Active substanceTramadolTramadol
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  • Dosage form: & nbspInjection.
    Composition:
    1 ml of the preparation contains:
    Active substance:
    Tramadol hydrochloride 50.00 mg
    Excipients: sodium acetate, anhydrous 2.50 mg, water for injection q.s. up to 1.00 ml.
    Description:A clear, colorless solution with virtually no visible mechanical impurities.
    Pharmacotherapeutic group:An analgesic with a mixed mechanism of action.
    ATX: & nbsp

    N.02.A.X.02   Tramadol

    Pharmacodynamics:Opioid synthetic analgesic, which has a central effect and action on the spinal cord (contributes to the discovery of potassium and calcium channels, causes hyperpolarization of membranes and inhibits pain impulses), enhances the action of sedative drugs (LS). Activates opioid receptors (mu, delta, kappa) on the pre- and postsynaptic membranes of the afferent fibers of the nociceptive system in the brain and gastrointestinal tract (GI tract).
    Slows down the destruction of catecholamines, stabilizes their concentration in the central nervous system (CNS).
    Tramadol is a racemic mixture of 2 enantiomers - dextrorotatory (+) and levorotatory (-), each of which exhibits a different receptor affinity.
    The dextrorotatory enantiomer of tramadol is a selective agonist of mu-opioid receptors, and selectively inhibits the reverse neuronal capture of serotonin, while the levorotatory inhibits the reverse neuronal seizure of norepinephrine. Mono-O-desmethyltramadol (M1 metabolite) also selectively stimulates mu-opioid receptors.
    The affinity of tramadol for opioid receptors is ten times weaker than that of codeine, and 6000 times weaker than morphine. Expression of analgesic action is 5-10 times weaker than morphine.
    Analgesic effect is due to a decrease in nociceptive activity and an increase in the antinociceptive systems of the body.
    Oppresses the respiratory center, excites the start zone of the vomiting center, the nucleus of the oculomotor nerve. With prolonged use, the development of tolerance is possible.
    Pharmacokinetics:

    Distribution

    The volume of distribution after intravenous injection in young, healthy volunteers is 203 liters. Connection with blood plasma proteins - 30%. Penetrates through the blood-brain and placental barrier; 0,1% is excreted in breast milk. The concentration of tramadol in the umbilical cord blood is 80% of its concentration in the mother's blood.

    Metabolism

    Approximately 85% of tramadol is metabolized. Tramadol metabolized by N- and O-demethylation. In addition to the O-demethylated metabolite (M1), all other metabolites are pharmacologically inactive. Although animal experiments showed a high ability to bind a metabolite M1 with mu-opioid receptors in comparison with tramadol, in studies in healthy volunteers M1 the metabolite showed no analgesic effect. Excretion

    90% of tramadol and its metabolites are excreted by the kidneys, and the rest - through

    intestines. The half-life (T1/2) for tramadol and its metabolites is 5 to 6 hours. Impaired renal function reduces the rate and extent of excretion, therefore, in patients with creatinine clearance less than 30 ml / min, it is recommended to reduce the dose and increase the interval between tramadol administration.

    Metabolism of tramadol and metabolite M1 decreased in patients with severe cirrhosis of the liver, which requires dose adjustment.

    In patients older than 75 years, the maximum concentration of tramadol in the blood plasma is increased and T1/2, therefore for this group of patients dose adjustment is necessary. About 7% of tramadol is excreted by hemodialysis.

    Indications:
    - pain syndrome of strong and medium intensity of different etiology (including trauma, postoperative period, pain in cancer patients);

    - Anesthesia for painful diagnostic and therapeutic manipulations.
    Contraindications:
    -increased sensitivity to tramadol u and other analgesics;

    -States accompanied by respiratory depression or severe CNS depression (including alcohol poisoning, hypnotic drugs, narcotic analgesics and other psychoactive drugs);

    -pharmacoresistance epilepsy;

    -heavy liver and / or renal failure (CC less than 10 ml / min);

    - The use of tramadol as a drug for the treatment of the syndrome of "withdrawal" of drugs;

    -Children under 1 year of age (for this dosage form);

    - simultaneous application of monoamine oxidase inhibitors (MAO) and within 14 days after their cancellation;

    - suicidal tendencies, propensity to abuse of psychoactive substances;

    -Birth, the period of breastfeeding (application is possible only for vital indications).

