Index of drugs

Symptomatic treatment of moderate and 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 contains 37.5 mg (75 mg) of tramadol hydrochloride and 325 mg (650 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 metabolised by O-demethylation (via CYP2D6) to the M1 metabolite and N-demethylation (via 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 metabolised 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 mercapturic 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 auxiliary substances. Acute intoxication with alcohol, hypnotics, centrally acting analgesics, opioids or psychotropic drugs. Do not use the drug in patients treated with MAO inhibitors and before the 2nd week of their discontinuation. Severe hepatic failure. Non-treatable epilepsy.

Use in children <12 years is not recommended, with severe respiratory insufficiency, severe renal impairment (creatinine clearance <10 ml / min) and in the treatment of opioid addiction (tramadol, although it is an opioid receptor agonist, does not abrogate the symptoms of discontinuation of morphine ). 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 without a doctor's indication. 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 those taking other seizure-lowering medicines, particularly selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, centrally acting analgesics or local anesthetics. Patients with epilepsy that are effectively controlled by therapy or patients with a tendency to convulsions may be treated with the preparation only when absolutely necessary. The simultaneous use of opioid agonist-antagonist (nalbuphine, buprenorphine, pentazocine) is not recommended. Use cautiously in patients addicted to opioids, cranial injury, susceptible to convulsions, biliary disorders, shock, impaired consciousness of unexplained etiology, impairment of respiratory center or 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 (one study reported that tramadol increased intraoperative awareness).

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 disturbances, vomiting, constipation, dry mouth, diarrhea, abdominal pain, indigestion, bloating, increased sweating, pruritus. Uncommon: depression, hallucinations, nightmares, amnesia, involuntary muscle spasms, tinnitus, paresthesia, palpitation, tachycardia, arrhythmia, hypertension, dyspnoea, dysphagia, tarry stools, skin reactions (eg rash, urticaria), albuminuria, micturition disorders (diarrhea and urinary stagnation), chills, hot flushes, chest pains, increased liver transaminases. Rarely: addiction to the drug, ataxia, convulsions, blurred vision. Very rare: abuse. In addition, tramadol may include: orthostatic hypotension, bradycardia, collapse, Warfarin effects, including prolonged prothrombin time; allergic reactions from the respiratory system (eg dyspnea, bronchospasm, wheezing, angioneurotic edema) and anaphylaxis; change in appetite, muscle weakness, respiratory depression, mood changes (usually euphoria, sporadic dysphoria), changes in activity (usually decrease, occasionally increase) and changes in cognitive and sensory skills (eg disorders in decision making and perception), worsening asthma, syndrome symptoms withdrawal, similar to those occurring after discontinuation of opioids (agitation, anxiety, nervousness, insomnia, agitation, tremor and gastrointestinal symptoms). In addition, hypersensitivity reactions (such as skin rash), thrombocytopenia, agranulocytosis, and hypoprrotrombinemia may occur with paraffinamol when used in combination with warfarin.

Orally. The dose should be adjusted to the severity of the pain and the individual response of the patient to treatment. In general, the lowest effective analgesic dose should be used. Adults and adolescents (≥12 years): the recommended starting dose is 75 mg tramadol hydrochloride and 650 mg paracetamol. If necessary, additional doses may be used, not exceeding the daily dose of 300 mg tramadol hydrochloride and 2600 mg paracetamol. The dose interval should not be shorter than 6 hours. Do not use the preparation longer than absolutely necessary. If, due to the nature and severity of the disease, repeated or long-term use of the preparation is necessary, the patient should be closely and regularly monitored (with interruption of treatment, if possible) to verify the need for further treatment. In elderly patients <75 years without clinical signs of liver or kidney failure, dosage adjustment is not usually necessary. In patients> 75 years, if necessary, the interval between consecutive doses should be extended depending on the patient's needs. In patients with renal and / or hepatic insufficiency, the prolongation of intervals between consecutive doses should be carefully considered depending on the patient's needs. Because tramadol is removed very slowly from the body by hemodialysis or hemofiltration, the use of the drug after dialysis to maintain analgesia is usually not required. The tablets should be swallowed with a sufficient amount of liquid. Division line on the table 37.5 mg + 325 mg only facilitates crushing to facilitate ingestion. Division line on the table 75 mg + 650 mg can be divided into halves.