Durogezik® Matrix (Durogesic® Matrix)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceFentanylFentanyl
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    • Dosage form: & nbsptransdermal therapeutic system
    Composition:

    Durogezik® Matrix is ​​produced in five modifications of different force of action, the composition of which is the same when calculated per unit area of ​​the TTC. Systems with an area of ​​5.25, 10.5, 21.0, 31.5 and 42.0 cm2 12,5, 25, 50, 75 and 100 μg fentanyl per hour, which is approximately 0.3, 0.6, 1.2, 1.8 and 2.4 mg per day are released into the systemic blood stream. The remaining components of the system do not have pharmacological activity.

    Active substance: fentanyl (TTC 12.5 μg / h contains 2.1 mg of fentanyl, a TTC of 25 μg / h contains 4.2 mg of fentanyl, a TTC of 50 μg / h contains 8.4 mg of fentanyl, a TCT of 75 μg / h contains 12.6 mg fentanyl, TTS 100 μg / h contains 16.8 mg fentanyl).

    Excipients: a substrate is a polyethylene terephthalate (PET) and ethylene vinyl acetate (EVA) copolymer, an adhesive layer is a polyacrylateDuro-Tak® 87-4287), protective film - siliconeized polyethylene terephthalate (PET).

    Description:

    A translucent rectangular transdermal therapeutic system with rounded corners, a matte substrate, a colorless adhesive layer and a transparent removable protective coating.

    The name of the adhesive on the substrate is the trade name "Durogesic" with a warning marking ®, the dosage of the preparation (12/25/50/75/100 µg fentanyl/h) in Latin:

    at 12.5 mcg / h - orange inscriptions (indicated dosage "12 µg fentanyl/h"),

    at 25 mcg / h - inscriptions of pink color,

    at 50 mcg / h - inscriptions of light green color,

    at 75 μg / h - blue inscriptions,

    at 100 mcg / h - inscriptions of gray color.

    Pharmacotherapeutic group:analgesic narcotic
    ATX: & nbsp

    N.01.A.H.01   Fentanyl

    Pharmacodynamics:

    Fentanyl - a synthetic analgesic, interacting predominantly with µ-opioid receptors. 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. Increases the activity of the antinociceptive system, increases the threshold of pain sensitivity.Violates the transmission of excitation by specific and nonspecific painful pathways to the nuclei of the thalamus, the hypothalamus, the 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, slows the heart rhythm, excites the centers of the vagus nerve and vomiting 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 (TTC) of Durogesic® Matrix 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, fentanyl. After the application of Durogesic® Matrix, the concentration of fentanyl in blood plasma gradually increases during the first 12-24 hours and remains relatively constant over the remainder of the time. The level of fentanyl concentration in the blood plasma is proportional to the size of the TTS.

    By the end of the second 72-hour application, an equilibrium concentration is achieved in the blood plasma, 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 removal of the TTC Durogezik® Matrix, the fentanyl concentration in the blood plasma gradually decreases, with a half-life of approximately 17 (13-22) hours after the 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% unchanged, 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 Durogesic® Matrix 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 monitored to identify symptoms of fentanyl toxicity and, if necessary, reduce the dose of Durogesic® Matrix.

    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 detect symptoms of fentanyl toxicity and, if necessary, reduce the dose of Durogesic® Matrix.

    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 insufficiency taking Durogesic® Matrix should be carefully monitored to detect symptoms of fentanyl toxicity and, if necessary, reduce the dose of the drug, Durogesic® Matrix.
    Indications:

    - Chronic pain syndrome of strong and moderate severity:

    - pain caused by an oncological disease;

    - pain syndrome of non-oncological genesis, requiring repeated anesthesia with narcotic analgesics, for example neuropathic pain (pain syndrome with diabetic polyneuropathy, nerve trauma, syringomyelia, multiple sclerosis, shingles (Herpes zoster), arthritis and arthrosis, phantom pain after limb amputation, etc.

    Contraindications:

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

    - children's age till 18 years;

    - 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.

    Carefully:

    - In chronic 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;

    - with the simultaneous administration of insulin, glucocorticoids, antihypertensive drugs and MAO inhibitors.

    Pregnancy and lactation:

    Data on the use of Durogesic® Matrix in pregnant women is not enough. There were cases of withdrawal syndrome in newborns, whose mothers were chronicly used by Durogesic® Matrix during pregnancy. Durogezik® Matrix should not be used during pregnancy, except in cases of acute need.

    It is not recommended to use Durogesic® Matrix at birth, fentanyl penetrates the placenta and can cause respiratory depression in the newborn.

