Fentanyl TTS (Fendivia) in the treatment of pain syndrome during the stages of radiation treatment for tongue cancer (clinical observation)

Fendivia™

Transdermal patches containing fentanyl release the active substance within 72 hours. The release rate of fentanyl is 12.5; 25; 50; 75 and 100 μg/hour, and the area of ​​the corresponding active surface is 4.2; 8.4; 16.8; 25.2 and 33.6 cm2.

The required dosage of fentanyl is individualized and should be assessed regularly after each use.

Mode of application

The drug is used transdermally.

The fentanyl patch should be applied to a flat surface of intact, non-irradiated skin of the torso or upper arm. For application, it is recommended to choose a place with minimal hair (preferably without hair). Before application, the hair at the application site should be cut (do not shave!). If before applying the patch the application site needs to be washed, then this should be done with clean water. Do not use soaps, lotions, oils, alcohol or other products as they may cause skin irritation or change its properties. Before application, the skin must be completely dry.

Because the transdermal patch is protected by a waterproof outer protective film, it can be left on for short periods of showering.

The fentanyl transdermal patch should be applied immediately after removal from the heat seal pouch. After removing the protective film, the transdermal patch must be pressed firmly with the palm of your hand at the application site for approximately 30 seconds. Make sure that the patch fits snugly against the skin, especially around the edges. Additional fixation of the patch may be required. The drug should be worn continuously for 72 hours, after which it must be changed to a new patch. A new transdermal patch should always be applied to a different area of ​​the skin, without covering the site of the previous application. The patch can be reapplied to the same application site no earlier than after 7 days.

The transdermal patch should not be divided or cut (see section "Special Instructions").

Selection of initial dosage

The dosage level of fentanyl is established depending on the level of opioid use in the previous period, as well as taking into account the possible development of tolerance, concomitant drug treatment, the general health of the patient and the severity of the disease.

If the response to opioids for a given pain syndrome is not fully understood, the initial dosage should not exceed 25 mcg/hour.

Switching from other opioids

When a patient switches from oral or parenteral opioids to fentanyl treatment, the initial dosage is calculated as follows:

1) The amount of analgesics required in the last 24 hours should be determined;

2) The amount obtained should be converted to the appropriate oral dose of morphine using Table 1;

3) The appropriate dose of fentanyl should be determined using Table 2.

Table 1: Drug dosages equivalent in analgesic effectiveness

All intramuscular (IM) and oral (PO) doses presented in the table are equivalent in the analgesic effect of 10 mg of morphine administered intramuscularly.

*Based on study results obtained after a single dose of drug administration, with IM administration of each drug compared to morphine to achieve equivalent efficacy. Oral doses are the doses recommended for switching from the parenteral route of administration to the oral route of administration.

**The efficacy ratio of 3:1 for intramuscular/oral morphine is based on research findings in the treatment of patients with chronic pain.

Table 2: Recommended starting dose of Fendivia™ based on daily oral morphine dose

An initial assessment of the maximum analgesic effect of Fendivia™ can be carried out no earlier than 24 hours after application. This limitation is due to the fact that the increase in serum fentanyl concentrations in the first 24 hours after application occurs gradually. Therefore, when switching from one drug to another, previous analgesic therapy should be discontinued gradually after the application of the initial dose of Fendivia™ until its analgesic effect has stabilized.

Dose selection and maintenance therapy

The transdermal patch should be replaced with a new one every 72 hours. The dose is selected individually until the required level of pain relief is achieved. If a significant decrease in the analgesic effect occurs 48-72 hours after application of the initial dose, then replacement of the patch may be necessary after 48 hours. A dose of 12.5 mcg/hour is usually sufficient for dose selection in the lower dosage range. If pain relief turns out to be insufficient by the end of the period of action of the first application, then the dose can be increased after 3 days until the desired effect is obtained.

