Instructions for use DUROGESIK MATRIX

Pharmacological properties of the drug Durogesic

Pharmacodynamics . Fentanyl is a synthetic analgesic that primarily interacts with μ-opioid receptors. Increases the activity of the antinocioceptive system, increases the pain threshold. It disrupts the transmission of excitation along specific and nonspecific pain pathways to the nucleus of the thalamus, hypothalamus, and amygdala complex. The main therapeutic effects of the drug are analgesic and sedative. The minimum effective analgesic concentration of fentanyl in serum in patients who have not previously taken opioid analgesics is 0.3–1.5 ng/ml. The total duration of action of the drug is 72 hours. It causes a depressant effect on the respiratory center, slows the heart rate, stimulates the centers of the vagus nerve and the vomiting center. Increases the tone of smooth muscles of the biliary tract, sphincters (including the ureter, bladder, sphincter of Oddi), inhibits intestinal peristalsis, increases water absorption in the gastrointestinal tract. Virtually no effect on blood pressure. Reduces renal blood flow. Increases the content of amylase and lipase in the blood. Promotes sleep (mainly due to the elimination of pain). Causes euphoria. The rate of development of dependence on the drug and tolerance to the analgesic effect has significant individual differences. Pharmacokinetics. Durogesic provides continuous systemic release of fentanyl for 72 hours after application. Durogesic is manufactured in four modifications of varying strengths, the composition of which is the same when recalculated per unit area of ​​the patch. The 10, 20, 30, and 40 cm systems are designed to release 25, 50, 75, and 100 mcg of fentanyl per hour into the systemic circulation, which is approximately 0.6; 1.2; 1.8 and 2.4 mg/day. Fentanyl is released at a relatively constant rate, which is determined by the copolymer membrane and the diffusion of fentanyl through the skin. This effect is realized using the unique development of the Janssen-Cilag company Polyacrylate adhesive Duro-Tac 4287b. Due to the unique action of this component, there is no need to include ethyl alcohol in the composition of the drug. After application of Durogesic, the concentration of fentanyl in the blood serum gradually increases over the first 12–24 hours and remains relatively constant for the rest of the time. The magnitude of fentanyl serum concentration is proportional to the size of the TTC. After repeated applications, an equilibrium serum concentration is achieved, which is maintained with subsequent TTC applications of the same size. The average content of fentanyl fractions in blood plasma not bound to plasma proteins is 13–21%. After removal of TTS, fentanyl serum concentrations gradually decrease, with an elimination half-life of approximately 17 hours (13–22 hours). Prolonged absorption of fentanyl from the skin (mainly after 4 administrations) explains the slow disappearance of the drug from the serum. In elderly, malnourished or debilitated patients, the clearance of fentanyl may be reduced, resulting in a prolonged half-life of the drug. Fentanyl metabolism occurs primarily in the liver (N-dealkylation and hydroxylation), as well as in the kidneys, intestines and adrenal glands. About 75% of fentanyl is excreted in the urine, mainly in the form of metabolites, while ≤10% of the drug is excreted unchanged. Almost 9% of the drug is excreted in the feces, mainly in the form of metabolites. Passes into breast milk.

Interaction with other drugs and analogues

The simultaneous use of a system with fentanyl and triazole derivatives (Fluconazole, Intraconazole, Ketoconazole), macrolides (Erythromycin, Clarithromycin), calcium antagonists (Verapamil, Diltiazem), some antiarrhythmic drugs (Amiodarone) enhances the work of the patch and may provoke undesirable effects. This must be taken into account in patients with concomitant pathologies.

Drugs such as Carbamazepine, Rifampicin, Phenobarbital, and Phenytoin lead to a decrease in the level of fentanyl in the blood. Barbiturate derivatives are also capable of depressing the respiratory center, and therefore their simultaneous use while wearing TTS is prohibited.

Among the most effective substitutes are:

1. 
   Fendivia is a structural analogue of the active substance. Among the excipients it contains dimethicone and hyprolose. Bioavailability is 84%. May penetrate the blood-brain barrier and into breast milk. The cost ranges from 4,000 to 8,000 rubles.

