Symptomatic treatment of moderate to severe pain. The use of the drug should be limited to patients in whom moderate to severe pain requires the combined use of tramadol and paracetamol.
Tramadol is a centrally acting opioid analgesic. It is a pure, non-selective agonist at the μ, δ and κ opioid receptors, with particular affinity for the μ-receptor. Other mechanisms of analgesia include inhibition of norepinephrine neuronal reuptake and the severity of serotonin release. Tramadol also works antitussive. In contrast to morphine, the wide range of doses of tramadol do not inhibit the respiratory system, does not interfere with gastrointestinal motility and does not have a significant impact on the cardiovascular system. The strength of tramadol is determined to be 1/10 to 1/6 of the strength of morphine. Tramadol is administered in racemic form. It is absorbed quickly and almost completely after oral administration. The bioavailability of a 100 mg single dose is about 75%; during long-term bioavailability increases to about 90%. About 30% of tramadol is excreted in the urine in unchanged form, while 60% in the form of metabolites. T0,5 is about 5 hours. After oral administration, Paracetamol is absorbed quickly and almost completely. It is metabolized mainly in the liver in two metabolic pathways: glucuronidation and sulfur coupling. The hepatotoxic intermediate metabolite N-acetyl-p-benzoquinimine formed in a small amount is rapidly conjugated to reduced glutathione and excreted in the urine after conjugation with cysteine or mercapturic acid. In the case of a significant overdose of Paracetamol, the amount of this metabolite increases. T0,5 paracetamol is 2-3 hours. Paracetamol is excreted mainly in the urine in the form of glucuronides and sulphates, less than 9% in the unchanged form. In kidney failure T0,5 both tramadol and paracetamol are prolonged.
Contraindications:
Hypersensitivity to the active substances or to any of the excipients. acute intoxication with alcohol, hypnotics, centrally acting analgesics, opioids or psychotropic drugs. Do not use in patients treated with MAO inhibitors or within two weeks after such treatment. Severe hepatic failure. Epilepsy resistant to treatment.
Precautions:
To avoid unintentional overdose, patients should not take more than the recommended dose and use other medicines containing paracetamol or tramadol hydrochloride without consulting a doctor. It is not recommended for patients with severe renal impairment (creatinine clearance <10 ml / min). The risk of paracetamol overdose is greater in patients with alcoholic liver disease without cirrhosis. Use in patients with severe respiratory distress is not recommended. Tramadol should not be used as a substitution therapy in opioid-dependent patients because it does not relieve symptoms after discontinuation of morphine, although it is an opioid receptor agonist. Convulsions have been observed with tramadol in patients with a tendency to have seizures or other seizure-lowering medicines, in particular selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, centrally acting analgesics or local anesthetics, and in some patients treated with tramadol at the recommended doses. Patients with controlled or suspected epilepsy should only use the product under exceptional circumstances. Concomitant use of opioid receptor agonists (nalbuphine, buprenorphine or pentazocine) is not recommended. Particularly cautiously used in patients addicted to opioids, patients with head injuries, susceptible to convulsions, with biliary disorders, in shock, with consciousness disorders of unexplained etiology, with central or peripheral respiratory disorders or with increased intracranial pressure. Overdose of paracetamol may cause toxic liver damage in some patients. Tramadol used in therapeutic doses may cause withdrawal symptoms. There may be withdrawal symptoms similar to those seen with opiates. Addiction and abuse cases have rarely been reported.During general anesthesia with enflurane and nitrous oxide, tramadol increases the risk of awakening during surgery - use in case of shallow general anesthesia is not recommended.
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: headache, tremor; confusion, mood variability (anxiety, nervousness, euphoria), sleep disorders; vomiting, constipation, dry mouth, diarrhea, abdominal pain, dyspepsia, bloating; excessive sweating, pruritus. Uncommon: hypertension, palpitations, tachycardia, arrhythmia; involuntary muscle spasms, paresthesia, tinnitus; depression, hallucinations, nightmares, oblivion; dyspnoea; dysphagia, tarry stools; increase in aminotransferases; skin reactions (eg rash, urticaria); albuminuria, impaired urination (painful urination and retention of urine); chills, hot flushes, chest pains. Rare: ataxia, convulsions; addiction to the drug; out of focus vision. Very rare: abuse. Although during the clinical trials the following adverse reactions related to the use of tramadol or paracetamol have not been observed, their occurrence can not be ruled out. During the use of tramadol may occur: rarely - allergic reactions with respiratory symptoms (eg dyspnea, bronchospasm, wheezing, angioneurotic edema), anaphylactic reaction, suppression of breathing, changes in appetite, muscle weakness, symptoms of withdrawal syndrome (panic attacks, severe anxiety, hallucinations, paresthesia, tinnitus and atypical CNS disorders), changes in Warfarin, including prolonged prothrombin time; frequency unknown - changes in mood (usually excitement, sometimes dysphoria), changes in activity (usually limiting, sometimes increasing), changes in cognitive and sensory skills (eg decision making disorders, behavior or perception), bradycardia, orthostatic hypotension, collapse, worsening of asthma symptoms , withdrawal symptoms similar to symptoms occurring during opiate withdrawal (agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor, gastrointestinal disorders). During the use of paracetamol you may experience: rarely - hypersensitivity reactions (including skin rash); very rare - severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis); frequency not known - blood disorders such as thrombocytopenia, agranulocytosis (not necessarily related to the use of paracetamol) and, if the preparation is used with warfarin-like drugs, hypoproterombinemia (reported in some but not all studies).
Dosage:
Orally. The use of the preparation should be limited to patients in whom moderate to severe pain requires the combined use of tramadol and paracetamol. The dose should be determined individually depending on the intensity of pain and the individual sensitivity of the patient to pain.Adults and adolescents> 12 years:the recommended starting dose is 2 tablets. (75 mg tramadol hydrochloride and 650 mg paracetamol). If necessary, additional doses may be used, not exceeding 8 tables. (300 mg tramadol, 2600 mg paracetamol) per day. The intervals between doses should be at least 6 hours. The drug should under no circumstances be used for longer than is strictly necessary. If the nature or severity of the disease requires repeated or long-term administration of the preparation, the patient should be carefully and regularly monitored (also during periods of disuse, if possible) to verify the need for continued use.Special groups of patients. Elderly patients may be given normal doses; in patients> 75 years, it is recommended that the minimum interval between doses should not be shorter than 6 h. Due to the content of tramadol, it is not recommended for patients with severe renal insufficiency (creatinine clearance <10 ml / min). In patients with moderate renal impairment (creatinine clearance 10-30 ml / min), the interval between doses should be extended to 12 hours. Because tramadol is removed very slowly by hemodialysis or haemofiltration, tramadol administration after hemodialysis is not necessary. In patients with moderate hepatic impairment, consideration should be given to increasing the intervals between doses.In patients with severe hepatic insufficiency, the use of the drug is contraindicated. The efficacy and safety of the preparation have not been established in children under 12 years of age, therefore it is not recommended for use in this patient population.Way of giving. The tablets should be taken whole with liquid. They must not be crushed or chewed.
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