Tapentadol – a potent analgesic, is an agonist of the mu-opioid receptors and an inhibitor of the reuptake of norepinephrine. Tapentadol directly exerts analgesic effects without a pharmacologically active metabolite. Tapentadol demonstrated efficacy in pain nociceptive, neuropathic, visceral genesis and pain caused testosterone enanthate results by inflammation. In clinical studies confirmed the analgesic efficacy tapentadola with nociceptive pain (including post-operative orthopedic and abdominal pain as well as chronic pain in osteoarthritis of the hip or knee).
The effect on the cardiovascular system: a careful examination of the interval QT, no effects from taking therapeutic and higher than therapeutic doses tapentadola in respect of the QT interval has not been established. Tapentadol had no significant effects on other ECG parameters (heart rate, PR interval, complex QRS, T wave morphology and U).
After oral administration of the drug in tablets Paleksiya coated membrane shell, tapentadol is rapidly and completely absorbed. The mean absolute bioavailability following oral administration of a single dose on an empty stomach tablets, coated membrane shell is about 32% because of the high first-pass metabolism. Tapentadola maximum concentration observed in plasma after 1.25 hours after oral administration, tablets coated with a foil wrapper. Proportional to dose increase C max (maximum concentration) and AUC (area under the curve “concentration – time”) is marked after oral administration of tablets, coated membrane liner within the therapeutic dose range. Long-term acceptance tapentadola inside (every six hours) at doses of 75 mg to 175 mg, tablets, coated shell membrane showed that accumulation tapentadola ratio is from 1.4 to 1.7 and from 1.7 to 2.0 for its major metabolite – tapentadola-O-glucuronide, mainly It was determined by dosing interval tapentadola and half-life.Tapentadola equilibrium concentration in plasma is reached on the second day after the start of ingestion of tablets, coated foil wrapper. The impact of food AUC and C max increased by 25% and 16%, respectively, ingestion of tablets, coated membrane shell after taking fatty high-calorie foods.
Time to reach testosterone enanthate resultsdelayed by 1.5 hours when taking high-calorie foods. It was considered clinically significant. Paleksiya The drug can be taken orally, both before and after the meal. Distribution Tapentadol has a large volume of distribution. Following intravenous administration the volume of distribution in tapentadola terminal elimination phase (Vd) is 540 ± 98 liters. Binding to plasma proteins is low and does not exceed 20%. Metabolism Tapentadol expressed undergoes metabolism. About 97% of the compound is metabolized. The main way tapentadola metabolism is conjugation with glucuronic acid. After oral administration, roughly 70% of the dose excreted in urine as conjugated forms (55% and 15% of glucuronide tapentadola sulfate). Uridine diphosphate-glucuronyl transferase (UGT) is the main enzyme involved in the process of glyukuronirovaniya (mainly isozymes UGT1A6, UGT1A9 and UGT2B7). A total of 3% tapentadola excreted in the urine in an unmodified form. Tapentadol also metabolized to N-dezmetiltapentadola (13%) by CYP2C19 and CYP2C9 isozyme until gidroksitapentadola (2%) by isoenzyme CYP2D6, which are further subjected to conjugation.
For this reason, tapentadola metabolism mediated by the cytochrome P450 isoenzyme system is of lesser importance compared to glucuronidation. None of the metabolites tapentadola not possess analgesic activity. Excretion Tapentadol and its metabolites are excreted almost completely (99%) by the kidneys. Total clearance after intravenous administration is 1530 ± 177 ml / min. Terminal half-life after reception tapentadola into tablets, coated foil liner averages 4 h. Special categories of patients Elderly patients AUC tapentadola similar in older (65-78 years) and middle-aged patients (19-43 years), while in elderly patients the average value of C max by 16% lower than those of middle age. kidney dysfunction AUC and C maxtapentadola comparable in patients with varying degrees of renal functional activity (from normal to severe impairment). Conversely, with the growth of the severity of renal impairment showed an increase in the area under the curve “concentration-time» (AUC) tapentadola-O-glucuronide. In patients with mild, moderate and severe renal impairment, there was an increase AUC tapentadola-O-glucuronide in the 1.5, 2.5 and 5.5 times compared with patients with normal renal function, respectively. Abnormal liver function in patients with impaired function liver reception tapentadola characterized inward higher AUC and concentration in serum as compared with patients with normal liver function. Relationship tapentadola pharmacokinetic parameters for groups of patients with mild to moderate hepatic impairment when compared with a group of patients with normal liver function accounted for 1.7 and 4.2, respectively, for AUC; 1.4 and 2.5 respectively for the C max ; and 1.2 and 1.4 respectively for the half-life. The rate of tapentadola-O-glucuronide in patients with more severe hepatic impairment below.
Tapentadol mainly metabolized through testosterone enanthate results (glyukuronirovaniya), and only a small amount is metabolized by oxidative processes 1 phase. Because glucuronidation is a system of high capacity, low affinity, any clinically significant interaction associated with glyukuronirovaniya unlikely. This is confirmed by the experience of simultaneous application tapentadola with naproxen and probenecid, tapentadola observed AUC increase of 17% and 57%, respectively. In an application with acetylsalicylic acid and paracetamol is no change tapentadola pharmacokinetic parameters were observed. Tapentadol is not an inducer or inhibitor of cytochrome P450 isoenzymes. Therefore, clinically significant interactions mediated by cytochrome P450 isoenzymes system are unlikely.