2. Dolforin is available in the form of a transdermal therapeutic system based on the active component fentanyl, 5 or 10 pieces per package. Approved for use from 18 years of age. The cost depends on the number of packages, varies from 4,000 to 13,000 rubles.
3. Fentadol Matrix – TTS, 5, 10 and 20 pieces in cardboard packaging. Opioid receptor agonist. The duration of action of the drug is 72 hours. Communication with blood proteins is from 80 to 89%. Should be used with caution in elderly people. Permitted to persons over 18 years of age. Price from 2300 rub.

Use of the drug Durogesic

The patch consists of a protective film and three functional layers. These layers are arranged in this order:

• outer layer;
• fentanyl matrix;
• silicone adhesive layer covered with a protective film.

The dose of Durogesic is selected individually depending on the patient's condition and should be regularly assessed after TTC application. Durogesic should be applied to the flat surface of the skin of the torso or upper arms. For application, it is recommended to choose a place with minimal hair. Before application, the hair at the application site must be cut (not shaved). If the application site needs to be washed before applying the system, this should be done with clean water. Do not use soaps, lotions, oils or other products as they may irritate the skin or change its properties. Before application, the skin must be completely dry. Apply durogesic immediately after opening the sealed bag. TTC must be pressed firmly with the palm of your hand onto the application site for 30 seconds. Make sure that the system fits snugly against the skin, especially around the edges. Durogesic is designed for continuous use for 72 hours. The new system can be glued to another area of ​​the skin after removing the previously glued system. The transdermal system can only be applied to one area of ​​skin at intervals of several days. Initial dose When first used, the dose (system size) is adjusted based on previous use of opioid analgesics, degree of tolerance and patient condition. In opioid-naïve patients, Durogesic is used first at the lowest dose of 25 mcg/hour. The same dose is used if the patient has previously received trimeperidine. In patients with opioid tolerance, switching from oral or parenteral opioids to Durogesic requires:

• calculate previous 24-hour analgesia requirements;
• convert this amount to an equivalent oral dose of morphine using the table. 1. All doses of IM and oral opioid analgesics, according to Table. 1, are equivalent in analgesic effect to 10 mg of morphine IM.
• find in table. 2 the 24-hour dose of morphine required for the patient and the corresponding dose of Durogesic.

Conversion to equivalent analgesic dose Table 1:

*Based on single-dose studies in which an IM dose of each drug listed was compared with morphine to establish the relative potency of the drugs. The above oral doses are recommended when switching from parenteral to oral routes of administration. **The ratio of the strength of action of morphine for IM - oral route of administration is 1:3; based on clinical experience gained in the treatment of patients with chronic pain.

Recommended dose of Durogesic (depending on the daily oral dose of morphine)* Table 2:

*During clinical trials, these daily morphine dosage values ​​were used as the basis for switching to Durogesic.

An initial assessment of the maximum analgesic effect of Durogesic cannot be made earlier than 24 hours after application of the system, both in patients who have not previously taken opioids and in patients with opioid tolerance. This period of time is due to a gradual increase in the concentration of fentanyl in the blood serum after application. To successfully switch from one drug to another, previous analgesic therapy should be discontinued gradually after application of the initial dose of Durogesic. Dose selection and maintenance therapy The TTC patch must be replaced with a new one every 72 hours. The dose is selected individually depending on the achievement of the required pain relief. If after application of the initial dose adequate pain relief is not achieved, then after 3 days the dose can be increased. Then the dose can be increased every 3 days. As a rule, the dose is increased by 25 mcg/hour at a time, but it is necessary to take into account the patient's condition and the need for additional pain relief (an oral dose of morphine 90 mg/day approximately corresponds to a dose of Durogesic 25 mcg/hour). Multiple TTCs may be used simultaneously to achieve a dose of 100 mcg/hour. Patients may periodically need additional doses of short-acting analgesics when sudden pain occurs. Some patients may require additional or alternative routes of opioid analgesic administration when receiving doses of Durogesic greater than 300 mcg/hour.

The doctor prescribed you Durogesic

Your doctor prescribed Durogesic for you and told you about its practical use.

What is the Fentanyl Durogesic Transdermal Therapeutic System (TTS)?

Durogesic is a thin translucent rectangular plaster for gluing to the skin. Durogesic contains the powerful painkiller fentanyl. Fentanyl enters the body through the skin and has an analgesic effect for 3 days (72 hours). Durogesic is intended for the treatment of severe pain that has existed for more than three months (this pain is called chronic).

