Brilinta - Instructions For Use, Price, 90 Mg Tablets, Analogues, Reviews

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Brilinta

Brilinta: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Brilinta

ATX code: B01AC24

Active ingredient: ticagrelor (Ticagrelor)

Manufacturer: AstraZeneca AB (Sweden); ZiO-Health, JSC (Russia)

Description and photo updated: 2019-27-08

Prices in pharmacies: from 2478 rubles.

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Brilinta is a drug that inhibits platelet aggregation.

Release form and composition

The drug is produced in the form of film-coated tablets: biconvex, round, pink or yellow film shell (60 or 90 mg, respectively), engraving on one side - the number "60" or "90" above the letter T (14 pcs. in blisters made of Al / PVC / PVDC, in a cardboard box with first opening control 1, 4 or 12 blisters and instructions for use of Brilints).

1 tablet contains:

• active substance: ticagrelor - 60 or 90 mg;
• auxiliary components: mannitol, calcium hydrogen phosphate, sodium carboxymethyl starch, hyprolose, magnesium stearate;
• film shell: hypromellose 2910, titanium dioxide (E171), macrogol 400; additionally for 60 mg - iron dye black oxide, iron dye red oxide; additionally for 90 mg - talc, dye iron oxide yellow.

Pharmacological properties

Pharmacodynamics

The active component of Brilinta - ticagrelor, is a representative of the chemical class of cyclopentyltriazolopyrimidines, a selective and reversible direct acting P2Y12 receptor antagonist. The substance prevents ADP-mediated (adenosine diphosphate-mediated) P2Y12-dependent activation and platelet aggregation. Ticagrelor does not prevent ADP binding, but when it interacts with the platelet P2Y12 receptor, ADP-induced signal transduction is prevented. Since platelets are involved in the initiation and / or occurrence of thrombotic complications of atherosclerosis, it has been shown that against the background of inhibition of platelet function, the likelihood of cardiovascular events, such as stroke, myocardial infarction or death, decreases.

Ticagrelor has an additional mechanism of action, while local concentrations of endogenous adenosine increase (by inhibition of the endogenous equilibrium type 1 nucleoside transporter - ENT-1).

The formation of adenosine occurs locally in places of hypoxia and tissue damage, which is provided by the release of ATP (adenosine triphosphate) and ADP. Since in nature the cleavage of adenosine is limited to the intracellular space, inhibition of ENT-1 by the substance leads to an increase in T _1/2 (half-life) of adenosine and, thereby, to an increase in its local extracellular concentration against the background of an increase in the local adenosine response. Ticagrelor does not have a clinically significant direct effect on adenosine receptors (A1, A2A, A2B, A3), and the substance is not metabolized to adenosine either.

The main effects of adenosine are vasodilation, cardioprotection, inhibition of platelet aggregation, modulation of inflammation and dyspnea, which may affect the clinical profile of ticagrelor.

Ticagrelor in healthy volunteers and in patients with ACS (acute coronary syndrome) enhances the effects of adenosine, such as vasodilation (assessed by an increase in coronary blood flow), inhibition of platelet function and dyspnea. Despite this, the relationship between increased local adenosine concentrations and clinical outcomes (morbidity and mortality) has not been proven.

In patients with a stable course of coronary artery disease (coronary heart disease) against the background of the use of ASA (acetylsalicylic acid), ticagrelor begins to have a rapid effect. This is confirmed by the results of determining the average IAT (inhibition of platelet aggregation).

When planning CABG (coronary artery bypass grafting), it should be borne in mind that the likelihood of bleeding increases in cases when ticagrelor is stopped less than 96 hours before the procedure.

When switching from clopidogrel (1 time per day, 75 mg) to Brilinta (2 times a day, 90 mg), an increase in the absolute IAT value by 26.4% is observed, and when changing from ticagrelor to clopidogrel, the absolute IAT value decreases by 24, five%. Therapy from clopidogrel to ticagrelor can be changed without interrupting the antithrombotic effect.

The clinical efficacy of Brilinta was confirmed by the results of two phase 3 studies: the PLATO study (acute coronary syndrome), the PEGASUS study (burdened history of myocardial infarction).

In the process of comparing the efficacy of ticagrelor at doses of 90 and 60 mg, the use of ticagrelor at a dose of 60 mg showed a better tolerance and safety profile in relation to the risk of bleeding and dyspnea. In this regard, in order to prevent the occurrence of atherothrombotic complications (cardiovascular death, myocardial infarction and stroke), patients with a burdened history of myocardial infarction (myocardial infarction was transferred one year or more ago) and the presence of a high risk of developing atherothrombotic complications are recommended to take 60 mg Brilints 2 times a day in combination with ASA.