    Carefully:
    The failure of the kidney function (QC 10-30 ml / min) and / or liver, craniocerebral trauma,

    (disorders of consciousness of different genesis, convulsions, intracranial hypertension, epilepsy, abdominal pain of an unclear genesis ("acute" abdomen), simultaneous use with selective serotonin reuptake inhibitors (some antidepressants and drugs that reduce appetite), tricyclic antidepressants, other tricyclic connections (for example, promethazine), antimigraine drugs (triptans), narcotic analgesics, neyrolithics, etc. JIC, reducing the threshold of convulsive activity; propensity to form addiction (alcoholism, drug or drug dependence).
    Pregnancy and lactation:
    Safety of the drug Tramadol during pregnancy is not established. High doses can have adverse effects on the fetus and the newborn. The application is possible only under the strictest medical supervision and in individual, exceptional cases, if the potential benefit to the mother justifies the risk to the child.
    It should be borne in mind that during breastfeeding, approximately 0.1% of the dose of tramadol is secreted into breast milk.
    During pregnancy and during breastfeeding, the drug Tramadol it is possible only for vital indications.
    Dosing and Administration:

    Intravenous, intramuscular, subcutaneous, infusion.

    The dose is set individually and varies depending on the severity of the pain.

    Adults and children over 14 years of age: single dose of 50-100 mg (1-2 ampoules). The maximum daily dose: 400 mg.

    Children from 1 year to 14 years: 1 - 2 mg / kg body weight.

    The maximum daily dose: 4-8 mg / kg of body weight.

    The drug can be re-entered after 4-6 hours.

    Intravenously, the drug is administered very slowly (no more than 1 ml of solution / min), which corresponds to 50 mg of tramadol or in diluted form with a solution for infusions.

    If the effect is insufficient, then after 20-30 minutes after intravenous administration it is possible to continue infusion at a rate of 12 mg / h or additionally appoint orally.

    Daily dose of the drug Tramadol for adults in any dosage form should not exceed 400 mg / day, except for cases of pain relief in cancer patients and in severe postoperative pain. In these cases, you can increase the daily dose to 1600 mg / day.

    Patients with renal insufficiency (CC less than 30 ml / min) and liver failure require individual dose adjustment (lengthening is possible T1/2) and 12-hour interval between the use of the next dose of the drug Tramadol.

    In patients older than 75 years, do not exceed the daily dose of more than 300 mg / kg. Tramadol should not be used for longer than necessary for treatment.

    Side effects:

    Pob.Odzoe action

    Classification of the incidence of adverse events (WHO):

    very often> 1/10

    often from> 1/100 to <1/10

    infrequently from> 1/1000 to <1/100

    rarely from> 1/10000 to <1/1000

    very rarely from <1/10000, including individual messages.

    From the central and peripheral nervous system:

    very often: dizziness;

    often: headache;

    infrequently: anxiety, confusion, drowsiness;

    rarely: euphoria, emotional instability, nightmares, cognitive disorders, hallucinations, amnesia; disorders of coordination of movements, convulsions, paresthesia, tremor, impaired concentration, epileptiform seizures; with prolonged use, it is possible to develop drug dependence; very rarely: panic attacks, ringing in the ears;

    From the cardiovascular system:

    rarely: tachycardia, palpitations, cardiovascular collapse, fainting,

    orthostatic hypotension, cardiovascular failure; very rarely: bradycardia, increased blood pressure;

    From the respiratory system:

    rarely: dyspnea, respiratory depression, pulmonary edema;

    From the sense organs:

    very rarely: decreased visual acuity, sometimes mydriasis, a taste disorder;

    From the digestive system:

    very often: nausea;

    often: vomiting, constipation or diarrhea, dryness of the oral mucosa;

    infrequently: indigestion, abdominal pain, bloating;

    rarely: difficulty swallowing;

    very rarely: increased activity of "liver" transaminases;

    From the skin:

    often: sweating;

    From the genitourinary system:

    infrequent: urinary retention, increased frequency of urination, menstrual irregularity, signs of menopause;

    rarely: dysuria;

    From the musculoskeletal system: rarely: muscle weakness;

    From the side of metabolism:

    infrequently: anorexia;

    rarely: weight loss;

    Other: with prolonged use - drug dependence; with a sharp abolition - the "cancellation" syndrome.

    Overdose:

    Symptoms: impairment of consciousness (up to coma), cramps, lowering blood pressure, tachycardia, narrowing or dilating pupils, respiratory depression.

    Treatment: with severe intoxication with loss of consciousness and superficial, weak breathing, it is necessary to introduce antagonists of opioid receptors (naloxone), and with cerebral convulsions - preparations of benzodiazepine series (diazepam), intravenously. Hemodialysis is ineffective. Excretion of tramadol by hemodialysis is about 7%.

