The beautiful Brilinta made a pleasant company for aspirin

Brilinta is a drug whose action is aimed at preventing the formation of blood clots.

As a result, cells lose their ability to stick together and form clots. The drug belongs to the pharmacological group of anticoagulants and antiplatelet agents.

On this page you will find all the information about Brilinta: complete instructions for use for this drug, average prices in pharmacies, complete and incomplete analogues of the drug, as well as reviews of people who have already used Brilinta. Would you like to leave your opinion? Please write in the comments.

Release form and composition

The dosage form of Brilinta is film-coated tablets. The main active ingredient of the drug is ticagrelor, the concentration of which in 1 tablet is 90 mg.

The composition of the shell covering the tablet includes the following excipients:

• Titanium dioxide E 171 – 1.7 mg.
• Hypromellose 2910 – 5.6 mg.
• Talc – 1.0 mg.
• Yellow iron oxide dye E172 – 0.1 mg.
• Macrogol 400 – 0.6 mg.

Also contains excipients:

• Calcium hydrogen phosphate – 63 mg.
• Mannitol – 126 mg.
• Sodium carboxymethyl starch – 9 mg.
• Magnesium stearate – 3 mg.
• Hyprolose – 9 mg.

The tablets are packaged in 56 and 112 pieces. The cardboard package also contains instructions for use of the drug.

Pharmacological effect

The active substance of the drug, ticagrelor, is an oral, selective and reversible direct-acting P2Y12 receptor antagonist, part of the chemical class of cyclopentyltriazolopyrimidines and preventing ADP (adenosine diphosphate)-mediated P2Y12-dependent platelet aggregation and activation. The interaction of ticagrelor with the P2Y12 platelet receptor prevents ADP-induced signal transduction. By inhibiting platelet function, the drug helps reduce the risk of cardiovascular events such as stroke, myocardial infarction, and death.

Ticagrelor also has an additional mechanism of action by increasing local concentrations of endogenous adenosine through inhibition of the endogenous equilibrium nucleoside transporter type I (ENT-1). In patients with acute coronary syndrome (ACS) and healthy volunteers, ticagrelor increased the effects of adenosine such as vasodilation, suppression of platelet function, and dyspnea. However, the relationship between morbidity and mortality rates and elevated local adenosine concentrations has not been proven.

Instructions for Brilinta (method and dosage)

The medicine is taken orally, regardless of food intake.

Instructions for use Brilinta

Treatment begins with a dosage of 180 mg (2 tablets of Brilint 90 mg). Then, from the 2nd day, take one tablet 2 times a day.

Also, in addition, if there are no direct contraindications, it is recommended to prescribe acetylsalicylic acid .

The maintenance dosage of Aspirin ranges from 75 to 150 mg, depending on the doctor’s recommendations.

The maximum daily dosage of Brilinta is 180 mg.

The course of treatment is usually one year.

In patients with acute coronary syndrome, abrupt discontinuation of the drug may result in an increased risk of myocardial infarction or cardiovascular death .

For the same reason, you should not skip the next dose of medication. If the patient forgets to take a pill, the next one can only be taken at the appointed time.

If it is necessary to switch from analogue drugs to Brilinta, it is recommended to consult a doctor. Patients who have been taking Clopidogrel can immediately switch to Ticagrelor . The conversion process from Prasugrel to this drug has not been studied.

Indications for use

Brilinta, used simultaneously with acetylsalicylic acid, is indicated for the prevention of atherothrombotic events in patients with acute coronary syndrome:

• Unstable angina.
• Non-ST-segment elevation myocardial infarction or ST-segment elevation myocardial infarction [STEMI]), including patients receiving drug therapy and patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)).

The beautiful Brilinta made a pleasant company for aspirin

AstraZeneca reported that Brilinta/Brilique (ticagrelor) plus aspirin provided a statistically significant reduction in the likelihood of major cardiovascular events in a special group of patients compared with aspirin alone.

The THEMIS (NCT01991795) Phase III clinical trial (randomized, placebo-controlled, double-blind, multicenter, international) was conducted in more than 19 thousand patients with coronary artery disease (CAD) and type 2 diabetes, without heart attacks ( history of myocardial infarction) or stroke. The addition of ticagrelor to aspirin was found to result in a clear reduction in the incidence of major cardiovascular events (MACE) such as death, myocardial infarction or stroke. The diagnosis of CAD was valid in the case of previous percutaneous coronary intervention, coronary artery bypass grafting, or at least 50% narrowing of the coronary arteries.

Ticagrelor blocks adenosine diphosphate (ADP) receptors of the P2Y12 subtype, thereby preventing ADP-mediated platelet activation and aggregation. Unlike other antiplatelet agents such as clopidogrel and prasugrel, it binds to a different ADP site, resulting in allosteric antagonism and reversible blockade. The molecule does not require hepatic activation, meaning it also works in patients with genetic variants of the CYP2C19 enzyme.

Brilinta/Brilik, approved in 2011, is intended to reduce the incidence of death due to cardiovascular events, myocardial infarction and stroke in patients with acute coronary syndrome (ACS) and a history of myocardial infarction. The drug also reduces the likelihood of stent thrombosis in patients with ACS who have undergone a stenting procedure.

In 2020, Brilinta/Brilik failed to demonstrate superiority over clopidogrel in preventing atherothrombotic events (cardiovascular death, myocardial infarction, or ischemic stroke) in patients with symptomatic peripheral arterial disease (PAD). Ticagrelor also failed to outperform aspirin in preventing atherothrombotic events in patients with acute ischemic stroke or transient ischemic attack.

