Index of drugs

Symptomatic treatment of moderate to severe pain. The use of the preparation should be limited to patients in whom treatment of moderate to severe pain requires the use of tramadol in combination with paracetamol.

1 tabl powl. contains 37.5 mg of tramadol hydrochloride and 325 mg of paracetamol.

Tramadol is an opioid analgesic with central effects. It is a pure, non-selective agonist of mi, delta and kappa opioid receptors, with particular affinity for mi receptors. Other analgesic mechanisms include inhibition of noradrenaline neuronal uptake and facilitation of serotonin release. Tramadol also has an antitussive effect. The exact mechanism of analgesic action of Paracetamol is unknown and may include central and peripheral effects. After oral administration of the preparation, tramadol (racemic form) is absorbed quickly and almost completely (bioavailability is 75%, increased to 90% during long-term use). It binds to 20% of plasma proteins, has high affinity for tissues. Tramadol is metabolized by O-demethylation (mediated by CYP2D6) to the M1 metabolite and N-demethylation (with the participation of CYP3A) to the M2 metabolite. The M1 metabolite has analgesic properties that are stronger than the parent compound. Approximately 30% of the accepted dose of tramadol is excreted in the urine in unchanged form, 60% - in the form of metabolites. T_0,5 is 5.1 / 4.7 h for +/- tramadol and 7 h for the M1 metabolite. Paracetamol undergoes rapid and almost complete absorption, reaching C_max after about 1 hour. It is metabolized mainly in the liver in two metabolic pathways: conjugation with glucuronic acid or sulfuric acid. The latter mechanism easily saturates after administration of higher than therapeutic doses. A small fraction (less than 4%) is metabolized by cytochrome P-450 to the active intermediate metabolite (N-acetyl-p-benzoquinone), which under normal conditions is rapidly coupled to reduced glutathione and excreted in the urine after conjugation with cysteine ​​and mercaptouric acid ; in the case of acute overdose, the amount of this metabolite increases. Paracetamol is mainly excreted in the urine. Less than 9% of paracetamol is excreted in the urine in unchanged form. T_0,5 paracetamol is 2-3 hours. In the case of renal failure T_0,5 both compounds are prolonged.

Hypersensitivity to tramadol, paracetamol or any of the excipients. Acute intoxication with alcohol, hypnotics, centrally acting analgesics, opioids or psychotropic drugs. Tramadol / paracetamol should not be administered to patients who take MAO inhibitors or within 14 days after discontinuation of MAO inhibitors. Severe hepatic impairment. Non-treatable epilepsy.

It is not recommended for children <12 years, for patients with severe renal impairment (creatinine clearance <10 ml / min), severe respiratory insufficiency or for the treatment of opioid addiction. In order to avoid accidental overdose, patients should be advised not to exceed the recommended dose and not take other medicines containing paracetamol or tramadol at the same time. The risk of paracetamol overdose is greater in patients with alcoholic liver damage without cirrhosis. Seizures have been reported in patients treated with tramadol susceptible to onset of convulsions or taking other drugs that lower the seizure threshold, particularly selective serotonin reuptake inhibitors, tricyclic antidepressants, neuroleptics, centrally acting analgesics or local anesthetics. Patients with epilepsy undergoing treatment or those susceptible to convulsions should be treated with the preparation only when clearly necessary. The simultaneous use of opioid agonist-antagonist (nalbuphine, buprenorphine, pentazocine) is not recommended. Use cautiously in patients addicted to opioids, head injuries, susceptible to convulsive disorders, with biliary disorders, in shock, with consciousness disorders of unexplained etiology, with central or peripheral respiratory disorders or with increased intracranial pressure. In some patients, overdose of paracetamol may lead to toxic liver damage. At therapeutic doses, tramadol may induce withdrawal symptoms. Cases of addiction and abuse of the preparation have rarely been reported. The use of tramadol during shallow narcosis with enflurane and nitrous oxide should be avoided.

Due to the content of tramadol, do not use the preparation during pregnancy and breastfeeding.

Very common: dizziness, drowsiness, nausea. Common: headache, trembling, confusion, moodiness (anxiety, nervousness, euphoria), sleep disorders, vomiting, constipation, dry mouth, diarrhea, abdominal pain, dyspepsia, bloating, sweating, pruritus. Uncommon: depression, hallucinations, nightmares, loss of amnesia, involuntary muscle spasms, paresthesia, tinnitus, palpitations, tachycardia, arrhythmia, hypertension, hot flushes, shortness of breath, swallowing disorders, tarry stools, skin reactions (eg rash , urticaria), albuminuria, impaired urination (painful urination or urinary retention), chills, chest pains, increased liver transaminases. Rarely: addiction to the drug, ataxia, convulsions, blurred vision. In addition, you may experience: orthostatic hypotension, bradycardia, collapse; changes in Warfarin effect, including prolongation of prothrombin time; allergic reactions from the respiratory system (eg dyspnea, bronchospasm, wheezing, angioneurotic edema) and anaphylaxis; change in appetite, muscle weakness and breathing disorders; mood changes (usually euphoria, sporadic dysphoria), changes in physical activity (usually reduction, occasionally increase) and changes in cognitive and sensory skills (eg difficulties in making decisions and perception disorders); worsening asthma; symptoms of withdrawal syndrome, similar to those occurring after discontinuation of opioids (agitation, anxiety, nervousness, insomnia, agitation, tremor and gastrointestinal discomfort); sudden discontinuation can rarely cause other symptoms (panic attacks, severe anxiety, hallucinations, paresthesia, tinnitus and unusual nervous system symptoms, skin rash, thrombocytopenia, agranulocytosis, hypoprothrombinemia when used concomitantly with warfarin preparations.

Oral. The dose should be adjusted to the severity of the pain and the patient's sensitivity to the pain experienced. As a rule, the lowest effective dose should be selected to ensure analgesia. Adults and adolescents (aged 12 years and above): the recommended starting dose is 2 tablets. If necessary, you can take additional doses, not exceeding 8 tablets a day. The preparation should be taken at intervals of not less than 6 hours. In patients up to 75 years of age without clinical signs of liver or kidney failure, dose adjustment is not usually necessary. In elderly patients (> 75 years), in patients with renal insufficiency and / or liver function and in patients with moderate hepatic impairment, elimination may be prolonged, therefore, if necessary, the interval between doses should be increased, depending on the patient's needs .
Table. should be swallowed whole with water; they should not be divided or chewed.