Fentadol Matrix - instructions for use, dose, side effects, contraindications

protective film (area): polyethylene terephthalate (siliconized) 10.5 cm², 21.0 cm², 31.5 cm², or 42.0 cm², respectively for dosages: 25, 50, 75, 100 μg / h.

Description:

A translucent rectangular patch (TTC patch) with rounded corners and a transparent protective film.

On the substrate of the patch in Latin, the name of the active ingredient is indicated (fentanyl) (2 times) and dosage (25 μg / h, 50 μg / h, 75 μg / h or 100 μg / h).

Dosing mg / h	Size (area) cm²
25	10,5 ±10%
50	21 ±10%
75	31,5 ±10%
100	42 ±10%

Pharmacotherapeutic group:analgesic narcotic

ATX: & nbsp

N.01.A.H.01 Fentanyl

Pharmacodynamics:

Fentanyl is an opioid analgesic, an opioid receptor agonist (predominantly μ-receptors) of the central nervous system (CNS), spinal cord and peripheral tissues. Increases the activity of the antinociceptive system, raises the threshold of pain sensitivity.

The main therapeutic effects of the drug are analgesic and sedative.

Duration of the drug - 72 h.

Has a depressing effect on the respiratory center, slows the heart rhythm, excites the centers of the vagus nerve and vomiting center. Increases the tone of the smooth muscles of the bile ducts, the pathways, sphincters (including the urethra, bladder, sphincter of Oddi), reduces intestinal motility, improves the absorption of water from the gastrointestinal tract (GIT).

Virtually no effect on blood pressure (BP), reduces renal blood flow.

In the blood raises the concentration, amylase and lipase; reduces the concentration of somatotropic hormone (STH), catecholamines, cortisol, prolactin. Promotes the onset of sleep (mainly in connection with the removal of the pain syndrome). Causes euphoria. The rate of development of drug dependence and tolerance to analgesic effect has significant individual differences.

The minimum effective analgesic concentration of fentanyl in plasma in patients not previously used narcotic analgesics is 0.3-1.5 ng / ml, with fentanyl concentrations in serum above 2 ng / ml, the likelihood of side effects increases.

Unlike other narcotic analgesics, it is much less likely to cause histamine reactions.

The transdermal therapeutic system (TTS) is a dosage form for maintaining a constant release of fentanyl for 72 hours.

Pharmacokinetics:

The connection with plasma proteins - 80-89% (mainly with albumins and lipoproteins, depends on the pH of the plasma). The volume of distribution is 60-80 l (3.1-7.8 l / kg). The fentanyl fraction in the plasma unbound with plasma proteins is 13-21%.

After the application of TTS fentanyl accumulates in adipose tissue and muscles and then slowly released into the blood. The release of fentanyl occurs at a constant rate for 72 hours, with the therapeutic serum concentration gradually increasing in the first 12-24 hours and remains relatively constant over the remainder of the period.

The concentration of fentanyl in blood plasma is proportional to the area of the TTS.

After repeated applications, an equilibrium concentration in the blood plasma is achieved, which is maintained by subsequent TTS applications of the same size. After removal of TTS, the fentanyl concentration in the blood plasma gradually decreases, while the half-life (T_1/2) is about 17 hours (13-22 hours). Continued absorption of fentanyl from the skin (more typically after 4 applications) explains the slow disappearance of the drug from the blood plasma. In elderly, debilitated or weakened patients, the clearance of fentanyl can be reduced, which leads to an elongation of T_1/2fentanyl.

Fentanyl is metabolized predominantly in the liver (by N-dealkylation and hydroxylation) involving cytochrome P450 (isoenzyme CYP3A4), as well as in the kidneys, intestines and adrenal glands. The main metabolite of norfentanil is inactive.

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

It penetrates the blood-brain barrier (GEB), the placenta and into breast milk.

Indications:

Chronic pain syndrome of strong and moderate severity:

- pain caused by an oncological disease;

- pain syndrome of non-oncological genesis, requiring repeated analgesia with narcotic analgesics (for example, neuropathy, arthritis and arthrosis, "phantom" pain after limb amputation).