In 2020, Brilinta/Brilik demonstrated a safety profile comparable to clopidogrel in terms of the risk of serious bleeding when used in patients under 75 years of age experiencing myocardial infarction. The bottom line is that in low-income countries, antiplatelet drugs are usually used instead of percutaneous coronary intervention.

Meanwhile, the anticoagulant Xarelto (rivaroxaban), promoted by Johnson & Johnson and Bayer, expanded its already extensive list of indications to include patients with CAD or PAD: combining rivaroxaban with aspirin reduces the risk of MACE. This will generate billions of additional dollars in sales.

Be that as it may, if AstraZeneca wants to increase sales of Brilint/Brilik, it needs to reconsider its pricing policy, because now ticagrelor is many times more expensive (in the USA, 23 times more expensive) than clopidogrel, which is abundantly represented by generic copies. Nevertheless, in 2020, Brilinta/Brilik managed to achieve bestseller status: sales exceeded the $1 billion mark.

How sales forecasts for Brilinta/Brilique (ticagrelor) changed - not at all in favor of AstraZeneca. Image: Vantage/EvaluatePharma.

Contraindications

Absolute contraindications

• history of intracranial hemorrhage;
• moderate or severe liver failure;
• hypersensitivity to the active substance or to any excipient;
• the presence of pathological bleeding;
• pregnancy and lactation;
• coadministration of ticagrelor with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir) as coadministration may result in a significant increase in ticagrelor exposure.

Relative (Brilinta should be taken with caution):

• concomitant therapy with drugs that increase the risk of bleeding [nonsteroidal anti-inflammatory drugs (NSAIDs), oral anticoagulants and/or fibrinolytics] for 24 hours before taking ticagrelor;
• predisposition to the development of bleeding (recent injuries, recent operations, bleeding disorders, active or recent gastrointestinal bleeding);
• combined use with drugs that cause bradycardia;
• chronic obstructive pulmonary disease (COPD) and bronchial asthma (if shortness of breath is prolonged, a new episode occurs, or shortness of breath worsens, an examination is required; in case of intolerance, ticagrelor therapy should be discontinued);
• increased risk of developing bradycardia [sick sinus syndrome (patients without a pacemaker), atrioventricular block of the second or third degree, fainting associated with bradycardia], since the experience of clinical use of Brilinta is insufficient;
• moderate or severe renal failure;
• concomitant therapy with angiotensin receptor antagonists;
• history of hyperuricemia or gouty arthritis (the use of ticagrelor in hyperuricemic nephropathy should be avoided);
• combined use with powerful P-glycoprotein inhibitors (quinidine and verapamil), since there are no clinical observational data;
• concomitant use with digoxin [if indicated, careful clinical and laboratory monitoring of heart rate (HR), electrocardiogram (ECG) and plasma concentrations of digoxin is recommended];
• age 75 years and older.

The combined use of Brilinta with ASA in a high maintenance dose exceeding 300 mg is not recommended.

Brilinta

Trade name of the drug : Brilinta
International nonproprietary name : Ticagrelor

Dosage form : film-coated tablets

Active ingredient: ticagrelor

Pharmacotherapeutic group : antiplatelet agents

Pharmacological properties:

Brilinta contains ticagrelor, a member of the cyclopentyltriazolopyrimidine chemical class, which is a selective and reversible antagonist of the P2Y 12 adenosine diphosphate (ADP) receptor and can prevent DP-mediated platelet activation and aggregation. Ticagrelor is active when taken orally and interacts reversibly with the platelet P2Y 12 ADP receptor. Ticagrelor does not interact with the binding site of ADP itself, but its interaction with the P2Y 12 platelet receptor for ADP prevents signal transduction. In patients with stable coronary artery disease (CHD), ticagrelor begins to act quickly on the background of the use of cetylsalicylic acid, 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 achieved 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 achieved 2 hours after taking the drug. When planning CABG, the risk of bleeding increases if ticagrelor is stopped less than 96 hours before the procedure.

Indications for use:

Brilinta, used concomitantly with acetylsalicylic acid, is indicated for the prevention of atherothrombotic events in patients with acute coronary syndrome: unstable angina, non-ST segment elevation myocardial infarction or ST-segment elevation myocardial infarction [STEMI]), including patients receiving drug therapy and patients undergoing cutaneous coronary intervention (CSI) or coronary artery bypass grafting (CABG).

Contraindications:

Hypersensitivity to ticagrelor or any of the components of the drug, active pathological bleeding, history of intracranial hemorrhage, moderate or severe liver failure, combined use of ticagrelor with strong CYP3A4 inhibitors (for example, ketoconazole, clarithromycin, nefazodone, ritonavir and atazanavir), children under 18 years of age years (due to the lack of data on the effectiveness and safety of use in this group of patients), use during pregnancy and breastfeeding. There are no or limited data on the use of Brilint in pregnant women. In animal studies, ticagrelor caused a slight decrease in maternal weight gain, a decrease in the viability of the newborn and its body weight, and growth retardation.

