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

active substance: fentanyl 2.50, 5.00, 7.50 or 10.00 mg respectively for dosages: 25 μg / h = 10 cm, 50 μg / h = 20 cm², 75 μg / h = 30 cm², 100 μg / h = 40 cm²;

Excipients: Ethanol 96% 102.79, 205.58, 308.37, 411.16 mg; hydroxyethylcellulose 4.44, 8.88, 13.32, 17.76 mg, purified water 168.07, 336.14, 504.21, 672.28 mg;

components of a plaster: external film 15.12 cm²= 78.62 mg, 26.84 cm²= 139.57 mg, 38.09 cm² = 198.07 mg, 49.98 cm² = 259.90 mg, polysiloxane adhesive 15.12 cm² = 65.02 mg, 26.84 cm² = 115.41 mg, 38.09 cm²= 163.79 mg, 49.98 cm² = 214.91 mg, a copolymer of ethylene and vinyl acetate of 15.12 cm² = 71.37 mg, 26.84 cm² = 126.68 mg, 38.09 cm²= 179.78 mg, 49.98 cm² = 235.91 mg.

Description:

Rectangular plaster with rounded corners, convex reservoir in the center filled with a colorless transparent solution, and a protective film. On the substrate of the patch there is an inscription "fentanyl"and indicated the dosage (25 μg/h, 50 µg/h, 75 µg /h, 100 µg /h).

Dosage (μg)	Size (mm) (length / width)
25	48,0±1;38,0±1
50	65,5±1;49,0±1
75	76,5±1;60±1
100	86,5±1;70±1

Pharmacotherapeutic group:analgesic narcotic

ATX: & nbsp

N.01.A.H.01 Fentanyl

Pharmacodynamics:

Fentanyl is an opioid analgesic, an opioid receptor agonist (mainly p-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, sphincters (including the urethra, bladder, sphincter of Oddi), reduces peristalsis, intestines, improves the absorption of water from the gastrointestinal tract (GIT).

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

Increases the concentration of amylase and lipase in the blood; 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, while the therapeutic concentration in the serum, blood gradually rises 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 application, an equilibrium concentration in the blood plasma is reached, 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 way of Ndealkylation 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 multiple analgesia with narcotic analgesics (eg, neuropathy, arthritis and arthrosis, "phantom" pain after amputation of limbs).

Contraindications:

- Hypersensitivity to the active substance or excipients of TTS;

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

- TTS should not be used for the treatment of 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, both during the entire period of MAO inhibitors application and for 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 lesions of the central nervous system;

- intestinal obstruction;

- severe bronchial asthma or acute attack of bronchial asthma;

- the period of labor contractions and childbirth (including cesarean section), due to the 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,stricture of the urethra, drug dependence (including narcotic dependence), alcoholism, suicidal tendencies, hyperthermia, myasthenia gravis, simultaneous intake of insulin, glucocorticosteroids (GCS), antihypertensive 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 sedation and respiratory depression in a breast-fed baby. Consequently; 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:

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

TTS is applied to intact and unirradiated skin surface with minimal hair covering: chest, back, shoulders. If you need to remove the hairline - it should be cut (do not shave!).

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!

Preparation Fentadol® The tank should be used immediately after removal from a sealed original package:

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

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 the TTC application, the Fentadol® Tank should be washed with clean water (no 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® Tank 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® Tank is selected individually, based on the previous use of narcotic analgesics, and taking into account the possible development - 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® Tank.

The dose can be subsequently reduced or increased if necessary by 12.5-25 μg / hr to achieve the lowest effective dose of the drug Fentadol® Tank, 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 Fentadol® Tank.)

Patients who had previously taken narcotic analgesics

In the transition from oral or parenteral use of narcotic analgesics to the drug Fentadol® Tank in patients with tolerance to narcotic analgesics, the initial dose is calculated as follows:

- determine; total daily dose of previously used narcotic 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® Tank" (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® Tank, 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 medicinal facilities	Equivalent analgesic dose (mg)
Name of medicinal facilities	w / m	inwards
Morphine	10	30 (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® Tank (depending on the daily oral dose of morphine)

The oral daily dose of morphine (mg / day)	Dose of Fentadol® Tank (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

Initial evaluation of the maximum analgesic effect of the preparation Fentadol® The reservoir can be conducted 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 a 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® Tank 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

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

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 is Fentadol®. The reservoir is more than 300 μg / h, the possibility of using additional or alternative methods of analgesia or alternative methods of administering narcotic analgesics should be considered.

