Fentanyl. Durogesic matrix - instructions for use Fentanyl half-life

Active ingredient: 50 mcg of fentanyl in 1 ml of solution.

Excipients: citric acid, water for injection.

Pharmacodynamics. Fentanyl is a short-acting opioid analgesic. Like morphine and promedol, fentanyl is an agonist primarily at the mu-opioid receptor. Activates the endogenous antinociceptive system and thus disrupts the interneuronal transmission of pain impulses at various levels of the central nervous system (CNS), and also changes the emotional coloring of pain.

In terms of pharmacological properties, fentanyl is close to morphine: it increases the threshold of pain sensitivity to painful stimuli of various modalities, inhibits conditioned reflexes, has a depressant effect on the central nervous system, and suppresses the activity of the respiratory center. It differs from morphine in its greater activity (100 times greater in analgesic effect than morphine), shorter duration of action and more pronounced ability to depress the respiratory center.

When administered parenterally, it has a rapid analgesic effect. When administered intravenously, the maximum effect develops after 1-3 minutes and lasts for 15-20 minutes; When administered intramuscularly, the maximum effect develops after 3-10 minutes, the duration of action is 1-2 hours.

Pharmacokinetics. To achieve an average level of pain relief, the fentanyl concentration should reach 15-20 ng/ml. Communication with plasma proteins - 79-87%. Clearance is 400-500 ml/min, half-life is 10-30 minutes, volume of distribution is 60-80 l. Rapidly redistributed from the blood and brain to muscles and adipose tissue.

Metabolized in the liver (N-dealkylation and hydroxylation), kidneys, intestines and adrenal glands.

It is excreted by the kidneys (75% - in the form of metabolites and 10% - unchanged) and with bile (9% - in the form of metabolites).Passes into breast milk.

Directions for use and dosage:

Features of application:

Side effects:

Interaction with other drugs:

Contraindications:

Overdose:

Storage conditions:

List II. "List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation", in specially equipped premises with a license for the specified type of activity. At a temperature not higher than 25 °C. Keep out of the reach of children. Shelf life - 4 years. Do not use after the expiration date stated on the package.

Vacation conditions:

On prescription

Package:

Solution for intravenous and intramuscular administration, 50 mcg/ml. Packaging: in ampoules of 1 ml and 2 ml. 5 ampoules per blister pack made of polyvinyl chloride film and aluminum foil. 1 or 2 blister packs with instructions for use of the drug, a knife or an ampoule scarifier in a cardboard pack. 20, 50 or 100 blister packs along with an equal number of instructions for use, respectively, with knives or ampoule scarifiers in cardboard boxes or corrugated cardboard boxes. When packaging ampoules with rings or break points, knives or ampoule scarifiers are not inserted.

To eliminate persistent pain and during certain surgical interventions, the use of Fentanyl is justified. This medicine belongs to the group of synthetic opioid narcotic analgesics, and therefore can have a narcotic effect and cause addiction. The use of the drug can be dangerous, so it is used only as prescribed by a doctor in dosages not exceeding the values ​​​​specified in the instructions.

The INN and trade name of the drug is Fentanyl. The name of the drug in Latin is Fentanyl.

ATX

In the international ATC classification, this medicine has code N01AH01.

Release forms and composition

The medication is produced in 2 dosage forms - a patch (transdermal therapeutic system) and a solution for intravenous and intramuscular administration. The main active ingredient of Fentanyl is the compound of the same name.

The injection solution also includes monohydrate, citric acid and prepared water. The patches include an adhesive layer, a backing layer and a protective film. Fentanyl solution 0.005% is available in ampoules of 2 and 10 ml. The cardboard package contains 5 or 10 ampoules. The patches are available with a contact area from 4.2 cm² to 33.6 cm². They are presented in cardboard packaging of 5 pieces.

pharmachologic effect

The analgesic activity of fentanyl at a dose of 0.1 mg is equivalent to the effect of 10 mg of morphine. The active substance of this drug affects the opioid receptors of the central nervous system and peripheral nerve fibers. The medication quickly increases the pain threshold because it suppresses the propagation of impulses signaling pain along nerve fibers to the cells of the central nervous system responsible for their analysis.

This opioid medication changes the perception of pain. The medicine has a mild hypnotic effect. The drug not only has a pronounced analgesic and sedative effect, it can cause a feeling of euphoria, so the development of physical and mental dependence is possible. In addition, with repeated use of the product, tolerance to the active substance Fentanyl may occur.