Typically, the dose is increased by 12.5 mcg/hour or 25 mcg/hour at a time, but the patient's condition and the need for additional pain relief must be taken into account. To achieve a dose greater than 100 mcg/hour, multiple patches can be used simultaneously. If breakthrough pain occurs, patients may periodically require additional doses of short-acting analgesics. If the dose of Fendivia™ exceeds 300 mcg/hour, additional or alternative methods of pain management or alternative routes of administration of opioid analgesics should be considered.

When switching from long-term morphine treatment to transdermal fentanyl, withdrawal syndrome may occur despite adequate analgesic effect. When withdrawal syndrome occurs, it is recommended that patients be given short-acting morphine in low doses.

Stopping treatment with Fendivia™

If it is necessary to discontinue use of the transdermal patch, then replacement with any other opioids should be made gradually, starting with a low dose and increasing it slowly. This is due to the fact that the fentanyl content in the blood serum decreases gradually after removal of the patch; it takes at least 17 hours to reduce serum fentanyl concentrations by 50%. As a general rule, withdrawal from opioid pain relief should be done gradually to avoid withdrawal symptoms (nausea, vomiting, diarrhea, restlessness and muscle tremors).

Use in children

The use of Fendivia™ transdermal patch for the treatment of children is not recommended.

Fendivia

The use of Fendivia should be used as part of a comprehensive treatment of pain in patients subject to an adequate medical, social and psychological assessment of their condition.

If severe side effects occur, the patient should be monitored for 24 hours after removal of the fentanyl transdermal patch due to the prolonged T1/2 of fentanyl.

Both unused and used transdermal patches containing fentanyl should be kept out of the reach of children.

Transdermal patches should not be separated or cut into pieces because The quality, effectiveness and safety of the divided patch have not been established.

As with other potent opioids, respiratory depression may occur in some patients when using the fentanyl transdermal patch and should be monitored for this effect. Respiratory depression may persist after patch removal. The incidence of respiratory depression increases with increasing doses of fentanyl. Neurotropic drugs may enhance the effect of respiratory depression. In patients with existing symptoms of respiratory depression, fentanyl should be administered with extreme caution and only in small doses.

If the patient is to undergo procedures that completely relieve pain (eg, regional analgesia), it is advisable to consider the possibility of respiratory depression. Before performing these procedures, the dosage of fentanyl should be reduced or replaced with a fast or short-acting opioid drug.

In patients with chronic obstructive pulmonary disease or other pulmonary diseases, fentanyl may cause more dangerous side effects. In these patients, opioids may decrease respiratory function and increase airway resistance.

Tolerance and physical and psychological dependence can develop with the regular administration of opioids, but are rarely encountered in the treatment of tumor-related pain.

Fendivia should be used with caution in patients who may be particularly sensitive to elevated CO2 levels. Such patients are those who have experienced increased intracranial pressure, impaired consciousness, or coma. Fentanyl should be administered with caution to patients diagnosed with a brain tumor.

Fentanyl may cause bradycardia. Therefore, Fendivia should be administered with caution to patients with bradyarrhythmia.

Opioids may cause hypotension, especially in hypovolemic patients. Therefore, it is necessary to take precautions when treating patients with arterial hypotension and/or hypovolemia.

Fentanyl is metabolized in the liver, so delayed elimination may occur in patients with liver disease. Patients with impaired liver function should be monitored, and if necessary, the dose of the drug for such patients should be reduced.

Less than 10% of fentanyl is excreted unchanged by the kidneys and, unlike morphine, there are no active metabolites excreted by the kidneys. Data obtained from IV administration of fentanyl to patients with renal failure suggest that the Vd of fentanyl may change during dialysis. This may affect serum concentrations of the drug. If patients with impaired renal function receive transdermal fentanyl, they should be closely monitored for signs of fentanyl toxicity and the dosage of the drug should be reduced in such patients if necessary.

Patients with elevated body temperature require particularly careful monitoring for opioid side effects and, if necessary, fentanyl dosage adjustment. Patients should also be advised to avoid exposing Fendivia transdermal patch application sites to direct external heat sources, such as heating pads, hot water bottles, heated blankets, heat lamps, hot baths, and Jacuzzis, as there is a potential for a temperature-dependent increase in the release of fentanyl from the patch.

