Active substanceTramadolTramadol
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  • Dosage form: & nbspdrops for oral administration
    Composition:

    1 ml of the preparation contains:

    Active substance:

    Tramadol hydrochloride 100.00 mg

    Auxiliary substances: sucrose 200.00 mg, glycerol 180.00 mg, propylene glycol 160.00 mg, polysorbate 20 1.00 mg, potassium sorbate 1.64 mg, sodium saccharinate dihydrate 5.00 mg, peppermint flavoring 0.10 mg , flavoring anise 0.10 mg, water purified to 1.0 ml

    Description:

    Transparent colorless or slightly brownish solution with a characteristic smell of mint and anise.

    Pharmacotherapeutic group:An analgesic with a mixed mechanism of action. It refers to the list of the strongest substances of the Standing Committee on Drug Control of the Ministry of Health and Social Development.
    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. 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 the mu-opioid receptors, and selectively inhibits the reverse neuronal seizure of serotonin, while the levorotatory inhibits the reverse neuronal seizure of norepinephrine. Mono-O-desmethyltramadol (Ml 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.

    Pharmacokinetics:

    Pharmacokinetics

    Absorption - 90%, with oral bioavailability - 75% (increases with repeated use). Time to reach the maximum concentration (TCmah) after ingestion - 1h, Ml metabolite - 3 hours.

    Penetrates through blood-brain and placental barriers, 0.1% of tramadol is excreted in breast milk. The volume of distribution - 306 liters, connection with plasma proteins - 20 %.

    In the liver, it is metabolized by N- and O-demethylation followed by conjugation with glucuronic acid. 11 metabolites were detected, of which mono-O-desmethyltramadol (Ml) has pharmacological activity. The half-life (T%) in the second phase is 6 h (tramadol), 7.9 hours (mono-O-desmethyltramadol); in patients older than 75 years - 7.4 h (tramadol); with cirrhosis of the liver - 13.3± 4.9 hours (tramadol), 18.5 ± 9.4 hours (mono-O-desmethyltramadol), in severe cases - 22.3 hours and 36 hours, respectively; with chronic renal failure (creatinine clearance (CK) less than 5 ml / min) - 11 ± 3.2 h (tramadol), 16.9 ± 3 h (mono-O-desmethyltramadol), in severe cases -19.5 h and 43.2 h respectively.

    It is excreted by the kidneys (25-35% unchanged), the average cumulative index of renal excretion is 94%. About 7% is excreted by hemodialysis.

    Indications:

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

    - anesthesia in the conduct of painful diagnostic and therapeutic manipulations.

    Contraindications:

    - Hypersensitivity to tramadol and other analgesics;

    - Conditions accompanied by respiratory depression or severe depression of the central nervous system (including alcohol poisoning, hypnotics drugs, narcotic analgesics and other psychoactive drugs);

    - pharmacovirus-resistant epilepsy;

    - severe renal and / or hepatic insufficiency (CC less than 10 ml / min);

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

    - Children's age up to 1 year;

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

    - suicidal tendencies, propensity to abuse of psychoactive substances;

    - pregnancy, lactation period (during pregnancy and during breastfeeding, the application is possible only according to vital indications);

    - deficiency of sugar / isomaltase, intolerance to fructose, glucose-galactose malabsorption.

    Carefully:

    Disturbance of renal function (QC 10-30 ml / min) and / or liver, craniocerebral trauma, disorders of consciousness of various genesis, convulsions, intracranial hypertension, epilepsy, abdominal pain of unclear genesis "acute" abdomen, simultaneous application with selective inhibitors reuptake of serotonin (some antidepressants and drugs that reduce appetite),tricyclic antidepressants, other tricyclic compounds (eg, trimetazine), antimigraine drugs (tryptans), narcotic analgesics, antipsychotics, and other drugs that reduce the threshold of convulsive activity, a propensity for dependence (alcoholism, drug or drug dependence).

    Pregnancy and lactation:

    Safety of use 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 taken into account that during lactation approximately 0.1% of the dose is secreted into breast milk.

    Dosing and Administration:

    Inside. The dose depends on the severity of the pain syndrome and individethe patient's sensitivity. The time of taking the drug does not depend on the time of eating.

    Adults and adolescents over 12 years of age:

    A single dose is 20-40 drops (equivalent to 50 mg) of tramadol.

    In case of insufficiency or in the absence of an analgesic effect, after 50-60 minutes, 50 mg of tramadol is taken repeatedly.

    In severe pain syndrome, a higher single dose of tramadol (100 mg) may be administered as the initial dosage.

    The daily dose is up to 160 drops for ingestion Tramadol.

    Children 1-12 years old:

    As a single dose appoint 1-2 mg of tramadol per 1 kg of body weight.

    The maximum daily dose for children is 4-8 mg / kg / day.

