Active substanceTramadolTramadol
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  • Dosage form: & nbspCapsules.
    Composition:

    Active substance:

    tramadol hydrochloride

    - 50.0 mg.

    Excipients:

    lactose monohydrate

    - 66.57 mg,

    microcrystalline cellulose

    - 66.58 mg,

    magnesium stearate

    1.85 mg.

    Hard gelatin capsule № 2

    - 61.0 mg.

    Capsule body:

    titanium dioxide (E 171)

    -2%,

    gelatin

    up to 100%.

    Capsule cap:

    dye indigo carmine (E 132)

    - 0,1333 %,

    titanium dioxide (E 171)

    - 1 %,

    gelatin

    up to 100%.

    Description:

    Hard gelatin capsules number 2, the capsule body is white, the lid is blue. Contents of the capsules: powder white or white with a yellowish hue.

    Pharmacotherapeutic group:An analgesic with a mixed mechanism of action.
    ATX: & nbsp
  • Tramadol
  • Pharmacodynamics:Tramadol is an opioid analgesic with a central mechanism of action. Is a nonselective complete agonist µ-, δ- and κ-opioid receptors with a high affinity for µreceptors. The second mechanism of action of tramadol, which enhances its analgesic effect, is the suppression of norepinephrine reuptake by neurons and increased release of serotonin. Tramadol has antitussive action. In contrast to morphine, in therapeutic doses does not depress respiration and to a lesser extent affect intestinal motility. Influence on the cardiovascular system is weakly expressed. The analgesic potential of tramadol is 1 / 10-1 / 6 of the activity of morphine.
    Pharmacokinetics:

    When taking capsules, absorption is more than 90%. The average absolute bioavailability is about 70% regardless of the intake of food.The decrease in bioavailability to 70% is due to the effect of "first passage" through the liver. In comparison with other opioid analgesics, the absolute bioavailability of the drug Tramadol is extremely high. After ingesting 100 mg of tramadol in the form of capsules by young healthy volunteers, the maximum concentration in the blood plasma (Cmax) is 208-280 μg / l, the time of reaching C max 1.6-2 h.

    Binding to plasma proteins is about 20%. Adheres through blood-brain and placental barriers. Insignificant amounts of tramadol and its demethylated derivative (0.1% and 0.02%, respectively) are excreted in breast milk.

    In the metabolism of tramadol, the isoenzymes CYP3A4 and CYP2D6 take part, the suppression of these isoenzymes by other substances can affect the concentration of tramadol and its active metabolite in the blood. To date, clinically significant interactions with other drugs mediated by this mechanism have not been identified.

    Tramadol and its metabolites are excreted mainly in the urine, the average cumulative index of renal excretion is 90%.

    The half-life of tramadol (T1 / 2) is approximately 6 hours, regardless of the route of administration.In patients older than 75 years, the elimination half-life can be increased by a factor of 1.4; with cirrhosis of the liver to 13.3 ± 4.9 h (tramadol), 18.5 ± 9.4 h (O-demethyltramadol), in severe cases - 22.3 h and 36 h respectively. T1 / 2 with renal insufficiency (creatinine clearance 5 ml / min) - 11 ± 3.2 h (tramadol), 16.9 ± 3 h (O-demethyltramadol), in severe cases - 19.5 h and 43.2 h respectively. In the liver, it is metabolized by N-and O-demethylation followed by conjugation with glucuronic acid. Only O-demethyltramadol has pharmacological activity. There are significant individual differences in the concentration of other metabolites. 11 metabolites of tramadol were found in urine. In therapeutic doses tramadol has a linear pharmacokinetic profile.

    The ratio of the concentration of tramadol in the blood serum and the analgesic effect is dose-dependent, which varies in individual individuals. The concentration of tramadol in the serum of 100-300 ng / ml is usually effective.

    Indications:

    Pain syndrome of medium and high intensity of different etiology (for example, pain in cancer patients, in trauma and in the postoperative period.