Interaction with other drugs:

Drugs metabolized by the CYP3A4 isoenzyme simvastatin: concomitant use of ticagrelor and simvastatin increases the Cmax and AUC of simvastatin by 81% and 56%, respectively; Cmax and AUC of simvastatin acid increase by 64% and 52%, respectively, while in some cases these indicators increase 2-3 times. Concomitant use of simvastatin at a dose above 40 mg/day with ticagrelor may lead to the development of side effects of simvastatin. Therefore, if this combination is necessary, the ratio of potential risks and benefits of therapy should be assessed. The combined use of Brilinta with simvastatin and lovastatin at a dose exceeding 40 mg is not recommended.

Atorvastatin: Concomitant use of atorvastatin and ticagrelor increases the Cmax and AUC of atorvastatin acid metabolites by 23% and 36%, respectively. A similar increase in Cmax and AUC values ​​is observed for all metabolites of atorvastatin acid. These changes were considered clinically insignificant. Similar effects to statins metabolized by CYP3A4 cannot be excluded. In the PLATO study, 93% of patients in the group receiving ticagrelor and various statins did not experience any adverse events related to statin safety. Ticagrelor is a moderate CYP3A4 inhibitor. Concomitant use of Brilint with CYP3A4 substrates with a narrow therapeutic index (for example, cisapride or ergot alkaloids) is not recommended because Ticagrelor may increase the exposure of these drugs. Medicines metabolized by the CYP2C9 isoenzyme. Concomitant use of ticagrelor and tolbutamide did not change plasma concentrations of either drug. This indicates that ticagrelor is not a CYP2C9 inhibitor and is unlikely to affect the CYP2C9-mediated metabolism of drugs like warfarin and tolbutamide. Oral contraceptives: Concomitant use of ticagrelor, levonorgestrel and ethinyl estradiol increases the exposure of ethinyl estradiol by approximately 20%, but does not affect the pharmacokinetics of levonorgestrel. No clinically significant effect on contraceptive efficacy is expected with simultaneous use of levonorgestrel, ethinyl estradiol and Brilint. P-glycoprotein (P-gp) substrate (including digoxin and cyclosporine).

Concomitant use of digoxin with ticagrelor increases the Cmax and AUC of digoxin by 75% and 28%, respectively. When taken together with ticagrelor, on average, Cmin of digoxin increased by 30%, in some cases - by 2 times. Cmax and AUC of ticagrelor did not change with digoxin use. Therefore, it is recommended to carry out appropriate clinical and/or laboratory monitoring during simultaneous use of Brilint and P-gp-dependent drugs with a narrow therapeutic index, such as digoxin and cyclosporine. Other concomitant therapy: When using Brilinta together with drugs that can cause bradycardia, caution should be exercised. However, in the PLATO study, no clinically significant adverse events were observed when combined with one or more drugs known to cause bradycardia (eg, 96% beta blockers, 33% calcium antagonists including diltiazem and verapamil, and 4% digoxin). In the PLATO study, Brilinta was predominantly prescribed in combination with cetylsalicylic acid, proton pump inhibitors, statins, beta-blockers, ACE inhibitors and angiotensin receptor antagonists on a long-term basis, as well as with heparin, low molecular weight heparins, glycoprotein IIb/IIIa receptor inhibitors for intravenous in administration as part of short-term therapy. The results of these studies did not reveal any clinically significant adverse interactions. Co-administration of Brilint with heparin, noxaparin or desmopressin had no effect on aPTT, activated clotting time (ABC) and factor Xa tests, however, due to potential pharmacodynamic interactions, caution is required when co-administering with drugs that affect hemostasis. Due to reports of subcutaneous hemorrhage with selective serotonin reuptake inhibitors (eg, paroxetine, sertraline and citalopram), caution is recommended when coadministering them with Brilinta.

Directions for use and dosage:

The drug is taken orally, regardless of food intake. The use of the drug Brilint should begin with a single loading dose of 180 mg (2 tablets of 90 mg) and then continue taking 90 mg 2. At the same time, in the absence of specific contraindications, acetylsalicylic acid is prescribed (from 75 mg to 150 mg with constant use), daily. Interruptions in therapy should be avoided. If a dose of Brilint is missed, the patient should take only one 90 mg tablet (next dose) at the scheduled time. If necessary, patients taking clopidogrel can be switched to taking Brilinta.

It is recommended to carry out therapy with Brilinta for 12 months, except in cases of clinical need for early discontinuation of the drug. Data on the use of ticagrelor beyond 12 months are limited. In patients with acute coronary syndrome, early discontinuation of any antiplatelet therapy, including Brilint, 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.

Elderly patients do not require dose adjustment. Patients with renal failure do not require dose adjustment of the drug. There is no information on the use of Brilint in patients on hemodialysis, so its use in these patients is not indicated. Patients with mild hepatic impairment do not require dose adjustment. Brilinta has not been studied in patients with moderate or severe liver failure, therefore use in this category of patients is contraindicated. The safety and effectiveness of Brilint in children and adolescents under 18 years of age for its approved indication in adults has not been established.

Side effect:

In the PLATO study, the most common adverse reactions reported in patients receiving ticagrelor were shortness of breath, bruising, and nosebleeds.

Shelf life : 2 years.

Conditions for dispensing from pharmacies : by prescription.

Manufacturer:

AstraZeneca Pharmaceuticals LP, (USA)

Instructions for use

The instructions for use indicate that Brilint is taken orally, regardless of food intake.

