Brilinta pills 60mg, 56pcs

Composition

Active ingredient: ticagrelor 60 mgm Auxiliary substances: mannitol 84 mg, calcium hydrophosphate 42 mg, sodium carboxymethyl starch 6 mg, hyprolose 6 mg, magnesium stearate 2 mg; tablet shell: 4.4 mg hypromellose, titanium dioxide (E 171) 2.2 mg, macrogol 400 0.4 mg, dye iron oxide black 0,001 mg, dye iron oxide red 0,01 mg.

Pharmacological properties

Pharmacotherapeutic group: antiplatelet Crestwood ATKH: 01 AC 24 Pharmacological svojstvennym dastiarakec of Brilinta® contains in its composition of ticagrelor, the representative chemical class cyclopentenopyridine, which is an oral, selective and reversible antagonist of the P2Y12 receptor direct action and prevents adenosine diphosphate-mediated P 2Y12-dependent activation and platelet aggregation. Ticagrelor does not prevent the binding of adenosine diphosphate (ADP), but its interaction with the P2Y12 platelet receptor prevents ADP-induced signal transduction. Since platelets are involved in the initiation and/or development of thrombotic complications of atherosclerosis, inhibition of platelet function has been shown to reduce the risk of cardiovascular events such as cardiovascular death, myocardial infarction, or stroke. Ticagrelor has an additional mechanism of action, increasing local concentrations of endogenous adenosine by inhibiting endogenous equilibrium nucleoside transporter type 1 (ENT-1). Adenosine is formed locally at sites of hypoxia and tissue damage by release from adenosine triphosphate and ADP. Since adenosine cleavage is essentially confined to the intracellular space, inhibition of ENT-1 by ticagrelor prolongs the half-life of adenosine and thereby increases its local extracellular concentration, enhancing the local adenosine response. Ticagrelor has no clinically significant direct effect on adenosine receptors (A1, A2A, A2B, A3) and is not metabolized to adenosine. Adenosine has several effects, which include: vasodilation, cardioprotection, inhibition of platelet aggregation, modulation of inflammation, and the occurrence of dyspnea, which may affect the clinical profile of ticagrelor. In healthy volunteers and in patients with acute coronary syndrome (ACS), ticagrelor was shown to enhance the following effects of adenosine: vasodilation (estimated as an increase in coronary blood flow in healthy volunteers and in patients with ACS), inhibition of platelet function (in vitro in human whole blood), and dyspnea. However, the association of elevated local concentrations of adenosine with clinical outcomes (e. g., morbidity and mortality rates) has not been proven. Pharmacodynamicanachal actions In patients with a stable course of coronary heart disease (CHD), ticagrelor begins to act quickly against the background of acetylsalicylic acid (ASA), which is confirmed by the results of determining the average value of platelet aggregation inhibition (IAT): 0.5 hours after taking a loading dose of 180 mg of ticagrelor, the average IAT value is approximately 41%, the maximum IAT value of 89% is reached 2-4 hours after taking the drug and is maintained for 2-8 hours. In 90% of patients, the final IAT value of more than 70% is reached 2 hours after taking the drug. End of Action When planning CABG, the risk of bleeding increases if ticagrelor is stopped less than 96 hours before the procedure. Data on switching from one drug to another Switching from clopidogrel 75 mg once a day to Brilinta® 90 mg twice a day leads to an increase in the absolute value of IAT by 26.4%, and changing therapy from ticagrelor to clopidogrel leads to a decrease in the absolute value of IAT by 24.5%. You can change therapy from clopidogrel to ticagrelor without interrupting the antithrombotic effect (see the section “Dosage and use”). Clinical efficacy and safety The clinical efficacy of Brilinta® is confirmed by the results of two phase 3 studies. The PLATO (Acute Coronary Syndrome)study The Platelet Inhibition and Patient Outcomes (PLATelet Inhibition and Patient Outcomes) study included 18,624 patients who developed symptoms of unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction in the last 24 hours and were treated conservatively, either by percutaneous coronary intervention (PCI), or by coronary artery bypass grafting (CABG). In this study, ticagrelor 90 mg twice daily was compared with clopidogrel 75 mg daily for its effectiveness in preventing the development of a combined endpoint of cardiovascular death, myocardial infarction, or stroke due to its effect on the incidence of cardiovascular deaths and myocardial infarction. The loading dose was 300 mg of clopidogrel (600 mg was also allowed for PCI) or 180 mg of ticagrelor. PEGASUS study (history of myocardial infarction) The PEGASUS TIMI-54 study with 21162 patients was conducted to evaluate the prevention of atherothrombotic complications with ticagrelor in two doses (90 mg twice daily or 60 mg twice daily) in combination with a low dose of ASA (75-150 mg) compared with ASA monotherapy in patients with a history of myocardial infarction and additional risk factors for atherothrombosis. The study included patients aged 50 years and older with a history of myocardial infarction (within 1-3 years prior to randomization), and with at least one of the following risk factors for atherothrombosis: age ≥65 years, diabetes mellitus requiring drug therapy, second previous myocardial infarction, confirmed multivessel coronary artery disease, or chronic non-terminal renal dysfunction. Brilinta® 60 mg twice daily and 90 mg twice daily in combination with ASA was effective in preventing atherothrombotic complications (combined endpoint of cardiovascular death, myocardial infarction, and stroke), with a sustained therapeutic effect maintained throughout the study period, resulting in a 16% reduction in relative risk (COP) and a 1.27% reduction in absolute risk (SAR) with ticagrelor 60 mg and a 15% reduction in COP and 1.19% reduction in ticagrelor 90 mg. With comparable efficacy of ticagrelor 90 mg and 60 mg, ticagrelor 60 mg showed better tolerability and safety profile with respect to the risk of bleeding and shortness of breath. Therefore, to prevent atherothrombotic complications (cardiovascular death, myocardial infarction and stroke) in patients with a history of myocardial infarction (myocardial infarction was postponed one year or more ago) and a high risk of developing atherothrombotic complications, Brilinta® 60 mg twice daily in combination with ASA is recommended. Brilinta ® 60 mg twice daily significantly reduced the primary combined endpoint of cardiovascular death, myocardial infarction, and stroke, with a reduction in each of its components: cardiovascular death rate by 17%, myocardial infarction rate by 16%, and stroke rate by 25%. Ticagrelor 60 mg in combination with ASA reduced the number of deaths from cardiovascular causes and deaths from all causes, although statistical significance was not achieved. The combined end-point HR from day 1 to day 360 (17% HR) and from day 361 onwards (16% HR) was comparable, with maintenance of the effect of therapy during the study lasting up to 48 months (median 33 months), thereby showing that ticagrelor therapy can be continued as long as the patient remains at high risk of developing atherothrombotic complications (see the section “Dosage and use”). The effectiveness of Brilinta® 60 mg twice daily has been demonstrated in various subgroups of patients, regardless of body weight, gender, medical history, region, and does not depend on the use of other cardiovascular agents, including lipid-lowering drugs, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, calcium channel blockers, nitrates, and proton pump inhibitors (see the section “Interaction with other drugs”). drug interactions and other types of drug interactions”). Pharmacokineticaticagrelor exhibits linear pharmacokinetics, and the exposure of ticagrelor and the active metabolite (AR-C124910XX) is approximately proportional to the dose up to 1260 mg. Absorption rate Ticagrelor is rapidly absorbed with a median Tmax of approximately 1.5 hours. The formation of the main circulating metabolite AR-C124910XX (also active) from ticagrelor occurs rapidly with a median Tmax of approximately 