Durogesic is not intended for the treatment of acute pain, which may subside within a few days (during acute injuries, surgical interventions and other medical procedures).

What is fentanyl?

Fentanyl is a strong pain reliever contained in the Durogesic patch, which has been successfully used for effective pain control for about 5 years in Russia and more than 10 years in Europe and America.

Fentanyl belongs to the group of opioid analgesics (opioids). This is a large group of drugs that relieve moderate to severe pain. Opioids interact with certain centers of the central nervous system that affect the sensation of pain. Fentanyl affects the subtle structures of these centers, called opioid receptors, and changes the sensation of pain.

How does Durogesic work?

Thanks to the unique structure of the Durogesic patch, fentanyl in microdoses constantly enters the body over the course of 3 days (72 hours). A special membrane located under the adhesive layer of the patch and controls the rate of fentanyl release is responsible for this process.

After Durogesic is applied to the skin, the fentanyl from the patch begins to penetrate the membrane into the skin. Fentanyl is concentrated in the subcutaneous fat tissue, creating a so-called depot. After the depot is formed, fentanyl is transported through the bloodstream to the central nervous system, where it changes the perception of pain and provides pain relief.

How quickly does Durogesic take effect?

When you use Durogesic for the first time, the onset of its pain-relieving effect may be delayed by 24 hours. During this time, a depot of fentanyl is formed in the skin, then fentanyl evenly penetrates into the bloodstream in small quantities and begins to relieve pain. Your doctor may prescribe additional pain relief for you during this period.

During the remaining 48 hours of action of the first patch you applied, the concentration of fentanyl in the blood plasma is maintained at a constant level. This means that the strength of pain relief is also constant.

Each subsequent Durogesic patch maintains the effect of the previous one and does not require additional pain relief in the first hours after application.

If you continue to feel pain, be sure to contact your doctor.

How long does Durogesic last?

To control long-term pain, you should change Durogesic patches every 3 days as directed by your healthcare professional.

How to apply the patch?

Applying the patch is easy if you proceed step by step.

1. Preparing the site for applying the patch: Select a flat surface on the upper chest, back or arm. Trim any hair that might interfere with the patch. Wash the patch area with clean, warm water without soap. Dry the area where the patch will be applied thoroughly.

2. Remove the sealed bag with Durogesic plaster from the cardboard box.

3. Remove the patch from the sealed bag

4. Remove the patch from the thick transparent protective film

5. Apply the Durogesic patch to the prepared area for gluing, press the Durogesic patch firmly with your palm for 30 seconds. Make sure the patch adheres well to the skin, especially around the edges.

6.

Wash your hands.

How to remove used Durogesic patch?

Before applying a new Durogesic patch, you must remove the used patch from the skin.

1. Remove the patch from the skin

2. Fold it in half with the sticky side facing in

3. Save the used patch

4. Give it to your doctor.

Make sure new and used Durogesic patches are kept out of the reach of children and pets.

How often should the patch be changed?

The Durogesic patch should be changed once every 3 days, as prescribed by your doctor. Give the used patch to your doctor.

For each subsequent patch, choose a different one.

location on the upper chest, back, or arms.

What should I do if the patch does not adhere securely to the skin or has come off?

If, despite your adherence to the recommendations for gluing, Durogesik does not adhere to the skin securely or the corners of the plaster have come off, reinforce the plaster on top along the edges with strips of medical adhesive plaster.

If Durogesik has come off completely, the patch must be replaced with a new one. Use the new Durogesic patch for the next 3 days as directed by your healthcare professional.

Don't forget to tell your doctor when the patch comes off and replaces it with a new one!

Is it possible to take water procedures during treatment with Durogesic?

Yes, you can. You can take a shower or bath, swim in ponds. While swimming, do not direct a strong stream of water at the area of ​​the glued patch or rub it with a washcloth, and after bathing, gently pat it dry with a towel without rubbing the skin.

If you have any doubts, you can also place a small piece of plastic film over the area of ​​the adhesive tape and tape it around the edges with medical adhesive tape. This method is required when taking a bath.

Do not take a hot bath or visit a bathhouse or sauna during treatment with Durogesic, as an increase in body temperature can lead to a change in the analgesic effect of the drug.