1. The use of the drug should begin with a single loading dose of 180 mg (2 tablets of 90 mg each) and then continue taking 90 mg 2 times a day.
2. At the same time, in the absence of specific contraindications, acetylsalicylic acid is prescribed (from 75 mg to 150 mg with constant use), daily.
3. For patients with difficulty swallowing, the tablet (or 2 tablets if taking a loading dose) should be crushed to a fine powder, mixed in 1/2 glass of drinking water and the resulting suspension should be drunk immediately. Mix the remainder with an additional 1/2 cup of drinking water and drink the resulting suspension. The suspension can also be administered through a nasogastric tube (CH8 or larger). After administering the suspension, it is necessary to rinse the nasogastric tube with water so that the dose of the drug completely enters the patient’s stomach.
4. Interruptions in therapy should be avoided. If a dose of Brilinta is missed, the patient should take only one 90 mg tablet (next dose) at the scheduled time.

If necessary, patients taking clopidogrel can be switched to taking Brilinta. It is recommended to carry out therapy with Brilinta for 12 months, except in cases of clinical need for early discontinuation of the drug. Data on the use of ticagrelor beyond 12 months are limited. In patients with acute coronary syndrome, early 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.

Brilinta instructions for use (tablets)

Pharmacological properties

Pharmacokinetics

Absorption

Ticagrelor is rapidly absorbed with an average tmax of approximately 1.5 hours.

The formation of the main circulating metabolite AR-C124910XX (also active) from ticagrelor occurs quickly with an average tmax of approximately 2.5 hours.

Cmax and AUC of ticagrelor and the active metabolite increase proportionally to the dose over the dose range studied (30 - 1260 mg).

The average absolute bioavailability of ticagrelor is 36%.

Ingestion of a high-fat meal did not affect the Cmax of ticagrelor or the AUC of the active metabolite, but resulted in a 21% increase in the AUC of ticagrelor and a 22% decrease in the Cmax of the active metabolite.

These small changes are of minimal clinical significance, therefore, ticagrelor can be prescribed without regard to food intake.

Ticagrelor, as well as its active metabolite, are P-gp substrates.

Distribution

The volume of distribution of ticagrelor at steady state is 87.5 L.

Ticagrelor and the active metabolite are widely bound to plasma proteins (> 99.0%).

Metabolism

CYP3A4 is the main enzyme responsible for the metabolism of ticagrelor, and the formation of the active metabolite and their interactions with other CYP3A4 substrates range from activation to inhibition.

The main metabolite of ticagrelor is AR-C124910XX, which is also active, as confirmed by the results of assessing binding to the platelet P2Y12 ADP receptor in vitro.

Systemic exposure of the active metabolite is approximately 30–40% of the exposure of ticagrelor.

Excretion

The main route of elimination of ticagrelor is through hepatic metabolism.

When isotope-labeled ticagrelor is administered, the average excretion of radioactive substances is approximately 84% (57.8% excreted in feces, 26.5% in urine).

Excretion of ticagrelor and the active metabolite in urine is less than 1% of the dose.

The active metabolite is mainly excreted in bile.

The average half-life t1/2 of ticagrelor and the active metabolite was 7 hours and 8.5 hours, respectively.

Special populations of patients

Elderly patients

Elderly patients with ACS (aged 75 years and older) had higher exposure to ticagrelor and the active metabolite (Cmax and AUC approximately 25%) compared to younger patients.

These differences are not considered clinically significant.

Children

There are no data on the use of ticagrelor in children.

Floor

Women had higher exposure to ticagrelor and the active metabolite compared to men. These differences are not considered clinically significant.

Ethnic groups

The average bioavailability of the drug in patients of Asian origin is 39% higher than in Caucasians.

The bioavailability of ticagrelor is 18% lower in black patients compared to Caucasian patients.

In pharmacological studies, exposure (Cmax and AUC) to ticagrelor in Japanese subjects was approximately 40% (20% after adjustment for body weight) higher than in Caucasians.

Exposure in Hispanics or Latinos was similar to that in Caucasians.

Kidney failure

Ticagrelor exposure was approximately 20% lower and exposure to the active metabolite was approximately 17% greater in patients with severe renal impairment (creatinine clearance <30 mL/min) compared to patients with normal renal function.

There is no need to adjust the dose of the drug in patients with renal failure.

There is no information on the use of the drug in patients on hemodialysis.

Liver failure

Ticagrelor Cmax and AUC were 12% and 23% higher in patients with mild hepatic impairment compared with healthy volunteers, respectively, but ticagrelor inhibition of platelet aggregation was similar in the two groups.

There is no need to adjust the dose of the drug in patients with mild hepatic impairment.

Ticagrelor has not been studied in patients with severe hepatic impairment, and there is no pharmacokinetic information for patients with moderate hepatic impairment.

No dose adjustment is required for patients with moderate hepatic impairment.

Pharmacodynamics

Mechanism of action

Brilinta contains ticagrelor, a member of the cyclopentyltriazolopyrimidine (CPTP) chemical class, which is an oral, direct-acting, selective and reversible P2Y12 receptor antagonist that prevents the activation and aggregation of ADP-mediated P2Y12-dependent platelets.

Ticagrelor does not prevent ADP binding, but when it interacts with the P2Y12 receptor, it prevents ADP-induced signal transduction.

Because platelets are involved in the initiation and/or development of thrombotic complications of atherosclerotic disease, inhibition of platelet function has been shown to reduce the risk of cardiovascular events such as death, myocardial infarction, and stroke.