Use of the drug Fentadol® Tank in specific patient groups

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 Fentadol® Tank

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 events 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 nervous system

Often: drowsiness, dizziness, headache, insomnia;

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

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

From the sense organs

often: vertigo;

infrequently: decreased clearness of vision;

rarely: miosis.

From the side of the cardiovascular system

often: palpitation, tachycardia, hypertension;

infrequently: bradycardia, hypotension, cyanosis;

rarely: arrhythmia.

From the respiratory system

often: dyspnea;

infrequently: respiratory insufficiency, respiratory distress syndrome;

rarely: apnea, gimoveitilation;

frequency is unknown: bradypnoe.

From the gastrointestinal tract

Often: nausea, vomiting, constipation;

often: diarrhea, dry mouth, abdominal pain, upper abdominal pain, dyspepsia;

infrequently: intestinal obstruction;

rarely: partial intestinal obstruction.

From the skin and subcutaneous tissues

often; hyperhidrosis, pruritus, rash, erythema;

infrequently: eczema, allergic dermatitis, dermatitis, contact dermatitis, etc.Skin diseases.

From the side of the musculoskeletal system

often: muscular 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: reaction in place of application, flu-like syndrome, sensation of body temperature change, withdrawal syndrome, hypersensitivity at the site of application, hyperthermia;

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

From the immune system

often: hypersensitivity;

frequency 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 mental dependence, short-term stiffness of the muscles (including the thoracic) can develop.

When switching from previously taken narcotic analgesics to the use of the drug Fentadol®The reservoir, or in the event of a sudden cessation of therapy, can have a "cancellation" syndrome, characterized by nausea, vomiting, diarrhea, anxiety and chills.

Overdose:

Symptomsdizziness, drowsiness, retardation, nervousness, general weakness, inhibition of cardiovascular activity, lowering of blood pressure, bradycardia, sticky sweat, miosis, rigidity of muscles, suppression of the respiratory center with Chain-Stokes respiration and / or cyanosis, coma, bradypnoea, apnea.

Treatment: removal of TTS, physical and verbal stimulation of the patient to restore breathing ("slapping on the cheeks," treatment 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 as infusion of 2 mg of naloxone dissolved in 500 ml of 0.9% solution of sodium chloride or 5% dextrose solution (0.004 mg / ml). 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.

Perform 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 that exert a depressing effect on the central nervous system, including other narcotic analgesics, sedatives and hypnotic drugs, general anesthetics, phenothiazines, tranquilizers, central muscle relaxants, antihistamines, sedatives, alcohol may increase the risk development and strengthening of hypoventilation, lowering blood pressure, excessive sedation, coma, or fatal (taking any of these drugs concomitantly with the use of Fentadol^® Tank, requires special monitoring of the patient).

If there is a need for a joint use of the drug Fentadol® Tank with one of the above medicines, a dose adjustment of one or both drugs is necessary.

Inhibitors CYP3A4

Fentanyl has a high clearance, it is rapidly and largely metabolized, mainly with the participation of the isoenzyme CYP3A4. Simultaneous reception isoenzyme CYP3A4 inhibitors (e.g., erythromycin, ritonavir, ketoconazole, itraconazole, fluconazole, vorikomazola, troleapdomitsina, clarithromycin, nelfiiavira, nefazodone, verapamil, diltiazem, cimetidine, amiodarone) fentanyl administered transdermally, may result in increased fentanyl plasma concentration blood. This can enhance or prolong both the therapeutic effect and undesirable phenomena that can cause pronounced hypoventilation.

Careful observation of patients is necessary. The combined administration of ritonavir or another strong inhibitor of isoenzyme CYP3A4 with transdermal administration of fentanyl is not recommended unless careful monitoring of the patient's condition is carried out. Fentanyl enhances the effect of antihypertensive drugs.