If after taking water procedures the patch comes off, see the paragraph “What to do if the patch does not adhere to the skin securely or comes off?”.

Is it possible to cut the patch?

No. The structure of Durogesic is such that only an intact one, completely glued to the skin, acts correctly. The effect of Durogesic may change significantly if the patch is cut or damaged.

If the gel contained in the patch accidentally gets on the skin when Durogesic is damaged, rinse it with running water. Do not use soap or solutions containing alcohol to remove the gel.

Can my friends use my Durogesic patches?

No. Durogesic can only be used by those patients to whom it has been prescribed by the attending physician.

What should you do if you continue to feel pain despite pain relief treatment?

If you continue to experience periodic attacks of pain, this does not mean that the patch is not working. Durogesic provides constant pain relief and while taking it you were able to resume your daily activities, which may cause periodic pain. You should contact your doctor, he will prescribe treatment for such attacks.

You and your doctor may find it helpful to keep a diary of your daily activities and note the occurrence of occasional pain. Write down the time of occurrence of periodic pain, your activity at this time, the severity of the pain. Record which painkillers you took, when and in what doses during the day.

Share this information with your healthcare provider; it will help you assess whether the dosage of Durogesic is sufficient for you.

How can you explain to the doctor the degree and nature of the pain?

Keeping a diary of your well-being and physical activity during the day will help your doctor select the dose of the drug you need. Below is a facial pain rating scale.

When you feel pain, choose an expression that describes your condition.

Can you stop taking Durogesic yourself if you feel better?

No. If you feel better, it only means that Durogesic is effective enough to treat your pain. Only the attending physician can decide the duration of your treatment with Durogesic.

How to store unused Durogesic patches?

The cardboard box contains 5 Durogesic patches in sealed foil bags. Remove the patch from the bag immediately before use. After you have prepared the place for gluing the patch, tear the bag along the edge and remove the Durogesic patch from it. Store unopened Durogesic bags out of the reach of children and animals at a temperature of 15-25 °C. Compliance with storage rules will preserve the quality of the drug.

Contraindications to the use of the drug Durogesic

Hypersensitivity to fentanyl or to adhesive substances included in the system. Durogesic should not be used for acute or postoperative pain due to the inability to titrate the dose over a short treatment period, which may result in severe or life-threatening hypoventilation. Durogesic should not be applied to irritated, irritated or damaged skin. Durogesic is contraindicated in conditions accompanied by depression of the respiratory center. The safety and effectiveness of Durogesic in children have not been established, therefore its use in this category of patients is not recommended. Durogesic should be taken with caution in chronic lung diseases, increased intracranial pressure, including brain tumors, bradyarrhythmia, arterial hypotension, renal and liver failure, in patients with a history of hepatic colic and in the elderly.

Side effects of the drug Durogesic

From the respiratory system : hypoventilation, bronchospasm and respiratory depression (in case of overdose). From the side of the central nervous system: confusion, euphoria, hallucinations, drowsiness, headache. From the gastrointestinal tract: nausea, vomiting, constipation, history of biliary colic. Other : bradycardia, decreased blood pressure, urinary retention, itching, increased sweating, short-term muscle stiffness (including pectoral), tolerance, as well as physical and mental dependence. Sometimes local reactions are observed, such as rash, erythema and itching at the application site. These reactions usually resolve within 24 hours of stopping TTC. In some patients, when switching from narcotic analgesics taken before using Durogesic, opioid withdrawal syndrome (nausea, vomiting, diarrhea, anxiety, chills) may occur.

Possible side effects and overdose

Side effects are manifested by both general and local reactions of the body to the drug. The use of the Durogesic system may be accompanied by the following undesirable effects:

• memory loss, confusion, headache;
• jumps in heart rate;
• dryness of the oral mucosa;

• 
  vomiting, nausea;

• insomnia;
• weakness, lethargy;
• euphoria, anxiety and depression;
• respiratory dysfunction, shortness of breath;
• fluctuations in blood pressure;
• dyspeptic syndrome;
• urinary retention;
• skin sensitivity disorder, itching, rash, increased sweating;
• sexual dysfunction;
• development of tolerance, dependence, withdrawal syndrome;

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Exceeding the recommended dosage and violating the dosage regimen is unacceptable. The following symptoms and conditions may occur:

• hypoventilation;
• suppression of the respiratory center until breathing stops;
• a sharp decrease in blood pressure and heart rate;
• increased muscle tone;

In case of a possible overdose, it is necessary to urgently remove the patch and call an ambulance. Naloxone can be taken as an antidote.

