Fentanyl - instructions for use, dose, side effects, contraindications

substrate - copolymer of polyethylene terephthalate and ethylene vinyl acetate - 273 (54.6 / 109Д / 163.8 / 218.4 mg, respectively, for dosages of 12.5 / 25/50/75/100 μg / h; protective film - polyethylene terephthalate siliconeized 55.7 / 111.5 / 223.0 / 334.4 / 445.9 mg, respectively, for dosages of 12.5 / 25/50/75/100 μg / h.

Description:

A translucent rectangular patch (TTC) with rounded corners, a translucent substrate,colorless adhesive layer and a transparent removable protective film.

Pharmacotherapeutic group:Analgesic narcotic drug. It refers to List II of the List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation

ATX: & nbsp

N.01.A.H.01 Fentanyl

Pharmacodynamics:

Fentanyl - a synthetic analgesic interacting predominantly with μ-opioid receptors, increases the activity of the antinociceptive system, increases the threshold of pain sensitivity, disrupts the transmission of excitation by specific and nonspecific painful pathways to the nuclei of the thalamus, hypothalamus, amygdala complex.

The main therapeutic effects of the drug are analgesic and sedative. The minimum effective anesthetic concentration of fentanyl in plasma in patients who did not previously use opioid analgesics is 0.3-1.5 ng / ml. The total time of action of the drug is 72 hours.

Has a depressing effect on the respiratory center. Increases the tone of smooth muscles of the bile ducts, sphincters (including urethra, bladder, sphincter of Oddi), reduces peristalsis of the intestine, improves the absorption of water from the gastrointestinal tract (GIT).Virtually no effect on blood pressure (BP), reduces renal blood flow. In the blood increases the content of amylase and lipase. Promotes the onset of sleep. Causes euphoria.

The rate of development of drug dependence and tolerance to analgesic effect has significant individual differences.

Pharmacokinetics:

Absorption

The transdermal therapeutic system (TTS) Fentanyl provides a constant systemic release of fentanyl within 72 hours after application. Fentanyl is released at a relatively constant rate. The concentration gradient between TTS and low concentrations in the skin provides release of fentanyl. After the application of TTS Fentanyl, the fentanyl concentration in the blood plasma gradually increases during the first 12-24 hours and remains constant over the remaining period of time. The level of fentanyl concentration in the blood plasma is proportional to the size of the TTS.

By the end of the 72-hour application, an equilibrium concentration of fentanyl in the blood plasma is achieved, which is maintained by subsequent TTS applications of the same size.

The pharmacokinetic model shows that fentanyl concentrations in plasma can increase by an average of 14% (ranging from 0 to 26%) if the new TTS is glued after 24 hours compared to the pasted 72 hours, as recommended.

Distribution

The binding of fentanyl to plasma proteins is about 84%.

Metabolism

Fentanyl is a compound with a high clearance, which is rapidly metabolized in the liver, preferably by an enzyme CYP3A4. The main metabolite, norfentanil, is inactive. With transdermal administration fentanyl is not metabolized in the skin, as determined in studies on human keratocytes and in clinical trials (92% of the dose of fentanyl (TTC), unchanged in the bloodstream).

Excretion

After removing the TTC Fentanyl the fentanyl concentration in the blood plasma is gradually reduced, with a half-life of approximately 17 (13-22) hours after a 24 hour TTC application. After a 72 hour TTS application, the elimination half-life is approximately 20-27 hours.

The continued absorption of fentanyl from the skin explains the slower disappearance of the drug from the blood plasma compared to the intravenous administration of fentanyl, when the half-life is approximately 7 (3-12) hours.

72 hours after intravenous administration of fentanyl, approximately 75% of the dose of fentanyl is excreted in the urine, mainly in the form of metabolites and less than 10% in unchanged form. About 9% is excreted with feces, mainly in the form of metabolites.

Special patient groups

Elderly patients

Data from fentanyl studies with intravenous administration suggest that elderly patients may experience reduced clearance and longer half-life, and in addition, such patients may be more sensitive to fentanyl than younger patients. In studies of the drug TTS fentanyl on healthy elderly volunteers, it has been established that the pharmacokinetics of fentanyl in elderly people does not differ significantly from the pharmacokinetics in young healthy people, although in elderly the peak concentrations are lower and the half-life is prolonged to about 34 hours.