Inductors CYP3A4

Joint application with inductance inducers CYP3A4 (eg, rifampicin, carbamazepine, phenobarbital, phenytoin) can lead to a decrease in fentanyl concentration in the 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 isoenzyme CYP3A4, the inductor effect gradually decreases and can lead to an increase in the fentanyl concentration in the blood plasma, which can cause an increase in the intensity or duration of both therapeutic and undesirable phenomena, and can lead to severe respiratory failure. In this situation, careful monitoring and, if necessary, adjusting the dose should be carried out. Beta-adrenoblockers can reduce the frequency and severity of hypertensive reaction in cardiac surgery (including sternotomy), but increase the risk of bradycardia.

Combined use with mixed agonist antagonists

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

Use with buprenorphine, nalbuphine, pentazocine is not recommended.These drugs have a high affinity for opioid receptors and have relatively low internal activity and can cause withdrawal symptoms in opioid-dependent patients.

Miorelaksanty

Muscle relaxants prevent or eliminate muscle rigidity; muscle relaxants with m-cholinoblocking activity (including pancuronium bromide) reduce the risk of bradycardia and lowering 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 blood pressure lowering (especially in the background of an aggravated cardiological history) and increase the risk of serious adverse cardiovascular events.

Nitrous oxide

Nitrous oxide increases muscle rigidity.

It is necessary to reduce the dose of fentanyl when used simultaneously with insulin, GCS and hypotensive Drugs.

MAO inhibitors

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

Serotonergic drugs

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

Special instructions:

The drug Fentadol® Tank can only be used by highly qualified personnel in a specialized hospital as part of a comprehensive treatment of pain syndrome in patients with adequate medical, social and psychological evaluation of their condition.

Preparation of Fentadol® The reservoir can not be administered to relieve acute or postoperative pain. there is no possibility to select an adequate dose for short-term use.

It is impossible to reliably establish the interchangeability of TTS with fentanyl of different manufacturers when used in one patient.Therefore, it should be especially emphasized that the replacement of the TTS of one manufacturer by the TTS of the other should not be performed without the appropriate consultation of a physician.

There is a possibility of occurrence and development of a serious and life-threatening hypoventilation of the lungs (or respiratory depression) as a result of TTS application. Patients who have experienced severe adverse events with TTS use require careful monitoring of their condition for another 24 hours after removal of the TTS, The fentanyl concentration in the plasma decreases gradually and its 50% reduction is achieved within approximately 17 hours (13-22 hours).

The drug Fentadol® The tank should be kept out of the reach of children, and after use!

TTS Fentadol® Tank 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 packages must be returned to the pharmacist.

Use in patients who have not previously taken narcotic analgesics

When using TTC Fentadol® Tank in patients who had not previously taken narcotic analgesics,cases of significant respiratory depression and / or death were rarely reported when used as initial analgesic therapy. The risk of developing serious or life-threatening hypoventilation exists even if a minimum dose of TTS is used. Fentadol Tank as an initial analgesic therapy in patients who have not previously taken narcotic analgesics.

It is recommended to use the preparation Fentadol® Tank in patients demonstrating tolerance to narcotic analgesics.

Respiratory failure

As with the use of other potent narcotic analgesics, with the use of the drug Fentadol® Tank, some patients may exhibit pronounced respiratory failure. Patients should be closely monitored to identify such effects. Respiratory failure may continue after removal of the TTS Fentadol® Tank. The degree of respiratory failure increases with increasing dose of the drug Fentadol® Tank. Drugs that affect the central nervous system can enhance respiratory failure,

Chronic lung diseases

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

Patients with malignant myasthenia gravis

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

Increased intracranial pressure

TGS Fentadol® The reservoir 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® The reservoir should be used with caution in patients with intracranial tumors.

Cardiovascular diseases

Fentanyl may cause bradycardia, so it should be used with caution in patients with bradyarrhythmia.

In patients with arterial hypotension, TTS Fentadol® Tank should be used with caution. Opioids can cause a decrease in blood pressure, especially in patients with hypovodermia.Concomitant lowering of blood pressure and / or hypovolemia should be corrected before starting treatment with TTS Fentadol® Tank.

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® Tank showed no 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 reduction in the dose of the drug Fentadol® Tank is necessary.

