Symptomatic treatment of moderate to severe pain. Use of the preparation should be limited to those patients who require a combination of tramadol and paracetamol.
Tramadol is a centrally acting opioid analgesic. It is a pure, non-selective agonist of opioid mi, delta and kappa receptors, with particular affinity for the mi receptor. Other mechanisms of analgesia include inhibition of norepinephrine neuronal reuptake and the severity of serotonin release. In contrast to the morphine tramadol used in the recommended doses does not inhibit respiratory function, does not disturb gastrointestinal motility and has no significant effect on the cardiovascular system. The strength of tramadol is determined to be 1/10 to 1/6 of the strength of morphine. Paracetamol is an analgesic medicine - the exact mechanism of action is unknown, it can include central and peripheral effects. After oral administration, tramadol (racemic form) is absorbed quickly and almost completely (bioavailability is 75%, increased to 90% during long-term use). Achievemax after 1.8 h. Tramadol is metabolised by O-demethylation (mediated by CYP2D6) to the M1 metabolite and N-demethylation (involving RC3A) to the M2 metabolite. The M1 metabolite has analgesic properties and its potency is greater than the parent substance. Approximately 30% of the accepted dose of tramadol is excreted in the urine in unchanged form, 60% - in the form of metabolites. T0,5 is 5.1 / 4.7 h for +/- tramadol and 7 h for the M1 metabolite. Paracetamol undergoes rapid and almost complete absorption, reaching Cmax after about 1 hour. It is metabolized mainly in the liver in two metabolic pathways: glucuronidation and the rest of 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 quickly inactivated by reduced glutathione and excreted in urine upon conjugation with cysteine or mercapturic acid . If high doses of paracetamol are taken, the amount of this metabolite increases. Paracetamol is mainly excreted in the urine as glucuronides and sulphates. Less than 9% of paracetamol is excreted unchanged in the urine. T0,5 paracetamol is 2-3 hours. In the case of renal failure T0,5 both tramadol and paracetamol are prolonged.
Contraindications:
Hypersensitivity to tramadol, paracetamol or any of the excipients. acute intoxication with alcohol, hypnotics, centrally acting analgesics, opioids or psychotropic drugs. Severe hepatic failure. Epilepsy resistant to treatment. Do not use in patients who take or have taken MAO inhibitors within 2 weeks prior to treatment.
Precautions:
Do not use in children <12 years, in patients with severe renal insufficiency (creatinine clearance <10 ml / min), with severe respiratory insufficiency or in the treatment of opioid addiction. Do not use with opioid agonist-antagonist (nalbuphine, buprenorphine, pentazocine). Avoid using tramadol during shallow anesthesia with enflurane and nitrous oxide. In patients with compensated epilepsy and patients susceptible to convulsions, the preparation can be used only when it is absolutely necessary. Particularly cautiously used in patients addicted to opioids, patients with head injuries, convulsive states, biliary disorders, shock, impaired consciousness of unexplained etiology, central or peripheral respiratory disorders, increased intracranial pressure. Exercise caution in patients with moderate renal or hepatic impairment (increase the interval between doses). Overdose of paracetamol may cause toxic liver damage in some patients.The risk of paracetamol overdose is greater in patients with liver disease not caused by alcohol-related cirrhosis. Therapy with withdrawal symptoms may occur after the therapeutic doses of tramadol. Cases of addiction and abuse of tramadol have rarely been reported.
Pregnancy and lactation:
Due to the content of tramadol, do not use the preparation during pregnancy and breastfeeding.
Side effects:
Very common: dizziness, drowsiness, nausea. Common: confusion, changeability of mood (anxiety, nervousness, euphoria), sleep disturbances, headache, tremor, vomiting, constipation, dry mouth, diarrhea, abdominal pain, indigestion, bloating, excessive sweating, pruritus. Uncommon: depression, hallucinations, nightmares, amnesia, involuntary muscle contractions, paresthesia, tinnitus, palpitations, tachycardia, arrhythmias, hypertension, dyspnoea, dysphagia, black stools, transaminase elevations, skin reactions (e.g. rash, urticaria), albuminuria, micturition disorders (dysuria and urinary retention), chills, hot flushes, chest pain. Rare: addiction, ataxia, convulsions, blurred vision. Very rare: abuse. Undesirable effects on individual components may be a potential adverse event when using the product, even if not observed in clinical trials. Tramadol: orthostatic hypotension, bradycardia, collapse, mood changes (usually euphoria, sporadic dysphoria), changes in activity (usually reduction, occasionally increase), changes in the ability to cognitive and sensory perception (eg decision-making behavior, perception disorders). Rare: change in Warfarin (including prolonged prothrombin time), hypersensitivity reactions from the respiratory system (dyspnea, bronchospasm, wheezing), angioneurotic edema, anaphylaxis, changes in appetite, weakening of the musculoskeletal system, inhibition of respiration. Cases of deterioration of asthma have been reported but no causal relationship has been established. After discontinuation, withdrawal symptoms may occur: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremors, gastrointestinal disturbances and less frequently: panic attacks, severe anxiety, hallucinations, paresthesia, ringing in the ears and other symptoms from the o.u.n. Paracetamol: hypersensitivity reactions (including skin rash), haematological abnormalities (including thrombocytopenia and agranulocytosis - may not have been associated with the use of paracetamol). Several reports suggest the possibility of hypoproyrombinemia when co-administered with warfarin; in other studies, prothrombin time changes have not been demonstrated.
Dosage:
Orally. The dose should be determined individually depending on the intensity of pain and the patient's response. The lowest effective pain relief should be given. Adults and adolescents (from 12 years of age): the recommended starting dose is 2 tablets. If necessary, further doses may be taken, not exceeding 8 tabl. per day. The dose interval should not be shorter than 6 hours. In patients> 75 years, the dose interval should be longer than 6 hours. In patients with moderate renal impairment (creatinine clearance 10-30 ml / min), the dose interval should be 12 h. Administration after dialysis to maintain analgesia is not necessary because tramadol is removed by hemodialysis or hemofiltration very slowly. In patients with moderate hepatic impairment, dose intervals should be extended. Table. should be swallowed whole with water; do not break, do not chew.
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