Brilinta (Ticagrelor) tablets

DOSAGE FORMS

tablet film coated 90mg

MANUFACTURERS

AstraZeneca AB (Sweden)

GROUP

Antiplatelet agents

COMPOSITION

Composition of 1 tablet: active ingredient: ticagrelor 90mg. Auxiliary substances: mannitol 126mg, calcium hydrogen phosphate 63mg, carboximetilkrahmal sodium 9mg, 9mg hyprolose, magnesium stearate 3mg, in the composition of the membrane shell of the tablet: hypromellose, titanium dioxide, talc, macrogol, dye iron oxide yellow.

INTERNATIONAL NONPROPRIETARY NAME

Ticagrelor

PHARMACOLOGICAL ACTION

Antiplatelet drug. Drug Brilinta contains in its composition of ticagrelor, the representative of the chemical class of cyclopentenopyridine, which is a selective and reversible antagonist of the P2Y12 receptor for adenosine diphosphate (ADP) and can prevent ADP-mediated activation and aggregation of platelets. Ticagrelor active ingestion and reversibly interact with the P2Y12 ADP-receptor of platelets. Ticagrelor does not interact with the binding site of the ADP, but its interaction with P2Y12 receptor of platelets to ADP prevents the transduction of signals.In patients with a stable course of coronary heart disease (CHD) on the background of acetylsalicylic acid ticagrelor begins to act quickly, as evidenced by the results of determining the average value of inhibition of platelet aggregation (IAT): 0.5 hours after receiving a loading dose of ticagrelor 180mg the average value of IAT is about 41%, the maximum value of IAT 89% is achieved after 2-4 hours after ingestion and is maintained for 2-8 hours. 90% of patients the final value of IAT more than 70% is achieved 2 hours after administration of the drug.Ticagrelor is rapidly absorbed with an average tmax of about 1.5 hours. The formation of the main circulating metabolite AR-C124910XX (also active) from ticagrelor occurs rapidly with an average tmax of approximately 2.5 hours. The average absolute bioavailability of ticagrelor is 36%. The volume of distribution of ticagrelor at steady state are 87.5 L. Ticagrelor and its active metabolite are actively associated with blood plasma proteins (>99%) in.The main route of ticagrelor elimination is via hepatic metabolism. The excretion of ticagrelor and its active metabolite in the urine is less than 1% of the dose. Mainly active metabolite is excreted in the bile. The average half-life of ticagrelor and its active metabolite were 7 and 8.5 hours, respectively.

INDICATIONS FOR USE

Brilinta applied simultaneously with acetylsalicylic acid, is indicated for the prevention of atherothrombotic events in patients with acute coronary syndrome (unstable angina, myocardial infarction without ST-segment elevation or myocardial infarction with ST-segment elevation [STEMI]) including patients receiving drug therapy, and patients subjected to percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)).

CONTRAINDICATIONS

Hypersensitivity to ticagrelor or any component of the drug, active pathological bleeding, intracranial hemorrhage history of moderate or severe hepatic insufficiency, concomitant use of ticagrelor with strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir and atazanavir), children up to age 18 years (due to the lack of data about the effectiveness and safety of use in this group of patients).

SIDE EFFECTS

The most frequent observed adverse events in patients treated with ticagrelor were dyspnoea, bruises and nosebleeds. Adverse drug reactions by frequency and class system of the bodies: metabolism and nutrition: hyperuricaemia. Nervous system: intracranial hemorrhage, headache, dizziness, paresthesia, confusion. The organs of vision: haemorrhage (intraocular, conjunctival, retinal). Hearing: bleeding in the ear, vertigo. Respiratory system: dyspnea, epistaxis, hemoptysis. Digestive system: gastrointestinal bleeding, vomiting blood, bleeding from ulcers of the gastrointestinal tract, hemorrhoidal bleeding, gastritis, bleeding in the oral cavity (including gingival bleeding), vomiting, diarrhea, abdominal pain, nausea, dyspepsia.Skin and subcutaneous tissue: subcutaneous or cutaneous hemorrhage, bruises, rash, itch. Musculoskeletal system: hemarthrosis. Urinary system: bleeding from the urinary tract. Reproductive system: vaginal bleeding (including metrorrhagia). Deviations of laboratory parameters: the increase in the concentration of creatinine in the blood. Other: bleeding at the site of the procedure, bleeding after the procedure, the wound bleeding, traumatic bleeding.