2.5 hours. After taking ticagrelor 90 mg on an empty stomach, the cmax is 529 ng / ml and the AUC is 3451 ng * h/ml. The ratio of Cmax and AUC of the metabolite to ticagrelor is 0.28 and 0.42, respectively. The average absolute bioavailability of ticagrelor is 36%. Fatty food intake results in a 21% increase in the AUC of ticagrelor and a 22% decrease in the Cmax of the active metabolite, but does not affect the Cmax of ticagrelor or the AUC of the active metabolite. These small changes are of minimal clinical significance; therefore, ticagrelor can be prescribed regardless of food intake. Ticagrelor as a suspension of crushed tablets in drinking water, taken orally or introduced into the stomach through a nasogastric tube, is bioequivalent to ticagrelor taken orally in the form of tablets of Brilinta® (AUC and Cmax of ticagrelor and the active metabolite in the range of 80-125%). When taking the suspension, the initial exposure (0.5 and 1 hour after use) was higher than when taking ticagrelor in the form of Brilinta ® tablets, but later (from 2 to 48 hours) the concentration profile was almost the same.Distribution The volume of distribution of ticagrelor at steady state is 87.5 l. Ticagrelor and the active metabolite are actively bound to plasma proteins (> 99.0%). The CYP3A4 biotransformation is the main isoenzyme responsible for the metabolism of ticagrelor and the formation of the active metabolite, and their interactions with other CYP3A substrates range from activation to inhibition. Ticagrelor and the active metabolite are weak inhibitors of glycoprotein P (P-gp). The main metabolite of ticagrelor is AR-C124910XX, which is also active, which is confirmed by the results of evaluation of binding to the P2Y12 platelet ADP receptor in vitro. The systemic exposure of the active metabolite is approximately 30-40% of that of ticagrelor. Elimination The main route of elimination of ticagrelor is through hepatic metabolism. On average, approximately 84% of radioactivity (57.8%) is released in the faeces and 26.5% in the urine when ticagrelor is labeled with the isotope. Urinary excretion of ticagrelor and the active metabolite is less than 1% of the dose. The active metabolite is mainly excreted in the bile. The mean elimination half-lives of ticagrelor and the active metabolite were 7 and 8.5 hours, respectively. Special patient populationprivate patients In elderly patients (aged 75 years and older) patients with ACS had a higher exposure to ticagrelor (Cmax and AUC were approximately 25% higher) and the active metabolite compared to younger patients. These differences are not considered clinically significant (see section “Dosage and use”). Children Ticagrelor has not been evaluated in children (see section “Contraindications”). Women had higher exposure to ticagrelor and its active metabolite compared to men. These differences are not considered clinically significant. Impaired renal function Ticagrelor exposure is approximately 20% lower and its active metabolite approximately 17% higher in patients with severe renal impairment (creatinine clearance Hepatic impairment The cmax and AUC of ticagrelor were 12% and 23% higher in patients with mild hepatic impairment compared to healthy subjects, but the effect of Brilinta on IAT was comparable in both groups. No dose adjustment is required in patients with mild hepatic impairment. Ticagrelor has not been studied in patients with severe hepatic impairment, and there is no information on pharmacokinetic parameters in patients with moderate hepatic impairment (see sections “Contraindications”, “Dosage and use” and “Special Instructions”). Ethnic groups The average bioavailability of the drug in Asian patients is 39% higher than in Caucasian patients. The bioavailability of ticagrelor was 18% lower in black patients compared to Caucasian patients, and in clinical pharmacology studies, the exposure (Cmax and AUC) of ticagrelor in Japanese was approximately 40% (20% after correction for body weight) higher than in Caucasians. The exposure of Spanish or Latin American patients was similar to that of Caucasian patients.