    Fentanyl is excreted in breast milk and may cause sedation / respiratory depression in children. Therefore, Durogezik® Matrix should not be used by nursing mothers.

    Dosing and Administration:

    The dose of Durogesic® Matrix is ​​selected individually depending on the patient's condition and should be evaluated regularly after TTC application.

    Durogezik® Matrix should be applied on a 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 use, the transdermal system must be checked carefully for damage. TTS, divided into parts, cut or otherwise damaged in any case should not be used.

    Durogezik® Matrix should be glued immediately after removal from the sealed bag. To remove the transdermal system 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 transdermal system in half in the middle and remove each half of the protective film, without touching your fingers with the sticky layer.The transdermal system 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.

    Durogezik® Matrix 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

    The initial dose of Durogesic® Matrix is ​​selected based on the previous use of opioid analgesics. It is recommended to prescribe Durogesic® Matrix 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

    To switch from oral or parenteral forms of opioids to Durogesic® Matrix in patients with tolerance to opioids it is necessary to be guided by "Transfer to an equivalent analgesic dose", presented below.The dosage can be subsequently reduced or increased, if necessary, by 12 or 25 μg / hr to achieve the lowest dose of Durogesic® Matrix, depending on the response and additional requirements for anesthesia.

    Patients who had not previously taken opioids

    The experience of using Durogesic® Matrix in patients who had not previously taken opioids is limited. In cases where it is necessary to administer Durogesic® Matrix to patients who have not previously taken opioids, it is recommended to start with small doses of rapid-release opioids (for example, morphine, tramadol and codeine) equivalent to 25 μg / h of Durogesic® Matrix. After this, patients can be transferred to a dose of 25 μg / h of Durogesic® Matrix.

    Dosage can be subsequently reduced or increased if necessary by 12 or 25 μg / h to achieve the lowest dose of Durogesic® Matrix, depending on the response and additional pain management requirements (see "Transfer to an equivalent analgesic dose").

    Transfer to an equivalent analgesic dose

    1. Calculate the previous 24-hour need for analgesia

    2. 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.

    3. Find the dose of Durogesic® Matrix, equivalent to the 24-hour dose of morphine, required by the patient, using Table 2 or 3:

    a) Table 2 is applicable for 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

    The equivalent analgesic dose (mg)

    Name

    preparation

    at/m *

    Inside

    Morphine

    10

    30 (with regular administration) **

    60 (with a single or intermittent administration)

    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: Recommended initial dose of Durogesic® Matrix (depending on the daily oral dose of morphine) *

    Oral 24-hour dose of morphine (mg / day)

    The dose of Durogesic® Matrix (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

    * In clinical trials, these values ​​of daily doses of morphine were used as the basis for the transition to Durogesic® Matrix.

    Table 3: Recommended initial dose of Durogesic® Matrix on the basis of a daily oral dose of morphine (for patients on stable, well tolerated opioid therapy.

    Oral 24-hour dose of morphine (mg / day)

    The dose of Durogesic® Matrix (μg / h)

    <44

    12,5

    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

    The initial evaluation of the maximal analgesic effect of Durogesic® Matrix can not be performed less than 24 hours after the application. This time interval is due to a gradual increase in serum fentanyl concentration after application.

    For a successful transition from one drug to another, previous analgesic therapy should be discontinued gradually after the initial dose of Durogesic® Matrix is ​​applied.

    Dose selection and maintenance therapy

    TDS Durogezik® Matrix 12.5 mg / h is used to select the dose. TTC Durogezik® Matrix should be replaced every 72 hours. The dose is selected individually, observing the balance between the achievement of the necessary anesthesia and the patient's tolerance. If after the application of the initial dose adequate anesthesia is not achieved, then through 3 days the dose can 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 durogesic® Matrix 12 , 5 μg / h and 25 μg / h, respectively).

    To achieve a dose of more than 100 μg / h, several TTS can be used simultaneously. Patients may occasionally require additional doses of short-acting analgesics in the event of "breakthrough" pain.

    Some patients may require additional or alternative methods of administering opioid analgesics when using a dose of Durogesic® Matrix, exceeding 300 μg / h.

    Symptoms of cancellation are possible after discontinuation or after adjusting the dose of the drug (see Section "Side Effects"). The data in Tables 2 and 3 are not intended to be transferred from Durogesic® Matrix to other opioid preparations in order to avoid possible overdose.

    Side effects:

    Side effects are given with 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

    Disorders 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, very rarely - intestinal obstruction, dyspepsia.

