It violates the transfer of excitation in the specific and non-specific pain pathways to the nuclei of the thalamus, hypothalamus, amygdala. The main therapeutic effects of the drug is an analgesic and sedative. Minimum effective analgesic concentration of fentanyl in the plasma of patients who have not previously used opioid analgesics is 0.3-1.5 ng / ml. The total duration of the preparation -. 72 hours have a depressing effect on the respiratory center, slows the heart rate, stimulates centers of the vagus nerve and the what is tren vomiting center. Increases tone biliary tract smooth muscle sphincters (including the urethra, bladder, sphincter of Oddi) reduces peristalsis, improves water absorption from the gastrointestinal tract (GIT). Almost no effect on blood pressure (BP) reduces renal blood flow. The content of the blood increases amylase and lipase. It promotes the onset of sleep. It is euphoric. The speed of the development of drug dependence and tolerance to the analgesic effect has significant individual differences. Pharmacokinetics Absorption transdermal therapeutic system (TTS) provides continuous systemic release of fentanyl during the 72 hours after application. Fentanyl is released at a relatively constant rate. The concentration gradient between the TTC and low concentrations in the skin ensures the release of fentanyl. After application of the preparation fentanyl plasma concentration gradually increases during the first 12-24 hours and remains relatively constant over the remaining period of time. The concentration level of fentanyl in the plasma is proportional to the size of the TTS. By the end of the second 72-hour application reached equilibrium concentration in the blood plasma, which is maintained by subsequent applications of a TTS of the same size. Pharmacokinetic model indicates that fentanyl concentration in the plasma can be increased by an average of 14 % (ranging from 0 to 26%) if the new TTS adhered after 24 hours compared with glued after 72 hours as recommended. Distribution Binding fentanyl plasma proteins is approximately 84%. Metabolism fentanyl – a compound with a high ground clearance, It is rapidly metabolized in the liver, mainly by the enzyme CYP3A4. The main metabolite, norfentanil, inactive. When transdermal administration of fentanyl is not metabolized in the skin, as determined in studies in keratinocytes humans and in clinical trials (92% of the dose of fentanyl (TTS), in an unmodified form reported in the bloodstream). Excretion After removal TTC ® Matrix concentration of fentanyl in plasma gradually decreases, and the half-life of about 17 (13-22) hours after a 24-hour transdermal applications. After 72-hour half-life transdermal application is about 20-27 hours. The continued absorption of fentanyl skin explains slower disappearance of the drug from the blood plasma compared to the intravenous administration of fentanyl, when the half-life of approximately 7 (3-12) hours. After 72 hours after intravenous administration of fentanyl, fentanyl about 75% of the dose excreted in the urine primarily as metabolites and less than 10% unchanged. About 9% excreted in feces mainly as metabolites. Special groups of patients Elderly patients Data from fentanyl studies with intravenous administration, suggests that elderly patients may reduce clearance and to lengthen the half-life of the drug, and in addition, such patients may be more sensitive to fentanyl than younger patients. In drug research ® matrix in healthy elderly volunteers found that fentanyl pharmacokinetics in the elderly not differ significantly from the pharmacokinetics in healthy young people, elderly although lower peak concentrations and half-life is extended to approximately 34 hours. Elderly patients should be carefully monitored to detect signs of fentanyl toxicity and the need to reduce the dose of the drug ® Matrix. Patients with hepatic impairment. The pharmacokinetics of a single dose of 50 mcg / h has been studied in patients with liver cirrhosis. Despite the fact that the time to reach maximum concentration and half-life were not changed, the mean values of the maximum concentration and area under the concentration-time increased by 35% and 73% respectively. Patients with liver failure should be carefully monitored to detect toxicity symptoms fentanyl and if necessary to reduce the dose matrix. Patients with renal failure. The data obtained from fentanyl studies with intravenous injection in patients after renal transplantation suggest that fentanyl clearance at this groups of patients can what is tren be reduced. Patients with renal insufficiency receiving , should be carefully monitored to detect signs of fentanyl toxicity and the need to reduce the dose of the drug .
Chronic pain severe and moderate severity:
- pain caused by cancer;
- pain than cancer genesis, which requires multiple analgesic narcotic analgesics, such as neuropathic pain (pain in diabetic neuropathy, nerve trauma, syringomyelia, multiple sclerosis, shingles (Herpes zoster)), arthritis and arthrosis, phantom pain after the amputation of limbs, etc. .