    Contraindications:

    - Hypersensitivity to tramadol or any of the components of the drug;
    - Acute intoxication with alcohol, hypnotics, analgesics, opioids or other psychotropic drugs;
    - The combined use of tramadol with monoamine oxidase (MAO) inhibitors is contraindicated, and also within 14 days after the end of their administration;
    - Epilepsy, not amenable to adequate drug control;
    - Contraindicated the use of tramadol as a drug for the treatment of the syndrome of "withdrawal" of drugs;
    - Contraindicated during pregnancy. During breastfeeding the drug can be prescribed only for vital indications. In the case of a single dose, there is no need to interrupt breastfeeding;
    - Contraindication of the drug Tramadol in capsules for children under 14 years;
    - Patients with rarely encountered hereditary intolerance to galactose, lactase deficiency in lobes, or glucose-galactose malabsorption should not take this drug.

    Carefully:

    Tramadol should be used with caution:
    - in patients with opioid dependence;
    - with craniocerebral trauma, in patients with shock, in patients with impaired consciousness of unclear genesis, in patients with respiratory disorders and disruption of the respiratory center, with increased intracranial pressure;
    - the drug should be used with caution in patients with established severe intolerance to opioids of allergic and non-allergic genesis;
    - with epilepsy, amenable to adequate drug control, or patients who are susceptible to seizures, tramadol can only be used for life indications (see "Special instructions");
    - In patients with a tendency to abuse drugs or drug dependence, tramadol should be treated with short courses and under medical supervision (see "Special instructions").

    Pregnancy and lactation:

    Tramadol penetrates the placental barrier. Convincing evidence of the safety of the use of tramadol during pregnancy in humans is not obtained, therefore tramadol Do not use during pregnancy. Long-term use of tramadol during pregnancy can lead to the development of symptoms of "cancellation" in a newborn.

    Tramadol does not affect uterine contractility. In newborns tramadol can cause a change in the frequency of respiration, which is usually not clinically relevant.

    About 0.1% of the dose of tramadol administered to the mother is excreted with milk during lactation. Tramadol should not be used during pregnancy and lactation. After a single dose of tramadol, there is usually no need to interrupt breastfeeding.

    Dosing and Administration:

    Tramadol capsules should be taken orally. Tramadol capsules are swallowed whole, without chewing and not opening, with a sufficient amount of liquid, regardless of food intake.

    Doses should be selected individually, depending on the intensity of the pain syndrome and the individual sensitivity of the patient. The recommended doses are indicative. The duration of treatment with the drug is determined individually.

    In the treatment it is always necessary to select the minimum effective dose of the drug. In the treatment of chronic pain syndrome should adhere to a specific schedule for taking the drug.

    Do not exceed the daily dose of tramadol - 400 mg, except in special circumstances (for example, oncological pain or severe postoperative pain).

    Adults and adolescents over 14 years of age

    A single dose of 50 mg of tramadol.In the case of an insufficient analgesic effect, after 50-60 minutes, 50 mg of tramadol is taken again. With intensive pain, the recommended single dose of 100 mg of tramadol.

    Depending on the intensity of the pain syndrome, the analgesic effect is usually maintained for 4-6 hours. In the postoperative period, short-term administration of higher doses of the drug Tramadol in the early period after the operation.

    Patients of advanced age (up to 75 years) without clinical manifestations of hepatic or renal insufficiency there is usually no need to change the dose of tramadol.

    Patients older than 75 years excretion of the drug may be slowed down. Therefore, if it seems necessary, the break between the drug intake can be increased according to the patient's condition.

    Patients with renal insufficiency or on dialysis and patients with hepatic insufficiency. If the kidney and / or liver function is disrupted, the excretion of tramadol from the body is slowed. If necessary, the interval between doses of the drug should be increased.

    Duration of therapy

    Tramadol should never be used for longer than necessary.With long-term use of tramadol, due to the intensity or etiology of the pain syndrome, periodic monitoring (if necessary with interruptions in taking the drug) is necessary to determine the need for further therapy and dose optimization.

    Side effects:

    The most frequent adverse reactions are nausea and dizziness, noted in more than 10% of patients.
    The frequency is defined as follows:
    Very often:> 1/10;
    Frequently:> 1/100 <1/10;
    Infrequently:> 1/1000 <1/100;
    Rarely:> 1/10 000 <1/1000;
    Very rarely: <1/10 000;
    Insufficient data: can not be determined on the basis of available data.