Ticagrelor also increases local endogenous adenosine levels through inhibition of steady-state nucleoside transporter subtype 1 (ENT-1).

Ticagrelor has been documented to increase the following adenosine-induced effects in healthy participants and patients with CABG: vasodilation (measured by increased coronary blood flow in healthy volunteers and patients with CABG; headache), inhibition of platelet function (in human whole blood outside the living body) and shortness of breath.

However, the relationship between the observed increases in adenosine and clinical outcomes (eg, morbidity-mortality) has not been clearly established.

Start of action

In patients with stable coronary artery disease on the background of the use of acetylsalicylic acid, Brilinta demonstrates a rapid onset of pharmacological action, which is confirmed by the results of determining the average value of platelet aggregation inhibition (IAT) for ticagrelor: 0.5 hours after taking a loading dose of 180 mg Brilinta average IAT value is approximately 41%, the maximum IAT value of 89% is achieved 2-4 hours after taking the drug and persists for 2-8 hours.

In 90% of patients, the final IAT value of more than 70% is achieved 2 hours after taking the drug.

End of action

If a CABG procedure is planned, the risk of bleeding from ticagrelor is increased compared with clopidogrel if it is stopped less than 96 hours before the procedure.

Data on switching from one drug to another

Switching from clopidogrel 75 ml to ticagrelor 90 mg twice daily resulted in a 26.4% increase in absolute IAT value, and changing therapy from ticagrelor to clopidogrel resulted in a 24.5% decrease in absolute IAT value. It is possible to change therapy from clopidogrel to ticagrelor without interrupting the antithrombotic effect.

Side effects

1. Musculoskeletal system: hemarthrosis;
2. Metabolic processes: hyperuricemia;
3. Sense organs: intraocular, retinal and conjunctival hemorrhages, vertigo, hemorrhages in the ear;
4. Nervous system: headaches, paresthesia, intracranial hemorrhage, dizziness, confusion;
5. Respiratory system: hemoptysis, shortness of breath, nosebleeds;
6. Skin lesions: rash, hemorrhages, itching, bruises;
7. Urinary system: bleeding from the urinary tract;
8. Digestive system: gastritis, constipation or diarrhea, nausea or vomiting, abdominal pain, dyspepsia, bleeding;
9. Laboratory test results: increased creatinine levels in the blood;
10. Reproductive system: metrorrhagia, vaginal bleeding.

BRILINTA TAB. P/P/O 90MG No. 168

Summary of Safety Profile The safety profile of Brilinta was assessed in two phase 3 studies (PLATO and PEGASUS), which included more than 39,000 patients (see section "Pharmacological properties"). The following are the adverse reactions observed in these clinical studies. In the PLATO study, patients receiving Brilinta were more likely to discontinue therapy due to adverse events than patients receiving clopidogrel (7.4% versus 5.4%). In the PEGASUS trial, the rate of treatment discontinuation due to adverse events was higher with Brilinta than with ASA monotherapy (16.1% in the ticagrelor 60 mg + ASA group compared with 8.5% in the ASA monotherapy group). The most commonly reported adverse reactions in patients taking ticagrelor were bleeding and shortness of breath (see section "Special Instructions").

List of adverse reactions in table form. Adverse reactions from clinical studies of Brilinta are presented by organ system class and frequency of occurrence and are listed in descending order of severity. The frequency of adverse reactions is determined using the following symbols: very often (?1/10), often (?1/100, <1/10), infrequently (?1/1000, <1/100), rarely (?1 /10000, <1/1000), very rare (<1/10000), unspecified frequency (cannot be estimated from the data obtained).

Table 1. Adverse reactions by incidence and organ system class observed in the phase 3 clinical studies PLATO and PEGASUS.

a For example, bleeding from a bladder tumor, from a stomach tumor, from a colon tumor.

b for example, increased tendency to bruise, spontaneous hematoma, bleeding diathesis.

observed during post-marketing use.

d shows the incidence of laboratory abnormalities (increased uric acid concentration above the upper limit of normal from a baseline value that was within the normal range or less than the lower limit of normal. Increased creatinine concentration > 50% of baseline), rather than the incidence of adverse events reported. e.g., conjunctival, retinal, intraocular hemorrhage.

f for example, epistaxis (nosebleeds), hemoptysis.

g e.g. gingival bleeding, rectal bleeding, bleeding from stomach ulcers.

h for example, ecchymosis, cutaneous hemorrhage, petechiae.

i for example, hemarthrosis, hemorrhage into the muscle,

jfor example, hematuria, hemorrhagic cystitis.

k for example, vaginal bleeding, hematospermia, postmenopausal bleeding.

l for example, bruise, traumatic hematoma, traumatic bleeding.

Description of some adverse reactions. Bleeding. The following definitions of bleeding were used in the PLATO and PEGASUS studies: - Major lethal/life-threatening bleeding as defined by PLATO: lethal, or any intracranial hemorrhage, or bleeding into the pericardial cavity with cardiac tamponade; or with hypovolemic shock or severe hypotension requiring the use of vasoconstrictors/inotropes or surgery, or clinically overt bleeding accompanied by a decrease in hemoglobin concentration of more than 50 g/L, or a transfusion of 4 or more units of red blood cells.

- Major other bleeding as defined by PLATO: causing significant disability of the patient, or clinically obvious bleeding, accompanied by a decrease in hemoglobin concentration by 30-50 g/L, or a transfusion of 2-3 units of red blood cells.