With therapy 2 times a day at 60 mg, the primary combined endpoint of cardiovascular death, stroke and myocardial infarction is significantly reduced.

When combined with ASA, there is a decrease in the number of deaths from cardiovascular causes and deaths from other causes (statistical significance was not achieved).

The use of ticagrelor can be continued as long as the patient has a high risk of atherothrombotic complications.

The effectiveness of Brilinta at a dose of 60 mg 2 times a day has been demonstrated in various subgroups of patients, regardless of gender, body weight, region, and anamnesis. It also does not depend on the use of other cardiovascular drugs, including lipid-lowering drugs, beta-blockers, ACE (angiotensin converting enzyme) inhibitors, angiotensin II receptor antagonists, calcium channel blockers, proton pump inhibitors and nitrates.

Pharmacokinetics

Ticagrelor is characterized by linear pharmacokinetics; the exposure of the substance and its active metabolite (AR-C124910XX) is approximately proportional to the dose up to 1260 mg.

The absorption of ticagrelor occurs quickly, the average value of T _max (time to reach the maximum concentration of the substance) is about 1.5 hours. The formation of the main (also active) metabolite AR-C124910XX, circulating in the blood, occurs rapidly with an average T _{max of} approximately 2.5 hours. After taking on an empty stomach at a dose of 90 mg C _max (maximum concentration of the substance) is 529 ng / ml, AUC (area under the concentration-time curve) - 3451 ng × h / ml. The ratio of C _max and AUC of the metabolite to ticagrelor is 0.28 and 0.42, respectively.

The average absolute bioavailability of the substance is 36%. An increase in the AUC of ticagrelor by 21% and a decrease in the C _{max of the} active metabolite by 22% is observed due to the intake of fatty foods. These changes have minimal clinical significance, and therefore Brilinta can be used regardless of the regimen and diet.

Ticagrelor in the form of a suspension obtained by dissolving crushed tablets in drinking water, taken orally or introduced through a nasogastric tube into the stomach, is bioequivalent to a substance taken orally in the form of tablets (AUC and C _{max of} ticagrelor and its main metabolite are in the range from 80 to 125%). The initial exposure in the case of taking the suspension (30 and 60 minutes after administration) is higher than when taking ticagrelor in the form of Brilinta tablets, but later (in the range of 2–48 hours) the concentration profile is practically the same.

Ticagrelor and its active metabolite have a high level of binding to plasma proteins (> 99%). V _d (volume of distribution) of ticagrelor in equilibrium is 87.5 liters.

The main isoenzyme responsible for the metabolism of ticagrelor and the formation of an active metabolite is CYP3A4; their interaction with other CYP3A substrates can vary from activation to inhibition. Ticagrelor and its active metabolite are weak inhibitors of P-glycoprotein (P-gp).

The activity of the main metabolite was confirmed by the results of evaluating the binding to P2Y12 of the platelet ADP receptor. The systemic exposure of AR-C124910XX is about 30–40% of the exposure of ticagrelor.

The main route of excretion of the substance is hepatic metabolism. With the excretion of isotope-labeled ticagrelor, about 84% of radioactivity is released on average (with feces - 57.8%, with urine - 26.5%). Excretion of ticagrelor and AR-C124910XX in the urine is less than 1% of the dose. The active metabolite is excreted mainly in the bile. The average T _{1/2 of} ticagrelor and AR-C124910XX is 7 and 8.5 hours, respectively.

In elderly patients (75 years and older) with ACS, there is a higher exposure of ticagrelor (C _max and AUC values are approximately 25% higher) and an active metabolite in comparison with young patients. These differences are not considered clinically significant.

There is no information on the use of ticagrelor in children.

Women have a higher exposure to ticagrelor and AR-C124910XX compared to men. These differences are not considered clinically significant.

In patients with severe renal impairment (with creatinine clearance <30 ml / min), compared with patients with no renal impairment, the exposure of ticagrelor is approximately 20% lower, and the active metabolite is approximately 17% higher.

In patients with mild hepatic impairment, the C _max and AUC values of ticagrelor increase (by 12 and 23%, respectively, compared with healthy volunteers), while the effect of Brilinta on IAT is comparable in both groups. No dose adjustment is required for this category of patients. The experience of using the drug in patients with moderate and severe liver dysfunction is insufficient / absent.