    Disorders from the cardiovascular system:
    Infrequent: effects on cardiovascular regulation (palpitations, tachycardia, orthostatic hypotension or collapse). These side effects are mainly observed with intravenous administration of the drug or with significant physical exertion.
    Rarely: bradycardia, increased blood pressure.

    Disorders from the metabolism and nutrition:
    Rarely: changes in appetite.

    Disturbances from the respiratory system:
    Rarely: respiratory depression, shortness of breath.
    At a significant excess of the recommended doses with simultaneous use of other drugs that depress the central nervous system (CNS), respiratory depression is possible.
    There was a deterioration in bronchial asthma, however, there was no causal relationship with the drug.

    Impaired nervous system:
    Very often: dizziness.
    Often: headache, drowsiness.
    Rarely: speech disorders, paresthesia, tremor, epileptiform seizures, involuntary muscle contractions, coordination disorders, fainting. Epileptiform seizures are possible after applying high doses of tramadol and with simultaneous use with drugs that lower the threshold of convulsive readiness.

    Disorders of the psyche:
    Rarely: hallucinations, confusion, sleep disturbances, anxiety, delirium and nightmares. After the use of tramadol, various rarely observed undesirable reactions from the psyche are possible (depending on the personality characteristics of the patient and the duration of treatment). These side effects include mood changes (usually euphoria, sometimes dysphoria), a change in activity (usually a decrease,sometimes an increase), a violation of cognitive functions and perception (eg, decision-making, perception disorders). Perhaps the development of drug dependence.

    Disorders from the side of the organ of vision:
    Rarely: miosis, mydriasis, blurred vision.

    Disorders from the gastrointestinal tract:
    Very often: nausea.
    Often: constipation, dry mouth, vomiting.
    Infrequent: vomiting, a feeling of heaviness in the epigastrium, flatulence, diarrhea.

    Disturbances from the skin and subcutaneous tissues:
    Often: sweating.
    Infrequent: itching, rash, hives.

    Disturbances from the musculoskeletal and connective tissue:
    Rarely: muscle weakness.

    Disorders from the liver and bile ducts:
    In some cases there was an increase in the activity of "hepatic" enzymes, which coincided in time with tramadol therapy.

    From the side of the kidneys and the urinary system:
    Rarely: disturbances of urination (difficulty with urination, dysuria and urinary retention).

    Immune system disorders:
    Rarely: allergic reactions (dyspnea, bronchospasm, wheezing, angioedema) and anaphylaxis.

    General disorders:
    Often: fatigue.
    Rarely: the possible symptoms of "withdrawal" are similar to the symptoms of "withdrawal" of opioids: agitation, anxiety, nervousness, sleep disturbance, hyperkinesia, tremor and gastrointestinal symptoms.

    Other symptoms that are very rare with tramadol cancellation include panic attacks, severe anxiety, hallucinations, paresthesia, ringing in the ears and other extremely rare CNS symptoms (confusion, hallucinations, depersonalization, derealization, paranoia).

    If any of these side effects occur, or if there are other side effects not indicated in the instructions, tell your doctor.
    Overdose:

    In case of an overdose of tramadol, symptoms characteristic of opioid analgesics of the central action should be expected.

    Possible Symptoms: miosis, vomiting, collapse, consciousness up to coma, convulsions, depression of the respiratory center to apnea.

    Treated: airway patency. Maintain respiration and cardiovascular activity depending on the symptomatology. If breathing is disturbed, enter naloxone. When convulsions should be administered intravenously diazepam. When an overdose of the drug in oral dosage forms, it is necessary to wash the stomach and prescribe Activated carbon within the first two hours after an overdose. After taking especially large doses of the drug in capsules, removing the contents of the stomach can be effective at a later date.

    Hemodialysis and hemofiltration are ineffective.