Contraindications:

Hypersensitivity to the active substance or excipients of TTS;

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

- TTS should not be used to treat acute or postoperative pain due to the lack of the possibility of selecting an adequate dose in a short period of time and the likelihood of developing a life-threatening respiratory depression;

- simultaneous use with monoamine oxidase (MAO) inhibitors, as in during the entire period of application of MAO inhibitors, and within 14 days after their cancellation;

- irritation and violation of the integrity of the skin, radiation dermatitis in the place of the intended application;

- diarrhea on the background of pseudomembranous colitis, caused by the intake of cephalosporins, lincosamides, penicillins;

- toxic dyspepsia;

- severe CNS lesions;

- intestinal obstruction;

- severe bronchial asthma or an acute attack of bronchial asthma;

- the period of labor contractions and childbirth (including cesarean section), in connection with probability of fetal / newborn respiratory depression;

- age to 18 years.

Carefully:

Respiratory failure (pneumonia, atelectasis and lung infarction, bronchial asthma, chronic obstructive bronchitis, propensity to bronchospasm), intracranial hypertension, brain tumors, traumatic brain injury, bradyarrhythmia, arterial hypotension, renal and hepatic insufficiency, renal or hepatic colic in history), cholelithiasis, hypothyroidism, elderly, debilitated and weakened patients, acute surgical diseases of the abdominal cavity before diagnosis, general severe condition of the pas yenta, benign prostatic hyperplasia, urethral stricture, drug dependence (including narcotic), alcoholism,suicidal tendencies, hyperthermia, simultaneous reception of insulin, glucocorticosteroids (GCS), hypotensive drugs.

Pregnancy and lactation:

Data on the application of the TTC, containing fentanyl, pregnant women are not enough.

Fentanyl during pregnancy should be used only in cases of acute need, when the intended benefit to the mother exceeds the potential risk to the fetus.

Long-term use of TTS with fentanyl during pregnancy can cause a "cancellation" syndrome in newborns.

Fentanyl should not be taken during labor and delivery (including cesarean section), because fentanyl penetrates the placenta and can cause respiratory depression of the fetus or newborn.

Fentanyl is excreted in breast milk and can cause sedative, effects and respiratory depression in a breast-fed baby. Therefore, if it is necessary to prescribe the drug during lactation, breastfeeding should be terminated (for the entire duration of administration and within 72 hours after removal of the TTS).

Dosing and Administration:

The dose of the drug Fentadol® Matrix is selected individually depending on the patient's condition, the effectiveness of the dose should be regularly evaluated after each TTC application.

TTS is applied to intact and unirradiated skin surface with minimal hair covering: chest, back, shoulders. If it is necessary to remove the hair cover, it should be cut (not shaved!).

If the place of application is to be washed before applying the TTS, it should be done with clean water. Do not use soap, lotions, oils, alcohol or other products. they can cause skin irritation or change its properties.

Before application, the skin should be absolutely dry. Because TTS is protected by a waterproof outer protective film, it can be removed without a brief stay in the shower.

Before applying the TTC, it is necessary to check carefully for damage: the TTS cut or damaged in any other way should not be used!

The drug Fentadol® Matrix should be used immediately after removal from a sealed original package:

1. Separate part of the protective film from the back of the TTC.

2. Apply a part of the TTS that is free of the film to the selected area of the skin and squeeze it well.

3. Remove the remaining part of the protective film without touching the adhesive layer with your fingers.

4.After removing the entire protective film, it is necessary to tightly press the TTS palm in place of the application for about 30 seconds. It should be ensured that the TTS tightly adheres to the skin, especially along the edges. If necessary, additional fixation of the TTC may be used.

5. After applying TTC Fentadol® Matrix, wash your hands with clean water (without soap).

TTS should be pasted for 72 hours, after which it must be changed to a new one (in exceptional cases, the replacement of the TTS is made 48 hours, but not earlier!).

New TTS should always be applied to another area of the skin, without seizing the place of the previous application. At the same place applications TTS can be applied again not earlier than 7 days later.

The analgesic effect may persist for some time after removal of the TTS.

TTS Fentadol® Matrix should not be divided or cut!

If after removal of the TTS on the skin there are its residues, it is necessary to remove them with a large amount of water with soap.

Do not use alcohol and other solvents for this purpose. organic; Solvents (due to the effect of TTS) can penetrate through the skin.

Selection of initial dose

The initial dose of the drug Fentadol® Matrix is selected individually, based on the previous use of narcotic analgesics, and also taking into account the possible development of tolerance and its degree, concomitant drug treatment, the general condition of the patient (including body surface area, age, degree of exhaustion).