Pharmacokinetics

The active substance of the drug is fat-soluble. The distribution of the drug after administration is uneven, and first traces of it are found in the kidneys, liver and other organs with an active blood supply. Subsequently, it saturates other body tissues. The highest concentration of the drug in the blood is observed within 3 minutes after injection into a vein, and when injected into a muscle, it reaches its highest point after half an hour.

The high level of drug concentration in the blood persists for approximately 2 hours. During this period, a pronounced analgesic effect is observed. Metabolism of the active substance occurs in the liver. The drug is excreted primarily in the urine. Up to 10% of the dose is excreted unchanged. After a single use, the drug is completely eliminated from the body within 6-12 hours. When using a patch, the active substance is delivered to the tissues of the central nervous system and peripheral nerves for at least 72 hours.

This method of administering the drug allows you to maintain its concentration in the blood at the same level for a long time.

Indications for use

The most common indication for the use of Fentanyl is neuroleptanalgesia. This is a method of intravenous anesthesia in which the patient is conscious, but does not feel pain or emotions. A similar method of pain relief is used for a wide range of diagnostic and surgical interventions, incl. on the abdominal organs.

Plasters are often used to administer local anesthesia. The medication can be used for anesthesia for people taking antipsychotics and tranquilizers, incl. Droperidol and Xanax. In addition, when a patient is put under anesthesia, a combination of Fentanyl and Propofol is possible.

The use of Fentanyl is often indicated to eliminate persistent cancer pain in adults and children. For inoperable tumors that cannot be eliminated by radiation and chemotherapy, the drug can be used in the form of a patch. In addition, it is possible to use the medication to eliminate intense pain during myocardial infarction. The use of Fentanyl is justified to eliminate chronic pain syndrome in various pathologies, if it is impossible to achieve a positive effect through the use of other medications.

Contraindications

The use of Fentanyl is unacceptable for the treatment of people suffering from bronchial asthma and severe respiratory diseases. The product should not be used if patients have a tendency to allergic reactions or hypersensitivity to individual components of the drug. The use of Fentanyl as anesthesia during obstetric operations is not recommended.

How to take Fentanyl?

Approximately 15 minutes before the patient is put under anesthesia before surgery, IV medication is administered in a dosage of 0.05 to 0.1 mg per kg of body weight. During surgery, intravenous administration is carried out at a dose of 0.05 to 0.2 mg per kg of body weight every 30 minutes. For pathologies accompanied by intense pain, Fentanyl patches are used, which are attached to the skin for 72 hours.

For diabetes

When performing anesthesia in patients suffering from diabetes mellitus, the use of Fentanyl in combination with Propofol and Diazepam is indicated during anesthesia. The dose is selected individually.

Side effects

Rhythm disturbances and a decrease in blood pressure are often observed during the use of the drug. In rare cases, cardiac arrest may occur due to the action of this drug. Side effects from other organs and systems are also possible.

Gastrointestinal tract

After using the medicine, there is a high probability of developing biliary colic. In addition, stool disturbances, nausea and vomiting are often observed.

Blood-forming organs

Bone marrow depression occurs extremely rarely.

central nervous system

When using Fentanyl, increased intracranial pressure and frequent headaches are possible. Among other things, side effects may include drowsiness, euphoria, and visual disturbances.

From the urinary system

Rarely, acute urinary retention occurs in patients treated with Fentanyl.

From the respiratory system

The medication has a depressant effect on the respiratory center in the brain, so breathing may stop.

Allergies

Both when using the solution and when using patches, skin rashes and itching may occur. In rare cases, laryngospasm and Quincke's edema occur.

special instructions

The use of Fentanyl patches requires complete avoidance of sunbathing procedures. You should also avoid visiting saunas and steam baths. This drug should not be used for anesthesia in the absence of conditions for artificial ventilation.

Alcohol compatibility

During Fentanyl therapy, you should avoid drinking alcohol.

Impact on the ability to operate machinery

You should avoid driving a car while undergoing treatment with Fentanyl.

Use during pregnancy and lactation

Treatment with Fentanyl is unacceptable during pregnancy, since the risk to the fetus is extremely high due to the increased likelihood of developing severe pathologies. If a woman took this medication while pregnant, the newborn may experience severe withdrawal symptoms. If you need to use the medication after childbirth, you should stop breastfeeding your baby.