— Minor bleeding as defined by PLATO: requires medical intervention to stop or treat the bleeding.

— Major bleeding as defined by TIMI: fatal, or any intracranial hemorrhage, or clinically overt bleeding associated with a decrease in hemoglobin concentration of 50 g/L or more, or, if hemoglobin data are not available, a decrease in hematocrit of 15%.

- Major other bleeding according to TIMI definition: non-fatal, non-intracranial major bleeding according to TIMI definition.

- Minor bleeding according to TIMI definition: clinically obvious bleeding, accompanied by a decrease in hemoglobin concentration by 30-50 g/l.

- Bleeding requiring medical intervention, as defined by TIMI: requires medical intervention or leads to hospitalization or urgent evaluation.

- Lethal hemorrhage: results in the death of the patient within 7 days. PLATO Bleeding Incidence Data (Kaplan-Meier Estimated (%) at Month 12) Brilinta and clopidogrel did not differ in the incidence of major bleeding according to PLATO criteria overall (11.6% and 11.2%, respectively), fatal/ life-threatening bleeding according to PLATO criteria (5.8% in both groups). However, the incidence of combined major and minor bleeding according to PLATO criteria was higher in the ticagrelor group (16.1%) compared with clopidogrel (14.6%, p = 0.0084). There were several cases of fatal bleeding: 20 (0.2% of patients) in the ticagrelor group and 23 (0.3% of patients) in the clopidogrel group. Age, sex, weight, ethnicity, geographic region, comorbidities, concomitant therapies, and medical history, including previous stroke and transient ischemic attack, did not influence the incidence of overall and nonprocedure-related major bleeding according to PLATO criteria. No groups were identified with an increased risk of bleeding. CABG-Related Bleeding: In the PLATO study, 42% of 1584 patients (12% of the cohort) undergoing CABG experienced major fatal/life-threatening bleeding, with no difference in either treatment group. Fatal bleeding associated with CABG surgery occurred in 6 patients in each treatment group (see section "Special Instructions"). Non-CABG and non-procedure-related bleeding: Brilinta and clopidogrel did not differ in the incidence of major fatal/life-threatening non-CABG bleeding according to PLATO criteria, but ticagrelor was more likely to have major bleeding according to overall criteria. PLATO (4.5% vs. 3.8%; p=0.0264). When removing procedure-related bleeding events, there were more bleeding events in the ticagrelor group (3.1%) than in the clopidogrel group (2.3%; P = 0.0058). Discontinuation due to nonprocedure-related bleeding was more common with ticagrelor (2.9%) compared with clopidogrel (1.2%, p < 0.001). Intracranial hemorrhage: More non-procedure-related intracranial hemorrhage occurred in the ticagrelor group (n=27 hemorrhages in 26 patients, 0.3%) than in the clopidogrel group (n=14 hemorrhages, 0.2%), of which 11 hemorrhages occurred. on ticagrelor and 1 on clopidogrel were fatal. However, there were no significant differences in the total number of fatal bleeding events. The percentage of intracranial hemorrhage was low in both treatment groups, given the significant comorbidities and risk factors for cardiovascular complications in the study population. Bleeding event data from the PEGASUS study (Kaplan-Meier estimate (%) at month 36) In the PEGASUS study, TIMI-defined major bleeding occurred more frequently (2.3%) with Brilinta 60 mg twice daily than with monotherapy ASA (1.1%). There was no increase in the risk of fatal bleeding, but only a slight increase in the incidence of intracranial hemorrhage (0.6%) compared with ASA monotherapy (0.5%). Several cases of fatal bleeding were noted: 11 (0.3%) in the Brilinta 60 mg group and 12 (0.3%) in the ASA monotherapy group. The increased risk of TIMI major bleeding with Brilinta 60 mg was primarily due to a higher incidence of other TIMI major bleeding due to gastrointestinal events. With the use of Brilinta 60 mg, there was an increase in the frequency of major or minor bleeding according to the TIMI definition (3.4% when using Brilinta 60 mg compared to 1.4% with ASA monotherapy), major bleeding according to the PLATO definition (3.5% compared with 1.4%) and major or minor bleeding as defined by PLATO (15.2% compared with 6.2%).

Treatment discontinuation due to bleeding was more common with Brilinta 60 mg than with ASA monotherapy (6.2% and 1.5%, respectively). Most of these bleeds were less severe (classified as bleeds requiring medical attention, as defined by TIMI), such as epistaxis, bruising, and hematomas. The profile of TIMI major bleeding, TIMI major or minor bleeding, and PLATO major bleeding for Brilinta 60 mg was comparable across several prespecified subgroups (eg, age, sex, weight, race, geographic region, concomitant diseases, concomitant medications and medical history). Intracranial hemorrhage: Spontaneous intracranial hemorrhage was observed with a similar frequency when using Brilinta 60 mg and ASA monotherapy (n = 13 hemorrhages, 0.2% in both treatment groups). The incidence of intracranial hemorrhage due to trauma and procedure was slightly higher with Brilinta 60 mg (n=15 hemorrhages, 0.2%) compared with ASA monotherapy (n=10 hemorrhages, 0.1%). There were 6 fatal intracranial hemorrhages when taking Brilinta 60 mg and 5 when taking ASA monotherapy. The incidence of intracranial hemorrhage was low in both treatment groups, given the significant comorbidities and cardiovascular risk factors in the study population. Dyspnea In the PLATO study, adverse events of dyspnea occurred in 13.8% of patients receiving ticagrelor 90 mg twice daily and in 7.8% of patients receiving clopidogrel 75 mg once daily. Most symptoms of dyspnea were mild to moderate in intensity and often resolved without discontinuation of therapy. Typically, shortness of breath developed at the beginning of therapy and in 87% of patients it was a single episode. Dyspnea as a serious adverse event was reported in 0.7% of patients receiving ticagrelor and in 0.4% of patients receiving clopidogrel. Patients who reported developing dyspnea were older and often initially had dyspnea, congestive heart failure, COPD, or asthma. Data from the PLATO trial do not indicate that the higher incidence of dyspnea with Brilinta is associated with the development of new or worsening heart or lung disease. Brilinta does not affect respiratory function parameters (see section “Special instructions”). In the PEGASUS study, shortness of breath was observed in 14.2% of patients taking Brilinta 60 mg twice daily and in 5.5% of patients taking ASA monotherapy. As in the PLATO study, most cases of shortness of breath were mild to moderate in intensity (see section "Special Instructions").