Patients who had not previously taken narcotic analgesics

In the absence of previous treatment with narcotic analgesics it is recommended to begin treatment with small doses of 25 μg / h of the drug Fentadol® Matrix.

The dose may be subsequently reduced or increased if necessary by 12.5-25 μg / h to achieve the lowest effective dose of the drug Fentadol® Matrix, depending on the effect and the need for additional analgesia (see Table 1, "Transfer to an equivalent analgesic dose" and Table No. 2 "Recommended dose of the drug Fentadol® Matrix.)

Patients who had previously taken narcotic analgesics

When switching from oral or parenteral use of narcotic analgesics to the drug Fentadol® Matrix in patients with tolerance to narcotic analgesics, the initial doseis calculated as follows:

- determine the total daily dose of previously used narcotic drugs. analgesics;

- the resulting total dose is transferred to the appropriate oral dose of morphine using Table 1 "Transfer to an equivalent analgesic dose";

- the appropriate dose of fentanyl is determined using Table No. 2, "Recommended dose of Fentadol® Matrix" (depending on the daily oral dose of morphine).

The dose can be subsequently reduced or increased if necessary by 12.5-25 μg / h to achieve the minimum effective dose of the drug Fentadol® Matrix, depending on the reaction and the need for additional analgesia.

All intramuscular (IM) and oral doses of narcotic analgesics listed in Table 1 are equivalent in terms of the analgesic effect of 10 mg of morphine IM.

Table 1. Transfer to an equivalent analgesic dose

Name of the medicinal product	Equivalent analgesic dose (mg)
Name of the medicinal product	w / m	inwards
Morphine	10	10 (with regular administration) 60 (with a single or intermittent administration)
Omnompon	45	-
Hydromorphone	1,5	7,5
Methadone	10	20
Oxycodone	15	30
Levorphanol	2	4
Oxymorphone	1	10 (rectally)
Pethidine	75	-
Codeine	130	200
Buprenorphine	0,4	0.8 (sublingually)
Ketobemidone	10	30

Table 2. Recommended dose of the drug Fentadol® Matrix (depending on the daily oral dose of morphine)

The oral daily dose of morphine (mg / day)	Dose of Fentadol® Matrix (μg / h)
<134	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

The initial evaluation of the maximum analgesic effect of the drug Fentadol® Matrix can be performed no earlier than 24 hours after the application. This restriction is due to the fact that the increase in serum fentanyl concentration in the first 24 hours after the application is gradual. Therefore, for successful transition from one drug to another, previous analgesic therapy should be canceled gradually after the application of the initial dose of the drug Fentadol® Matrix until its analgesic effect stabilizes.

In the first 12 hours after the appointment of TTS with fentanyl, patients should continue to receive narcotic analgesics in the previous dose; if the application is more than 12 hours, this analgesic is prescribed as required.

Dose selection and maintenance therapy

The TTS should be replaced every 72 hours.The dose is selected individually before the desired analgesic effect is achieved.

If, after 48-72 hours after the initial dose, a significant reduction in the analgesic effect occurs, the replacement of the TTS may be required after 48 hours.

A dose of 25 μg / h is usually sufficient to select a dose in the lower dose range. If the analgesia was insufficient by the end of the first application period, the dose can be increased every 3 days until the required effect.

Usually, the dose is increased by 12.5-25 μg / h for 1 time, however, the patient's condition and the need for additional analgesia must be taken into account.

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

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

If the required dose of the drug Fentadol® Matrix exceeds 300 μg / h, consideration should be given to the possibility of using additional or alternative methods of analgesia or alternative methods of administering narcotic analgesics.

The use of the drug Fentadol® Matrix specific groups of patients

In elderly, debilitated and weakened patients, as well as in patients with renal or hepatic insufficiency, the dose should be reduced if necessary.

Discontinuation of treatment with the drug Fentadol® Matrix

If it is necessary to interrupt the use of TTS, then substitution for any other narcotic analgesics should be carried out gradually, starting with a low dose and slowly increasing it. This is due to the fact that the content of fentanyl in the blood serum after removal of the TTS decreases gradually; to reduce the serum fentanyl concentration by 50%, at least 17 hours are required.

The abolition of narcotic analgesics should be gradual in order to avoid the syndrome of "withdrawal" (nausea, vomiting, diarrhea, anxiety and muscular tremor).

