BRILIQUE® (ticagrelor)

BRILIQUE (ticagrelor) is the only P2Y12 inhibitor licensed in combination with aspirin to protect patients with prior MI and a high risk* of atherothrombotic events against subsequent CV events in both the acute and long-term treatment settings†1

*High risk is defined as ≥1 additional atherothrombotic risk factor (age ≥65 years, >1 prior MI, multivessel coronary artery disease, diabetes requiring medication, chronic non-end-stage renal dysfunction)1

BRILIQUE (ticagrelor) 90mg twice daily  in combination with  acetylsalicylic acid (ASA) is indicated for patients with Acute Coronary Syndromes (ACS) for up to 12 months. BRILIQUE (ticagrelor) 90mg twice daily is not indicated for use in patients beyond 12 months. There are limited data on the efficacy and safety of BRILIQUE (ticagrelor) 60mg beyond 3 years of extended treatment

Product Information

Indications1

BRILIQUE (ticagrelor), co-administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with:

  • acute coronary syndromes (ACS)
  • a history of myocardial infarction (MI) and a high risk* of developing an atherothrombotic event

BRILIQUE (ticagrelor) is the only P2Y12 inhibitor licensed in combination with ASA to protect post-MI patients at high risk of atherothrombotic events against subsequent CV events in both the acute and long-term treatment settings.1,2,3

 

* High risk is defined as ≥1 additional atherothrombotic risk factor (age ≥65 years, >1 prior MI, multivessel coronary artery disease, diabetes requiring medication, chronic non-end-stage renal dysfunction)1

BRILIQUE (ticagrelor) 90mg  twice daily  in combination with ASA is indicated for patients with ACS for up to 12 months. BRILIQUE (ticagrelor) 90mg twise daily is not indicated for use in patients beyond 12 months. There are limited data on the efficacy and safety of BRILIQUE (ticagrelor) 60mg beyond 3 years of extended treatment

BRILIQUE (ticagrelor) 90mg use in acute coronary syndrome1

BRILIQUE (ticagrelor) 90mg treatment should be initiated with a single 180mg loading dose and then continued at 90mg twice daily.

Treatment with BRILIQUE (ticagrelor) 90mg twice daily is recommended for 12 months in ACS patients unless discontinuation is clinically indicated.

BRILIQUE (ticagrelor) 60mg after an MI in those at high-risk*1

BRILIQUE (ticagrelor) 60mg  twice daily is the recommended dose when an extended treatment is required for patients with a history of MI of ≥1 year and high risk* of an atherothrombotic event.

Treatment may be started without interruption as continuation therapy after the initial one year treatment with BRILIQUE (ticagrelor) 90mg (or other adenosine diphosphate (ADP) receptor inhibitor therapy) in MI patients with a high risk* of an atherothrombotic event. Treatment can also be initiated up to 2 years from the MI, or within one year after stopping previous ADP receptor inhibitor treatment.

There are limited data on the efficacy and safety of BRILIQUE (ticagrelor) 60mg beyond 3 years of extended treatment.

If a switch is needed, the first dose of BRILIQUE (ticagrelor) should be administered 24 hours following the last dose of the other antiplatelet medication.

BRILIQUE (ticagrelor) is the only P2Y12 inhibitor approved in both long- and short-term settings1

Study design overviews for PLATO and PEGASUS-TIMI 54
Study design overviews for PLATO and PEGASUS-TIMI 54

Prescribing BRILIQUE (ticagrelor) 90mg

BRILIQUE (ticagrelor) 90mg can be used in a wide range of ACS patients

BRILIQUE (ticagrelor) 90mg twice daily, co-administered with aspirin, is indicated for the prevention of atherothrombotic events in adult patients with ACS (unstable angina [UA], non ST-segment-elevated MI [NSTEMI] or ST-segment-elevation MI [STEMI]), including patients managed medically, and those who are managed with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), for up to 12 months unless discontinuation is clinically indicated.1,6

BRILIQUE (ticagrelor) 90mg loading and maintenance dose

Treatment with BRILIQUE (ticagrelor) should be initiated with a single 180mg loading dose (two tablets of 90mg) and then continued at 90mg twice daily with concomitant ASA.1

The image shows the starting and maintenance dose for BRILIQUE 90mg for up to 12 months of treatment
The image shows the starting and maintenance dose for BRILIQUE 90mg for up to 12 months of treatment

Guidelines in the UK recommend a loading dose of ASA 300 mg in ASA naive patients

No dose adjustment is required across ACS patient populations including:1

Switching from clopidogrel to BRILIQUE (ticagrelor) 90mg

Patients can be switched from clopidogrel to BRILIQUE (ticagrelor) 90mg twice daily without interruption of antiplatelet effect1. If a switch is needed in the chronic setting the maintenance dose (90mg twice daily) should be commenced 24 hours following the last dose of the other antiplatelet medication. In the acute phase international guidelines e.g. ESC13, endorse giving a loading dose of ticagrelor (180 mg) before commencing the maintenance dose of 90 mg twice daily as usual.