    Metabolic and nutritional disorders: often - anorexia.

    From the side of the cardiovascular system: often - palpitation, 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, anaphylactoid reactions.

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

    Other: often - fatigue, chills, malaise, fatigue, peripheral edema, infrequently - application-site reactions (including dermatitis, eczema, hypersensitivity), "withdrawal", flu-like symptoms, very rarely - sense changes in body temperature, pyrexia.

    As for other opioid analgesics, repeated use of Durogesic® Matrix can develop physical and mental dependence and tolerance.

    In the transition from the previously received narcotic analgesics for use Dyurogezik® Matrix preparation or in case of a sudden cessation of therapy possible symptoms associated with opioid withdrawal (nausea, vomiting, diarrhea, anxiety, vomiting). There were very rare cases of withdrawal syndrome in newborns, whose mothers were chronicly used by Durogesic® Matrix during pregnancy.

    Overdose:

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

    Treatment: removal of TTS, physical and verbal stimulation (the patient should be "patted" on the cheeks, call by name, etc.), if necessary - auxiliary and artificial ventilation (IVL). The introduction of a specific antagonist - naloxone. Respiratory depression in overdose may last longer than the opioid antagonist, so it may be necessary to re-administer naloxone. Symptomatic and supportive of important life functions therapy (including the introduction of muscle relaxants, IVL, with bradycardia - 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:

    Simultaneous use of other drugs that provide oppressive effect on the central nervous system, including opioids, sedatives and hypnotics, general anesthetics, phenothiazines, tranquilizers, central muscle relaxants, antihistamines with sedative effect,and alcoholic beverages, may increase the risk of additive suppressive effect, hypoventilation of the lungs, lowering blood pressure, excessive sedation, or to cause death (either of these drugs taken simultaneously with Durogezik® Matrix, requires special monitoring for the patient). Simultaneous administration of cytochrome P450 inhibitors CYP3A4, may lead to an increase in plasma fentanyl concentration. The consequence of this is an increase or lengthening of 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 cytochrome inhibitors CYP3A4 is not recommended, except for careful monitoring of patients (see section "Special instructions").

    Joint application of the drug with inducers of isoenzyme CYP3A4 (eg, rifampicin, carbamazepine, phenobarbital, phenytoin) may lead to a decrease in fentanyl concentration in the blood plasma and a decrease in 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 means. Beta-blockers can reduce the incidence and severity of hypertensive reaction in cardiosurgery (including sternotomy), but increase the risk of bradycardia.

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

    The muscle relaxants prevent or eliminate muscle rigidity; muscle relaxants with vagolytic activity (including pancuronium bromide) reduce the risk of bradycardia and hypotension (especially when using beta-blockers and other vasodilators) and may increase the risk of tachycardia and hypertension; muscle relaxants that do not have a vagolytic activity (incl.succinylcholine), do not reduce the risk of bradycardia and hypertension (especially in the background of an aggravated cardiological history) and increase the risk of serious cardiovascular side effects system.

    Nitrous oxide enhances muscle rigidity; 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 that fentanyl be co-administered with inhibitors of MAO. Were noted serious and unpredictable interactions with MAO inhibitors, with enhanced effects opioids or serotonergic effects.

    Therefore, it is not recommended to prescribe Durogesic® Matrix 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), inhibitors monoamine oxidase (MAOI) may increase the risk of 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 of the TTC Durogesic Matrix, as the fentanyl concentration in the plasma decreases gradually and its 50% reduction is achieved within approximately 17 (13 -22) hours. Durogesic® Matrix should be stored out of the reach of children, both before and after use.

    TTC Durogezik® Matrix can not be cut.

    Application in patients who have not previously taken opioids and in patients who do not have tolerance for opioids. When TTC Durogesic® Matrix was used, patients who had not previously taken opioids very rarely experienced 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 lung exists even if a minimum dose of TTC Durogesic® Matrix is ​​used as an initial opioid therapy in patients who have not previously taken opioids. It is recommended to prescribe Durogesic® Matrix to patients demonstrating opioid tolerance.

    Inhibition of respiration

    As with the use of other potent opioid analgesics, with the use of Durogesic® Matrix, 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 TTC Durogezik Matrix. The degree of respiratory depression increases with an increase in the dose of Durogesic® Matrix. Drugs that affect the central nervous system can increase respiratory depression.

    Chronic lung diseases

    Durogezik® Matrix 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 pressures

    Durogezik® Matrix should be used with caution in patients who may be particularly sensitive to increase of CO2. These patients are those who have had an increase intracranial pressure, impaired consciousness or coma.Durogezik® Matrix should be used with caution in patients with a brain tumor.

