hours after surgery (see section 4.4).
Any extrapyramidal symptoms can usually be reduced or controlled with antiparkinsonian drugs. Postoperative somnolence is frequently reported following the use of droperidol.
After the use of Fentanest associated with droperidol, increases in blood pressure with or without pre-existing hypertension have also been reported. This could be due to an as yet unexplained alteration in sympathetic activity secondary to high doses of the two drugs; however, the phenomenon is often attributed to sympathetic stimulation of anesthetic or surgical origin during the light stage of anesthesia.
04.9 Overdose
Signs and symptoms - the manifestations of an overdose of Fentanest are nothing more than an extension of its pharmacological actions. Depending on the individual sensitivity, the clinical picture is mainly determined by the degree of respiratory depression which can vary from bradypnea to apnea.
Treatment - in the presence of hypoventilation or apnea, oxygen should be administered and assisted or controlled breathing should be used, as indicated. The airways must be kept open and for this purpose it may be appropriate to use an oropharyngeal cannula and an endotracheal tube.
If respiratory depression is associated with muscle stiffness, it may be necessary to use a curarizer to facilitate assisted or controlled breathing. The patient will be carefully observed for 24 hours, while normal body heat is maintained and adequate fluid intake.
Patients must be carefully monitored, body heat and proper fluid intake must be maintained. In case of severe or persistent hypotension, the presence of hypovolemia should be suspected, to be addressed with appropriate parenteral fluid therapy. As indicated, a specific narcotic antagonist, such as nalorphin, levallorphane or naloxone, should be kept ready for use to address the respiratory depression induced by fentanyl.
However, this does not preclude the use of more immediate countermeasures.
It should be noted that the duration of respiratory depression following an overdose of fentanyl may exceed the duration of action of the narcotic antagonist.
For more detailed information on the use of these antagonists, consult the instruction sheets of the individual products.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Fentanyl is a mimetic morphine capable of causing surgical analgesia of 50-100 times greater than that of morphine.
After i.v. at a dosage of 1 - 2 mcg / kg. the analgesic effect sets in within 2-3 minutes and persists for about 30 minutes.
05.2 "Pharmacokinetic properties
Fentanyl exhibits triphasic plasma kinetics with a half-life of approximately 3.7 hours.
Plasma clearance is high (approximately 12 mL / min / kg) and the total volume of distribution is approximately 4.2 L / kg.
Plasma protein binding at therapeutic concentrations and pH 7.4 is approximately 85%
05.3 Preclinical safety data
Acute toxicity was evaluated in rats and mice:
Rat (i.v./s.c.): 2.3 mg / kg - 9.5 mg / kg
Mouse (i.v./s.c.): 13 mg / kg - 70 mg / kg
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, water for injections.
06.2 Incompatibility
Fentanest should not be mixed with alkaline or buffered solutions.
06.3 Period of validity
3 years
06.4 Special precautions for storage
None
06.5 Nature of the immediate packaging and contents of the package
Colorless type I glass ampoule containing 0.1 mg fentanyl in 2 ml of solution. Pack of 5 ampoules.
06.6 Instructions for use and handling
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Italia S.r.l., Via Isonzo 71, 04100 Latina
08.0 MARKETING AUTHORIZATION NUMBER
AIC 020473029
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
January 27, 2000 / May 31, 2005
10.0 DATE OF REVISION OF THE TEXT
November 18, 2010