Elderly patients should be carefully observed to identify symptoms of fentanyl toxicity and, if necessary, reduce the dose of the drug TTS fentanyl.

Patients with hepatic insufficiency

The pharmacokinetics of a single dose of 50 μg / h was studied in patients with cirrhosis of the liver.Despite the fact that the time to reach the maximum concentration and the half-life did not change, the average values of the maximum concentration and area under the concentration-time curve increased by 35% and 73%, respectively. Patients with hepatic impairment should be carefully monitored to identify symptoms of fentanyl toxicity and, if necessary, reduce the dose of the drug Fentanyl TTC.

Patients with renal insufficiency

Data from fentanyl studies for intravenous administration in patients after kidney transplantation suggest that fentanyl clearance in this group of patients may be reduced. Patients with renal failure receiving TTC Fentanyl, should be carefully observed to detect symptoms of fentanyl toxicity and, if necessary, reduce the dose of the drug Fentanyl TTC.

Indications:

Severe chronic pain, which is adequately suppressed only with the help of opioid analgesics.

Contraindications:

- Hypersensitivity to fentanyl or to adhesive substances included in the system;

- depression of the respiratory center, including acute respiratory depression;

- acute pain or postoperative pain requiring a short period of treatment;

- pregnancy and lactation;

- diarrhea against pseudomembranous colitis caused by cephalosporins, lincosamides, penicillins;

- toxic diarrhea;

- irritated, irradiated or damaged skin at the place of application;

- children's age till 18 years.

Carefully:

- Pchronic lung diseases;

- with intracranial hypertension;

- with tumors of the brain;

- with craniocerebral injuries;

- with bradyarrhythmias;

- with arterial hypotension;

- with renal and hepatic insufficiency;

- in patients with hepatic or renal colic, including in the anamnesis;

- with cholelithiasis;

- hypothyroidism;

- in elderly, debilitated and weakened patients (see section "Special instructions");

- with acute surgical diseases of the abdominal cavity before diagnosis;

- at the general or common serious condition;

- with benign prostatic hypertrophy;

- with urethral stricture;

- with drug dependence;

- with alcoholism;

- with suicidal tendencies;

- with hyperthermia;

- while taking insulin, glucocorticoids, antihypertensive drugs and monoamine oxidase (MAO) inhibitors.

Pregnancy and lactation:

Data on the use of the drug TTS Fentanyl in pregnant women is not enough.

With intravenous administration, fentanyl was passed through the placenta for pregnant women for anesthesia. There were cases of the syndrome of "cancellation" in newborn children, whose mothers were chronically applied fentanyl during pregnancy.

Fentanyl TTS should not be used during pregnancy, except in cases of acute need. It is not recommended to use Fentanyl TTS at delivery, tk. this drug is contraindicated for the removal of acute pain or postoperative pain. Moreover, since. fentanyl penetrates the placenta, it can cause respiratory depression in the newborn. Fentanyl is excreted in breast milk and can cause sedation / respiratory depression in children. Consequently, Fentanyl TTS should not be used by nursing mothers.

Dosing and Administration:

Dose of the drug Fentanyl TTS is selected individually depending on the patient's condition and should be regularlyevaluated after application. Fentanyl TTS should be applied to the flat surface of the skin of the trunk or upper parts of the hands. For the application it is recommended to choose a place with a minimal hair cover. Before application, the hair should be cut at the application site (do not shave!). If the application site needs to be cleaned before applying the patch, then it should be done with clean water. Do not use soap, lotions, oils or other products, as they can cause skin irritation or alter its properties. Before application, the skin should be absolutely dry. Before applying the TTC it is necessary to check carefully for damage. TTS, divided into parts, cut or otherwise damaged, should in no case be used.

Fentanyl TTS should be glued immediately after removal from the sealed packet. To remove the TTS from the bag, fold the top of the sachet along the notch (indicated by the arrow) and tear it off. Then open the package as you open the book. The protective film has a cut in the middle. Fold the TTS in half in the middle and remove each half of the protective film, without touching your fingers with the sticky layer. TTS should be pressed firmly with the palm of the hand in place of the application for 30 seconds.It should be ensured that the patch is tight against the skin, especially around the edges. After sticking the TTC, wash your hands with clean water.