Prescription of Fentanyl for children

For surgical treatment of children, the medication is used in a dosage of 0.002 mg/kg. During surgery, intravenous administration of the drug may be prescribed in a dose of 0.1 to 0.15 mg per kg. Intramuscular administration is possible in a dose of 0.15 to 0.25 mg.

Use in old age

Overdose

If you use too much of the drug, breathing problems may occur. In addition, some patients experienced hypotension and severe muscle spasms following an overdose of this opiate. In severe cases, stupor, convulsions and coma may develop.

Interaction with other drugs

Using Fentanyl with other medications that have a sedative, hypnotic effect, or with opioids increases the risk of side effects. If a patient uses CYP3A4 inhibitors while using Fentanyl, the concentration of the latter in the blood will be increased, which will increase the duration of the effect. Simultaneous administration of a CYP3A4 inducer leads to a decrease in the effectiveness of the opiate.

Analogs

Medicines that have similar effects to Fentanyl include:

1. Durogesic.
2. Fentadol.
3. Fendivia.
4. Dolforin.
5. Lunaldin.

Conditions for dispensing from a pharmacy

The medication is dispensed in pharmacies with a doctor's prescription.

Can I buy it without a prescription?

When purchasing a product from unofficial sellers, there is a high probability of purchasing a counterfeit or expired drug.

Fentanyl price

In Russia, the price of Fentanyl solution ranges from 125 to 870 rubles. The cost of the patch ranges from 1800 to 4700 rubles.

Storage conditions of the drug

The optimal storage temperature for the medication is 25°C.

Best before date

The drug can be stored for no more than 4 years.

Pharmacological properties

Pharmacodynamics

Fentanyl is an opioid analgesic with high affinity for the mu-opioid receptor.

Fentanyl can be used as an analgesic component during general anesthesia or alone. Fentanyl may reduce cardiac output by slowing the heart rate, which is an advantage for cardiovascular conditions where it is desirable to reduce the stress response. 100 mcg of fentanyl (2 ml) is approximately equivalent in analgesic activity to 10 mg of morphine. The drug exhibits its effect quickly, but the maximum analgesic effect and inhibitory effect on the respiratory center occurs only after a few minutes. The duration of the analgesic effect with a single intravenous dose of up to 100 mcg is about 30 minutes. The depth of analgesia depends on the dose of the drug and can be adjusted according to the intensity of pain. Fentanyl has a high therapeutic breadth. In rats, the therapeutic index (LD 50 /ED 50) for the lowest degree of analgesia is 277, compared with 69.5 and 4.6 for morphine and pethidine, respectively.

Like other opioid analgesics, fentanyl, depending on the dose and rate of administration, can cause muscle rigidity, euphoria, miosis and bradycardia.

Histamine release assays and skin prick tests in humans, as well as in vivo tests in dogs, have shown that clinically significant histamine release is rare with fentanyl use. The specific opioid antagonist for fentanyl is naloxone.

Pharmacokinetics

Fentanyl is a lipid-soluble drug and its pharmacokinetics can be described using a three-compartment model. Following intravenous administration, high concentrations of fentanyl occur rapidly in well-perfused tissues such as the lungs, kidneys, and brain. Subsequently, the drug is redistributed to other tissues. It accumulates slowly in skeletal muscle and at an even slower rate in adipose tissue, from which it is gradually released into the blood. Up to 80% of fentanyl is bound to blood plasma proteins.

Fentanyl is primarily metabolized in the liver, probably by N-dealkylation, and is excreted primarily in the urine. Less than 10% is excreted unchanged. The half-life of fentanyl is 3.7 hours.

Indications for use

Fentanyl is used for neuroleptanalgesia (in combination with droperidol), for premedication (as part of certain regimens), for induction of anesthesia, for pain relief (during short-term extracavitary operations), as an additional agent during operations under local anesthesia, for pain syndrome of strong and moderate intensity with myocardial infarction, renal and hepatic colic.

Fentanyl is used for the relief of constant (persistent) moderate and severe chronic pain that requires constant, round-the-clock administration of opioids over a long period of time and cannot be relieved in another way (for example, non-steroidal anti-inflammatory drugs (or in patients with contraindications to the use of drugs of this group) ), a combination of opioids or immediate-release opioid preparations).

