Index of drugs

Adults. Treatment of chronic, refractory cancer pain. Treatment of chronic, refractory pain.Children. Long-term treatment of severe, chronic pain in children from 2 years of age receiving analgesic opioid medicines.

1 transdermal patch system with an area of ​​15 cm² contains 4.8 mg fentanyl, which corresponds to the release rate of fentanyl 25 μg / h.

A strong painkiller with high affinity for the μ-type opioid receptor. The transdermal system provides continuous systemic release of fentanyl over an application period of 72 h. Fentanyl is released at a relatively constant rate. After the first application of the patch, the concentration of fentanyl in the blood gradually increases, stabilizing between 12 and 24 h and remains relatively constant throughout the remaining 72-hour administration period. During the second 72-hour application, the balance of drug concentration in the blood is reached, which persists in subsequent applications of the same patch size. Fentanyl is bound to plasma proteins in approximately 84%. It is rapidly and extensively metabolised, mainly by CYP3A4 in the liver. The main metabolite, norfentanyl, is inactive. After removing the patch, the concentration of fentanyl in the blood decreases gradually, decreasing to about 50% after about 17 h (range 13-22 h) after administration lasting 24 h. After administration lasting 72 h, the average T_0,5 is from 20-27 h. 75% of the fentanyl dose is excreted in the urine, mainly as metabolites; approximately 9% of the dose is excreted in the faeces, mainly in the form of metabolites.

Hypersensitivity to fentanyl or other substances used in the patch. Do not use in the treatment of acute or post-operative pain (no possibility to adjust the dosage during short-term use). Severe disorder o.u.n. Severe respiratory depression.

Patients who have experienced serious adverse events should be monitored for 24 hours after removal of the patch, as the fentanyl concentration in the blood decreases gradually by approximately 50% within 17 h (range 13-22 h). In very rare cases, the use of the drug as initiating therapy with opioids (even at the lowest available dose) in patients who have not previously received opioids has been associated with clinically significant respiratory depression and / or death - it is recommended that the preparation be used in patients with proven tolerance to opioids. When a patch is used to treat chronic, refractory pain, which requires long-term therapy, it is strongly recommended that the physician define the expected results of treatment with respect to pain intensity and quality of life in accordance with local pain management guidelines; in the event that the assumed goals have not been achieved, the physician in consultation with the patient should decide to discontinue the treatment. Patients should be monitored for significant respiratory depression. Depression of the respiratory center may persist after removal of the patch. The likelihood of developing respiratory depression increases with a higher dose. Drugs acting on o.u.n. may increase depression of the respiratory center. Due to the risk of increased fentanyl in the blood, worsening or prolonging both therapeutic effects and side effects, co-administration of fentanyl with CYP3A4 inhibitors is not recommended unless the patient is closely monitored for signs of respiratory depression and, if appropriate, adjusted dosage. Co-administration of fentanyl with buprenorphine, nalbuphine or pentazocine is not recommended. Patients with COPD or other lung diseases may have more severe side effects; in such patients, opioids may inhibit the activity of the respiratory center and increase resistance in the airways. In the case of repeated use of opioids, such as fentanyl, tolerance to the drug and physical and psychological dependence may develop.A greater risk of addiction and abuse of opioids exists in patients who have historically been drug-dependent and / or alcohol-abused - these patients may still be adequately treated with modified-release opioid formulations, but it must be monitored for symptoms of misuse, abuse or addiction. The drug should be used with caution in patients particularly sensitive to intracranial effects of CO retention₂such as patients with confirmed increased intracranial pressure, with consciousness disorders or in a coma. Caution should be exercised when using fentanyl in patients with brain tumors. Use with caution in patients with bradyarrhythmias. The symptomatic hypotension and / or hypovolaemia should be corrected before starting fentanyl. Patients with impaired liver or kidney function as well as elderly patients should be monitored for signs of fentanyl toxicity and the dose reduced as necessary. Caution should be exercised when using the preparation in patients with myasthenia because non-epileptic myoclonic reactions may occur. If the skin temperature rises to 40 degrees Celsius, the concentration of fentanyl in the blood may increase by 1/3 - patients who develop fever should be monitored for adverse reactions typical of opioids, and if necessary, adjust the dose of the preparation. There is a possibility of a temperature-dependent increased release of fentanyl from the transdermal patch, resulting in a possible overdose and death (warming of the patch increases the average fentanyl AUC by 120% and average C values_max by 61%) - excessive exposure of the adhesive patch to external heat sources, such as electric cushions, hot water bottles, electric blankets, heated water beds, heating or tanning lamps, intense sunbaths, prolonged hot baths, saunas or hot spa baths. It can only be used in children 2 years of age or older who can tolerate opioid treatment. Do not use in children under 2 years of age. Do not use in children who have not used opioids before. In children, to avoid accidental ingestion by a child, care should be taken when choosing the application site and check that the transdermal patch adheres closely to the skin.