Fentanyl TTS is designed for continuous use within 72 hours. The new system can be glued to another area of the skin after removing the previously pasted patch. For the same skin area, the transdermal system can be glued only at intervals of several days.

Selection of initial dose

Initial dose of the drug Fentanyl TTC is selected based on the previous use of opioid analgesics. It is recommended to appoint

Fentanyl TTS to patients demonstrating opioid tolerance. Other factors are also taken into account: the general condition of the patient, incl. body size, age, degree of depletion and the degree of opioid tolerance.

Patients previously taking opioids

For the transition from oral or parenteral forms of opioids to the drug Fentanyl TTS in patients with tolerance to opioids should be guided by "Transfer to an equivalent analgesic dose", presented below. Dosage can be subsequently reduced or increased if necessary by 12.5 or 25 μg / h to achieve the lowest dose of the drug Fentanyl TTC, depending on the reaction and additional requirements for anesthesia.

Patients who had not previously taken opioids

Experience with the drug Fentanyl TTS in patients who had not previously taken opioids is limited. In cases where the administration of the drug is necessary Fentanyl TTS, patients who have not previously taken opioids should start with small doses of rapid-release opioids (for example, morphine, tramadol and codeine), equivalent to 25 μg / h of the preparation Fentanyl TTC. After this, patients can be transferred to a dose of 25 μg / h of the drug Fentanyl TTC. Dosage can be subsequently reduced or increased if necessary by 12.5 or 25 μg / h to achieve the lowest dose of the drug Fentanyl TTC, depending on the response and additional requirements for anesthesia (see "Transfer to an equivalent analgesic dose").

Transfer to an equivalent analgesic dose

- Calculate the previous 24-hour need for analgesia.

- Transfer this amount to an equivalent oral dose of morphine using Table 1. "All intramuscular and oral doses of opioid analgesics given in this table are equivalent to the analgesic effect of 10 mg morphine IM."

- Find the required dose of the drug for the patient Fentanyl TTS, equivalent to a 24-hour dose of morphine, using Table 2 or 3:

a) Table 2 is applicable to patients requiring a transfer from another opioid administration schedule (the ratio of the oral morphine dose to the transdermal form of fentanyl is about 150: 1).

b) Table 3 is applicable to patients on stable, well tolerated opioid therapy (the ratio of the oral morphine dose to the transdermal form of fentanyl is about 100: 1).

Table 1: Transfer to an equivalent analgesic dose

Name of the drug	Equivalent analgesic dose, mg
Name of the drug	in / m *	inwards
Morphine	10	30 (with regular administration) **
Omnompon	45	-
Hydromorphone	1,5	7,5
Methadone	10	20
Oxycodone	15	30
Levorphanol	2	4
Oxymorphone	1	10 (rectally)
Diamorphine	5	60
Pethidine	75	-
Codeine	130	200
Buprenorphine	0,4	0.8 (sublingually)

* These oral doses are recommended when switching from parenteral to oral administration.

** The ratio of morphine action to intramuscular / oral administration is based on the clinical experience obtained in the treatment of patients with chronic pain.

Table 2: The recommended initial dose of the drug Fentanyl TTS (depending on the daily oral dose of morphine)

Oral 24-hour dose of morphine, mg / day	Dose of the drug Fentanyl TTC, μg / h
<135	25
135-224	50
225-314	75
315-404	100
405-494	125
495-584	150
585-674	175
675-764	200
765-854	225
855-944	250
945-1034	275
1035-1124	300

Table 3: The recommended initial dose of the drug Fentanyl TTC, based on a daily oral dose of morphine (for patients on stable, well tolerated opioid therapy)

Oral 24-hour dose of morphine, mg / day	Dose of the drug Fentanyl TTC, μg / h
<44	12,5-25
45-89	25
90-149	50
150-209	75
210-269	100
270-329	125
330-389	150
390-449	175
450-509	200
510-569	225
570-629	250
630-689	275
690-749	300

An initial assessment of the maximum analgesic effect of Fentanyl TTS can not be made less than 24 hours after the application. This the time interval is due to the gradual increase in fentanyl concentration in the serum after application.