Side effects:

According to the World Health Organization (WHO) undesirable reactions

are classified according to their frequency of development as follows: very often (≥ 1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10000, <1/1000) and very rarely (<1/10000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

From the central nervous system

Often: drowsiness, dizziness, headache;

often: tremor, paresthesia, depression, anxiety, hallucinations, insomnia, confusion, anorexia;

infrequently: disorientation, euphoria, hypoesthesia, seizures (including clonic convulsions and a large epileptic fit), amnesia, agitation.

From the sense organs

often: vertigo;

rarely: miosis.

From the side of the cardiovascular system

often: a feeling of palpitations, tachycardia, hypertension;

infrequently: bradycardia, hypotension, cyanosis;

rarely: arrhythmia.

Co of the respiratory system

often: dyspnea;

infrequently: respiratory depression, respiratory distress syndrome;

rarely: apnea, hypoventilation;

frequency is unknown: bradypnoe.

Co side of the gastrointestinal tract

Often: nausea, vomiting, constipation;

often: diarrhea, dry mouth, abdominal pain, upper abdominal pain, dispensaryTTCand I;

infrequently: intestinal obstruction;

rarely: partial intestinal obstruction.

From the skin and subcutaneous tissues

often: hyperhidrosis, itching, rash, erythema;

infrequently: eczema, allergic dermatitis, dermatitis, contact dermatitis.

From the side of the musculoskeletal system

often: muscle spasm;

infrequently: twitching of muscles.

From the genitourinary system

often: retention of urine; infrequently: erectile dysfunction, sexual dysfunction.

Other

often: fatigue, malaise, peripheral edema, asthenia, chills;

infrequently: reactions in place applications, influenza-like syndrome, sensation of changes in body temperature, withdrawal syndrome, hypersensitivity in the place of application, hyperthermia;

rarely: eczema at the site of application, dermatitis at the site of application.

From the immune system

often: hypersensitivity;

frequency is unknown: anaphylactic shock, anaphylactic reactions, anaphylactoid reactions. The rash, erythema and itching at the site of application in most cases disappear within one day after removal of the TTS.

With long-term use of fentanyl, as with the use of other narcotic analgesics, tolerance, physical and TTCshort-term dependence stiffness of muscles (including pectorals). When moving from previously taken narcotic drugs analgesics for the use of the drug Fentadol® Matrix, or in the event of a sudden cessation of therapy, a "cancellation" syndrome is possible that is characterized by nausea, vomiting, diarrhea,anxiety and chills.

Overdose:

Symptoms: dizziness, drowsiness, inhibition, nervousness, general weakness, depression, cardiovascular activity, decreased blood pressure, bradycardia, sticky sweat, miosis, muscle stiffness, respiratory center depression with Chain-Stokes breathing and / or cyanosis, coma condition, bradypnoea, apnea.

Treatment: removal, TTS, physical and verbal stimulation of the patient to restore breathing ("slapping on the cheeks," addressing by name), the introduction of a specific antidote - naloxone. Inhibition of respiration in case of an overdose may last longer than the duration of the opioid receptor antagonist, so there may be a need for repeated intravenous (iv) naloxone (or continuous infusion). The use of an opioid receptor antagonist can lead to the development of a sharp pain syndrome and the release of catecholamines.

The recommended initial dose for adults is 0.4-2 mg of naloxone IV. If necessary, you can inject the same dose every 2-3 minutes or inject 2 mg of naloxone dissolved in 500 ml of a 0.9% solution of sodium chloride or a 5% solution of dextrose (0.004 mg / ml) in the form of infusions.The rate of administration should be adjusted to the previous bolus injections and the patient's individual response. If IV administration is not possible, then naloxone can be administered intramuscularly (IM) or subcutaneously (SC). After a / m or n / to the introduction of naloxone, the onset of action will be slower than in / in the introduction. In / m administration gives a more prolonged effect than intravenously.

Conduct symptomatic and supportive vital functions of therapy (including the introduction of muscle relaxants, artificial ventilation of the lungs, with bradycardia - the introduction of atropine, with a pronounced decrease in blood pressure - replenishment of the volume of circulating blood).