Overdose

Symptoms: In the only dose-escalation study, gastrointestinal adverse effects were dose-limiting. Other clinically significant adverse events that could occur with overdose were shortness of breath and ventricular pauses. In case of overdose, it is recommended to monitor for these adverse effects and perform ECG monitoring.

• Treatment: Brilinta is not eliminated by hemodialysis; no antidote is 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 the expected pharmacological effect of Brilinta overdose, therefore, if bleeding develops, appropriate supportive measures should be taken.

special instructions

1. Before starting Brilinta therapy, a careful assessment of the balance between the benefits of preventing atherothrombotic events and the possible threat of bleeding is required.
2. The shortness of breath that occurs during treatment is usually mild or moderate in nature and resolves during therapy.
3. The use of recombinant activated factor VIIa and/or antifibrinolytic treatment (aminocaproic or tranexamic acid) can lead to increased hemostasis. After determining the cause of bleeding and stopping it, it is possible to resume taking Brilinta.
4. There is no data confirming the hemostatic effectiveness of platelet transfusions during the use of ticagrelor. Brilinta is capable of inhibiting transfused platelets in the blood.
5. During CABG, the incidence of major bleeding with ticagrelor was the same as with clopidogrel on all days after discontinuation of therapy, with the exception of the first day, when the likelihood of major bleeding was higher with Brilinta.
6. Before undergoing elective surgery or using new medications, the attending physician must be informed about ticagrelor therapy. If a surgical procedure is scheduled for which an antithrombotic effect is not desired, Brilinta should be discontinued 7 days before surgery.
7. During Brilinta therapy, an increase in creatinine levels is possible, and therefore it is recommended to use the drug with extreme caution (assessing renal function) during concomitant treatment with angiotensin receptor antagonists.

Brilinta tablet film 90 mg pack contact cell/pack card x56

BRILINTA®* Registration number: LP 001059 Trade name: Brilinta® International nonproprietary name: ticagrelor Dosage form: film-coated tablets INDICATIONS FOR USE Brilinta®, used simultaneously with acetylsalicylic acid, is indicated for the prevention of atherothrombotic events in patients with acute coronary syndrome (unstable angina, non-ST-segment elevation myocardial infarction or ST-segment elevation myocardial infarction [STEMI]), including patients receiving drug therapy and patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)). CONTRAINDICATIONS • Hypersensitivity to ticagrelor or any of the components of the drug • Active pathological bleeding • History of intracranial hemorrhage • Moderate or severe hepatic impairment • Concomitant use of ticagrelor with strong CYP3A4 inhibitors (for example, ketoconazole, clarithromycin, nefazodone, ritonavir and atazanavir) • Pediatric age up to 18 years of age (due to the lack of data on the effectiveness and safety of use in this group of patients)