To successfully transition from one drug to another, previous analgesic therapy should be canceled gradually after the initial dose of Fentanyl TTS is applied.

Dose selection and maintenance therapy

To select the dose, Fentanyl TTS is used at 12.5 μg / h. The TTS should be replaced every 72 hours. The dose is selected, observing the balance between the achievement of the necessary anesthesia and the patient's tolerance. If the initial dose is not adequately anesthetized, then after 3 days the dose may be increased. Then the dose can be increased every 3 days.

At the beginning of therapy, in some patients, adequate analgesia may not be achieved during the third day of TTC application at this dosage range, and in this case, the TTC may need to be replaced after 48 hours rather than after 72 hours. If the duration of application is reduced by early removal of TTS, the concentration of fentanyl in plasma may increase.

Usually, the dose is increased by 12.5 μg / h or 25 μg / h at a time, however, the patient's condition and the need for additional analgesia should be taken into account (oral doses of morphine 45 mg / day and 90 mg / day are approximately equivalent to the doses of the drug Fentanyl TTC 12 , 5 μg / h and 25 μg / h, respectively).

To achieve a dose of more than 100 μg / h, several Fentanyl TTC patches can be used simultaneously.

In the event of "breakthrough" pain, patients may occasionally need additional doses of short-acting analgesics.

When using a dose of the drug Fentanyl TTS, exceeding 300 μg / h, some patients may need additional or alternative methods of administering narcotic analgesics.

Side effects:

Side effects are given with a frequency distribution and organ systems. The frequency of side effects was classified as follows: very frequent (> 1/10), frequent (> 1/100, <1/10) and infrequent (> 1/1000, <1/100), rare (> 1/10000, < 1/1000) and very rare (<1/10000, including individual cases).

From the nervous system: very often - drowsiness, dizziness, headache; infrequently - hypoesthesia; very rarely - convulsions (including clonic convulsions and a large epileptic fit), amnesia, confusion, loss of consciousness.

From the side of the psyche: very often - insomnia, often - depression, anxiety, confusion, hallucinations; infrequently - disorientation, euphoria; very rarely - agitation.

From the sense organs: often - vertigo; infrequently - miosis; very rarely - blurred vision.

From the respiratory system: infrequent - respiratory depression; very rarely - respiratory distress syndrome, apnea, bradypnoe, hypoventilation, dyspnea (see "Overdose").

From the digestive system: very often - nausea, vomiting; often - constipation, abdominal pain, diarrhea, dry mouth; infrequent - partial intestinal obstruction; rarely - intestinal obstruction, dyspepsia.

Disorders of metabolism and nutrition: often - anorexia.

From the side of the cardiovascular system (SSS): often - palpitations; infrequently - cyanosis; very rarely - tachycardia, bradycardia, increase or decrease in blood pressure.

From the musculoskeletal system: often - muscle spasms; infrequently, muscle twitching.

From the skin and subcutaneous tissues: often - erythema; infrequently - dermatitis (including allergic and contact), eczema and other skin disorders.

From the side of the urinary system: infrequently urinary retention.

From the immune system: often - hypersensitivity; very rarely - anaphylactic shock, anaphylactic reactions.

On the part of the reproductive system: infrequently - erectile dysfunction, sexual dysfunction.

Other: often - fatigue, chills, malaise, asthenia, peripheral edema; infrequently - local reactions at the place of application (including dermatitis, eczema, hypersensitivity), withdrawal syndrome; influenza-like symptoms; very rarely - sensation of changes in body temperature, pyrexia.

As for other narcotic analgesics, with repeated use of the drug Fentanyl TTS can develop physical and mental dependence and tolerance.

When switching from previously taken narcotic analgesics to the use of the drug Fentanyl TTS, or in the event of a sudden cessation of therapy, symptoms characteristic of the abolition of narcotic analgesics are possible (nausea, vomiting, diarrhea, anxiety, chills).

There were very rare cases of the "cancellation" syndrome in newborns whose mothers were chronically used Fentanyl TTS during pregnancy.

Overdose:

Symptoms: bradypnea, apnea, rigidity of muscles, respiratory center depression, lowering of blood pressure, bradycardia.