Do not use during pregnancy unless clearly necessary. Abstinence syndrome has been observed in newborns whose mothers used long-term fentanyl during pregnancy. The use of fentanyl in the form of a transdermal patch during labor is not recommended because it is not indicated for the treatment of acute or post-operative pain. Fentanyl crosses the placenta and its use during labor can cause respiratory depression in the newborn. Fentanyl passes into breast milk and can cause sedation and respiratory depression in the breast-fed baby. Breast-feeding should be discontinued during treatment with the preparation and for at least 72 hours after removal of the patch.

Very often: insomnia, drowsiness, dizziness, headache, nausea, vomiting, constipation. Common: hypersensitivity, anorexia, depression, anxiety, confusion, hallucinations, tremors, paresthesia, labyrinthopathy, palpitation, tachycardia, hypertension, dyspnoea, diarrhea, dry mouth, abdominal pain, epigastric pain, indigestion, excessive sweating, pruritus, rash, erythema, muscle cramps, urinary retention, fatigue, peripheral edema, weakness, feeling unwell, feeling cold. Uncommon: agitation, confusion, euphoric mood, hypoaesthesia, epileptic seizures (including clonic seizures and grand mai convulsions), amnesia, bradycardia, cyanosis, hypotension, respiratory depression, respiratory distress syndrome, intestinal obstruction, eczema, allergic dermatitis , skin disorders, dermatitis, contact dermatitis, muscle twitching, erectile dysfunction, sexual dysfunction, injection site reactions, flu-like symptoms, sensation of body temperature change, hypersensitivity at the patch site, withdrawal syndrome (including nausea, vomiting, diarrhea, anxiety and chills).Rare: pupillary constriction, apnea, hypoventilation, partial intestinal obstruction, skin inflammation at the application site, eczema at the application site. Not known: anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, slowing of breath.Children and youth. Very common: headache, vomiting, nausea, constipation, diarrhea, pruritus. Common: hypersensitivity, anorexia, insomnia, drowsiness, anxiety, depression, hallucinations, dizziness, hypoaesthesia, respiratory depression, abdominal pain, epigastric pain, dry mouth, rash, excessive sweating, erythema, muscle cramps, urinary retention, peripheral edema, fatigue, reaction at the site of application, weakness. Uncommon: confusion, prestige, pupil constriction, labyrinthine dizziness, cyanosis, contact dermatitis, skin disorders, allergic dermatitis, eczema, withdrawal syndrome, flu-like symptoms.