The transdermal patch should always be removed from the skin before using the sauna. Sauna use is only possible when the transdermal patch is replaced (at intervals of 72 hours). The new patch should be applied to a cool and completely dry area of ​​skin.

Results from studies of IV fentanyl show that elderly patients have decreased clearance, increased half-life, and are more sensitive to the drug than younger patients. Elderly patients should be closely monitored for signs of fentanyl toxicity and their dosage reduced if necessary.

Due to the fact that in debilitated and weakened patients the clearance decreases and the T1/2 half of fentanyl increases, such patients require careful monitoring to identify symptoms of a possible fentanyl overdose, and if necessary, they should reduce the dose of the drug.

Myoclonic convulsions may occur when using Fendivia. When treating patients with myasthenia gravis, precautions should be taken.

Alcohol consumption is not recommended when using Fendivia.

Even after use, transdermal patches still contain large amounts of fentanyl. For safety and environmental reasons, used transdermal patches, as well as unused patches, should be discarded. Used transdermal patches should be folded with the adhesive surfaces facing inward so that the release membrane is completely closed and returned to medical or pharmaceutical personnel. Unused transdermal patches should be returned to medical or pharmaceutical personnel.

Use in pediatrics

The use of Fendivia transdermal patch for the treatment of children is not recommended.

Impact on the ability to drive vehicles and operate machinery

Transdermal patches containing fentanyl may interfere with mental and/or physical functions required to perform potentially hazardous work, such as driving or operating machinery. This is mainly to be expected at the start of treatment, as well as with any change in dosage.

During the treatment period, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

There is no need to set restrictions for patients constantly taking an individually selected dose of the drug. In this case, the attending physician must decide whether the patient is allowed to operate the vehicle or equipment.

Fendivia 25 mcg/hour transdermal therapist system No. 5

Dosage

25 µg/h

Active substance

Fentanyl

Manufacturer

LTS Lohmann Therapy-System AG (Germany)

Shelf life

2 years

Storage conditions

Keep out of the reach of children.

Registration certificate number

LSR-005232/09 dated 10/30/2013

Compound

Characteristic

Description of the dosage form

Rectangular translucent patch with rounded edges on a removable transparent protective film. The protective film is larger in size than the patch. A sinusoidal cut divides the protective film to be removed into two parts.

The following inscriptions are applied to the patch using color printing:

1) Fendivia™ 12.5 μg/hour - patch width (18±0.5) mm, length (24±0.5) mm: “Fentanyl 12.5 μg/hour” - brown stamp;

2) Fendivia™ 25 μg/hour - patch width (24.6±0.5) mm, length (37±0.5) mm: “Fentanyl 25 μg/hour” - red stamp;

3) Fendivia™ 50 μg/hour - patch width (34±0.5) mm, length (51.3±0.5) mm: “Fentanyl 50 μg/hour” - green seal;

4) Fendivia™ 75 μg/hour - patch width (42±0.5) mm, length (61.7±0.5) mm: “Fentanyl 75 μg/hour” - light blue print;

5) Fendivia™ 100 μg/hour - patch width (49±0.5) mm, length (70±0.5) mm: “Fentanyl 100 μg/hour” - gray print.

Pharmacokinetics

The minimum effective analgesic concentration in the blood in patients who have not previously used opioid analgesics is 0.3–1.5 ng/ml.

Suction.

After the first application of the patch, the serum fentanyl concentration increases gradually, usually leveling off between 12 and 24 hours, and then remains relatively constant for the remaining 72-hour period. By the second 72-hour application of the patch, a constant concentration of the drug in the serum is achieved, which is maintained with subsequent applications of the same size patch. The concentration of fentanyl in the blood is proportional to the size of the TTC. The absorption of fentanyl may vary slightly depending on the site of application. Slightly reduced absorption of fentanyl (approximately 25%) was observed in studies conducted in healthy volunteers when the patch was applied to the chest compared with application to the upper arm and back.

Distribution.

