Active substanceTiclopidineTiclopidine
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  • Tiklid®
    pills inwards 
  • Dosage form: & nbspfilm coated tablets
    Composition:
    Active ingredient: ticlopidine hydrochloride 250 mg.
    Excipients: microcrystalline cellulose (90 microns), povidone K 30 (polyvidon K 30), citric acid anhydrous, corn starch, magnesium stearate, stearic acid.
    Sheath composition: white opadrai (hypromellose, titanium dioxide, macrogol, polysorbate 80).

    Description:
    Round biconvex tablets covered with a film coat of white or almost white color.

    Pharmacotherapeutic group:antiplatelet agent
    ATX: & nbsp

    B.01.A. C.05   Ticlopidine

    Pharmacodynamics:
    Ticlopidine is an inhibitor of platelet aggregation. It causes dose-dependent suppression of platelet aggregation and release of certain platelet factors, as well as prolongation of bleeding time.
    The drug does not have significant in vitro activity, but only in vivo. Ticlopidine metabolites have not been identified actively.
    Ticlopidine suppresses platelet aggregation by inhibiting ADP-dependent binding of fibrinogen to the platelet membrane.Unlike aspirin, it does not inhibit cyclooxygenase. Cyclic AMP of platelets, apparently, does not play a role in this mechanism of action.
    After discontinuation of the drug in most patients, the time of bleeding and other functions of platelets return to normal values ​​within one week. Suppression of platelet aggregation occurs within two days from the start of ticlopidine twice daily.
    The maximum effect is achieved on the 5-8th day of treatment at a dose of 250 mg twice a day.
    In a therapeutic dose ticlopidine inhibits ADP-induced (2.5 μmol / L) platelet aggregation by 50-70%. Lower doses cause a proportionally smaller suppression of platelet aggregation.

    Pharmacokinetics:
    After ingestion of a single dose standard dose of ticlopidine, rapid absorption is observed, reaching a maximum level in the plasma 2 hours after ingestion. Absorption is almost complete. The appointment of ticlopidine after meals improves bioavailability.
    Stable levels of the drug in the plasma are achieved after 7-10 days of administration of 250 mg twice a day. The average half-life of ticlopidine at stable levels is approximately 30-50 hours. However, the suppression of platelet aggregation does not depend on the concentration level of the drug in the plasma.
    Ticlopidine is metabolized in the liver. After ingestion of a drug labeled with a radioactive isotope, 50-60% was detected in urine, 23-30% in feces.
    Elderly patients:
    The main clinical trials were conducted with the participation of a group of middle-aged patients aged 64 years. Pharmacokinetics of ticlopidine in elderly patients is modified, but its pharmacological and therapeutic activity at a dosage of 500 mg per day does not depend on age.

    Indications:
    Prevention of arterial thrombotic complications (stroke, myocardial infarction, death from vascular disease) in patients who underwent an ischemic stroke caused by cerebral artery atherosclerosis.
    Prophylaxis of ischemic complications, especially coronary complications, in patients with coronary heart disease (CHD) and in patients with chronic lower limb arteries (intermittent claudication).
    Prevention of recurrent thrombosis in chronic hemodialysis.

    Contraindications:
    An allergy to ticlopidine in the anamnesis.
    Hemorrhagic diathesis.
    Diseases with a tendency to bleeding (peptic ulcer of the stomach or duodenum, hemorrhagic stroke).
    Diseases of the blood with prolonged bleeding time.
    Hematologic disorders (leukopenia, thrombocytopenia or agranulocytosis in anamnesis).
    Severe hepatic insufficiency.
    Pregnancy and lactation.

    Carefully:
    apply in patients with impaired liver function (see "Special instructions"), with renal insufficiency, with surgical interventions, injuries and other pathological conditions with a risk of bleeding. The effectiveness and safety of ticlopidine in children is not established.

    Dosing and Administration:
    Only for adults.
    For oral administration.
    For all indications, the drug is prescribed in a dose of 250 mg 2 times a day, during or after a meal. The maximum daily dose can be 1 gram (can be administered only for a short period of time).
    In chronic renal failure, a dose reduction

    Side effects:
    On the part of the hematopoiesis system
    Leukopenia (neutropenia, agranulocytosis), pancytopenia, bone marrow aplasia (especially pronounced in elderly patients) hemolytic anemia, thrombocytopenia (isolated, and conjugated with hemolytic anemia).Thrombotic thrombocytopenic purpura is very rare.
    On the part of the hemostasis system, G is a form of fermentation.
    From the gastrointestinal tract
    Nausea, diarrhea, pain in the stomach, rarely cytolytic and / or cholestatic hepatitis. Isolated or combined increase in alkaline phosphatase, transaminase, and bilirubin levels during the first 4 months of treatment.
    From the skin side
    Polymorphic skin rashes, often accompanied by itching. In very rare cases, erythema multiforme was noted.
    Allergic reactions
    In very rare cases, various forms of immunoallergic reactions were noted: extremely rare - anaphylactic reaction, angioedema, arthralgia, vasculitis, lupus syndrome, allergic nephropathy and pneumonitis. Very rare cases of high temperature are described.
    From the nervous system
    Dizziness, headache, tinnitus, asthenia.
    The level of lipids in the blood
    During 1-4 months of treatment with ticlopidine, an increase of 8-10% in HDL, LDL, VLDL and serum triglyceride levels can be observed. With continued treatment, no further increase is observed.The proportion between sub-fractions of lipoproteins (especially between HDL and LDL) remains unchanged. Clinical experiments have shown that this effect does not depend on age, sex, alcohol consumption or the presence of diabetes and does not affect cardiovascular risk.