Indications

Brilinta®, used simultaneously with acetylsalicylic acid, is indicated for the prevention of atherothrombotic complications in adult patients with a history of myocardial infarction (myocardial infarction was postponed one year or more ago) and a high risk of developing an atherothrombotic complication.

Contraindications

• Hypersensitivity to ticagrelor or any excipient of the drug.
• Active pathological bleeding.
• History of intracranial hemorrhage.
• Severe hepatic impairment.
• Co-use of ticagrelor with potent inhibitors of the CYP3A4 isoenzyme (for example, ketoconazole, clarithromycin, nefazodone, ritonavir and atazanavir).
• Children under 18 years of age (due to the lack of data on the effectiveness and safety of use in this group of patients).

With caution

Predisposition of patients to develop bleeding (for example, due to a recent injury, a recent operation, blood clotting disorders, moderate liver function disorders, active or recent gastrointestinal bleeding).

Patients with concomitant therapy with drugs that increase the risk of bleeding (i. e. nonsteroidal anti-inflammatory drugs, oral anticoagulants and / or fibrinolytics) within 24 hours before taking Brilinta®.

Patients with a history of myocardial infarction and previous ischemic stroke with a treatment duration of more than one year.

Patients with moderate hepatic impairment.

Patients at risk of developing bradycardia (for example, patients without a pacemaker with sinus node weakness syndrome, atrioventricular block of the 2nd or 3rd degree, syncope associated with bradycardia) (see the section “Special instructions”).

When used in combination with drugs that can cause bradycardia (see the section “Interaction with other drugs and other types of drug interactions”).

Patients with a history of bronchial asthma and/or chronic obstructive pulmonary disease (COPD).

The combined use of ticagrelor and a high maintenance dose of ASA (more than 300 mg) is not recommended.

When ticagrelor is co-administered with potent glycoprotein P inhibitors and moderate inhibitors of the CYP3A4 isoenzyme (for example, verapamil and quinidine) (see the section “Interaction with other drugs and other types of drug interaction”).

When using selective serotonin reuptake inhibitors (for example, paroxetine, sertraline and citalopram) together with ticagrelor (see the section “Interaction with other drugs and other types of drug interaction”).

When digoxin and Brilinta are used together, careful clinical and laboratory monitoring is recommended (heart rate, and if there are clinical indications, also ECG and digoxin concentration in the blood).

When using Brilinta® in combination with drugs that affect hemostasis (see the section “Interaction with other drugs and other types of drug interaction”).

Side effects

Brief overview of the safety Profile The safety profile of Brilinta® was evaluated in two phase 3 studies (PLATO and PEGASUS) involving more than 39,000 patients (see section “Pharmacological Properties”). The adverse reactions reported in these clinical trials are listed below. In the PLATO study, patients treated with Brilinta were more likely to discontinue therapy due to the development of adverse events than patients treated with clopidogrel (7.4% compared to 5.4%). In the PEGASUS study, the frequency of discontinuation of treatment due to adverse events was higher with Brilinta® than with ASA monotherapy (16.1% of patients in the ticagrelor 60 mg +ASA group compared to 8.5% in the ASA monotherapy group). The most frequently reported adverse reactions in patients taking ticagrelor were bleeding and shortness of breath (see section “Special instructions”).