INTERACTION

Contraindications concomitant use with potent inhibitors of CYP3A4 (clarithromycin, nefazodone, ritonavir and atazanavir), moderate inhibitors of CYP3A4 (eg, amprenavir, aprepitant, erythromycin, fluconazole) may be administered concurrently with the drug of Brilinta. The results of pharmacological studies of interaction concomitant use of ticagrelor with heparin, enoxaparin and acetylsalicylic acid or desmopressin does not affect the pharmacokinetics of ticagrelor and its active metabolite and ADP-dependent platelet aggregation. In the case of clinical indications for the administration of drugs that affect hemostasis, they should be used with caution in combination with drug Brilinta.No data on the joint application of the drug Brilinta with potent inhibitors of P glycoprotein (e.g., verapamil, quinidine, and cyclosporin) that may increase ticagrelor exposure. It is not recommended the combined use of the drug Brilinta with simvastatin and lovastatin at a dose of more than 4mg. In a joint application of the drug Brilinta with drugs that can cause bradycardia and affect hemostasis requires caution. In connection with reports of subcutaneous hemorrhage on the background of selective inhibitors of serotonin reuptake (e.g. paroxetine, sertraline and citalopram), caution should be used when co-administered with the drug of Brilinta.

METHOD OF APPLICATION AND DOSAGE

For the reception inside. Drug Brilinta can be taken regardless of meals. The drug of Brilinta should start with a single 180mg loading dose (two tablets of 90mg) and then continued the reception at 90mg twice a day. Patients taking the drug Brilinta must daily take aspirin (75mg to 150mg at constant reception) unless there are specific contraindications. Avoid interruptions in therapy. The patient missed the drug of Brilinta should take only one tablet 90mg (next dose) at the scheduled time. If necessary, patients receiving clopidogrel may be transferred to the drug of Brilinta. Recommended therapy with drug Brilinta within 12 months, except in cases of clinical necessity in early drug discontinuation. You need to avoid premature discontinuation of the drug.

OVERDOSE

Ticagrelor is well tolerated in a single dose of the drug to 900mg. In the only study with increasing doses adverse effects on the gastrointestinal tract was dose-limiting. Other clinically significant adverse events, which could occur in cases of overdose were dyspnea and ventricular pauses. In case of overdose it is recommended to conduct surveillance on the subject of these adverse events and to conduct ECG monitoring. Brilinta is not displayed in hemodialysis, the antidote is not known. In case of overdose symptomatic therapy in accordance with local standards. In connection with the inhibition of platelets increase the duration of bleeding is the intended pharmacological action of overdose of Brilinta, so if you develop bleeding it is necessary to conduct appropriate supportive measures.

SPECIAL INSTRUCTIONS

With caution the preparation is used in the following cases: the Predisposition of patients to the development of bleeding (for example, in connection with the recent injury, recent surgery, bleeding disorders, active or recent gastrointestinal bleeding). Patients with concomitant therapy with drugs that increase the risk of bleeding (ie, nonsteroidal anti-inflammatory drugs, oral anticoagulants and/or fibrinolytic) within 24 hours before dosing of Brilinta. Patients with an increased risk of bradycardia (e.g. patients with the syndrome sick sinus without pacemaker with atrioventricular block of 2nd or 3rd degree, syncope associated with bradycardia) due to lack of experience with the clinical use of drugs of Brilinta. In a joint application medication with drugs, causing bradycardia.Ticagrelor should be used with caution in patients with bronchial asthma and chronic obstructive pulmonary disease (COPD). If the patient reported the appearance of a new episode of shortness of breath, prolonged shortness of breath or worsening of dyspnea, it is necessary to survey, and in the case of intolerance, treatment with ticagrelor should be discontinued. On the background of the drug of Brilinta creatinine level may increase, therefore need to assess the renal functions in accordance with routine clinical practice, with emphasis on patients 75 years and older, patients with moderate or severe renal insufficiency, patients receiving treatment with receptor antagonists to angiotensin.Use caution in patients with hyperuricaemia or gouty arthritis in history. As a preventive action to avoid the use of ticagrelor in patients with hyperuricemic nephropathy. Not recommended concomitant use of ticagrelor and high maintenance doses of acetylsalicylic acid (more than 300mg). When used together digoxin and drug Brilinta recommended close clinical and laboratory monitoring (heart rate, and when there is clinical evidence also of the ECG and the concentration of digoxin in the blood). No data on joint use of ticagrelor with potent inhibitors of P glycoprotein (e.g., verapamil, quinidine, and cyclosporine), therefore their combined use should be done with caution.