CAUTION* Patients who are predisposed to bleeding (eg, due to recent trauma, recent surgery, bleeding disorders, active or recent gastrointestinal bleeding). Patients with concomitant therapy with drugs that increase the risk of bleeding (i.e. non-steroidal anti-inflammatory drugs, oral anticoagulants and/or fibrinolytics) within 24 hours before taking Brilinta®. Patients with an increased risk of developing bradycardia (for example, patients with sick sinus syndrome without a pacemaker, with 2nd or 3rd degree atrioventricular block, syncope associated with bradycardia) due to insufficient experience with the clinical use of Brilinta®. When used together with drugs that cause bradycardia. Ticagrelor should be used with caution in patients with asthma and chronic obstructive pulmonary disease (COPD). If the patient reports a new episode of dyspnea, prolonged dyspnea, or worsening dyspnea, evaluation should be performed and, if intolerable, treatment with ticagrelor should be discontinued. While taking Brilinta®, creatinine levels may increase, and therefore renal function should be assessed in accordance with routine clinical practice, paying particular attention to patients 75 years of age and older, patients with moderate or severe renal impairment, patients receiving therapy angiotensin receptor antagonists. Caution should be exercised in patients with a history of hyperuricemia or gouty arthritis. As a preventive measure, the use of ticagrelor should be avoided in patients with hyperuricemic nephropathy. The combined use of ticagrelor and a high maintenance dose of acetylsalicylic acid (more than 300 mg) is not recommended. When using digoxin and Brilinta® together, careful clinical and laboratory monitoring (heart rate, and, if clinically indicated, also ECG and digoxin concentration in the blood) is recommended. There are no data on the combined use of ticagrelor with potent P-glycoprotein inhibitors (for example, verapamil, quinidine and cyclosporine), and therefore their combined use should be carried out with caution. SIDE EFFECTS* In the PLATO study, the most common adverse events reported in patients taking ticagrelor were shortness of breath, bruises, and nosebleeds. Adverse reactions are classified by frequency and organ system class. The frequency of adverse reactions is determined using the following symbols: very often (≥1/10), often (≥1/100, 1/10), infrequently (≥1/1000, 1/100), rarely (≥1 /10,000, 1/1000) Adverse drug reactions by incidence and system organ class (SOC) Metabolism and nutrition. Rarely – hyperuricemia (hyperuricemia, increased concentration of uric acid in the blood). Nervous system. Uncommon: intracranial hemorrhage (cerebral hemorrhage, intracranial hemorrhage, hemorrhagic stroke), headache, dizziness, rarely: paresthesia, confusion. Organs of vision. Uncommon: hemorrhages (intraocular, conjunctival, retinal). Organs of hearing. Rarely - hemorrhage in the ear, vertigo. Respiratory system. Often - shortness of breath (shortness of breath, shortness of breath on exertion, shortness of breath at rest, shortness of breath at night), nosebleeds, infrequently - hemoptysis. Digestive system. Often - gastrointestinal bleeding (gastrointestinal bleeding, rectal bleeding, intestinal bleeding, melena, positive test for occult blood), uncommon - vomiting with blood, bleeding from a gastrointestinal ulcer (bleeding from a gastrointestinal ulcer, bleeding from a gastric ulcer, bleeding from duodenal ulcers, bleeding from peptic ulcers), hemorrhoidal bleeding, gastritis, bleeding in the oral cavity (including gingival bleeding), vomiting, diarrhea, abdominal pain, nausea, dyspepsia, rarely - retroperitoneal bleeding, constipation. Skin and subcutaneous tissues. Often - subcutaneous or cutaneous hemorrhages (subcutaneous hematoma, cutaneous and subcutaneous hemorrhages, petechiae), bruises (contusion, hematoma, ecchymosis, increased tendency to bruise, traumatic hematoma), uncommon - rash, itching. Musculoskeletal system. Rarely - hemarthrosis. Urinary system. Uncommon: bleeding from the urinary tract (hematuria, bleeding from the urinary tract). Reproductive system. Uncommon: vaginal bleeding (including metrorrhagia). Deviations of laboratory parameters. Rarely - an increase in the concentration of creatinine in the blood. Other. Often - bleeding at the site of the procedure (bleeding from the site of puncture of the vessel, hematoma at the site of puncture of the vessel, bleeding from the injection site, bleeding from the puncture site, bleeding from the catheterization site), infrequently - bleeding after the procedure, rarely - bleeding from the wound, traumatic bleeding . *Before using the drug, you must read the full text of the instructions

Drug interactions

When taking the drug, the following drug interactions should be taken into account:

• powerful inducers of CYP3A4 (phenobarbital, carbamazepine, phenytoin, dexamethasone, rifampicin) - decreased efficacy and exposure of the drug;
• potent inhibitors of CYP3A4 (atazanavir, ritonavir, nefazodone, clarithromycin, ketoconazole) - a significant increase in ticagrelor exposure;
• moderate inhibitors of CYP3A4 - increase in Cmax by 69%, and AUC by 2.7 times, with a decrease in Cmax of the active metabolite by 38%;
• lovastatin together with simvastatin more than 40 mg - increase in AUC of atorvastatin acid metabolites and Cmax by 36%, respectively;
• simvastatin at a dose of more than 40 mg/day - the occurrence of side effects of simvastatin, it is recommended to evaluate the feasibility before use;
• ethinyl estradiol and levonorgestrel - 20% increase in ethinyl estradiol exposure;
• cisapride, ergot alkaloids - increased exposure.

Reviews

We have selected some people's reviews about the drug Brilinta:

1. Sergey. Grandfather underwent surgery and was prescribed to drink Brilinta. Of course, despite the price, we immediately agreed, since it was necessary, we would find the money. Although it is not clear how much to drink and how much it will cost us, it is a fact! When Yeltsin had bypass surgery, the whole country was on edge for almost a month. And then the grandfather with a heart attack was immediately put on the table for bypass surgery. And now here are these tablets along with ascorbic acid (!), so that there are no blood clots. Grandfather, of course, is a real colonel, hardening, training and other physical training, but still. What has medicine come to? When the doctor wrote out the prescription, he warned, of course, that follow-up treatment would be long. But I’m telling you, it’s a fact! The fact that a heart attack happened just like that - it was stopped and is now being treated - no money is spared for that.
2. Misha. Of course, the prices are lethal for pensioners, but who cares? Now everyone lives at their own level and sees only their own problems.

Storage conditions and shelf life

The shelf life of the drug is 2 years; it is recommended to store it in a dry, warm place at 30 degrees, away from children.

Brilinta - tips and recommendations on News4Health.ru

Life in the modern world is replete with many factors that negatively affect human health. The main ones are poor ecology, questionable quality of food, contaminated drinking water, poor quality medical care, as well as stressful situations and bad habits. Therefore, it is so important to pay attention to regular healing of the body using various methods and means. Be sure to consult a specialist so as not to harm your health!