Interaction

Ticagrelor is mainly a substrate of the CYP3A4 isoenzyme and a weak inhibitor of the CYP3A4 isoenzyme. Ticagrelor is also a P-glycoprotein (P-gp) substrate and a weak P-gp inhibitor, and may increase the exposure of P-gp substrates. Effect of other medicinal products on Brilinta®Drugs metabolized by the CYP3A4 isoenzyme CYP3A4 inhibitors Potent CYP3A4 inhibitors: co-use of ketoconazole with ticagrelor increases the Cmax and AUC of ticagrelor by 2.4 and 7.3 times, respectively. Cmax and AUC of the active metabolite are reduced by 89% and 56%, respectively. Other potent CYP3A4 inhibitors (clarithromycin, nefazodone, ritonavir, and atazanavir) will have similar effects, so concomitant use of potent CYP3A4 inhibitors with Brilinta® is contraindicated (see section “Contraindications”). Moderate CYP3A4 inhibitors: co-use of diltiazem with ticagrelor increases the Cmax of ticagrelor by 69%, a 2.7-fold AUC, and reduces the Cmax of the active metabolite by 38%, a unchanged AUC. Ticagrelor does not affect the plasma concentrations of diltiazem. Other moderate CYP3A4 inhibitors (e. g., amprenavir, aprepitant, erythromycin, fluconazole) will have similar effects and may also be administered concomitantly with Brilinta. CYP3A4 inducers Co-use of rifampicin with ticagrelor reduces the Cmax and AUC of ticagrelor by 73% and 86%, respectively. The cmax of the active metabolite does not change, and the AUC decreases by 46%. Other inducers of CYP3A4 (e. g., phenytoin, carbamazepine, and phenobarbital) are also likely to reduce ticagrelor exposure. Concomitant use of ticagrelor with potent CYP3A inducers may reduce the exposure and efficacy of ticagrelor, so they should be avoided in combination with Brilinta. Cyclosporine (inhibitor of P-gp and CYP3A)Concomitant use of cyclosporine (600 mg) with ticagrelor increases the Cmax and AUC of ticagrelor by 2.3 and 2.8 times, respectively. At the same time, an increase in the AUC of the active metabolite by 32% and a decrease in Cmax by 15% in the presence of cyclosporine are noted. There are no data on the co-use of ticagrelor with other potent glycoprotein P inhibitors and moderate CYP3A4 inhibitors (for example, verapamil and quinidine), which can increase the exposure of ticagrelor. If their combined use cannot be avoided, it should be carried out with caution.Other pharmacological interaction studies have shown that concomitant use of ticagrelor with heparin, enoxaparin and ASA or desmopressin does not affect the pharmacokinetics of ticagrelor, its active metabolite, and ADP-induced platelet aggregation. If there are clinical indications for the use of drugs that affect hemostasis, they should be used with caution in combination with ticagrelor. A 2-fold increase in ticagrelor exposure was observed when large amounts of grapefruit juice were consumed daily (200 ml 3 times a day). Such an increase in ticagrelor exposure is not expected to be clinically relevant for most patients. Effect of Brilinta ® on other medicinal productsdrugs metabolized by the CYP3A4 isoenzyme Simvastatin: concomitant use of ticagrelor and simvastatin increases the Cmax and AUC of simvastatin by 81%) and 56%, respectively, and increases the Cmax and AUC of simvastatin acid by 64%) and 52%, respectively, while in some cases these indicators increase by 2-3 times. Concomitant use of simvastatin at a dose higher than 40 mg / day. treatment with ticagrelor may lead to the development of simvastatin side effects, and the potential risk-benefit ratio should be evaluated. Simvastatin did not affect the plasma concentration of ticagrelor. Ticagrelor may have a similar effect on lovastatin. Concomitant use of ticagrelor with simvastatin or lovastatin in doses exceeding 40 mg is not recommended. Atorvastatin: concomitant use of atorvastatin and ticagrelor increases