BRILIQUE (ticagrelor) ODT (orodispersible tablet)

BRILIQUE (ticagrelor) 90mg is the only P2Y12 inhibitor available as an orodispersible tablet (ODT)8

BRILIQUE (ticagrelor) 90 mg ODT simplifies treatment initiation in patients who are unable to swallow film-coated tablets.

BRILIQUE 90mg ODT
BRILIQUE 90mg ODT

A&E, accident and emergency; ICU, intensive care unit

Prescribing BRILIQUE (ticagrelor) 60mg

BRILIQUE (ticagrelor) 60mg is indicated for use in a high-risk population

BRILIQUE (ticagrelor) 60mg twice daily in combination with ASA is recommended when an extended treatment is required for patients with a history of MI of at least 1 year and a high risk of an atherothrombotic event.1

If a patient meets 1 or more DRAMA criteria, they can be considered for extended treatment with BRILIQUE 60 mg.1,15 The DRAMA criteria is defined as:

Pegasus inclusion criteria
Pegasus inclusion criteria

a. Chronic non-end-stage renal dysfunction. Estimated Creatinine Clearance < 60 mL/min.
b. Multivessel coronary artery disease based on an interim snapshot of the data, after completion of enrollment but during ongoing trial and data cleaning

Continuation with BRILIQUE (ticagrelor) 60mg after 1 year’s DAPT treatment

BRILIQUE (ticagrelor) 60mg twice daily  in combination with ASA may be initiated without interruption as a continuation therapy after the initial one-year treatment with BRILIQUE (ticagrelor) 90mg twice daily  or other ADP receptor inhibitor therapy in eligible patients with prior MI and a high risk of another atherthrombotic event, unless contraindicated.1

BRILIQUE 60mg is taken twice a day, once in the morning and once in the evening, in combination with ASA once daily
BRILIQUE 60mg is taken twice a day, once in the morning and once in the evening, in combination with ASA once daily

BRILIQUE (ticagrelor) 60mg can be initiated regardless of the prior P2Y12 inhibitor used

Treatment with BRILIQUE (ticagrelor) 60mg twice daily in combination with ASA may be started without interruption or as continuation therapy after the initial one-year treatment with BRILIQUE (ticagrelor) 90mg twice daily, or other ADP receptor inhibitor therapy, in high risk post-MI patients1

Administration

BRILIQUE (ticagrelor) can be taken with or without food.1

BRILIQUE (ticagrelor) is indicated for use either whole, or as crushed tablets, unlike the thienopyridines.1,2,3

BRILIQUE (ticagrelor) as crushed tablets mixed in water, can be given orally immediately or administered through a nasogastric tube.

BRILIQUE has two routes of administration for patients unable to swallow whole tablets
BRILIQUE has two routes of administration for patients unable to swallow whole tablets

The glass should be rinsed with a further half glass of water and the contents drunk immediately. It is important to flush the nasogastric tube through with water after administration of the mixture.

NG=nasogastric

Bioavailability of BRILIQUE (ticagrelor)

BRILIQUE (ticagrelor) as crushed tablets mixed in water has a comparable bioavailability to whole tablets with regards to AUC and Cmax for BRILIQUE (ticagrelor) and the active metabolite. Initial exposure (0.5 and 1 hour post-dose) from crushed BRILIQUE (ticagrelor) tablets mixed in water was higher compared to whole tablets, with a generally identical concentration profile thereafter (2 to 48 hours).1

In an open-label cross over study of 36 healthy subjects, administration of crushed ticagrelor 90 mg tablets (orally orvia nasograstric tube) resulted in higher ticagrelor plasma concentrations at early timepoints (0.5 and 1 h) vs. whole tablets.11

How to administer BRILIQUE (ticagrelor) ODT (orodispersible tablet)

Warnings and precautions

For a full list of warnings and precautions, please consult the BRILIQUE (ticagrelor) Summary of Product Characteristics, available at http/www.medicines.org.uk.