Transdermally.Adults. The starting dose. The initial dose selection should be based on the patient's opioid interview, taking into account the degree of tolerance to opioids (if present) and the current state of general and medical evaluation of the patient. In patients not previously using strong opioids, 25 μg / h transdermal patches should be used as a starting dose. If it is considered appropriate to use the medicine in patients who have never used opioids before, it is recommended that these patients begin to gradually increase their dosage with low-dose, short-acting opioid medicines. Then, these patients can be switched to a treatment with a release rate of 25 μg / h. If necessary, the dose may then be increased or decreased by 12 or 25 μg / h, until the lowest effective dose of fentanyl is obtained, depending on the patient's response and the additional need for analgesics. In patients who have previously tolerated opioid treatment, the starting dose should be determined based on the need for opioid analgesics in the last 24 hours. Below the recommended scheme for morphine replacement with oral patches: oral morphine dose <90 mg / day - release patch fentanyl 25 μg / h; oral dose of morphine 90-134 mg / day - fentanyl releasing patch 37 μg / h; an oral dose of morphine 135-189 mg / day - fentanyl releasing patch 50 μg / h; oral dose of morphine 190-224 mg / day - fentanyl releasing patch 62 μg / h; oral morphine dose 225-314 mg / day - fentanyl releasing patch 75 μg / h; oral dose of morphine 315-404 mg / day - fentanyl releasing patch 100 μg / h; oral dose of morphine 405-494 mg / day - fentanyl releasing patch 125 μg / h; oral dose of morphine 495-584 mg / day - fentanyl releasing patch 150 μg / h; oral dose of morphine 585-674 mg / day - fentanyl releasing patch 175 μg / h; oral dose of morphine 675-764 mg / day - fentanyl releasing patch 200 μg / h; oral dose of morphine 765-854 mg / day - fentanyl releasing patch 225 μg / h; oral dose of morphine 855-944 mg / day - fentanyl releasing patch 250 μg / h; oral dose of morphine 945-1034 mg / day - fentanyl releasing patch 275 μg / h; oral dose of morphine 1035-1124 mg / day - fentanyl releasing patch 300 μg / h. From the moment of sticking the first patch, you should gradually withdraw from the previously used analgesic treatment, until you have mastered the pain using only slices of fentanyl. For both patients who have not previously received strong opioids and those who have already tolerated such treatment, the initial assessment of analgesia should not be carried out within 24 hours of patch application, as the concentration of fentanyl in the blood increases gradually over time.Dose escalation and maintenance treatment. The patches should be changed every 72 hours. The dose should be increased individually for each patient until the patient has the proper analgesic effectiveness. If analgesia is insufficient at the end of the initial period of drug administration, the dose may be increased. If necessary, the dose should be adjusted in the following doses ranging from 25 μg / h to 75 μg / h: 25 μg / h, 37 μg / h, 50 μg / h, 62 μg / h and 75 g / h, then increasing by 25 μg / h, taking into account the need for additional analgesics and the severity of pain in the patient.More than one patch may be used to provide the required dose. Patients may periodically require additional doses of short-acting analgesics to control breakthrough pain. If you need more than 300 μg / h patches, you should consider the use of an additional or alternative method of treating pain.Discontinuation of treatment with patches. If you need to stop using the patches, replacing them with other opioid medicines should be gradual and start with a small, slowly increased dose. This is related to the gradual decrease in the concentration of fentanyl after removal of the patch. Reduction of fentanyl concentration in the blood by 50% lasts for 17 h or longer. As a general rule, it should be assumed that the opioid analgesia should be discontinued gradually to avoid withdrawal symptoms.Elderly patients. There may be reduced clearance, increased half-life and greater sensitivity to the drug in comparison; the dose may need to be reduced.Children and youth. Children aged ≥16 years: dosages such as adults. Children aged 2 to 16 years: patches should be used only in children and adolescents who tolerate treatment with opioid medicines and who use analgesics in a dose equivalent to at least 30 mg / day of oral morphine. Below the recommended scheme of change from oral morphine to patches: oral dose of morphine 30-44 mg / day - fentanyl releasing patch 12 μg / h; oral dose of morphine 45-134 mg / day - fentanyl releasing patch 25 μg / h. Replacement to a dose of the patch larger than 25 μg / h is the same for both adult patients as well as children and adolescents. The analgesic effect of the first dose of patches during the first 24 h will not be sufficient. For this reason, within the first 12 hours after the patient has been switched to patches, he should receive the dose of analgesics heretofore used. During the Next 12 hours, these analgesics should be administered according to clinical needs. Due to the fact that fentanyl concentrations reach the maximum value after 12-24 h, it is recommended to observe the patient for side effects for at least 48 h after starting treatment with patches or after increasing the dose.Dose adjustment and maintenance dose. If the analgesic effect of the patches is insufficient, an additional dose of morphine or other short-acting opioid should be administered. Depending on the need for additional analgesics and the severity of pain in children, the dose can be increased. In order to adjust the dose, it should be increased gradually, every 12 μg / h.Way of giving. The transdermal patch should be applied to non-irritated and non-irradiated skin with a flat surface, to the torso or upper arm. For young children, the recommended area for applying the patch is the upper back to minimize the risk of removal of the patch by the child. Choose a surface that is not covered with hair. If this is not possible, hair should be cut (but not shaved) before applying the system. If, before applying the patch, the application site requires cleaning, use water for this. Do not use soaps, olives, lotions or other substances that may irritate the skin or change its properties. The skin should be completely dry before applying the patch. Before use, check what state the patches are in. Do not use patches that are cut, split or damaged in any way. After removing both parts of the protective layer, the patch should be firmly pressed against the body surface with fingertips for about 30 seconds, making sure that it adheres completely, especially on the edges. The patch should be worn on the skin continuously for 72 h. The next patch should be stuck after removing the previous one, elsewhere on the skin. It should take a few days before using the next patch in the same place on the skin. It is not possible to provide interchangeable use of transdermal patch systems containing fentanyl from different brands. Do not change the patch containing one brand of fentanyl into another without prior specialist medical consultation regarding the replacement.