- sensitivity to fentanyl or adhesive substances forming part of the system
- Children up to age 18 years
- depression of the respiratory center, including acute respiratory distress
- acute pain or postoperative pain, requiring a short period of treatment
- pregnancy and lactation
- diarrhea with pseudomembranous colitis caused by cephalosporins, lincosamides, penicillins
- toxic diarrhea
- irritated, irradiated or damaged skin at the site of application.
- chronic lung disease;
- intracranial hypertension;
- for tumors of the brain;
- with traumatic brain injuries;
- when bradyarrhythmias;
- arterial hypotension;
- in renal and hepatic failure;
- in patients with liver or renal colic, including the anamnesis;
- the elderly, malnourished and debilitated patients (see “Special instructions”.);
- acute surgical diseases of the abdominal cavity before the diagnosis;
- the general condition;
- benign prostatic hypertrophy;
- when strictures of the urethra;
- with drug dependence;
- with suicidal tendencies;
- while taking insulin, glucocorticoids, antihypertensive drugs and MAO inhibitors.
Pregnancy and lactation
Data on the use of the drug in pregnant women is not enough. When intravenous anesthetic fentanyl observed passing through the placenta in pregnant women. Cases of withdrawal symptoms in newborns whose mothers chronically used during pregnancy. Should not be used during pregnancy except in cases of urgent need.
It is not recommended to use in childbirth because This drug is contraindicated to treat acute pain, or postoperative pain. Moreover, t. To. Fentanyl crosses the placenta, it can cause respiratory depression in the newborn.
Fentanyl is excreted in breast milk and may cause sedation / respiratory depression in children. Consequently, ® Matrix should not be applied to nursing mothers.
Dosing and Administration
Is selected individually depending on the patient’s condition should be regularly evaluated and after the application of the TTS.
should be applied on a flat surface of the skin of the trunk or upper arms. For the application it is recommended to choose a place with minimal scalp. Before applique hair at the site of application should be cut off (not shaved off!). If before the applique patch application site should be washed, then it should be done with clean water. Do not use soaps, lotions, oils, or other means, as they may cause skin irritation or to change its properties. Before applique skin is completely dry.
Before applying a transdermal system must be thoroughly inspected for damage. TTS, divided into parts, cut or otherwise damaged in any way should not be used.
Should be pasted immediately after removal from the sealed package. To remove the transdermal system from the package fold the upper part of the bag along the incision (indicated by arrow) and tear it off. Then open the package as open book. The protective film has a slit in the middle. Fold in half transdermal system in the middle of each half and remove the protective what is tren film without touching his fingers to the sticky layer. Transdermal system should be firmly put his hand on the area of application for 30 seconds. Make sure that the adhesive adheres to the skin, especially on the edges.After sticking the TTS wash your hands with clean water.
Is designed for continuous use for 72 hours. The new system can be applied to the other area of the skin after removal of the previously glued patch. At the same area of skin, the transdermal system may be pasted only at intervals of several days. Selection of the initial dose Starting dose matrix selected based on prior use of opioid analgesics. It is recommended to appoint patients demonstrate opioid tolerance. Also other factors are taken into account: the general condition of the patient, including body size, age, degree of exhaustion and the degree of opioid tolerance. Patients previously taking opioids for the transition from oral or parenteral opioids to the drug forms in patients with tolerance to opioids should be guided by “transfers to the equivalent analgesic dose” shown below. The dosage may subsequently be reduced or increased as necessary on the 12 or 25 ug / hr to achieve the lowest doses depending on the reaction and additional requirements for analgesia. Patients previously taking opioids Experience with drug matrix in patients previously not taking opioids is limited. In cases where use of the drug must be ® Matrix patients not previously treated with opioids, it is recommended to start with low doses of immediate-release opioids (eg, morphine, tramadol and codeine), equivalent to 25 mcg / h drug . Thereafter, patients may be converted to a dose of 25 ug / hr drug matrix. The dosage may subsequently be reduced or increased as necessary on the 12 or 25 ug / hr to achieve the lowest dose preparation matrix depending on the reaction and additional requirements to analgesia (cm. “Transfer the equivalent analgesic dose”). Translated to the equivalent analgesic dose