    Cardiovascular diseases

    Fentanyl can cause bradycardia and, thus, it should be used with caution in patients with bradyarrhythmias. Durogezik® Matrix should be used with caution 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 insufficiency taking Durogesic® Matrix should be under constant observation to detect symptoms of possible fentanyl toxicity, and if necessary, the dose of Durogesic® Matrix should be reduced.

    Opioid analgesics can increase the tone of the smooth muscles of the gastrointestinal tract and bile ducts. Durogezik® Matrix 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 disease insufficiency, taking Durogezik® Matrix should be under constant observation to identify symptoms of possible fentanyl toxicity and, if necessary, the dose of Durogesic® Matrix should be reduced.

    Serotonin syndrome

    Care should be taken when using the drug Durogesic® Matrix together with drugs that affect the serotonergic neurotransmitter system. Joint application with serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SSRIs), as well as with drugs that reduce serotonin metabolism (including inhibitors monoamine oxidase) 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, impaired coordination, rigidity) and / or gastrointestinal system disorders (nausea, vomiting , diarrhea).

    If you suspect a development of serotonin syndrome, therapy with Durogesic® Matrix should be discontinued.

    Interaction with inhibitors of isochrome CYP3A4

    With joint 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 the development of 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

    The accidental exposure of Durogesic® Matrix to 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 obtained from studies of intravenous administration of fentanyl suggest that elderly patients may experience reduced clearance and longer half-life of the drug, and in addition, such patients may be more sensitive to fentanyl than younger patients. Elderly patients taking Durogezik® Matrix should be under constant observation to identify symptoms of a possible fentanyl overdose and, if necessary, a dose of Durogesic® Matrix should be reduced.

    Effect on the digestive tract

    Opiates increase tone and reduce propulsive reduction of 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 are informed about measures of prevention of constipation and preventive use of laxatives.

    Additional measures precautions should be applied to patients suffering from chronic constipation. If paralytic intestinal infection is present or suspected obstruction, treatment with Durogesic® Matrix should be discontinued.

    Use in depleted and debilitated patients

    Since the depleted and weakened patients may decrease their 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 Durogesic® Matrix 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 addiction. 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 drug Durogezik® Matrix for other purposes may lead to overdose and / or death. Patients at an increased risk of abuse of opioids,may continue to receive adequate therapy with modified-release opioids, but should be monitored to identify possible signs of misuse, abuse, or dependence.

    Fever / external heat sources

    Pharmacokinetic model suggests that serum fentanyl concentrations can increase by about one-third if 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 the Durogezik® Matrix was pasted on the TTS, an increase in the mean values ​​was observed AUC by 120% and CmOh on 61%. All patients should avoid direct exposure to external heat sources such as heating lamps, sun lamps, intensive sun baths, hot water bottles, saunas, solarium, hot water baths, etc.,to the place of application of TTC Durogezik® Matrix.

    Termination of Durogesic® Matrix

    If it is necessary to terminate Durogezik® Matrix, 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 TTC Durogezik® Matrix, while a decrease in fentanyl concentration by 50% in serum takes 17 hours. The abolition of opioid analgesia should always be gradual in order to prevent the development of a "withdrawal syndrome".

    Removal of TTS

    The used TTS should be folded in half an adhesive side inside and returned to the doctor for destruction in the prescribed manner. Unused TTS should also be returned to the doctor for destruction.

    Before use, the drug should be stored in a sealed package.

    Effect on the ability to drive transp. cf. and fur:Durogezik® Matrix can affect the mental and / or physical functions necessary to carry out potentially dangerous work, such as driving a car or working with 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:The transdermal therapeutic system, 12.5 μg / hr, 25 μg / hr, 50 μg / hr, 75 μg / h and 100 μg / hr.
    Packaging:

    1 TTS in a package of combined material (polyethylene terephthalate, low density polyethylene, aluminum foil).

    For 5 packages together with the instruction for use are enclosed in a cardboard box.

    Storage conditions:

    Refers to the list of II drugs.

    Store at a temperature of 15-25 ° C.

    Keep out of the reach of children.

    Shelf life:

    2 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-002288/07
    Date of registration:17.08.2007
    The owner of the registration certificate:Johnson & Johnson, LLC Johnson & Johnson, LLC Russia
    Manufacturer: & nbsp
    Representation: & nbspJohnson & Johnson LLC Johnson & Johnson LLC Russia
    Information update date: & nbsp22.09.2015
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