Treatment: removal of the TTC plaster, physical and verbal stimulation (the patient should be "patted" on the cheeks, call by name, etc.), if necessary - auxiliary and artificial ventilation (IVL). Intravenous introduction of a specific antagonist - naloxone in doses from 0.4 mg to 2 mg; in the absence of effect after 2-3 min, the administration of naloxone is repeated. One should consider the possibility of developing the "withdrawal" syndrome when naloxone is administered to patients with dependence on morphine or fentanyl; In such cases, the doses of antagonists should be increased gradually.

Symptomatic and maintenance therapy: the introduction of muscle relaxants, IVL, with bradycardia - the introduction of 0.5-1 ml of 1% solution of atropine, with a decrease in blood pressure - replenishment of the volume of circulating blood. The disappearance of the analgesic effect can lead to the development of a sharp pain attack and the release of catecholamines.

Interaction:

The simultaneous use of other drugs that exert a depressing effect on the central nervous system, including opioids, sedatives and hypnotics, general anesthetics, phenothiazines, tranquilizers, central muscle relaxants, antihistamines with sedatives, and alcoholic beverages, may increase the risk of an additive suppressive effect, hypoventilation of the lungs, reduction of blood pressure, excessive sedation, to whom or to lead to a lethal outcome (taking any of these drugs simultaneously with the application HAND Fentanyl TTS requires special monitoring of the patient).

Simultaneous administration of cytochrome P450 inhibitors CYP3A4, can lead to an increase in the concentration of fentanyl in plasma. The consequence of this is an increase or lengthening, both the therapeutic effect and possible side effects, the development of severe respiratory depression.In these cases, the patient should be closely monitored. Joint use of transdermal forms of fentanyl with inhibitors of isoenzyme CYP3A4 is not recommended, except for careful monitoring of patients (see section "Special instructions").

Joint application of the drug with inducers of isoenzyme CYP3A4 (e.g., rifampicin, carbamazepine, phenobarbital, phenytoin) can lead to a decrease in the concentration of fentanyl in the blood plasma and reduce the therapeutic effect. It may be necessary to correct the dose of transdermal fentanyl. After discontinuation of therapy with isoenzyme inducers CYP3A4, the inductor effects decrease gradually, which can cause an increase in the fentanyl concentration in the blood plasma. This, in turn, can cause an increase or prolongation of the therapeutic effect and the severity of side effects, which can lead to serious respiratory depression. If necessary, carefully monitor the patient's condition and adjust the dose of the drug.

Fentanyl enhances the effect of antihypertensive drugs. β-adrenoblockers can reduce the frequency and severity of hypertensive reaction in cardiac surgery (including sternotomy), but increase the risk of developing bradycardia.

Buprenorphine, nalboufine, pentazocine, naloxone, naltrexone reduce the analgesic effect of fentanyl and eliminate its depressing effect on the respiratory center.

Muscle relaxants prevent or eliminate muscle rigidity; myorelaxants with m-cholinoblocking activity reduce the risk of bradycardia and lowering blood pressure (especially when using β-blockers and other vasodilators) and may increase the risk of developing tachycardia and hypertension; muscle relaxants that do not have vagolytic activity (including succinylcholine) do not reduce the risk of bradycardia and hypertension (especially in the background of a burdened cardiological history) and increase the risk of serious side effects from the SSS.

Nitrous oxide enhances muscle rigidity; the effect reduces buprenorphine.

It is necessary to reduce the dose of fentanyl with simultaneous use with insulin, glucocorticosteroids and antihypertensive drugs.

Inhibitors of monoamine oxidase (MAO)

It is not recommended to co-prescribe fentanyl with MAO inhibitors. Serious and unpredictable interactions with MAO inhibitors, with increased opioid effects or increased serotonergic effects were noted.Therefore it is not recommended to appoint Fentanyl TTS earlier than 14 days after the abolition of MAO inhibitors.

Serotonergic drugs

The combined use of fentanyl with serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SSRIs), MAO inhibitors may increase the risk of developing a serotonin syndrome - a potentially life-threatening condition.

Special instructions:

Patients with severe side effects should be carefully monitored for at least 24 hours (depending on the symptoms) after removal Fentanyl TTS, as the concentration of fentanyl in the plasma decreases gradually and its 50% reduction is achieved within approximately 17 (13-22) hours.