It is not recommended to use fentanyl for the relief of postoperative pain, except in cases where the administration of drugs with a high antinociceptive effect is required after palliative operations for cancer.

Patients who tolerate opioid therapy are those who have been taking at least 60 mg of morphine per day, at least 30 mg of oral oxycodone per day, or at least 8 mg of hydromorphone per day for a week or more.

Directions for use and dosage regimen

Fentanyl should only be used by highly trained personnel and in conditions where mechanical ventilation is available.

The dose of the drug should be selected individually in accordance with the age, body weight, physical condition and underlying disease of the patient, and it also depends on the type of surgery and anesthesia performed, and the use of other medications.

The initial dose should be reduced in elderly and debilitated patients. The effect of the initial dose must be taken into account when determining maintenance doses.

Fentanyl can be administered intravenously and intramuscularly. The drug can be administered intravenously to children and adults as a bolus or as an infusion.

Standard dosage regimen:

Adults and children over 12 years of age:

Doses greater than 200 mcg are used exclusively for anesthesia.

For premedication, 1-2 ml of the drug is administered intramuscularly before induction of anesthesia.

When given intravenously in patients without premedication, 2 mL of fentanyl can provide adequate analgesia for 10 to 20 minutes for low-pain surgeries. A bolus of 10 ml of fentanyl can provide analgesia for about 1 hour, which is used in operations with moderate pain intensity. Administration of fentanyl at a dose of 50 mcg/kg provides analgesia for 4–6 hours for operations with high pain intensity.

Fentanyl can also be given by intravenous infusion.

In mechanically ventilated patients, fentanyl may be given a loading dose of fentanyl rapidly at a rate of approximately 1 mcg/kg/min over the first 10 minutes, followed by a loading dose of approximately 0.1 mcg/kg/min. An alternative route of loading loading dose administration may be bolus administration. The infusion rate should be titrated according to the individual patient's response; it may be necessary to reduce the rate of administration. Administration should be stopped approximately 40 minutes before the end of surgery, unless it is planned to continue artificial ventilation after surgery.

If spontaneous breathing is maintained, lower rates of fentanyl administration may be required, for example, 0.05 - 0.08 mcg/kg/min. Higher rates of drug administration (up to 3 mcg/kg/min) are used for cardiac surgery.

To determine the required dose of fentanyl, it is important to correctly assess the possible degree of pain intensity, the effect of medications used for premedication, and the duration of the procedure.

Use in children. For children over 12 years of age, the dosage regimen is the same as for adults.

Standard dosage regimen for children from 2 to 12 years of age:

In children, it is used for analgesia during surgery, enhancing anesthesia while maintaining spontaneous breathing.

Analgesia in spontaneously breathing children should only be used as an adjunct to anesthetic management or as an adjunct to sedation (or as part of a sedation/analgesia technique), provided that qualified personnel and equipment are available to perform tracheal intubation and artificial respiration.

Side effect

To assess the frequency of occurrence of the following adverse reactions, the following gradations were used: very often (≥1/10), often (from ≥1/100 to<1/10), нечасто (от ≥ 1/1 000 до <1/100), редко (от ≥ 1/10 000 до < 1/1 000), очень редко (<1/10 000), неизвестно – частота не может быть оценена на основании имеющихся данных.

From the immune system: unknown – hypersensitivity (anaphylactic shock, anaphylactic reactions, urticaria).

Mental disorders: infrequently – euphoria.

From the nervous system: often – dyskinesia, sedation, dizziness; infrequently – headache; unknown – convulsions, loss of consciousness, myoclonus.

From the senses: often - impaired visual perception.

From the cardiovascular system: often – bradycardia, tachycardia, arrhythmia, hypotension, hypertension, pain along the vein; infrequently – phlebitis, fluctuations in blood pressure; unknown – cardiac arrest.

From the respiratory system: often – laryngospasm, bronchospasm, apnea; infrequently – hyperventilation, hiccups; unknown - respiratory depression.

From the gastrointestinal tract: very often - nausea, vomiting.

From the skin: often – allergic dermatitis; unknown - itching.

From the musculoskeletal system: very often – muscle rigidity (including the chest).

Others: often – postoperative confusion; uncommon – hypothermia, chills, postoperative agitation, complications of anesthesia from the respiratory tract.