Cmax and AUC of atorvastatin acid by 23% and 36%, respectively. A similar increase in AUC and Cmax values is observed for all atorvastatin acid metabolites. This increase was found to be clinically insignificant. A similar effect on other statins metabolized by the CYP3A4 isoenzyme cannot be excluded. In the PLATO study, patients treated with ticagrelor took various statins without any safety concerns in 93% of patients taking this group of drugs. Ticagrelor is a weak inhibitor of the CYP3A4 isoenzyme. The combined use of ticagrelor and substrates of the CYP3A4 isoenzyme with a narrow therapeutic index (for example, cisapride or ergot alkaloids) is not recommended, since ticagrelor can increase the exposure of these drugs. P-gp substrates (including digoxin, cyclosporine)Concomitant use of ticagrelor with digoxin increased the Cmax and AUC of digoxin by 75% and 28%, respectively. When co-administered with ticagrelor, the average value of the minimum digoxin concentration increased by about 30%, in some individual cases by two times. The cmax and AUC of ticagrelor and its active metabolite did not change with digoxin. Therefore, it is recommended to conduct appropriate clinical and / or laboratory monitoring (heart rate, and if there are clinical indications, also ECG and digoxin concentration in the blood) with the simultaneous use of ticagrelor and P-gp-dependent drugs with a narrow therapeutic index, such as digoxin. There was no effect of ticagrelor on the concentration of cyclosporine in the blood. Concomitant use of ticagrelor and tolbutamide did not alter the plasma concentrations of any of these drugs, suggesting that ticagrelor is not an inhibitor of the CYP2C9 isoenzyme, and it is unlikely that it affects the CYP2C9-mediated metabolism of drugs such as warfarin and tolbutamide. Oral contraceptives Co-use of ticagrelor, levonorgestrel, and ethinyl estradiol increases ethinyl estradiol exposure by approximately 20%, but does not affect the pharmacokinetics of levonorgestrel. No clinically significant effect on the effectiveness of contraception is expected with concomitant use of levonorgestrel, ethinyl estradiol and ticagrelor. Medications that may cause bradycardia Due to the detection of mainly asymptomatic ventricular pauses and bradycardia, Brilinta® should be taken with caution simultaneously with medications that may cause bradycardia (see the section “Special Instructions”). However, in the PLATO study, no clinically significant adverse events were observed when co-administered with one or more drugs that may cause bradycardia (for example,96% of patients were taking beta-blockers at the same time,33% – slow calcium channel blockers, diltiazem and verapamil, and 4% – digoxin). Other concomitant therapies In clinical trials, Brilinta® has been primarily co-administered with ASA, proton pump inhibitors, statins, beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor antagonists for long-term use for the treatment of concomitant diseases, as well as with heparin, low-molecular-weight heparins, and glycoprotein IIb/IIIa receptor inhibitors for intravenous use as part of short-term therapy. Based on the results of these studies, no clinically significant adverse interactions were identified. Co-use of Brilinta® with heparin, enoxaparin, or desmopressin did not affect activated partial thromboplastin time (APTT), activated clotting time (ABC), or factor Xa studies, but due to potential pharmacodynamic interactions, caution should be exercised when co-administered with drugs that affect hemostasis. Due to reports of subcutaneous hemorrhages associated with the use of selective serotonin reuptake inhibitors (for example, paroxetine, sertraline and citalopram), caution is recommended when taking them together with ticagrelor, as the risk of bleeding may increase.