Fentanyl TTS should be stored out of the reach of children, both before and after use.

Fentanyl TTS can not be cut.

Application the patients who had not previously taken opioids who did not have tolerance for opioids

When applying Fentanyl TTS in patients who had not previously taken opioids very rarely experienced cases of significant respiratory depression and / or death when used as an initial opioid therapy.The possibility of developing a serious or life-threatening hypoventilation of the lungs exists even if a minimum dose Fentanyl TTS as an initial opioid therapy in patients who had not previously taken opioids. It is recommended to appoint Fentanyl TTS to patients demonstrating opioid tolerance.

Inhibition of respiration

As with other narcotic analgesics, when using the drug Fentanyl TTS in some patients may experience significant respiratory depression. Patients should be carefully screened to identify such effects. The respiratory depression can continue even after removal of the TTS. The degree of respiratory depression increases with an increase in the dose of the drug Fentanyl TTC. Drugs that affect the central nervous system can increase respiratory depression.

Chronic lung diseases

Fentanyl can cause a number of severe side effects in patients with chronic obstructive and other lung diseases. In such patients, opioids can reduce the excitability of the respiratory center and increase respiratory resistance.

Increased intracranial pressure

Fentanyl TTS should be used with caution in patients who may be particularly sensitive to an increase in CO2. These patients are those who have experienced increased intracranial pressure, impaired consciousness or coma. Fentanyl TTS should be used with caution in patients with a brain tumor.

CAS diseases

Fentanyl may cause the development of bradycardia and, thus, it should be used with caution in patients with bradyarrhythmias. It should be used with caution Fentanyl TTS in patients with arterial hypotension.

Liver failure

As fentanyl metabolized to inactive metabolites in the liver, a violation of the liver can lead to a delay in removing the drug. Patients with hepatic impairment taking Fentanyl TTC should be under constant surveillance to detect symptoms of possible fentanyl toxicity, and if necessary, the dose of the drug Fentanyl TTS should be reduced. Opioid analgesics can increase the tone of the smooth muscles of the gastrointestinal tract and bile ducts.

Fentanyl TTS should be used with caution in patients with a history of hepatic colic.

Renal insufficiency

Less than 10% of fentanyl is excreted by the kidneys in an unchanged form, fentanyl has no known active metabolites that would be excreted by the kidneys. Patients with renal failure receiving Fentanyl TTC should be under constant surveillance to identify symptoms of possible fentanyl toxicity and, if necessary, the dose of the drug Fentanyl TTS should be reduced.

Serotonin syndrome

Care should be taken when using together Fentanyl TTS with drugs that affect the serotonergic neurotransmitter system. Co-administration with serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SSRIs), as well as with drugs that reduce serotonin metabolism (including MAO inhibitors) can lead to the development of a potentially life-threatening serotonin syndrome. This syndrome can occur when taking the recommended doses.

Serotonin syndrome may include mental disorders (agitation, hallucinations, coma), autonomic disorders (tachycardia, fluctuations in blood pressure, hyperthermia), neuromuscular disorders (hyperreflexia, coordination disorder, stiffness) and / or gastrointestinal disorders (nausea, vomiting, diarrhea) .

If there is a suspected development of serotonin syndrome, drug therapy Fentanyl The TTC should be canceled.

Interaction with cytochrome inhibitors CYP3A4

When combined with cytochrome inhibitors CYP3A4 (eg, ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefadozone, verapamil, diltiazem and amiodarone) it is possible to increase the concentration of fentanyl in plasma. The consequence of this is an increase or lengthening of both the therapeutic effect and possible side effects (respiratory depression). In these cases, the patient must be under constant medical supervision.

Therefore, the combined use of transdermal forms of fentanyl with cytochrome inhibitors CYP3A4 is not recommended, except when patients are under medical supervision.In case of symptoms of depressed breathing, the dose of the drug should be reduced.

Accidental impact of TTC

Accidental effects of the drug Fentanyl TTS on the skin (especially in children) with close physical contact with a patient using TTS can lead to opioid overdose. Patients should be warned that if the skin of a person who does not take the drug is accidentally exposed to the skin, the TTS should be immediately removed. For overdose symptoms, see Overdose.