Fentanyl is 84% ​​bound to plasma proteins and penetrates the blood-brain barrier, the placenta and into breast milk.

Biotransformation.

Fentanyl has linear biotransformation kinetics and is metabolized primarily in the liver via the CYP3A4 isoenzyme. The main metabolite of fentanyl, norfentanyl, is not active.

Elimination.

After removal of the fentanyl-containing patch, its serum concentration decreases gradually. T1/2 of fentanyl after application of TTS is 17 hours (13–22 hours) with a single application and 17–30.8 hours after 5 applications lasting 72 hours. Prolonged absorption of fentanyl during transdermal administration causes a slower elimination of the drug from the serum compared with IV administration.

Fentanyl is excreted by the kidneys (75% as metabolites and 10% unchanged) and with bile (9% as metabolites).

Special patient groups.

Impaired liver or kidney function may cause increased serum concentrations of fentanyl. In elderly, malnourished or debilitated patients, the clearance of fentanyl may be reduced, which may result in a longer half-life of the drug.

Pharmacodynamics

Fendivia™ is a transdermal patch that provides a continuous systemic supply of fentanyl for 72 hours. Fentanyl is an opioid analgesic with an affinity primarily for opiate μ-receptors of the central nervous system, spinal cord and peripheral tissues. Increases the activity of the antinociceptive system, increases the threshold of pain sensitivity. The drug primarily has analgesic and sedative effects. Fentanyl has a depressant effect on the respiratory center, slows down the heart rate, and stimulates the n.vagus

and vomiting center, increases the tone of smooth muscles of the biliary tract, sphincters (including the urethra, bladder and sphincter of Oddi), improves the absorption of water from the gastrointestinal tract. Reduces blood pressure, intestinal motility and renal blood flow. Increases the concentration of amylase and lipase in the blood; reduces the concentration of growth hormone, catecholamines, ACTH, cortisol, prolactin. Promotes the onset of sleep (mainly in connection with the relief of pain). Causes euphoria. The rate of development of drug dependence and tolerance to analgesic effects has significant individual differences. Rarely causes histamine reactions.

Contraindications

hypersensitivity to the active substance or excipients;

depression of the respiratory center, incl. acute respiratory depression;

irritated, irradiated or damaged skin at the site of application;

diarrhea against the background of pseudomembranous colitis caused by cephalosporins, lincosamides, penicillins;

toxic dyspepsia;

age under 18 years;

the drug should not be used for the treatment of acute or postoperative pain due to the inability to select a dose in a short period of time and the likelihood of developing life-threatening respiratory depression;

severe damage to the central nervous system;

simultaneous use of MAO inhibitors or administration within 14 days after their discontinuation.

Carefully:

for chronic lung diseases; intracranial hypertension; brain tumors; TBI; bradyarrhythmias; arterial hypotension; renal and liver failure; in patients with hepatic or renal colic (including a history); cholelithiasis; hypothyroidism; in elderly, emaciated and weakened patients; acute surgical diseases of the abdominal organs before diagnosis; general serious condition; benign prostatic hypertrophy; strictures of the urethra; drug addiction; alcoholism; suicidal tendencies; hyperthermia; simultaneous use of insulin, corticosteroids, antihypertensive drugs.

Use during pregnancy and breastfeeding

The safety of transdermal patches containing fentanyl during pregnancy has not been established.

Fentanyl should only be used when absolutely necessary during pregnancy. Long-term treatment during pregnancy may cause withdrawal syndrome in newborns.

Fentanyl should not be used during labor and delivery (including caesarean section) because Fentanyl crosses the placenta and may cause respiratory depression in the fetus or newborn.

Fentanyl is excreted into milk and may cause sedation and respiratory depression in a breast-fed baby. Therefore, if it is necessary to prescribe the drug during lactation, breastfeeding should be stopped (for the entire duration of use and 72 hours after the last use).

Directions for use and doses

Transdermal patches containing fentanyl release the active substance within 72 hours. The fentanyl release rate is 12.5; 25; 50; 75 and 100 μg/h, and the area of ​​the corresponding active surface is 4.2; 8.4; 16.8; 25.2 and 33.6 cm2.