Interaction:

With the simultaneous use of other drugs (drugs), which exert a depressing effect on the central nervous system, including other narcotic analgesics, sedatives and hypnotics, general anesthetics, phenothiazines, tranquilizers, central muscle relaxants, antihistaminic drugs with sedative effect, alcohol may increase the risk of developing and intensifying hypoventilation, reducing blood pressure, excessive sedation, coma or fatal (taking any of these drugs concomitantly with Fentadol® Matrix requires special monitoring of the patient).

If there is a need to jointly use the drug Fentadol® Matrix with one of the above drugs, you need a dose adjustment of one or both drugs.

Fentanyl has a high clearance, it quickly and to a large extent is metabolized, mainly, with the participation of the CYP3A4 isoenzyme.

Simultaneous administration of inhibitors of the isoenzyme CYP3A4 (eg, erythromycin, ritonavir, ketoconazole, itraconazole, diltiazem, cimetidine, antibiotics from the macrolide group) with fentanyl administered transdermally, can lead to an increase in fentanyl concentrations in the blood plasma. This can enhance or prolong both the therapeutic effect and side effects that can cause severe respiratory depression. Careful observation of patients is necessary. The combined administration of ritonavir or another potent inhibitor of the CYP3A4 isoenzyme with transdermal administration of fentanyl is not recommended unless careful monitoring of the patient is performed. Fentanyl enhances the effect of antihypertensive drugs.

Joint application with inducers of the isoenzyme CYP3A4 (for example, rifampicin, carbamazepine, phenobarbital, phenytoin) may lead to a decrease in the concentration of fentanyl in blood plasma and a decrease in the therapeutic effect.This may require a correction of the dose of fentanyl for transdermal administration. After cessation of treatment with inducers of the CYP3A4 isoenzyme, the inductor effect gradually decreases and may lead to an increase in the fentanyl concentration in the blood plasma, which may cause an increase in the intensity or duration of both therapeutic and undesirable effects, and may lead to severe respiratory depression. In this situation, careful monitoring should be carried out and, if necessary, the dose should be adjusted.

Beta-adrenoblockers can reduce the frequency and severity of hypertensive reaction in cardiac surgery (including sternotomy), but increase the risk of bradycardia.

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

Muscle relaxants prevent or eliminate muscle rigidity; muscle relaxants with m-cholinoblocking activity (including pancuronium bromide) reduce the risk development of bradycardia and reduction of blood pressure (especially when using beta-blockers and other vasodilators) and may increase the risk of tachycardia and increased blood pressure; muscle relaxants that do not possess m-cholinoblocking activity (including suxamethonium) do not reduce the risk of bradycardia and reducing blood pressure (especially in the background of a burdened cardiological history) and increase the risk of serious side effects from the cardiovascular system.

Nitrous oxide increases muscle rigidity.

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

It is not recommended to use fentanyl together with MAO inhibitors, both during the whole period of application inhibitors of MAO, and within 14 days after their cancellation, t. they increase the risk of serious complications in the use of fentanyl (enhancing the effect of narcotic drugs analgesics or increased serotonergic effects).

Special instructions:

The drug Fentadol® Matrix can only be used highly qualified staff in conditions specialized hospital, as part of a comprehensive treatment of pain in patients with adequate medical, social and psand theological assessment of their condition.

The drug Fentadol® Matrix can not be prescribed for the relief of acute or postoperative pain, There is no possibility to select an adequate dose for short-term use.

There is a probability the occurrence and development of serious and life-threatening hypoventilation of the lungs (or respiratory depression) as a result of the application of TTS.

Patients who experienced severe side effects when using TTS require careful monitoring of their condition for another 24 hours after removal of the TTC, The fentanyl concentration in the plasma decreases gradually and its 50% reduction is achieved within approximately 17 hours (13-22 hours).

The drug Fentadol® Matrix should be stored out of the reach of children both before and after use!

TTS Fentadol® Matrix should not be divided or cut into parts!

The used transdermal patches need to be folded with a sticky surface to each other, disposed of properly. Unused packaging it is necessary to return the pharmacy employee.

Use in patients who have not previously taken drugs analgesics

When applying TTS Fentadol Matrix in patients who had not previously taken narcotic drugs analgesics, there were very few cases of significant respiratory depression and / or death when used as an initial analgesic therapy.

The risk of developing a serious or life-threatening hypoventilation exists even if a minimum dose of TTS Fentadol® Matrix is used as an initial analgesic therapy in patients who have not previously taken narcotic analgesics. It is recommended to use the drug Fentadol® Matrix in patients demonstrating tolerance to narcotic analgesics.