The value of the average bioavailability of ticagrelor in Asian patients is higher than in patients of the Caucasian race, by 39%, and in patients of the Negroid race, it is lower by 18%. In studies of clinical pharmacology, the C _max and AUC of the substance in the Japanese are approximately 40% (after correction for body weight - by 20%) higher than in the Caucasians.

Indications for use

Brilinta is used as part of complex therapy with acetylsalicylic acid for the prevention of atherothrombotic events (cardiovascular death, myocardial infarction or stroke) in acute coronary syndrome (unstable angina pectoris, myocardial infarction with / without ST segment elevation), including in patients after coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) or pharmacotherapy.

Contraindications

Absolute:

• pathological bleeding in the active phase;
• history of cerebral hemorrhage;
• hepatic impairment: for 60 mg - severe; for 90 mg - moderate to severe;
• hemodialysis (there is no data on the safety and efficacy of Brilinta);
• combined use with potent CYP3A4 inhibitors (ketoconazole, clarithromycin, nefazodone, ritonavir, atazanavir);
• pregnancy and the period of breastfeeding (data from perinatal studies are absent or limited);
• children and adolescents under 18 years of age (there is no data on the safety and effectiveness of Brilinta in this age group);
• hypersensitivity to the active substance or auxiliary components of the drug.

Relative (Brilint tablets should be taken with caution):

• a predisposition to the development of bleeding (recent injuries, recent operations, bleeding disorders, active or recent gastrointestinal bleeding);
• 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;
• an increased risk of developing bradycardia [sick sinus syndrome (patients without a pacemaker), atrioventricular block II or III degree, fainting associated with bradycardia], since the experience of clinical use of Brilinta is insufficient;
• combined use with drugs that cause bradycardia;
• chronic obstructive pulmonary disease (COPD) and bronchial asthma (with prolonged dyspnea, a new episode or worsening dyspnea, an examination is required, in case of intolerance, ticagrelor therapy should be discontinued);
• violations of hepatic function of moderate severity (for 60 mg);
• a history of hyperuricemia or gouty arthritis (the use of ticagrelor in hyperuricemic nephropathy should be avoided);
• combined use with digoxin [if indicated, careful clinical and laboratory monitoring of heart rate (HR), electrocardiogram (ECG) and plasma concentration of digoxin is recommended];
• combined use with powerful inhibitors of P-glycoprotein (quinidine and verapamil), since there are no clinical data.

The use of ticagrelor with acetylsalicylic acid at a high maintenance dose of ≥ 300 mg is not recommended.

When using Brilinta, an increase in serum creatinine may be observed, and therefore, an assessment of renal function is required in accordance with routine clinical practice, patients over 75 years of age need special attention, patients with moderate to severe renal failure, and caution is necessary in combination therapy with angiotensin receptor antagonists.

Brilinta, instructions for use: method and dosage

Brilint's tablets are taken orally, regardless of the meal.

When difficulties in swallowing tablets should be milled to a fine powder, stir in ¹ / ₂ cup of drinking water and the resulting suspension is immediately drink. Then pour the same volume of drinking water into a glass and drink again to get the full dose of the drug. It is allowed to inject the suspension through a nasogastric tube, after administration, it is washed again with water so that the dose of the drug completely enters the patient's stomach.

With a burdened history of myocardial infarction (transferred one year ago or more), a loading dose is not required, the recommended dose is 60 mg 2 times a day. You can start therapy regardless of whether antiplatelet drugs were previously used and whether there were interruptions in treatment.

Long-term use of the drug is recommended, except in cases of clinical need for early withdrawal. The experience of using Brilinta in a single dose of 60 mg for more than 3 years in patients with a history of myocardial infarction is absent.

In the treatment of acute coronary syndrome (with unstable angina pectoris, myocardial infarction without / with ST segment elevation), at the beginning of use, a single loading dose is prescribed - 180 mg (two Brilint tablets 90 mg), then - twice a day, 90 mg. At the same time, it is required to take acetylsalicylic acid daily in a dose of 75 mg to 150 mg (in the absence of specific contraindications).

The recommended duration of therapy with Brilinta's drug is 12 months, except in cases of proven need for early withdrawal of the drug. Data on ticagrelor use over 12 months are limited.

Patients who started taking with a dose of Brilinta 90 mg 2 times a day during the acute period, after 1 year, can reduce a single dose to 60 mg without interruption.

It is advisable to avoid interruptions in therapy, but when skipping the next dose, take only the next dose (1 tablet 90 mg) at the appropriate time.