The required dosage of fentanyl is individualized and should be assessed regularly after each use.

Mode of application

Transdermal.

The fentanyl patch should be applied to a flat surface of intact, non-irradiated skin of the torso or upper arm. For application, it is recommended to choose a place with minimal hair (preferably without hair). Before application, the hair at the application site should be cut (do not shave!). If the application site needs to be washed before applying the patch, this should be done with clean water. Do not use soaps, lotions, oils, alcohol or other products as they may cause skin irritation or change its properties. Before application, the skin must be completely dry.

Because the transdermal patch is protected by a waterproof outer protective film, it can be left on for short periods of showering.

The fentanyl transdermal patch should be applied immediately after removal from the heat seal pouch. After removing the protective film, the transdermal patch must be pressed firmly with the palm of your hand at the application site for about 30 seconds. Make sure that the patch fits snugly against the skin, especially around the edges. Additional fixation of the patch may be required. The patch should be worn continuously for 72 hours, after which it must be replaced with a new one. A new transdermal patch should always be applied to a different area of ​​the skin, without covering the site of the previous application. The patch can be reapplied to the same application site no earlier than after 7 days.

The transdermal patch should not be divided or cut (see "Special Instructions").

Selection of initial dosage

The dosage level of fentanyl is established depending on the level of opioid use in the previous period, as well as taking into account the possible development of tolerance, concomitant drug treatment, the general health of the patient and the severity of the disease.

If the response to opioids for a given pain syndrome is not fully understood, the initial dosage should not exceed 25 mcg/hour.

Switching from other opioids

When a patient switches from oral or parenteral opioids to fentanyl treatment, the initial dosage is calculated as follows:

1. The amount of analgesics required over the last 24 hours should be determined.

2. The amount obtained should be converted to the appropriate oral dose of morphine using Table 1.

3. The appropriate dose of fentanyl should be determined using Table 2.

Table 1

Drug dosages equivalent in analgesic effectiveness

*Based on study results obtained after a single dose of the drug, with IM administration of each drug compared with morphine to achieve equivalent effectiveness. Oral doses are the doses recommended for switching from the parenteral route of administration to the oral route of administration.

**The efficacy ratio of 3:1 for intramuscular/oral morphine is based on research findings in the treatment of patients with chronic pain.

All doses administered IM and orally (PO) presented in the table are equivalent in the analgesic effect of 10 mg of morphine administered IM.

table 2

Recommended starting dose of Fendivia™ depending on the daily oral dose of morphine

An initial assessment of the maximum analgesic effect of Fendivia™ can be carried out no earlier than 24 hours after application. This limitation is due to the fact that the increase in serum fentanyl concentration in the first 24 hours after application occurs gradually. Therefore, when switching from one drug to another, previous analgesic therapy should be discontinued gradually after the application of the initial dose of Fendivia™ until its analgesic effect has stabilized.

Dose selection and maintenance therapy

The transdermal patch should be replaced with a new one every 72 hours. The dose is selected individually until the required level of pain relief is achieved. If a significant decrease in the analgesic effect occurs 48–72 hours after application of the initial dose, then replacement of the patch may be necessary after 48 hours. A dose of 12.5 mcg/hour is usually sufficient for dose selection in the lower dosage range. If pain relief turns out to be insufficient by the end of the period of action of the first application, then the dose can be increased after 3 days until the desired effect is obtained.

Typically, the dose is increased by 12.5 or 25 mcg/hour at a time, but the patient's condition and the need for additional pain relief must be taken into account. To achieve a dose greater than 100 mcg/hour, multiple patches can be used simultaneously. If breakthrough pain occurs, patients may periodically require additional doses of short-acting analgesics. If the dose of Fendivia™ exceeds 300 mcg/hour, additional or alternative methods of pain management or alternative routes of administration of opioid analgesics should be considered.