    The table shows typical dosing regimens for different age groups of children (1 drop contains 2.5 mg of tramadol):

    Age

    Body mass

    Number of drops

    1 year

    10 kg

    4-8

    3 years

    15 kg

    6-12

    6 years

    20 kg

    8-16

    9 years

    30 kg

    12-24

    12 years

    45 kg

    18-36

    Patients with impaired renal and / or liver function:

    In patients with impaired renal and / or liver function tramadol can last longer due to the possible extension of T1 / 2. For such patients, the doctor may recommend an increase in the interval between taking single doses. With QC less than 30 ml / min and in patients with hepatic insufficiency, an interval of 12 hours between taking the next doses of the drug Tramadol.

    The drug should be administered with caution to patients with impaired renal function (50-100 mg 2 times a day),and also to persons with cirrhosis of the liver (this group of patients with T1 / 2 tramadol is almost 3-fold increased).

    Patients older than 75 years

    In patients older than 75 years, the excretion of tramadol is slowed from the body, even when there are no clinical manifestations of renal and / or hepatic impairment. These patients also need to increase the interval between taking the drug.

    Do not exceed the maximum daily dose - not more than 160 drops for oral administration.

    Side effects:

    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:

    Often: dizziness;

    Often: headache;

    Infrequently: anxiety, confusion, drowsiness;

    Rarely: euphoria, emotional instability, sleep disturbance, nightmares, cognitive disorders, hallucinations, amnesia; disorders of coordination, convulsions, paresthesia, tremor, attention deficit disorder, epileptiform seizures, with prolonged use - the development of drug dependence;

    Rarely: panic attacks, ringing in the ears;

    From the side of the cardiovascular system:

    Rarely: tachycardia, palpitations, cardiovascular collapse, fainting, orthostatic hypotension, cardiovascular failure;

    Rarely: bradycardia, arterial hypertension;

    From the respiratory system:

    Rarely: shortness of breath, respiratory depression, pulmonary edema;

    From the sense organs:

    Rarely: decreased visual acuity, sometimes mydriasis, a taste disorder;

    From the digestive system:

    Often: nausea;

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

    Infrequently: dyspepsia, abdominal pain, bloating;

    Rarely: difficulty in swallowing;

    Rarely: increased activity of "liver" transaminases;

    From the skin:

    Often: sweating;

    Infrequently: skin rash, itchy skin;

    Rarely: hives;

    From the genitourinary system:

    Infrequently: urinary retention, increased frequency of urination, impairment menstrual cycle, signs of menopause;

    Rarely: dysuria;

    From the musculoskeletal system:

    Rarely: muscle weakness;

    From the side of metabolism:

    Infrequently: anorexia;

    Rarely: decreased body weight;

    Allergic reactions:

    Rarely: allergic reactions manifested by dyspnea, bronchospasm, wheezing, and also angioedema.

    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 enhances the effect of drugs, 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 reduces Ml metabolite due to competitive inhibition of isoenzyme CYP2D6.

    Inhibitor inhibitors CYP2D6 (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 and noradrenaline reuptake inhibitors, tricyclic antidepressants, MAO inhibitors, anti-migraine drugs (triptans), and drugs that disrupt the metabolism of tramadol (inhibitors of isoenzymes CYP2D6 and CYP3A4), when combined with tramadol can cause serotonin syndrome (confusion, agitation, hyperthermia, sweating, ataxia, hyperreflexia, myoclonus, diarrhea). The abolition of 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 (INR) and the appearance of ecchymoses in some patients.

    Pre- or post-operative use of an anti-emetic agent, a 5-HT3-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 adverse effects should stop taking the drug.

    Patients with cramps should remain under close 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 serum increases and its T1/2. Such patients are recommended smaller doses and / or increased intervals between drug intake 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 can cause disturbance of concentration of attention, hallucinations, confusion, dizziness and other side effects, therefore during drug treatment it is necessary to refrain from driving and other potentially dangerous activities requiring high concentration of attention and speed of psychomotor reactions.
    Form release / dosage:

    Drops for oral administration, 100 mg / ml.

    Packaging:

    10 ml of the preparation in a bottle of amber glass (Tin III) with a built-in dropper of low density polyethylene and a screw cap of polypropylene type "push and open" with control of the first opening.

    1 bottle is placed in a pack of cardboard along with instructions for use.

    Storage conditions:

    At temperatures not higher than 30 ° C, in the original packaging.

    Keep out of the reach of children.

    The drug belongs to the list of No. 1 potent substances of the Standing Committee on Drug Control of the Ministry of Health and Social Development.

    Shelf life:

    Shelf life 5 years.

    Do not use the drug after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:П N012155 / 03
    Date of registration:03.12.2010 / 24.09.2015
    Expiration Date:Unlimited
    Date of cancellation:2016-12-07
    The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO
    Manufacturer: & nbsp
    KRKA, d.d. Slovenia
    Representation: & nbspKRKA KRKA Slovenia
    Information update date: & nbsp07.12.2016
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