Inhibition of respiration

As with the use of other potent narcotic analgesics, with the use of the drug Fentadol® Matrix, some patients may exhibit marked oppression respiration. Patients should carefully monitor to identify similar effects.

The respiratory depression can continue even after removal of the TTS Fentadol® Matrix. Power Respiratory depression increases with increasing dose of the drug Fentadol® Matrix.

Chronic lung diseases

TTS Fentadol® Matrix can cause a number of severe side effects in patients with chronic obstructive and other lung diseases (reduce the excitability of the respiratory center and weaken breathing).

Patients with malignant myasthenia gravis

There may be non-epileptic (mio) clonic reactions. Treatment of patients with malignant myasthenia gravis should be carried out with caution.

Increased intracranial pressure

TTS Fentadol® Matrix should be used with caution in patients who may be particularly sensitive to increased CO levels₂(patients with increased intracranial pressure, impaired consciousness and coma). TTS Fentadol® Matrix should be used with caution in patients with intracranial tumors.

Cardiovascular diseases

Fentanyl may cause bradycardia and therefore it should be used with caution in patients with bradyarrhythmia. In patients with arterial hypotension, TTS Fentadol® Matrix should be used with caution.

Diseases of the liver

Because the fentanyl metabolized to inactive metabolites in the liver, liver disease can lead to a slower withdrawal of the drug from the body. In patients with cirrhosis of the liver, a single application of the drug Fentadol® Matrix did not show any change in pharmacokinetics, although the concentration of fentanyl in serum tended to increase.

Patients with hepatic impairment need careful monitoring to identify symptoms of fentanyl overdose. In this case, a decrease in the dose of the drug Fentadol® Matrix is necessary. Narcotic analgesics can increase the tone of a smooth

Muscles of the gastrointestinal tract and bile ducts. Pentadol® Matrix should be used with caution in patients with a history of hepatic colic.

Kidney Diseases

Less than 10% of fentanyl is excreted by the kidneys unchanged, known active metabolites that would be excreted by the kidneys, no.

Data obtained with intravenous administration of fentanyl in patients with renal insufficiency, suggest that the volume of fentanyl distribution may change during hemodialysis, which may affect the serum fentanyl concentration. Patients with renal disease Insufficiency needs careful monitoring. When symptoms of an overdose appear, the dose of TTS Fentadol® Matrix should be reduced.

When switching from long-term morphine treatment to transdermal administration of fentanyl, a "cancellation" syndrome may occur, despite adequate analgesic action of the drug.When there is a "withdrawal" syndrome, it is recommended that short-acting morphine in low doses be administered to patients.

Interaction with inhibitors of isoenzyme CYP3A4

When combined with inhibitors of the isoenzyme CYP3A4 (for example, ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, isfadosone, verapamil, diltiazem and amiodarone) may increase fentanyl concentration in the plasma, which may enhance or prolong both the therapeutic effect and side effects, in particular, cause severe respiratory depression. In such situations, you should carefully monitor the patient. On this basis, the joint use of TTS with fentanyl with inhibitors of the isoenzyme CYP3A4 is not recommended in the absence of careful monitoring of patients. Patients assigned to TTS Fentadol® Matrix simultaneously with inhibitors of the isoenzyme CYP3A4 should be observed for signs of respiratory depression; a dose adjustment may be required.

Serotonin syndrome

It should be used with caution fentanyl together with drugs that affect the serotonergic neurotransmitter systems.At simultaneous application of serotonergic drugs such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SSRIs), along with drugs that disrupt serotonin metabolism (including monoamine oxidase (MAO) inhibitors), a potentially life-threatening serotonin syndrome may develop.

This may occur if the recommended dose is observed. Serotonin syndrome can be manifested in the form of mental disorders (eg, agitation, hallucinations, coma), autonomic instability (eg, increased heart rate, lability arterial pressure, fever), neuromuscular disorders (for example, hyperreflexions, disorders of coordination of movements, rigidity) and / or symptoms from the gastrointestinal tract (for example, nausea, vomiting, diarrhea). When developing serotonin syndrome the drug should be stopped immediately.