Narcotic analgesics can increase the tone of the smooth muscles of the gastrointestinal tract and bile ducts, Fentadol® The reservoir should be used with caution in patients with hepatic colic in the anamnesis.

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 failure need careful monitoring. When symptoms of an overdose appear, the dose of TTS Fentadol® Tank should be reduced.

When transitioning from long-term morphine treatment to transdermal administration of fentanyl, a "cancellation" syndrome may occur, despite the adequate analgesic effect 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 isoenzyme inhibitors CYP3A4 (e.g., erythromycin, ritonavir, ketoconazole, itraconazole, fluconazole, voriconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, verapamil, diltiazem, cimetidine, amiodarone), fentanyl concentration in plasma may increase, which may enhance or prolong both the therapeutic effect and undesirable phenomena, in particular, cause pronounced respiratory failure.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 the TTS Fentadol® Tank simultaneously with CYP3A4 isoenzyme inhibitors should be observed for signs of respiratory failure; a dose adjustment may be required.

Serotonin syndrome

It should be used with caution fentanyl together with drugs that affect serotonergic neurotransmitter systems. With the simultaneous use of serotonergic drugs, such as selective inhibitors

serotonin reuptake (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SSRIs), along with drugs that disrupt serotonin metabolism (including monoamine oxidase (MAO) inhibitors), a life-threatening serotonin syndrome may develop. This may occur when the recommended dose is observed.

Serotonin syndrome can manifest itself in the form of impaired consciousness (eg, agitation, hallucinations, coma),vegetative instability (eg, increased heart rate, lability of blood pressure, fever), neuromuscular disorders (eg, hyperreflexia, impaired coordination of movements, rigidity) and / or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea).

With the development of serotonin syndrome, the use of the drug should be stopped immediately.

Joint use of agonist-antagonists

Joint use of buprenorphine, nalbuphine or pentazocine is not recommended.

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 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.

Application in elderly patients

The data obtained in studies of / in the administration of fentanyl suggest that in elderly patients the clearance and elongation may decrease T_1/2fentanyl. Elderly patients may be more sensitive to fentanyl than younger patients.In studies of TTS Fentadol®, the 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 lowering of the TTS Fentadol® Tank.

Use in depleted and diseased patients

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

Drug dependence and the possibility of abuse

When reintroducing narcotic analgesics may develop tolerance, as well as physical and mental 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® Tank for other than intended purpose may lead to an overdose and / or death.Patients at a high risk of abuse of narcotic analgesics should be closely monitored.

Hyperthermia / external heat sources

The pharmacokinetic model suggests that the serum fentanyl concentration may increase by about 1/3 with an increase in body temperature to 40 ° C. Therefore, patients with hyperthermia should be carefully monitored to identify the characteristic side effects of fentanyl and, if necessary, subsequent 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, hot water bottles, saunas, hot water baths, to the place of application of TTC Fentadol® Tank.

There is a risk of increased release of fentanyl as the body temperature rises, which can lead to overdose and death.

In healthy volunteers, there was an increase AUC by 120% and the average C_mOh 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 contractions of the smooth muscles of the gastrointestinal tract. As a result of an increase in the passage of food through the digestive tract, fentanyl may be constipated. Patients should be advised to take measures to prevent constipation, and preventative use of laxatives should be considered.

Additional precautions should be followed in patients with chronic constipation. In the presence of dynamic ileus or suspected dynamic ileus, treatment should cease fentanyl.

Termination of the use of the drug Fentadol® Storage tank

If necessary, eliminating the use of transdermal Fentadol® reservoir, replacement of the preparation other narcotic analgesics should be carried out gradually, starting with a low dose, due to the gradual reduction of fentanyl concentrations following transdermal Feptadol® removing tank at which 50% reduction in fentanyl concentration in serum is 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® The reservoir can affect the mental and / or physical functions necessary to carry out potentially dangerous work, such as driving vehicles or working with machinery. Patients receiving a stable defined dose in the absence of additional exposure to other medications 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 patch in a bag of paper / PE / A1 / PE.

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

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:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:PL-000213

Date of registration:16.02.2011

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® Tank (Fentadol® Reservuar)