In acute coronary syndrome, early withdrawal of any antiplatelet therapy, including Brilint's drug, may increase the likelihood of myocardial infarction or cardiovascular death due to the underlying disease. Therefore, premature discontinuation of the drug should be avoided.

If necessary, patients taking clopidogrel can be transferred to ticagrelor.

Side effects

The most common adverse reactions when taking ticagrelor are: bruising, nosebleeds, shortness of breath.

Other side effects Brilints classified by organ system and incidence using the following grading: very common (≥ 1/10), often (≥ 1/100 - <1/10), infrequently (≥ 1/1000 - <1/100), rarely (≥ 1/10 000 - <1/1000):

• metabolism: rarely - hyperuricemia, an increase in the plasma concentration of uric acid;
• nervous system: infrequently - cerebral / intracranial hemorrhage, hemorrhagic stroke, headache, dizziness; rarely - confusion, paresthesia;
• organ of vision: infrequently - hemorrhages (intraocular, conjunctival, retinal);
• organ of hearing: rarely - vertigo, hemorrhage in the ear;
• respiratory system: often - nosebleeds, shortness of breath (during exertion, at rest, at night); infrequently - hemoptysis;
• digestive system: often - gastrointestinal bleeding, rectal bleeding, intestinal bleeding, melena, positive occult blood test; infrequently - bleeding from ulcers (gastrointestinal tract, stomach, duodenum, peptic ulcer), hemorrhoidal bleeding, gastritis, bleeding in the oral cavity (including gingival), vomiting, diarrhea, abdominal pain, nausea, dyspepsia; rarely - constipation, retroperitoneal bleeding;
• skin and subcutaneous tissues: often - subcutaneous or cutaneous hemorrhages (subcutaneous hematoma, petechiae), bruises (bruising, hematoma, ecchymosis, increased tendency to bruising, traumatic hematoma); infrequently - rash, itching;
• musculoskeletal system: rarely - hemarthrosis;
• urinary system: infrequently - hematuria, bleeding from the urinary tract;
• reproductive system: infrequently - vaginal bleeding (including metrorrhagia);
• laboratory results: rarely - an increase in the content of creatinine in the blood;
• other reactions: rarely - traumatic bleeding, bleeding from a wound.

Overdose

A single dose of ticagrelor up to 900 mg is generally well tolerated.

The main symptoms of an overdose: adverse effects on the gastrointestinal tract (dose-limiting); ventricular pauses and shortness of breath. Due to the inhibition of platelets, an increase in the duration of bleeding is considered to be the putative pharmacological action of Brilinta.

Therapy: control of the condition in order to identify unwanted reactions, ECG monitoring is possible; symptomatic treatment according to local standards. If bleeding occurs, appropriate supportive measures are required.

The antidote is unknown. It is unlikely that ticagrelor is cleared by hemodialysis.

special instructions

Brilint's drug is prescribed after a careful assessment of the ratio of benefits from the prevention of atherothrombotic events with the risk of an increased likelihood of bleeding.

There are no data on the hemostatic efficacy of platelet transfusions while taking ticagrelor. Brilinta can inhibit transfused platelets in the blood.

Hemostasis can be enhanced by treatment with antifibrinolytics (aminocaproic or tranexamic acids) and / or recombinant activated factor VIIa. After diagnosing the cause of bleeding and stopping it, it is allowed to resume therapy with Brilinta.

The patient is obliged to inform the attending physician about Brilinta's therapy before starting new medications or planned surgery.

With CABG, the incidence of major bleeding in the case of taking ticagrelor on all days after discontinuation of therapy is the same as with clopidogrel, except for the first day, when the likelihood of major bleeding is higher when taking Brilinta.

The appointment of a planned operation, in which an antithrombotic effect is undesirable, requires the cancellation of therapy with Brilint's drug 7 days before the surgery.

Shortness of breath due to the use of Brilinta is usually mild to moderate in intensity and often goes away with continued treatment.

The use of ticagrelor can increase the level of creatinine; the mechanism of this effect is unknown. But in this regard, it is required to assess renal function a month after the start of Brilinta's intake, and then in accordance with routine clinical practice. Particular attention should be paid to patients over 75 years of age, patients with moderate or severe renal failure and receiving therapy with angiotensin receptor antagonists.

The risk of hyperuricemia is higher with ticagrelor therapy than with clopidogrel.

Influence on the ability to drive vehicles and complex mechanisms

The effect of Brilinta on the ability to control complex mechanisms and drive vehicles has not been studied. But it should be borne in mind that during the treatment of acute coronary syndrome, dizziness and confusion were observed. In the event of the development of such side effects, patients need to be careful when performing types of work that require increased concentration of attention and speed of psychomotor reactions.