Special instructions for the use of the drug Durogesic

Patients who experience severe side effects should be closely monitored for 24 hours after TTC removal, as fentanyl plasma concentrations decrease gradually and a 50% reduction is achieved within approximately 17 hours (13–22 hours). TTC Durogesic should not be cut, divided or damaged in any way as this may result in the uncontrolled release of fentanyl. Chronic lung diseases. Durogesic can cause a number of serious side effects in patients with COPD and other lung diseases. In such patients, opioids may reduce respiratory excitability and increase respiratory resistance. Increased intracranial pressure. Durogesic should be used with caution in patients who may be particularly sensitive to elevated levels of fentanyl. Such patients are those who have experienced increased intracranial pressure, impaired consciousness, or coma. Durogesic should be used with caution in patients with a brain tumor. Cardiovascular diseases . Fentanyl can cause bradycardia and should therefore be used with caution in patients with bradyarrhythmia, as well as in patients with arterial hypotension. Liver diseases . Because fentanyl is metabolized to inactive metabolites in the liver, liver disease may result in delayed release of the drug. In patients with liver cirrhosis, with a single dose of Durogesic, no changes in pharmacokinetics were observed, although the concentration of the drug in the blood serum tended to increase. Patients with hepatic impairment require careful monitoring for symptoms of fentanyl overdose. In this case, it is necessary to reduce the dose of Durogesic. Opioid analgesics can increase the tone of smooth muscles of the gastrointestinal tract and biliary tract. Therefore, Durogesic should be used with caution in patients with a history of hepatic colic. Kidney diseases. Less than 10% of fentanyl is excreted unchanged by the kidneys and, unlike morphine, fentanyl has no known active metabolites that are excreted by the kidneys. Data obtained from intravenous fentanyl in patients with renal failure suggest that the volume of distribution of fentanyl may be altered during hemodialysis, which may affect serum concentrations of the drug. Patients with renal failure require careful monitoring. If symptoms of overdose are detected, the dose of Durogesic must be reduced. Elderly patients . Data from studies of IV fentanyl suggest that elderly patients may have decreased clearance and increased half-life of the drug and may be more sensitive to fentanyl than younger patients. During studies of Durogesic, the pharmacokinetics of fentanyl in elderly patients did not differ significantly from the pharmacokinetics in younger patients, although the concentration of the latter in the blood serum was significantly higher. Elderly patients require careful monitoring for symptoms of possible fentanyl overdose, which will require a dose reduction of Durogesic. Respiratory depression. As with other potent opioid analgesics, significant respiratory depression may occur in some patients when using Durogesic. Patients should be carefully monitored for such effects. Respiratory depression may continue after removal of TTC Durogesic. Drug dependence. With repeated administration of opioids, tolerance and physical and psychological dependence can develop. Iatrogenic dependence with opioid use is rare. Fever/external heat sources. A pharmacokinetic model suggests that serum fentanyl concentrations may increase by approximately 1/3 if body temperature rises to 40°C. Therefore, patients with fever should be closely monitored for opioid-specific side effects and further dose adjustments if necessary. All patients should avoid direct exposure to external heat sources, such as heat lamps, intense sunbathing, heating pads, saunas, hot water baths, etc., at the site of Durogesic application. Stop using Durogesic. If it is necessary to discontinue the use of Durogesic, replacing this drug with other opioids should occur gradually, starting with a low dose. This drug replacement regimen is necessary due to the gradual decrease in fentanyl concentration after removal of Durogesic, with a 50% decrease in fentanyl serum concentration taking 17 hours. Withdrawal of opioid analgesia should always be gradual in order to prevent the development of withdrawal syndrome. During pregnancy and breastfeeding. The safety of fentanyl with respect to negative effects on fetal development has not been established. However, Durogesic should not be used by women of reproductive age unless the doctor determines that the potential benefit justifies the possible risk. Fentanyl passes into breast milk, so TTC Durogesic should not be taken during breastfeeding. Impact on the ability to drive vehicles and operate machinery . Durogesic may interfere with mental and/or physical functions necessary to perform potentially hazardous work, such as driving or operating machinery. Removing TTC . Used systems should be folded in half with the sticky side facing inward and returned to the doctor for destruction in the prescribed manner. Unused systems must be returned to the physician for destruction.