When fentanyl is used together with antipsychotics, the following adverse reactions may occur: chills and/or myoclonus, anxiety, postoperative hallucinations and extrapyramidal symptoms.

Contraindications

Hypersensitivity to any component of the drug, obstetric operations (before extraction of the fetus), severe hypertension in the pulmonary circulation, depression of the respiratory center, pneumonia, atelectasis and pulmonary infarction, bronchial asthma, tendency to bronchospasm, diseases of the extrapyramidal system, intracranial hypertension, intestinal obstruction, drug dependence, alcoholism, drug addiction, pregnancy, lactation (breastfeeding must be stopped), use in patients after surgical interventions on the biliary tract, relief of short-term and mild pain.

Overdose

Symptoms: dizziness, drowsiness, nervousness, general weakness, depression of the cardiovascular system, decreased blood pressure, bradycardia, clammy sweat, miosis, muscle rigidity, depression of the respiratory center, bradypnea, apnea.

Treatment: administration of a specific antagonist - naloxone; symptomatic therapy that supports vital functions (including the administration of muscle relaxants, artificial ventilation, for bradycardia - the administration of atropine, for a pronounced decrease in blood pressure - replenishment of circulating blood volume).

Precautionary measures

Fentanyl should only be used by highly qualified personnel. Fentanyl should be prescribed only by specialists who are knowledgeable in the management of long-term opioid analgesic therapy, identification and recovery from hypoventilation, including, if necessary, treatment with opioid receptor antagonists.

Fentanyl, like other opioid analgesics, can be subject to abuse both when used in accordance with its indications for use and when the drug is obtained illicitly. This risk must be taken into account when prescribing, prescribing and dispensing a drug in cases where there are concerns about misuse, abuse and other violations.

Patients at increased risk for opioid abuse include those with a family history of addiction (including drug or alcohol addiction) or certain mental health disorders (eg, major depression). Before prescribing opioid analgesics to a patient, the clinical risk of developing opioid dependence should be assessed. All patients receiving opioids should be monitored for signs of misuse, abuse, and dependence. Patients at increased risk for opioid abuse are recommended to remain on modified-release opioid formulations; These patients require constant monitoring for signs of opioid abuse.

Concerns about abuse, dependence, and inappropriate use should not be a reason for not providing appropriate pain management.

However, all patients receiving opioid analgesics require careful monitoring for signs of dependence and abuse, as there is a risk of developing dependence even with the proper use of opioid analgesics.

Fentanyl should not be used to relieve short-term or mild pain.

Concomitant use of drugs that affect the central nervous system requires special assessment and monitoring.

The use of fentanyl can cause respiratory depression, which is dose-dependent and can be relieved by the administration of a specific antagonist, naloxone. Additional doses of naloxone may be required because respiratory depression may last longer than the duration of action of the antagonist. Respiratory depression is one of the most dangerous complications of therapy with opioid agonists, which include fentanyl. The risk of developing respiratory depression is greater in elderly and debilitated patients, usually after a large initial dose in opioid-naïve patients or when opioids are co-administered with other drugs that depress respiratory function. Opioid-induced respiratory depression is manifested by decreased respiratory stimulation and decreased respiratory rate, often resulting in abnormal breathing (deep inspiration interrupted by an atypically long pause). Carbon dioxide retention due to respiratory depression may enhance the sedative effects of opioids. In this regard, overdose of drugs with sedative properties and opioids is especially dangerous.

Profound analgesia is accompanied by severe respiratory depression, which may persist or recur in the postoperative period. For this reason, careful monitoring of patients is necessary, as well as the availability of the necessary equipment and a specific antagonist for resuscitation measures. Hyperventilation during anesthesia may alter the patient's response to CO2 concentrations and cause respiratory depression in the postoperative period.

Fentanyl should be prescribed with extreme caution in patients with obstructive pulmonary disease or cor pulmonale, as well as in patients with a significant decrease in residual lung volume, hypoxia, hypercapnia, or a history of respiratory depression. In these patients, even normal therapeutic doses of fentanyl can significantly suppress respiratory function to the point of apnea. For these patients, alternative non-opioid therapy should be considered, and opioids should be prescribed only under close medical supervision and at the lowest effective dose.