Accidental impact of TTC

Accidental exposure of fentanyl to the skin (especially in children), in close physical contact with a patient using TTS, can lead to opioid overdose. Patients should be have been warned that if a person who does not take the drug accidentally affects the skin, the TTC must be immediately deleted.

Application in elderly patients

Data obtained from Studies in / in the administration of fentanyl, suggest that in elderly patients the clearance and lengthening of fentanyl may decrease. Elderly patients may be more sensitive to fentanyl than younger patients. During the studies of TTS Fentadol® Matrix pharmacokinetics of fentanyl in elderly patients did not differ significantly from pharmacokinetics in young patients, although serum concentrations were slightly higher. Elderly patients need careful monitoring to identify symptoms of a possible fentanyl overdose, which will require a decrease in the TTS dose of Fentadol® Matrix.

Use in depleted and debilitated patients

Since the depleted and weakened patients may decrease the clearance and lengthen T_1/2fentanyl, they need careful observation to identify the symptoms of a possible fentanyl overdose, which will require a decrease in the TTS dose of Fentadol® Matrix.

Drug dependence and the possibility of abuse

With the reintroduction of narcotic analgesics possible development of tolerance, as well as physical and pstheir dependence. Iatrogenic dependence on the use of narcotic analgesics is rarely observed. As with the use of other narcotic analgesics, there may be cases of abuse of fentanyl.

Abuse or intentional use of the drug Fentadol® Matrix for other purposes may lead to an overdose and / or death. Patients in the group at increased risk of abuse of narcotic analgesics should be under close supervision.

Hyperthermia / external heat sources

Pharmacokinetic model suggests that the concentration of fentanyl in the blood serum can increase by about 1/3 with an increase in body temperature to 40 FROM. Therefore, patients with hyperthermia should be closely monitored to identify the characteristic side effects of fentanyl and, if necessary, follow-up dose adjustment. All patients on the background of treatment should avoid direct exposure to external heat sources such as heating lamps, sun lamps, intensive sun baths,warmers, saunas, hot water baths, to the place of application of TTC Fentadol® Matrix.

In healthy volunteers there was an increase in AUC by 120% and mean C_m_Oh up to 61% as a result of the application of heat sources in the place of application of the TTC. Before visiting the sauna, the TTS should always be removed. Reception of the sauna is possible only when replacing the TTC (with an interval of 72 hours). New TTS should be applied to cold and absolutely dry skin.

Effect on the gastrointestinal tract

Opiates increase tone and reduce propulsive reduction of smooth muscles of the gastrointestinal tract. As a result of an increase in the passage time of food through the digestive tract, constipation may occur with fentanyl. Patients should be advised to take measures to prevent constipation, and should also consider preventive use laxatives.

Additional measures precautions should observe in patients with chronic constipation. In the presence of dynamic intestinal obstruction or with suspected dynamic intestinal obstruction, treatment fentanyl should be discontinued.

Discontinuation of the use of the drug Fentadol® Matrix

If it is necessary to terminate use of TTS Fentadol® Matrix, replacement of this drug with other narcotics analgesics should be carried out gradually, starting with low doses, due to a gradual decrease in the concentration of fentanyl after removal of TTS Fentadol® Matrix, in which a 50% reduction in serum fentanyl concentration takes about 17 hours. The withdrawal of the drug should always be gradual in order to avoid the development of the withdrawal syndrome.

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

TTC Fentadol® Matrix can affect psthe physical and / or physical functions necessary to carry out potentially hazardous work, such as driving vehicles or working with machinery. Patients receiving a stable defined dose in the absence of additional effects of other medicinal products drugs, do not necessarily restrict the use of the drug. You must observe caution at the beginning of treatment, with increasing doses, as well as with the use of other drugs, since the ability to drive and work with machinery can be compromised.

Form release / dosage:

Transdermal therapeutic system, 25 mcg / hour, 50 mcg / h, 75 mcg / h, 100 mcg / h.

Packaging:

One transdermal therapeutic system in a paper / PE / Al sachet/ PE.

For 5, 10 or 20 bags together with instructions for use in a cardboard pack.

Storage conditions:

Refers to the list of II narcotic drugs, psychotropic substances and their precursors, approved by Resolution of the Government of the Russian Federation No. 681 of 30.06.98.

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000279

Date of registration:17.02.2011

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

HEXAL AG Germany

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp21.09.2015

Illustrated instructions

Instructions

Fentadol® Matrix (Fentadol Matrix)