Instructions for use

There are no difficulties in using the Durogesic patch if the instructions are followed. First, you should prepare the area of ​​skin for application - remove the hair on a flat surface of the body. Then clean and dry the intended area of ​​skin.

Remove the system from the hermetically sealed individual bag and remove the protective film. Apply to a pre-prepared area and firmly fix with your palm for a few seconds, making sure that the fixation is good.

Instructions for use

The patch should be replaced every three days. It is forbidden to use the same place twice. If the fixation on the skin is poor, it is possible to strengthen the system using a surgical adhesive plaster around the edges. In cases of complete peeling off, you must immediately contact a specialist.

Before using the next patch, be sure to peel off the previous one, fold it with the adhesive side inward, save it and give it to your doctor.

During treatment, hygiene procedures are not contraindicated. It is forbidden to direct a direct stream of water to the application site, or to visit a bathhouse or sauna. It is not allowed to cut or disturb the structure of the system, since such actions lead to a decrease in efficiency.

The time of occurrence, duration and intensity of periodic pain during treatment should be recorded. This is important for further selection of an individual dose.

Durogesic Matrix patch

In the event of undesirable effects, the patient is subject to urgent hospitalization for round-the-clock monitoring by specialists to monitor his health and eliminate possible consequences. People with concomitant chronic diseases of the respiratory system and increased intracranial pressure should take it with caution.

The elimination of fentanyl from the body may be slower in people suffering from liver and kidney diseases. Increased body temperature increases side effects. With the systematic use of opioids, the development of physical and mental dependence is possible.

Should not be used in children who have not previously received opioid medications. TTS reduce concentration and can impair consciousness, which is why driving a vehicle is prohibited during the treatment period.

Drug interactions Durogesic

Concomitant use of other drugs that depress the central nervous system, including opioids, sedatives and hypnotics, general anesthesia, phenothiazines, tranquilizers, central muscle relaxants, antihistamines that have a sedative effect and alcoholic beverages, may increase the risk of, cause and intensify hypoventilation, decreased blood pressure , excessive sedation (taking any of these drugs simultaneously with the use of Durogesic requires special monitoring of the patient). Fentanyl is a fast-release drug that is rapidly and extensively metabolized, primarily by the cytochrome P450 enzyme CYP 3A4. Oral administration of itraconazole (a potential inhibitor of cytochrome P450 CYP 3A4) at a dose of 200 mg/day does not have a significant effect on the pharmacokinetic characteristics of fentanyl. Concomitant use of potential inhibitors of cytochrome P450 CYP 3A4, such as ritonavir, may lead to increased plasma concentrations of fentanyl. The consequence of this is an increase or prolongation of both the therapeutic effect and possible side effects, which can cause significant respiratory depression. In such cases, the patient needs especially careful monitoring. Concomitant use of ritonavir and transdermal fentanyl is not recommended unless the patient's condition is strictly controlled. Nitrous oxide increases muscle stiffness, an effect reduced by buprenorphine. It is necessary to reduce the dose of fentanyl when used simultaneously with insulin, corticosteroids and antihypertensive drugs. MAO inhibitors increase the risk of severe complications.

Overdose of the drug Durogesic, symptoms and treatment

Symptoms : bradypnea, apnea, muscle rigidity, depression of the respiratory center, decreased blood pressure, bradycardia. Treatment: removal of TTC, physical and verbal stimulation (the patient must be patted on the cheeks, called, etc.), if necessary, assisted ventilation and mechanical ventilation. Administration of a specific antagonist - naloxone. Respiratory depression in overdose may last longer than the duration of action of the opioid antagonist, so repeated administration of naloxone may be necessary. Symptomatic and supportive therapy for the vital functions of the body (including the administration of muscle relaxants, mechanical ventilation, for bradycardia - atropine, for a decrease in blood pressure - replenishment of the blood volume. The disappearance of the analgesic effect can lead to the development of a sharp pain attack.