Application during pregnancy and lactation

Brilinta is not prescribed during pregnancy / lactation.

Women of reproductive age should use appropriate methods of contraception to avoid pregnancy during therapy.

Pediatric use

Brilinta is not prescribed for patients under 18 years of age.

With impaired renal function

Reception of Brilinta is contraindicated in patients on hemodialysis.

For violations of liver function

Tablets at a dosage of 60 mg:

• severe liver failure: therapy is contraindicated;
• moderate hepatic impairment: Brilinta should be used with caution under medical supervision.

Tablets at a dosage of 90 mg: with moderate or severe hepatic impairment, therapy is contraindicated.

Use in the elderly

Due to the fact that Brilinta therapy may be accompanied by an increase in serum creatinine, when assessing renal function in accordance with routine clinical practice, special attention should be paid to patients over 75 years of age.

Drug interactions

• clarithromycin, ketoconazole, nefazodone, atazanavir, ritonavir (potent inhibitors of CYP3A4): concomitant use is contraindicated because it can lead to a significant increase in ticagrelor exposure;
• rifampicin, carbamazepine, phenytoin, phenobarbital (powerful inducers of CYP3A4): co-administration may reduce the exposure and effectiveness of ticagrelor;
• cisapride and ergot alkaloids (CYP3A4 substrates with a narrow therapeutic index): ticagrelor may increase exposure to these substances;
• simvastatin, lovastatin: it is not recommended to use in a dose of more than 40 mg per day in conjunction with ticagrelor;
• verapamil, quinidine (potent P-glycoprotein inhibitors): theoretically capable of increasing the exposure of ticagrelor, but there is no reliable data on such an interaction; if necessary, this combination therapy should be carried out with caution;
• levonorgestrel, ethinyl estradiol (oral contraceptives): ticagrelor increases the exposure of ethinyl estradiol by 20%, but does not affect the pharmacokinetics of levonorgestrel; does not have a clinically significant effect on the effectiveness of contraception;
• acetylsalicylic acid, proton pump inhibitors, statins, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists (in the framework of long-term administration), heparin, low molecular weight heparins, inhibitors of glycoprotein IIb / IIIa receptors (for intravenous administration) significant undesirable interactions based on the results of the studies;
• enoxaparin, desmopressin, heparin (drugs affecting hemostasis): effects on activated partial thromboplastin time (APTT), activated clotting time (ABC) and factor Xa studies have not been registered, however, caution is required when used with ticagrelor due to potential pharmacodynamic interactions;
• sertraline, paroxetine, citalopram (selective serotonin reuptake inhibitors): caution should be exercised in connection with reports of subcutaneous hemorrhages against the background of their combined use with Brilinta;
• grapefruit juice: with daily use in large volumes (from 200 ml 3 times a day), there was a 2-fold increase in the exposure of ticagrelor; this increase in ticagrelor exposure is predicted to be clinically insignificant in most patients.

Analogs

Brilinta's analogues are: Deplatt-75, Agrenox, Domenan, Thromboreductin, Monafram, Kardutol, Cardogrel, Klapitax, Rutsiromab, Zilt, Aggregal, Detromb and others.

Terms and conditions of storage

Store out of the reach of children at a temperature not exceeding 30 ° C.

Shelf life: 60 mg tablets - 2 years; tablets 90 mg - 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Brilint

According to reviews, Brilinta is an effective drug that rarely causes side effects. The main disadvantage is the high cost of the drug, while a long course of admission is usually prescribed, and there are no analogues for the active substance.

Price for Brilinta in pharmacies

The approximate price for Brilinta is: 60 mg tablets, 168 pcs. - 8043 rubles, tablets 90 mg, 56 pcs. - 4,334–4800 rubles, tablets 90 mg, 168 pcs. - 12,950-14,500 rubles.

Brilinta: prices in online pharmacies

Drug name Price Pharmacy

Brilinta 60 mg film-coated tablets 56 pcs. 2478 RUB Buy

Brilinta tablets p.o. 60mg 56 Pcs. 2848 RUB Buy

Brilinta 90 mg film-coated tablets 56 pcs. 3905 RUB Buy

Brilinta tablets p.o. 90mg 56 Pcs. RUB 5004 Buy

Brilinta 60 mg film-coated tablets 168 pcs. RUB 6993 Buy

Brilinta 90 mg film-coated tablets 168 pcs. RUB 12060 Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!