When switching from long-term morphine treatment to transdermal fentanyl, withdrawal syndrome may occur despite adequate analgesic effect. When withdrawal syndrome occurs, it is recommended that patients be given short-acting morphine in low doses.

Stopping treatment with Fendivia™

If it is necessary to discontinue use of the transdermal patch, then replacement with any other opioids should be done gradually, starting with a low dose and increasing it slowly. This is due to the fact that the fentanyl content in the blood serum decreases gradually after removal of the patch; It takes at least 17 hours to reduce serum fentanyl concentrations by 50%. As a general rule, withdrawal of opioid analgesia should be done gradually to avoid withdrawal symptoms (nausea, vomiting, diarrhea, restlessness and muscle tremors).

Use in children.

The use of Fendivia™ transdermal patch for the treatment of children is not recommended.

Side effects

The following terms are used to describe the frequency of undesirable effects: very often (>1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10000 , <1/1000), very rarely (<1/10000), including isolated reports.

The most dangerous side effect is respiratory depression.

Mental disorders:

very often - drowsiness; often - sedation, confusion, depression, anxiety, nervousness, hallucinations, anorexia nervosa; infrequently - euphoria, amnesia, insomnia, agitation; very rarely - delirium, asthenia, sexual dysfunction.

From the nervous system:

very often - hypersomnia, headache, dizziness; often - involuntary muscle contractions, hypoesthesia; infrequently - tremor, paresthesia, speech disorders; very rarely - ataxia, myoclonic convulsions.

Eye function disorders:

rarely - amblyopia.

From the cardiovascular system:

often - a feeling of palpitations; infrequently - bradycardia, tachycardia, arterial hypotension, arterial hypertension; rarely - arrhythmia, vasodilation.

From the respiratory system:

often - yawning, rhinitis; infrequently - dyspnea, hypoventilation; very rarely - respiratory depression (including respiratory failure, apnea and bradypnea), hemoptysis, obstructive pulmonary disease, pharyngitis, laryngospasm.

From the digestive system:

very often - nausea, vomiting, constipation; often - abdominal pain, xerostomia, dyspepsia; infrequently - diarrhea; rarely - hiccups; very rarely - intestinal obstruction, painful flatulence.

From the immune system:

infrequently - itching; very rarely - anaphylactic shock, anaphylactic reactions, anaphylactoid reactions, rash.

For the skin and subcutaneous tissues:

very often - sweating, itching; often - skin reaction at the site of application (change in the appearance of the skin, peeling, exudation, petechial erosion, microcracks, scab); Uncommon: rash, erythema.

Rash, erythema and itching at the application site in most cases disappear within one day after removing the patch.

From the kidneys and urinary system:

uncommon - urinary retention, urinary tract infections; very rarely - oliguria, pain in the bladder, spasm of the ureters.

Common disorders:

rarely - swelling, feeling of cold.

Other side effects:

Uncommon: conjunctivitis, fatigue, malaise, flu-like symptoms.

With long-term use of fentanyl, tolerance, physical and mental dependence, and short-term muscle stiffness (including pectoral) may develop. If a previously prescribed opioid analgesic is replaced by a transdermal patch containing fentanyl, or if therapy is suddenly stopped, a withdrawal syndrome may occur, including, for example, nausea, vomiting, diarrhea, restlessness, and tremors.

Interaction

The simultaneous use of barbituric acid derivatives should be avoided, because they may increase the respiratory depression caused by fentanyl.

Concomitant use of other CNS depressants, including opioids, anxiolytics, tranquilizers, hypnotics, general anesthetics, phenothiazine derivatives, muscle relaxants, sedating antihistamines, alcohol may cause additive sedative effects; Hypoventilation, hypotension, profound sedation, or coma may occur. Therefore, taking any of the above drugs requires monitoring the patient.

Nitrous oxide increases muscle stiffness; the effect is reduced by buprenorphine.

MAO inhibitors increase the effect of narcotic analgesics, especially in patients with heart failure. Therefore, you should not take fentanyl during the entire period of use of MAO inhibitors, as well as for 14 days after their discontinuation.