Pharmacokinetics tapentadola not changed under the influence of increasing the pH or motility of the gastrointestinal tract caused by omeprazole and metoclopramide, respectively.
Tapentadola Linking blood plasma proteins is low (approximately 20%). For this reason, the likelihood of pharmacokinetic interactions due to the replacement of the connection to plasma proteins is low.
Acute pain of medium and high severity. The drug is used only when the pain syndrome of moderate to severe intensity, requiring the appointment of opioid analgesics.
- giperchuvstvitelyyust tapeptadolu or to any of the excipients included in the formulation;
- in situations where the drugs are contraindicated agonists of mu-opioid receptor, i.e. patients CO significant respiratory depression (if you can not observe or the absence of resuscitative equipment), as well as in patients with acute or severe bronchial asthma or hypercapnia;
- the presence or suspicion of paralytic ileus;
- acute intoxication with alcohol, hypnotic drugs, centrally acting analgesics and psychotropic drugs;
- in patients receiving monoamine oxidase inhibitors (MAOIs) or have taken them within the last 14 days;
- severe renal testosterone enanthate results impairment;
- severe hepatic impairment;
- age of 18 years;
- lactase deficiency, lactose intolerance, glucose-galactose malabsorption
Paleksiya The drug should be used with caution:
- at increased risk of misuse or abuse of the drug;
- in violation of the respiratory function;
- in patients with traumatic brain injury and depression of consciousness;
- in patients with convulsive disorders or a history of any conditions that increase the risk of seizures;
- in patients with hepatic insufficiency of moderate severity;
- in patients with biliary tract disorders, and acute pancreatitis;
- patients with low blood pressure.
It recommended a gradual reduction in the dose of the drug Paleksiya before complete abolition. Care should be taken while the application Paleksiya drug with serotonergic drugs.
Use during pregnancy and during breastfeeding
Data on the use tapentadola during pregnancy is limited. In animal studies, teratogenic effects associated with tapentadolom not found. However, at doses exceeding the upper limit of therapeutic were identified fetal growth retardation and embryotoxicity (effects on the central nervous system associated with agonism in mu-opioid receptors). It was found impact on the postnatal development of the offspring in the appointment tapentadola at doses that do not cause adverse effects in pregnant females.
Use of the drug Paleksiya during pregnancy is permissible only if the potential benefit to the mother outweighs the potential risk to the fetus. Births Effect tapentadola when used during labor and delivery is not it is known. Apply tapentadol in childbirth, and just before birth is not recommended. Due tapentadola affinity for mu-opioid receptors, newborns whose mothers took tapentadol should be carefully monitored for the possible development of respiratory depression. Breastfeeding Information tapentadola excretion in breast milk is limited. Physico-chemical and pharmacodynamic / toxicological data on tapentadolu point to excretion in breast milk, so the risk of exposure to the breast-fed child can not be excluded. Paleksiya The drug should not be used during breastfeeding.
Dosing and Administration
As with the treatment of other analgesics with a central mechanism of action, the dose should be individualized according to the severity of pain, prior therapy, and the ability to monitor the patient. The recommended starting dose of the drug Paleksiya tablets coated membrane liner for oral administration is 50 mg, 75 mg or 100 mg every 4-6 hours depending on the baseline pain intensity. On the first day of taking the drug if it is unable to achieve pain control, within 1 hour after receiving the initial dose of a second dose may be taken. In the following, the usual recommended dose is 50 mg to 100 mg every 4-6 hours tapentadola and should be adjusted to maintain adequate analgesia with acceptable tolerability.
Preparation Paleksiya tablets coated membrane shell entirely taken orally with sufficient fluid is not liquid without breaking and without diluting. Preparation Paleksiya tablets coated membrane liner may be administered both before and after a meal.
The total initial daily dose of 700 mg tapentadola tablets coated membrane shell, the first day of treatment and maintenance daily dose of 600 mg tapentadola not prescribed and therefore not recommended.Completion of treatment In one-stage cease receiving tapentadola may develop the syndrome of “cancellation”. Recommended a gradual reduction in dose before the full abolition of the drug in order to prevent the syndrome of “cancellation”. Adults with chronic diseases Renal impairment No dose adjustment in patients with mild patients or moderate renal impairment is not required. Experience of use in patients with severe renal impairment is not, therefore, use of the drug in this group of patients is contraindicated. Abnormal liver function dose adjustment in patients with mild hepatic impairment is not required. Caution should be exercised when administered to patients with moderate hepatic insufficiency. Treatment of such patients should start with 50 mg tapentadola tablets coated membrane liner no more than once every 8 hours (up to three doses per day). Further treatment should be aimed at maintaining the analgesic effect with an acceptable level of tolerance, which is achieved by increasing or decreasing the interval between taking the drug. Experience of use in patients with severe hepatic impairment is not, and therefore the use in this group is contraindicated patients. Elderly patients (65 years and above) In general, the recommended dose for elderly patients with normal liver and kidney function are the same as for the middle-aged patients with normal renal function and liver. Because elderly patients are more likely to decline in renal and hepatic function, caution should be exercised when choosing a dose and do not exceed the recommended. Use in children The drug Paleksiya contraindicated for use in patients under the age of 1 8 years due to lack of efficacy and safety data. Running low dose t3 clen cycle trying to lose bodyfat isn’t a real hot idea imo.