    Overdose:
    Based on the results of animal experiments, an overdose of the drug may cause severe gastrointestinal intolerance. It is necessary to carefully monitor the function of vital organs and indicators of hemostasis (bleeding time). In case of overdosage, gastric lavage and the use of general supportive measures are recommended.

    Interaction:
    Some drugs can interact with ticlopidine because of their antiplatelet properties. These are substances such as aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), clopidogrel, tirofiban, eptifibatide, abciximab and iloprost. Simultaneous use of several inhibitory
    aggregation of platelets, agents, as well as their combination with heparin, oral anticoagulants and thrombolytic agents may significantly increase the risk of bleeding,therefore regular clinical and laboratory testing should be carried out.
    Combinations that require special care:
    Theophylline (base and salts) and aminophylline:
    An increase in the level of theophylline in plasma with a risk of overdose (decrease in plasma clearance of theophylline). Clinical control is required, as well as measurement of the levels of theophylline in plasma. The dosage of theophylline should be modified as necessary during treatment with ticlopidine and after its termination.
    Phenytoin:
    Elevated levels of phenytoin in plasma with signs of overdose (suppression of the metabolism of phenytoin). Clinical control and measurement of plasma phenytoin levels are required.
    Cyclosporine:
    Concentrations of cyclosporine in the blood are reduced. It is necessary to increase the dose of cyclosporine when controlling its concentration. After the withdrawal of ticlopidine, the dose should be reduced.
    Digoxin:
    Combined use with digoxin reduces by 15% the concentration of the latter in blood plasma.
    Other interactions: antacids, reducing absorption, reduce the concentration of ticlopidine in the blood plasma by 18%; simultaneous administration with cimetidine, may lead to a slower release of ticlopidine; Myelotoxic drugs increase the risk of oppression of bone marrow hematopoiesis.

    Special instructions:
    Ticlopidine may cause hematologic or hemorrhagic side effects, (see "Side effects").
    Hematological disorders are mainly associated with leukocytes. In the vast majority of cases, these side effects manifest themselves during the first three months of treatment. Sometimes there are severe cases (severe neutropenia, agranulocytosis), which can lead to death.
    Severe outcomes of hematologic or hemorrhagic side effects are more likely to occur under the following conditions:
    Non-compliance with control measures, late diagnosis and inadequate therapeutic intervention;
    Co-administration of anticoagulants or platelet aggregation inhibitors such as aspirin and NSAIDs.
    Hematological control
    At the beginning of treatment, a differentiated clinical blood test (including platelet count) should be performed, and then it should be repeated every two weeks during the first three months of therapy. If treatment is discontinued during the first three months, within two weeks after cessation of treatment, neutrophil and platelet control is necessary.
    In the case of neutropenia (<1500 neutrophils / mm3) or thrombocytopenia (<100,000
    thrombocytes / mm3), treatment should be discontinued, and control blood tests with platelet count and other blood elements should be performed until normal results are obtained.
    Control of hemostasis
    Ticlopidine should be used with caution in the risk of bleeding (see "Interactions with other drugs").
    If the patient is to undergo surgery, if the effect of platelet suppression is undesirable, treatment should be stopped at least ten days before surgery.
    In the case of urgent surgery, three methods can be used together or separately to reduce the risk of bleeding and reduce bleeding time:
    1) injection of 0.5-1.0 mg / kg of methylprednisolone intravenously, which can be repeated;
    2) administration of desmopressin in a dose of 0.2-0.4 μg / kg;
    3) transfusion of fresh platelets in the form of a platelet concentrate. Clinical control
    All patients taking ticlopidine, should be informed that the occurrence of fever, sore throat, ulceration in the oral cavity, prolonged or unusual bleeding, bruising, bloody vomiting and stool (melena) requires the patient to immediately seek medical attention.
    The clinical diagnosis of thrombotic thrombocytopenic purpura (TTP) can be put in the presence of thrombocytopenia, hemolytic anemia, neurological symptoms, kidney dysfunction and high temperature. The beginning may be unexpected. Most of the cases were recorded in the first 8 weeks after the initiation of therapy. The prognosis is very serious (deaths from TTP are known).
    The drug should be used with caution in patients with impaired liver function, and in the case of hepatitis or jaundice, treatment should be discontinued.
    With severe diarrhea, treatment should be stopped.

    Effect on the ability to drive transp. cf. and fur:not detected
    Form release / dosage:
    Tablets, film-coated 250 mg.
    10 tablets per blister PVC / Al.
    2 blisters together with instructions for use in a cardboard box.

    Packaging:

    10 tablets per blister PVC / Al.
    2 blisters together with instructions for use in a cardboard box.

    Storage conditions:
    Store in a dry place at a temperature of no higher than 25 ° C.
    Keep out of the reach of children.
    List B.

    Shelf life:
    3 years.
    Do not use the product after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:П N013007 / 01
    Date of registration:09.04.2008
    Date of cancellation:2017-07-19
    The owner of the registration certificate:Sanofi-Aventis FranceSanofi-Aventis France France
    Manufacturer: & nbsp
    Information update date: & nbsp19.07.2017
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