How to take, course of use and dosage

For oral use. Brilinta® can be taken regardless of food intake. For patients with difficulty swallowing, the Brilinta 60 mg tablet should be ground to a fine powder, stirred in half a glass of drinking water and immediately drink the resulting suspension. Mix the leftovers with an additional half cup of drinking water and drink the resulting suspension. The suspension can also be administered via a nasogastric tube (CH 8 or larger). After use of the suspension, the nasogastric tube should be flushed with water so that the dose of the drug completely enters the patient’s stomach. Patients with a history of myocardial infarction (myocardial infarction was postponed one year or more ago) do not require a loading dose of Brilinta®, the recommended dose is 60 mg twice a day. Long-term therapy with Brilinta® is recommended, except in cases of clinical need for early withdrawal of the drug (see the section “Pharmacodynamics”). There is no previous experience of using Brilinta 60 mg for more than three years in patients with a history of myocardial infarction. Patients taking Brilinta should take a low daily maintenance dose of ASA (75-150 mg) if there are no specific contraindications. Patients can start therapy with Brilinta ® 60 mg twice a day one year after a myocardial infarction, regardless of previous antiplatelet therapy and whether there are interruptions in therapy. Patients who have started taking Brilinta 90 mg twice daily during an acute condition may continue therapy with Brilinta 60 mg twice daily after one year without interruptions. Patients should discontinue their current antiplatelet therapy before starting Brilinta (in combination with ASA). When patients are transferred to Brilinta, the first dose should be administered 24 hours after the last dose of another antiplatelet agent. Premature discontinuation of any antiplatelet therapy, including Brilinta, may increase the risk of cardiovascular death or myocardial infarction as a result of the underlying disease. Premature discontinuation of the drug should be avoided. Interruptions in therapy should also be avoided. A patient who has missed taking Brilinta® should only take one 60 mg tablet (the next dose) at the scheduled time. Special patient groupslong-lived patients do not require dose adjustment (see section “Pharmacokinetics”). Patients with impaired renal function No dose adjustment is required in patients with impaired renal function (see section “Pharmacokinetics”). There is no available information about the treatment of patients on hemodialysis, so Brilinta® is not recommended for these patients. Patients with hepatic impairment Brilinta® has not been studied in patients with severe hepatic impairment, and the use of the drug in these patients is contraindicated (see the section “Contraindications”). Information on the treatment of patients with moderate hepatic impairment is limited. No dose adjustment is required in patients with mild or moderate hepatic impairment (see sections “Pharmacokinetics”, “Special Instructions”). Children The safety and efficacy of Brilinta® in children under 18 years of age according to an adult-approved indication have not been established (see section “Contraindications”).

Overdose

Ticagrelor is well tolerated in a single dose of the drug up to 900 mg. In the only dose-increasing study, the adverse effect on the gastrointestinal tract was dose-limiting. Other clinically significant adverse reactions that may occur with overdose are shortness of breath and ventricular pauses (see section “Side effects”). In case of overdose, these potential adverse reactions should be monitored for possible ECG monitoring. Ticagrelor is not expected to be eliminated by hemodialysis (see section “Special instructions”), and the antidote is not known.In case of overdose, symptomatic therapy should be carried out in accordance with local standards. Due to platelet inhibition, an increase in the duration of bleeding is a suspected pharmacological effect of an overdose with Brilinta®, so appropriate maintenance measures should be taken if bleeding develops.

Special instructions

Risk of bleeding

When prescribing Brilinta® to patients with an increased risk of bleeding, the ratio of the benefits of preventing atherothrombotic complications and the risk of bleeding should be evaluated.

If clinically indicated, Brilinta should be used with caution in the following situations::

• Predisposition of patients to develop bleeding (for example, due to a recent injury, a recent operation, blood clotting disorders, moderate liver function disorders, active or recent gastrointestinal bleeding). The use of Brilinta® is contraindicated in patients with active pathological bleeding, a history of intracranial hemorrhage, severe hepatic impairment (see the section “Contraindications”).
• Concomitant use of medications that may increase the risk of bleeding (for example, nonsteroidal anti-inflammatory drugs, oral anticoagulants and / or fibrinolytics taken within 24 hours before taking Brilinta®).

There are no data on the hemostatic efficacy of platelet transfusions when using ticagrelor in patients; circulating ticagrelor may inhibit transfused platelets in the blood. Since the concomitant use of Brilinta® and desmopressin did not reduce the standardized bleeding time, it is unlikely that desmopressin will effectively stop clinically significant bleeding (see the section “Interaction with other drugs and other types of drug interactions”).

Antifibrinolytic therapy (aminocaproic acid or tranexamic acid) and / or recombinant factor VIIa therapy may enhance hemostasis. After determining the cause of bleeding and stopping it, ticagrelor therapy can be resumed.

Surgical interventions

The patient should inform the doctor that they are taking Brilinta®before undergoing surgery or starting new medications.