    Interaction:

    Tramadol can not be used simultaneously or within 14 days after the abolition of MAO inhibitors. In patients treated with MAO inhibitors within 14 days before the use of the opioid analgesic pethidine, life-threatening drug interactions were observed that manifested symptoms of the central nervous system, respiratory and cardiovascular systems. Similar interactions with MAO inhibitors are possible with the administration of tramadol.

    The simultaneous use of tramadol and substances that suppress the activity of the central nervous system, including alcohol, can increase the side effects of the central nervous system. It is noted that with simultaneous or previous use of cimetidine (an inhibitor of microsomal enzymes of the liver) clinically significant interactions are unlikely.

    Simultaneous or previous use of carbamazepine (an inductor of microsomal liver enzymes) can reduce the analgesic effect of tramadol and shorten its duration.

    Tramadol can cause seizures and increase the effect of selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SSRIs), tricyclic antidepressants, antipsychotics and other drugs that lower the threshold for convulsive alertness (eg, bupropionin, mirtazapine), thus leading to the development of seizures. Simultaneous use of tramadol with other serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SSRIs), MAO inhibitors, tricyclic antidepressants and mirtazapine, can lead to the development of serotonin syndrome.

    Possible symptoms of serotonin syndrome: confusion, agitation, hyperthermia, sweating, ataxia, hyperreflexia, myoclonus and diarrhea. The abolition of serotonergic drugs causes rapid disappearance of symptoms.The necessary therapy is determined by the clinical picture and the severity of the symptoms.

    When simultaneous use of tramadol and coumarin derivatives (eg, warfarin), careful monitoring of patients is necessary, as some of them noted an increase in the international normalized ratio (INR) with the development of bleeding and ecchymosis.

    Other inhibitors of the CYP3A4 isoenzyme, for example, keteconazole and erythromycin, can slow the metabolism of tramadol (N-demethylation) and possibly active O-demethyltramadol. The clinical significance of this interaction has not been studied.

    There is limited evidence that pre- or post-operative use of a blocker of 5-HT3-serotonin receptors-ondansetron, increased the need for tramadol in patients with postoperative pain syndrome.
    Special instructions:

    In patients with opioid dependence, head trauma, shock, in patients with impaired consciousness of unclear etiology, respiratory disorders or respiratory center damage, increased intracranial pressure, tramadol should only be used with extreme caution.

    The drug should be used with caution in patients with severe intolerance to opioids of allergic and non-allergic origin.

    There have been cases of seizures in patients taking tramadol in recommended doses.

    The risk of seizures may increase if the recommended maximum daily dose of the drug is exceeded (400 mg).

    The administration of tramadol may increase the risk of seizures in patients taking drugs that reduce the convulsive threshold. Patients with epilepsy and patients prone to developing seizures should take tramadol only for life indications.

    Tramadol has a low potential for drug dependence. However, with prolonged use, addiction, physical and mental dependence is possible. In patients prone to abuse of medicines, or to the development of drug dependence, drug treatment Tramadol should be conducted only in short courses and under medical supervision.

    Tramadol is not applicable as a substitute therapy in patients with opioid dependence. Although tramadol is an agonist opioid receptors, it can not suppress the symptoms of "withdrawal" of morphine.

    Effect on the ability to drive transp. cf. and fur:

    Even at recommended doses tramadol can cause effects such as drowsiness, dizziness, and therefore it can disrupt the reaction of car drivers and machine operators. When taking the drug Tramadol it is necessary to refrain from managing motor transport and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, especially when used simultaneously with other psychotropic drugs or alcohol.

    Form release / dosage:Capsules 50 mg.
    Packaging:

    10 capsules per contour cell packaging made of polyvinylchloride film and aluminum foil. 1, 2 contour mesh packs together with instructions for the use of the drug are placed in a pack of cardboard.

    Storage conditions:

    In accordance with the rules for storage of potent substances.

    In the dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use at the end of the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003520
    Date of registration:23.03.2016
    Expiration Date:23.03.2021
    The owner of the registration certificate:MOSCOW ENDOCRINE FACTORY, FSUE MOSCOW ENDOCRINE FACTORY, FSUE Russia
    Manufacturer: & nbsp
    Information update date: & nbsp22.08.16
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