Fentanyl has a high clearance and is rapidly and extensively metabolized, mainly by cytochrome CYP3A4.

Concomitant use of strong CYP3A4 inhibitors (for example, ritonavir, ketoconazole, itraconazole, macrolide antibiotics) with fentanyl administered transdermally may lead to increased plasma fentanyl concentrations. This may enhance or prolong both the therapeutic effect and adverse reactions that can cause severe respiratory depression. In such situations, intensive care and more careful monitoring of the patient are necessary. The combination of ritonavir or another strong CYP3A4 inhibitor with transdermal fentanyl is not recommended unless the patient is closely monitored.

Strengthens the effect of antihypertensive drugs.

Buprenorphine, nalbuphine, pentazocine, naloxone, naltrexone reduce the analgesic effect of fentanyl, eliminate its inhibitory effect on the respiratory center and can induce withdrawal syndrome in patients with opioid addiction.

It is necessary to reduce the dose of fentanyl when used simultaneously with insulin, corticosteroids and antihypertensive drugs.

Muscle relaxants prevent or relieve muscle stiffness; muscle relaxants with vagolytic activity (including pancuronium bromide) reduce the risk of bradycardia and arterial hypotension (especially with the use of beta-blockers and vasodilators) and may increase the risk of tachycardia and arterial hypertension; muscle relaxants that do not have vagolytic activity (including succinylcholine) do not reduce the risk of bradycardia and arterial hypotension (especially against the background of a burdened cardiac history) and increase the risk of severe side effects from the cardiovascular system.

Overdose

Symptoms:

lethargy, coma, depression of the respiratory center with Cheyne-Stokes respiration and/or cyanosis. Other symptoms may include hypothermia, decreased muscle tone, bradycardia, and hypotension. Signs of toxicity include deep sedation, ataxia, miosis, convulsions and respiratory depression (which is the main symptom).

Treatment:

removing the patch, introducing a specific antagonist - naloxone, physical or verbal influence on the patient; symptomatic therapy that supports vital functions (including the administration of muscle relaxants and artificial ventilation, for bradycardia - the administration of atropine, for a pronounced decrease in blood pressure - replenishment of circulating blood volume).

The recommended starting dose for adults is 0.4–2 mg naloxone IV. If necessary, you can give the same dose every 2-3 minutes or prescribe a long-term administration of 2 mg of the drug dissolved in 500 ml of 0.9% sodium chloride solution or 5% dextrose solution (0.004 mg/ml). The rate of administration should be adjusted based on previous bolus infusions and individual patient response. If IV administration is not possible, then naloxone can be prescribed intramuscularly or subcutaneously. After intramuscular or subcutaneous administration of naloxone, the onset of action will be slower compared to intravenous administration. IM administration gives a more prolonged effect than intravenous administration. Respiratory depression due to overdose may persist longer than the effect of the opioid antagonist. Reversal of the analgesic effect may result in increased acute pain and release of catecholamines. If necessary, the patient should be treated in the intensive care unit.

special instructions

The drug should be used as part of a comprehensive treatment of pain in patients subject to an adequate medical, social and psychological assessment of their condition.

If severe side effects occur, the patient should be monitored for 24 hours after removal of the fentanyl transdermal patch due to the long half-life of fentanyl.

Both unused and used transdermal patches containing fentanyl should be kept out of the reach of children.

Transdermal patches should not be separated or cut into pieces because The quality, effectiveness and safety of the divided patch have not been established.

Respiratory depression.

As with other potent opioids, respiratory depression may occur in some patients when using the fentanyl transdermal patch and should be monitored for this effect. Respiratory depression may persist after patch removal. The incidence of respiratory depression increases with increasing doses of fentanyl. Neurotropic drugs may enhance the effect of respiratory depression (see “Interactions”). In patients with existing symptoms of respiratory depression, fentanyl should be administered with extreme caution and only in small doses.

If the patient is to undergo procedures that completely relieve pain (eg, regional analgesia), it is advisable to consider the possibility of respiratory depression. Before performing these procedures, the dosage of fentanyl should be reduced or replaced with a fast or short-acting opioid drug.