In the PLATO study, patients undergoing CABG experienced more bleeding when using Brilinta compared to clopidogrel when stopping therapy one day before surgery, but the incidence of major bleeding after stopping therapy 2 or more days before surgery was similar compared to clopidogrel (see section “Side effects”). If the patient is undergoing elective surgery and an antithrombotic effect is not desired, then therapy with Brilinta® should be discontinued 7 days before surgery (see the section “Pharmacodynamics”).

Patients with a previous ischemic stroke

Patients with ACS with a previous ischemic stroke can take Brilinta® for up to 12 months (PLATO study).

The PEGASUS study did not include patients with a history of myocardial infarction and previous ischemic stroke. Therefore, in the absence of data, therapy lasting more than 1 year should be carried out with caution.

Patients with moderate hepatic impairment

Experience with Brilinta® in patients with moderate hepatic impairment is limited, so caution should be exercised.

The use of Brilinta® is contraindicated in patients with severe hepatic impairment (see sections “Dosage and use”, “Contraindications” and “Pharmacokinetics”).

Patients at risk of developing bradycardia

Due to the detection of mostly asymptomatic ventricular pauses in a previous clinical trial, patients at increased risk of developing bradycardia (for example, patients without a pacemaker who are diagnosed with sinus node weakness syndrome, grade 2 or 3 atrioventricular block, or syncope associated with bradycardia) were not included in the main studies to evaluate the safety and efficacy of ticagrelor. Therefore, due to the limited clinical experience of using the drug in these patients, it is recommended to prescribe ticagrelor with caution to such patients (see the section “Pharmacodynamics”).

Additional precautions should be taken when Brilinta is co-administered with drugs that may cause bradycardia. However, there were no clinically significant side effects when co-administered with one or more drugs that may cause bradycardia (for example,96% of patients were taking beta-blockers at the same time,33% – slow calcium channel blockers, diltiazem and verapamil, and 4% – digoxin) (see the section “Interaction with other drugs and other types of drug interaction”).

In the PLATO sub-study using daily Holter ECG monitoring, more patients in the ticagrelor group had ventricular pauses of ≥3 seconds in the acute phase of ACS compared to clopidogrel. An increase in the number of ventricular pauses recorded by daily Holter monitoring during ticagrelor use was observed more often in patients with chronic heart failure compared to the general population in the acute phase of ACS, but not in the first month or compared with clopidogrel. Pauses in these patients were not accompanied by subsequent undesirable clinical consequences (including fainting and pacemaker installation).

Shortness of breath

Dyspnea has been reported in patients treated with Brilinta. Dyspnea is usually mild to moderate in intensity and often goes away without stopping therapy. Patients with bronchial asthma/COPD may have an increased absolute risk of shortness of breath when taking Brilinta® (see section “Side effects”).

Ticagrelor should be used with caution in patients with a history of asthma and/or COPD. The mechanism of dyspnea with ticagrelor is not clear. If the patient develops a new episode of shortness of breath, persists or worsens shortness of breath during the use of Brilinta®, then a full examination should be carried out, and in case of intolerance, the drug should be discontinued.

Other services

Based on the relationship observed in the PLATO study between the maintenance dose of ASA and the relative efficacy of ticagrelor compared to clopidogrel, the combined use of ticagrelor and a high maintenance dose of ASA (more than 300 mg) is not recommended (see section “With caution”).

Influence on the ability to drive vehicles and other mechanisms

No studies have been conducted on the effect of Brilinta® on the ability to drive vehicles and manage mechanisms. It is assumed that the drug Brilinta® does not affect or slightly affects the ability to drive vehicles and mechanisms. Dizziness and confusion have been reported during Brilinta therapy. In case of development of these phenomena, patients should be careful when driving vehicles and other mechanisms.

Form of production

Film-coated tablets

Storage conditions

At a temperature not exceeding 30 °C. Keep out of reach of children.

Shelf

life is 2 years.

Active ingredient

Ticagrelor

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Angina, Prevention of thrombosis, Myocardial infarction, Thrombophlebitis, Prevention of heart attacks and strokes