Head injuries and increased intracranial pressure

Fentanyl should not be prescribed to patients who may be particularly sensitive to the intracranial effects of elevated CO2 levels. This category of patients includes those with signs of increased intracranial pressure, impaired consciousness, or coma. Opioids may complicate the clinical assessment of patients with traumatic brain injury. Fentanyl should be administered with caution to patients with a brain tumor.

Muscle stiffness, including the pectoral muscles, may occur, which can be avoided by taking the following measures: slow intravenous administration, premedication with benzodiazepines and the use of muscle relaxants.

Myoclonic movements of a non-epileptogenic nature may occur. Bradycardia, including cardiac arrest, may occur if the patient has received an insufficient amount of anticholinergic drug or when fentanyl is used in combination with muscle relaxants that do not have vagolytic activity. Bradycardia can be treated with atropine.

With long-term use of fentanyl, tolerance and drug dependence may develop.

Opioids may cause hypotension, especially in hypovolemic patients. Necessary measures must be taken to maintain stable blood pressure.

Rapid bolus injections of opioid drugs should be avoided in patients with altered cerebral vascular elasticity: in such patients, a transient decrease in mean arterial pressure is sometimes accompanied by a transient decrease in cerebral perfusion pressure.

Patients on long-term opioid therapy or with opioid dependence may require higher doses of fentanyl.

The use of fentanyl requires caution in patients with the following conditions: uncontrolled hypothyroidism, pulmonary disease, reduced tidal volume, alcoholism, impaired liver or kidney function. Such patients also require long-term postoperative monitoring.

When using fentanyl together with antipsychotics (such as droperidol), it is necessary to take into account the difference in the duration of action of these drugs. When used simultaneously, the risk of hypotension increases. Antipsychotics may cause extrapyramidal symptoms, which can be controlled with antiparkinsonian drugs.

As with other opioids, due to its anticholinergic effects, the use of fentanyl can lead to increased pressure in the bile duct and, in isolated cases, spasms of the sphincter of Oddi may occur.

In patients with myasthenia gravis, careful consideration should be given to the use of certain anticholinergics and neuromuscular blocking agents before and during general anesthesia, which includes intravenous fentanyl.

Use of fentanyl during labor may cause respiratory depression in the newborn.

Interactions with alcohol and drugs of abuse

Fentanyl may have additive CNS depressant effects when administered in conjunction with alcohol, other opioids, or illicit drugs with similar CNS effects.

Use in children. The safety of fentanyl has not been demonstrated in children under 2 years of age. Fentanyl should only be prescribed to children over 2 years of age who have demonstrated opioid tolerance.

Analgesia in spontaneously breathing children should only be used as an adjunct to anesthetic management or as an adjunct to sedation (or as part of a sedation/analgesia technique), provided that qualified personnel and equipment are available to perform tracheal intubation and artificial respiration. Accidental administration of fentanyl, especially in children, can lead to a fatal overdose of the drug.

Use in the elderly. Data from studies of intravenous fentanyl suggest that elderly patients may have decreased clearance and prolonged half-life and may be more sensitive to fentanyl than younger patients. Elderly patients should be closely monitored for symptoms of possible fentanyl overdose, which will require a reduction in the fentanyl dose.

Use during pregnancy and lactation. There is insufficient data regarding the use of fentanyl in pregnant women. Fentanyl crosses the placenta in early pregnancy. Animal studies have shown reproductive toxicity, but the implications for humans are unknown. Long-term use of fentanyl during pregnancy can lead to neonatal withdrawal syndrome, which can be life-threatening if left untreated. If it is necessary to take opioids for an extended period of time in pregnancy, the patient should be warned of the risk of neonatal withdrawal syndrome and ensure that appropriate treatment will be available.

The use of fentanyl (IV or IM) during childbirth (including cesarean section) is not recommended because fentanyl crosses the placenta and also because the fetal respiratory center is particularly sensitive to opiates. If a decision is made to use fentanyl, a ready-to-use antidote must be available.

Fentanyl is excreted in breast milk and may cause sedation/respiratory depression in infants, so do not breastfeed for 24 hours after taking the drug. The risk/benefit ratio of breastfeeding after fentanyl use should be considered.

Serotonin syndrome

Caution should be exercised when concomitantly using fentanyl with drugs that affect the serotonergic neurotransmitter system.

