Active substanceTramadolTramadol
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  • Dosage form: & nbsprectal suppositories
    Composition:

    1 suppository contains:

    Active substance:

    Tramadol hydrochloride 100.00 mg

    Excipient:

    Fat solid 900.00 mg

    Description:

    Cylindrical conical suppositories white or almost white.

    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 opiate 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. With prolonged use, it is possible to develop tolerance.

    Pharmacokinetics:

    Suction

    With rectal administration tramadol quickly and almost completely absorbed. Bioavailability after rectal administration is approximately 80%. Serum concentration of 100 mg / l (minimal for development of analgesic effect) is achieved after approximately 0.8 hours and maintained for 6 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.Identified 11 metabolites, of which mono-O-desmethyltramadol (Ml) has pharmacological activity. The half-life (T%) in the second phase is 6 h (tramadol), 7.9 h (mono-O-desmethyltramadol); in patients older than 75 years - 7.4 h (tramadol); with cirrhosis of the liver - 13.3 ± 4.9 h (tramadol), 18.5 ± 9.4 h (mono-O-desmethyltramadol), in severe cases - 22.3 h and 36 h, 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 medium intensity of different etiology (including trauma, postoperative period, pain in cancer patients);

    - Anesthesia for painful diagnostic and therapeutic manipulations.

    Contraindications:

    - Hypersensitivity to tramadol and other analgesics;

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

    - pharmacovirus-resistant epilepsy;

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

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

    - Children's age (up to 14 years);

    - 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).

    Carefully:Violation 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 in an unclear genesis "acute" abdomen), simultaneous application with selective serotonin reuptake inhibitors (some antidepressants and drugs that reduce appetite), tricyclic antidepressants, other tricyclic compounds (for example, promethazine), antimigrenous drugs (triptans), narcotic analgesics, antipsychotics and etc.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 borne in mind that during lactation approximately 0.1% of the dose of the drug is secreted into breast milk.

    During pregnancy and during breastfeeding, the drug Tramadol it is possible only for vital indications.

    Dosing and Administration:

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

    Adults and children over 14 years of age: 1 suppository 3-4 times a day.

    Repeated use of the drug is possible not earlier than 3-5 hours.

    The maximum daily dose is not more than 400 mg / day (4 suppositories of 100 mg), except for cases of pain relief in cancer patients and with severe postoperative pain; in these cases, you can increase the dose to 600 mg / day (6 suppositories).

    Patients with impaired renal / hepatic function

    In patients with impaired renal and / or liver function tramadol can last longer due to possible lengthening 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 maximum daily dose for patients with impaired renal function should not exceed 200 mg (2 suppositories).

    Patients on hemodialysis are given regular doses of the drug Tramadol even on the day of dialysis.

    Patients with cirrhosis recommended 100 mg per day (1 suppository). 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 daily dose of 300 mg (3 suppositories).

    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, nightmares, cognitive disorders, hallucinations, amnesia, movement coordination disorders, seizures, paresthesia; tremor, impaired concentration, epileptiform seizures, with prolonged use - the development of drug dependence;

    Rarely: panic attacks, ringing in the ears;

    From the cardiovascular system:

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

    Rarely: bradycardia, increased blood pressure;

    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;

    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 (eg urticaria, pruritus, exanthema, bullous rash, angioedema) and anaphylaxis, which can cause azole dyes E122, E124 and E151.

    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 convulsions - preparations of the 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 action 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 care.

    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 increases. Such patients are recommended smaller doses and / or an increase in the interval between taking the drug Tramadol.

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

    Azole dyes E122, E124 and E151 in susceptible people can cause reactions of an allergic type, including those with signs of anaphylaxis and bronchospasm, especially in persons with bronchial asthma or allergic diseases in the anamnesis.

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

    A drug Tramadol can cause a violation of concentration, hallucinations, confusion, dizziness and other side effects, so during drug treatment it is necessary to refrain from managing motor transport and other activities.potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

    Form release / dosage:

    Suppositories rectal, 100 mg.

    Packaging:

    5 suppositories per strip from Al / PE.

    1 strip 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.

    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 / 04
    Date of registration:25.10.2010 / 25.09.2015
    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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