Chronic lung diseases.

In patients with chronic obstructive pulmonary disease or other pulmonary diseases, fentanyl may cause more dangerous side effects. In these patients, opioids may decrease respiratory function and increase airway resistance.

Drug addiction.

Tolerance and physical and psychological dependence can develop with the regular administration of opioids, but are rarely encountered in the treatment of tumor-related pain.

Increased intracranial pressure.

Fendivia™ should be used with caution in patients who may be particularly sensitive to elevated CO2 levels. Such patients are those who have experienced increased intracranial pressure, impaired consciousness, or coma. Fentanyl should be administered with caution to patients diagnosed with a brain tumor.

Heart diseases.

Fentanyl may cause bradycardia. Therefore, Fendivia™ should be administered with caution to patients with bradyarrhythmia.

Opioids may cause hypotension, especially in hypovolemic patients. Therefore, it is necessary to take precautions when treating patients with arterial hypotension and/or hypovolemia.

Liver dysfunction.

Fentanyl is metabolized in the liver, so delayed elimination may occur in patients with liver disease. Patients with impaired liver function should be monitored, and if necessary, the dose of the drug for such patients should be reduced.

Renal dysfunction.

Less than 10% of fentanyl is excreted unchanged by the kidneys and, unlike morphine, there are no active metabolites excreted by the kidneys. Data obtained from IV administration of fentanyl to patients with renal failure suggest that the volume of distribution of fentanyl may be altered during dialysis. This may affect serum concentrations of the drug. If patients with impaired renal function receive transdermal fentanyl, they should be closely monitored for signs of fentanyl toxicity and the dosage of the drug should be reduced in such patients if necessary.

Use in patients with elevated body temperature/exposed to external heat sources

Patients with elevated body temperature require particularly close monitoring for opioid side effects and, if necessary, fentanyl dosage adjustment. Patients should also be advised to avoid exposing fentanyl transdermal patch sites to direct external heat sources, such as heating pads, hot water bottles, heated blankets, heat lamps, hot baths, or Jacuzzis, as there is a possibility of a temperature-dependent increase in the release of fentanyl from the patch.

The transdermal patch should always be removed from the skin before using the sauna. Sauna use is only possible when the transdermal patch is replaced (at intervals of 72 hours). The new patch should be applied to a cool and completely dry area of ​​skin.

Use in elderly patients.

Results from studies of intravenous fentanyl show that elderly patients have decreased clearance, increased half-life, and increased sensitivity to the drug compared with younger patients. Elderly patients should be closely monitored for signs of fentanyl toxicity and the dose reduced if necessary.

Use in debilitated and weakened patients.

Because fentanyl clearance is reduced and the half-life of fentanyl is reduced in debilitated and debilitated patients, such patients should be closely monitored for symptoms of possible fentanyl overdose and should have their dosage reduced if necessary.

The possibility of developing myoclonic seizures should be taken into account. When treating patients with myasthenia gravis, precautions should be taken.

Removing TTS.

Even after use, transdermal patches still contain large amounts of fentanyl. For safety and environmental reasons, used transdermal patches, as well as unused patches, should be discarded. Used transdermal patches should be folded with the adhesive surfaces facing inward so that the release membrane is completely closed and returned to medical or pharmaceutical personnel. Unused transdermal patches should be returned to medical or pharmaceutical personnel.

Effect on the ability to operate a vehicle or equipment.

Transdermal patches containing fentanyl may interfere with mental and/or physical functions required to perform potentially hazardous work, such as driving or operating machinery. This is mainly possible at the beginning of treatment, as well as with any change in dosage.

Patients should check with their healthcare provider to determine whether they are allowed to operate a vehicle or equipment.

During the treatment period, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drinking alcohol is not recommended.

Conditions for dispensing from pharmacies

On prescription. Belongs to list II of narcotic drugs.

Pharmgroups

Analgesic narcotic drug (Opioid narcotic analgesics)

Pharmaceutical actions

analgesic, sedative