Concomitant use with serotonergic drugs, such as selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, as well as drugs that affect serotonin metabolism (including monoamine oxidase inhibitors), can lead to the development of life-threatening serotonin syndrome.

The development of serotonin syndrome can occur when medications are used in recommended doses.

The clinical picture of serotonin syndrome may include the following symptoms:

Changes in mental status (anxiety, hallucinations, coma);

Disorders of the autonomic nervous system (tachycardia, labile blood pressure, hyperthermia);

Neuromuscular disorders (hyperreflexia, lack of coordination, muscle rigidity);

Gastrointestinal symptoms (eg, nausea, vomiting, diarrhea).

If serotonin syndrome is suspected, fentanyl use should be discontinued immediately.

Impact on the ability to drive vehicles and other potentially dangerous mechanisms. Driving and engaging in other potentially hazardous activities are only possible if a sufficient amount of time has passed after using the drug.

Interaction with other drugs

Effects of other drugs on fentanyl

Barbiturates, benzodiazepines, antipsychotics, halogen gases, and other non-selective CNS depressants (eg, alcohol) may potentiate respiratory depression when used together with fentanyl. When using such drugs, the dose of fentanyl should be reduced.

Fentanyl is a drug with high clearance and is rapidly and extensively metabolized, mainly by CYP3A4.

Concomitant use of fentanyl with strong inhibitors of the cytochrome P450CYP3A4 isoenzyme (ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir and nefazodone) may lead to increased plasma concentrations of fentanyl, which increases the risk of adverse reactions, including life-threatening respiratory depression, or prolongs the symptoms of adverse reactions. reactions. Patients receiving fentanyl and strong CYP3A4 inhibitors concomitantly should be carefully monitored over an extended period of time, with dosage adjustments being made if necessary.

When fluconazole or voriconazole and fentanyl are used together, the duration of action of fentanyl may be increased.

It is recommended to stop using MAO inhibitors two weeks before surgery or anesthesia. However, there are several reports of the use of fentanyl without consequences during surgery or anesthesia in patients who were on therapy with MAO inhibitors.

The combined use of fentanyl and muscle relaxants that do not have vagolytic properties can lead to bradycardia, including cardiac arrest.

Concomitant use of fentanyl and droperidol increases the risk of hypotension.

Pre-administration or concomitant use of cimetidine may increase plasma concentrations of fentanyl with repeated use of these drugs.

Bradycardia may be aggravated by previous or concomitant use of drugs such as beta-blockers, suxamethonium, halothane, vecuronium, which themselves have the ability to cause bradycardia.

Effects of fentanyl on other drugs

When fentanyl is used concomitantly with other CNS depressants, the dose of the latter should be reduced.

Fentanyl increases plasma concentrations of etomidate and increases its half-life during the elimination phase.

Concomitant use of fentanyl and intravenous midazolam results in an increase in the half-life and a decrease in the overall clearance of midazolam. When using the above drugs together with fentanyl, their dose may need to be reduced.

Serotonergic drugs: Concomitant use of fentanyl with serotonergic drugs, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, may increase the risk of developing serotonin syndrome.

Storage conditions

Narcotic drug.

In a dark place at a temperature from 15 0 C to 25 0 C.

Keep out of the reach of children.

Best before date

Do not use after the expiration date stated on the package.

Package

In ampoules of 2 ml in blister packs No. 5×1, No. 5×2.

Release from pharmacies

Latin name: PhentanylComposition and release form:

1 ml of solution for injection contains fentanyl 0.05 mg; per package 5 ampoules of 1 and 2 ml.

Fentanyl excites opiate (mainly mu) receptors in the central nervous system, spinal cord and peripheral tissues. Increases the activity of the antinociceptive system, increases the threshold of pain sensitivity. Changes the emotional coloring of pain.

It has a strong but short-term (with a single administration) analgesic effect.

After intravenous administration, the maximum effect develops within 1-3 minutes and lasts 15-30 minutes. After intramuscular administration, the maximum effect occurs within 3-10 minutes.

Up to 79% of fentanyl binds to blood proteins. Clearance is 0.4-0.5 l/min. The half-life is 10-30 minutes. Rapidly redistributed from the blood and brain to muscles and adipose tissue. Biotransformed in the liver, kidneys, intestines and adrenal glands. It is excreted in urine (75% in the form of metabolites and 10% unchanged) and feces (9% in the form of metabolites). Passes into breast milk.