Application in elderly patients

Data from intravenous administration of fentanyl suggest that elderly patients will lose clearance and the half-life of the drug will lengthen, and in addition, such patients may be more sensitive to fentanyl than younger patients. Elderly patients taking Fentanyl TTS should be under constant surveillance to identify symptoms of a possible fentanyl overdose and, if necessary, the dose of the drug Fentanyl TTS should be reduced.

Effect on the digestive tract

Opioids increase tone and reduce propulsive contractions of the smooth muscles of the gastrointestinal tract.As a result, the time of gastrointestinal transit increases, which can be the cause of constipation. Patients should be informed about measures to prevent constipation and preventive use of laxatives. Additional precautions should be taken in patients with chronic constipation. If paralytic intestinal obstruction is present or suspected, treatment with the drug Fentanyl The TTC should be discontinued.

Application the depleted and debilitated patients

Since depleted and weakened patients may lose clearance and the half-life of the drug may be prolonged, exhausted and weakened patients should be under constant medical supervision to identify symptoms of a possible overdose, in which case the dose of the drug Fentanyl TTS should be reduced.

Drug dependence and the possibility of abuse

With the re-introduction of opioids, tolerance can develop, as well as physical and mental dependence. Iatrogenic dependence when using opioids is rarely observed.

As with the use of other opioid receptor agonists, there may be cases of abuse of fentanyl. Abuse or intentional use of the drug Fentanyl TTCs may not lead to overdose and / or death due to their intended purpose. Patients at an increased risk of opioid abuse may continue to receive adequate therapy with modified-release narcotic analgesics, however, should be closely monitored to identify possible signs of misuse, abuse, or dependence.

Fever/external heat sources

The pharmacokinetic model suggests that the serum fentanyl concentration may increase by about one-third if the body temperature rises to 40 ° C. Consequently, patients with fever should be under constant observation to identify opioid-specific side effects, and, if necessary, subsequent dose adjustment. An increase in the release of fentanyl from the TTS was observed with an increase in temperature, which could lead to an overdose and death of the patient.The study on healthy volunteers showed that when heated pasted Fentanyl TTC observed an increase in the mean values AUC by 120% and C_m_Oh on 61%. All patients should avoid direct exposure to the place of application Fentanyl TTS external heat sources, such as heating lamps, lamps for tanning, intensive sunbathing, hot-water bottles, saunas, solarium, hot water baths and the like.

Discontinuation of use of the drug

If it is necessary to stop using Fentanyl TTS, the replacement of this drug with other opioids should be gradual, starting with low doses. This mode of drug substitution is necessary due to a gradual decrease in the concentration of fentanyl after removal of TTS, while a decrease in the concentration of fentanyl by 50% in serum takes 17 hours. The abolition of opioid analgesia should always be gradual in order to prevent the development of the "withdrawal" syndrome.

Disposal instruction Fentanyl TTC

Unused TTS should be returned to the treating doctor for disposal. Used TTS should be folded in half an adhesive side inside and disposed of independently.

Effect on the ability to drive transp.cf. and fur:

Fentanyl transdermal may affect the mental and / or physical functions needed to perform potentially hazardous activities such as driving and operating machinery. During the period of treatment, it is necessary to refrain from driving and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Transdermal therapeutic system (TTS) with a release rate of 12.5 / 25/50/75/100 ug / hr.

Packaging:

1 TTS in a sachet of the combined material "Uplast".

For 5 sachets together with instructions for use in a pack of cardboard.

Storage conditions:

In accordance with narcotics storage rules included in the list II "List of narcotics, psychotropic substances, and precursors subject to control in the Russian Federation ".

At a temperature of 15 to 25 ° C.

Keep out of reach of children, both before and after use.

Shelf life:2 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004366

Date of registration:07.07.2017

Expiration Date:07.07.2022

The owner of the registration certificate:MOSCOW ENDOCRINE FACTORY, FSUE MOSCOW ENDOCRINE FACTORY, FSUE Russia

Manufacturer: & nbsp

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Information update date: & nbsp14.09.2017

Illustrated instructions

Instructions

Fentanyl (Phentanyl)