    Interaction:
    Tramadol can not be used concomitantly with MAO inhibitors or within 2 weeks after they are discontinued.
    With the simultaneous use of substances acting on the central nervous system (anesthetics, antidepressants, antipsychotics, sedatives, anxiolytics, hypnotics) or with the use of alcohol, there is a possibility of a synergistic effect, manifested by excessive sedation and increased analgesic effect. Tramadol strengthens the action of LC, depressing the central nervous system and ethanol.
    Inductors of microsomal oxidation (incl. carbamazepine, barbiturates) reduce the severity of the analgesic effect and the duration of the action. Due to the increased risk of seizures, the simultaneous use of carbamazepine and tramadol is not recommended. Long-term use of opioid analgesics or barbiturates stimulates the development of cross tolerance.
    Anxiolytics increase the severity of the analgesic effect; The duration of anesthesia increases with combination with barbiturates.
    Naloxone activates breathing, eliminating analgesia after the use of opioid analgesics.
    MAO inhibitors, furazolidone, procarbazine, antipsychotic drugs (neuroleptics) increase the risk of seizures (reduction of the convulsive threshold). Quinidine increases the plasma concentration of tramadol and decreases the M1 metabolite due to competitive inhibition of isoenzymes CYP2D6.
    Inhibitors of the CYP2D6 isoenzyme (such as fluoxetine, paroxetine and amitriptyline) reduce the metabolism of tramadol.
    Selective serotonin reuptake inhibitors (some antidepressants and drugs that reduce appetite), tricyclic antidepressants, other tricyclic compounds (for example, promethazine), antimigraine drugs (triptans), narcotic analgesics, MAO inhibitors, neuroleptics, etc. drugs that reduce the threshold of convulsive readiness, increase the risk of seizures.
    Selective serotonin reuptake inhibitors, serotonin reuptake inhibitors and norepinephrine, tricyclic antidepressants, MAO inhibitors, antimigraine drugs (triptans) and drugs that disrupt the metabolism of tramadol (inhibitors of CYP2D6 and CYP3A4 isoenzymes), while being used with tramadol, can cause serotonin syndrome (confusion , agitation, hyperthermia, sweating, ataxia, hyperreflexia, myoclonus, diarrhea).The abolition of J serotonergic drugs causes rapid relief of the symptoms of serotonin syndrome.
    Caution should be exercised with simultaneous therapy with tramadol and coumarin derivatives (eg, warfarin), since there are reports of an increase in the international normalized ratio (MHO) and the appearance of ecchymoses in some patients.
    Pre- or post-operative use of an anti-emetic agent, a 5-HTZ-serotonin receptor antagonist, increases the need for tramadol in patients with postoperative pain syndrome.

    Special instructions:
    Tramadol can be used in patients with hypersensitivity to opioids, but with great caution.
    Tramadol should be avoided for those who are addicted to addiction (alcoholism, drug or drug dependence). With the use of tramadol, the risk of suicide increases.
    With the development of severe undesirable effects, it is necessary to stop using the drug Tramadol.
    Patients with cerebral cramps should remain under careful medical supervision during drug treatment and within a few days after discontinuation.
    Tramadol is not suitable as a substitute therapy for opioid dependence.

    In patients with impaired liver function due to reduced hepatic clearance, the concentration of tramadol in the blood plasma increases and its T1/2. Such patients are recommended smaller doses and / or increased intervals between drug use Tramadol.

    Tramadol can, but with great caution, be used in patients with elevated intracranial pressure and a traumatic brain injury in the anamnesis.

    Effect on the ability to drive transp. cf. and fur:
    A drug Tramadol may cause impaired concentration, hallucinations, confusion, dizziness, and others. side effects, so during the application of the preparation Tramadol you must refrain from driving and other lesson. potentially hazardous activities that require high concentration and psychomotor speed reactions.
    Form release / dosage:
    Solution for injection 50 mg / ml.

    Packaging:
    1 ml or 2 ml of the drug in an ampoule of transparent neutral glass (type I, Ph.Eur.).
    The ampoule contains a colored dot and a color coding ring.5 ampoules of 1 ml or 2 ml are placed in a blister of PVC film and aluminum foil. 1 blister pack together with instructions for use in a cardboard box.
    Storage conditions:At a temperature of no higher than 25 ° C. Keep out of the reach of children.
    It refers to the list of the strongest substances of the Standing Committee on Drug Control of the Ministry of Health and Social Development.
    Shelf life:
    5 years. Do not use the drug after the expiration date.
    Terms of leave from pharmacies:On prescription
    Registration number:П N012155 / 02
    Date of registration:27.06.2011
    The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO
    Manufacturer: & nbsp
    KRKA, d.d. Slovenia
    Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO
    Information update date: & nbsp12.09.2015
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