BRILIQUE (ticagrelor) Contraindications1

  • Hypersensitivity to the active substance or to any of the excipients
  • Active pathological bleeding
  • History of intracranial haemorrhage
  • Severe hepatic impairment
  • Co-administration  of ticagrelor with strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, nefazodone,ritonavir and atazanavir), as co-administration may lead to a substantial increase in exposure to ticagrelor

BRILIQUE (ticagrelor) special warnings and precautions1

Bleeding risk

Use of BRILIQUE in patients at known increased risk of bleeding should be balanced against benefit in prevention of atherothrombotic events. If clinically indicated, BRILIQUE should be used with caution in patients with:

  • - propensity to bleed (e.g. due to recent trauma, recent surgery, coagulation disorders and active or recent GI bleeding)
  • - concomitant administration of medicinal products that may increase the risk of bleeding (e.g. NSAIDs, oral anticoagulants and/or fibrinolytics) within 24 hours of BRILIQUE dosing.

Moderate hepatic impairment

Caution is advised, as BRILIQUE has not been studied in patients with moderate hepatic impairment.
Risk of bradycardia

Caution is advised in patients with increased risk of bradycardic events (e.g. patients without a pacemaker who have experienced bradycardic related syncope second- or third-degree AV block or sick sinus syndrome), due to limited clinical experience.

Caution should be exercised when administering BRILIQUE concomitantly with medicinal products known to induce bradycardia.

Surgery

BRILIQUE should be discontinued 5 days prior to an intervention if a patient is to undergo elective surgery and antiplatelet effect is not desired.

Patients with prior ischaemic stroke

ACS patients with prior ischaemic stroke can be treated with BRILIQUE for up to 12 months. Treatment beyond 1 year is not recommended in these patients due to the absence of data.
Dyspnoea

Dyspnoea has been reported in patients treated with BRILIQUE. It is usually mild-to-moderate in intensity and often resolves without need for treatment discontinuation. However, if a patient reports new, prolonged or worsened dyspnoea this should be investigated fully and, if not tolerated, treatment should be stopped.

BRILIQUE should be used with caution in patients with a history of asthma and/or COPD, as they may have an increased absolute risk of experiencing dyspnoea.

Creatinine elevations
Creatinine levels may increase during treatment with BRILIQUE, therefore renal function should be checked according to routine medical practice. In patients with ACS, it is recommended that renal function is also checked one month after initiating treatment, paying special attention to patients aged ≥75 years, those with moderate/severe renal impairment and those receiving concomitant ARB treatment.
Uric acid increase
Caution is advised in patients with a history of hyperuricaemia or gouty arthritis. As a precautionary measure, the use of BRILIQUE in patients with uric acid nephropathy is discouraged.
High maintenance-dose aspirin (>300 mg) Co-administration of BRILIQUE and high maintenance-dose ASA (>300 mg) is not recommended.
Premature discontinuation Premature discontinuation with any antiplatelet therapy could result in an increased risk of CV death or MI due to the patient's underlying disease. Therefore, premature discontinuation of treatment should be avoided.
Pregnancy and lactation Women of childbearing potential should use appropriate contraceptive measures to avoid pregnancy during ticagrelor therapy. Ticagrelor is not recommended during pregnancy and/or breastfeeding.

ACS, acute coronary syndrome; ARB, angiotensin receptor blocker; ASA, acetylsalicylic acid; AV,atrioventricular; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; GI, gastrointestinal; MI,myocardial infarction; NSAID, non-steroidal anti-inflammatory drug.

Other adverse events1

For a full list of adverse events, please consult the BRILIQUE (ticagrelor) Summary of Product Characteristics, available at http/www.medicines.org.uk.

The most commonly reported adverse reactions in patients treated with BRILIQUE (ticagrelor) are bleeding and dyspnoea.

Very common

The following adverse reactions are very common (≥1/10) with BRILIQUE (ticagrelor):

  • Blood disorder bleedinga
  • Hyperuricaemiab
  • Dyspnoea

Common

The following adverse reactions are common (≥1/100 to <1/10) with BRILIQUE (ticagrelor):

  • Gout/gouty arthritis
  • Dizziness, syncope and headache
  • Vertigo
  • Hypotension
  • Respiratory system bleedingsc
  • Gastrointestinal haemorrhage,d diarrhoea, nausea, dyspepsia, constipation
  • Subcutaneous or dermal bleeding,e rash, pruritus
  • Urinary tract bleedingf
  • Blood creatinine increaseb
  • Post-procedural haemorrhage, traumatic bleedingsg

ae.g. an increased tendency to bruise, spontaneous haematoma, haemorrhagic diathesis

be.g. frequencies derived from lab observations (uric acid increases to >upper limit of normal from baseline below or within reference range. Creatinine increases of >50% from baseline) and not crude adverse event report frequency

ce.g. epistaxis, haemoptysis

de.g. gingival bleeding, rectal haemorrhage, gastric ulcer haemorrhage

ee.g. ecchymosis, skin haemorrhage, petechiae

fe.g. haematuria, cystitis haemorrhagic

ge.g. contusion, traumatic haematoma, traumatic haemorrhage