Brilinta 60 Special Precautions

Bleeding risk: As with other antiplatelet agents, the use of BRILINTA in patients at known increased risk for bleeding should be balanced against the benefit in terms of prevention of thrombotic events. If clinically indicated, BRILINTA should be used with caution in the following patient groups: Patients with a propensity to bleed (e.g. due to recent trauma, recent surgery, active or recent gastrointestinal bleeding, or moderate hepatic impairment) or who are at increased risk of trauma. The use of BRILINTA is contraindicated in patients with active pathological bleeding and in those with a history of intracranial haemorrhage, and severe hepatic impairment (see Contraindications).
Patients with concomitant administration of medicinal products that may increase the risk of bleeding (e.g. non-steroidal anti-inflammatory drugs (NSAIDS), oral anticoagulants, and/or fibrinolytics within 24 hours of BRILINTA dosing).
Platelet transfusion did not reverse the antiplatelet effect of BRILINTA in healthy volunteers and is unlikely to be of clinical benefit in patients with bleeding. Since co-administration of BRILINTA with desmopressin did not decrease template bleeding time, desmopressin is unlikely to be effective in managing clinical bleeding events.
Antifibrinolytic therapy (aminocaproic acid or tranexamic acid) and/or recombinant factor VIIa therapy may augment haemostasis. BRILINTA may be resumed after the cause of bleeding has been identified and controlled.
Surgery: If a patient requires surgery, physicians should consider each patient's clinical profile as well as the benefits and risks of continued antiplatelet therapy when determining when discontinuation of BRILINTA treatment should occur.
Because of the reversible binding of BRILINTA, restoration of platelet aggregation occurs faster with BRILINTA compared to clopidogrel. In the OFFSET Study, mean Inhibition of Platelet Aggregation (IPA) for BRILINTA at 72 hours post-dose was comparable to mean IPA for clopidogrel at 120 hours post-dose. The more rapid offset of effect may predict a reduced risk of bleeding complications, e.g. in settings where antiplatelet therapy must be temporarily discontinued due to surgery or trauma.
In PLATO, patients undergoing CABG, BRILINTA had a similar rate of major bleeds compared to clopidogrel at all days after stopping therapy except Day 1 where BRILINTA had a numerically higher rate of major bleeding.
If a patient is to undergo elective surgery and antiplatelet effect is not desired, BRILINTA should be discontinued 5 days prior to surgery (see Pharmacology: Pharmacodynamics under Actions).
Patients with prior ischaemic stroke: ACS patients with prior ischaemic stroke can be treated with BRILINTA for up to 12 months (PLATO Study).
In PEGASUS, patients with history of MI with prior ischaemic stroke were not included.
Therefore, in the absence of data, caution is advised for treatment beyond one year.
Patients with moderate hepatic impairment: There is limited experience with BRILINTA in patients with moderate hepatic impairment therefore, caution is advised in these patients. Use of BRILINTA is contraindicated in patients with severe hepatic impairment (see Dosage & Administration, Contraindications, and Pharmacology: Pharmacokinetics under Actions).
Bradyarrhythmia: Holter ECG monitoring has shown an increased frequency of mostly asymptomatic ventricular pauses during treatment with ticagrelor compared with clopidogrel. In phase 3 studies evaluating the safety and efficacy of BRILINTA, bradyarrhythmic events were reported in a similar frequency for ticagrelor and comparators (placebo, clopidogrel and ASA). Patients with an increased risk of bradycardic events (e.g. patients without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree atrioventricular (AV) block, or bradycardic-related syncope) have been excluded from BRILINTA outcome studies. Therefore, due to the limited clinical experience in these patients, caution is advised (see also Pharmacology: Pharmacodynamics under Actions).
Bradyarrhythmic events and AV blocks have been reported in the post-marketing setting in patients taking BRILINTA (see Adverse Reactions), primarily in patients with ACS, where cardiac ischemia and concomitant drugs reducing the heart rate or affecting cardiac conduction are potential confounders. The patient's clinical condition and concomitant medication should be assessed as potential causes prior to adjusting treatment.
Dyspnoea: Dyspnoea, usually mild to moderate in intensity and often resolving without need for treatment discontinuation, is reported in patients treated with BRILINTA (see Adverse Reactions). The mechanism has not yet been elucidated. If a patient reports new, prolonged or worsened dyspnoea this should be investigated fully, and if not tolerated, treatment with BRILINTA should be stopped.
Central Sleep Apnoea: Central sleep apnoea including Cheyne-Stokes respiration has been reported in the post-marketing setting in patients taking BRILINTA. If central sleep apnoea is suspected, further clinical assessment may be considered.
Thrombotic Thrombocytopenic Purpura (TTP): Thrombotic Thrombocytopenic Purpura has been reported very rarely with the use of BRILINTA. TTP is a serious condition and requires prompt treatment.
Interference with laboratory tests: Platelet function tests to diagnose Heparin induced thrombocytopenia (HIT): False negative results in platelet function test for heparin induced thrombocytopenia (HIT) have been reported in patients administered ticagrelor. This is related to inhibition of the P2Y₁₂-receptor on the healthy donor platelets in the test by ticagrelor in the patient's sera/plasma. Information on concomitant treatment with ticagrelor is required for interpretation of HIT platelet function tests.
Before considering discontinuation of ticagrelor, the benefit and risk of continued treatment should be assessed, taking both the prothrombotic state of HIT and the increased risk of bleeding with concomitant anticoagulant and ticagrelor treatment into consideration.
Uric acid increase: Hyperuricaemia may occur during treatment with ticagrelor (see Adverse Reactions). Caution is advised in patients with history of hyperuricaemia or gouty arthritis. As a precautionary measure, the use of ticagrelor in patients with uric acid nephropathy is discouraged.
Other: Based on a relationship observed in the PLATO Study between maintenance ASA dose and relative efficacy of ticagrelor compared to clopidogrel, co-administration of ticagrelor and high maintenance dose ASA (>300 mg) is not recommended (see Pharmacology: Pharmacodynamics under Actions).
Co-administration of BRILINTA with strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir) is contraindicated (see Contraindications and Interactions). Co-administration may lead to a substantial increase in BRILINTA exposure (see Interactions).
Discontinuations: Patients who require discontinuation of BRILINTA are at increased risk for cardiac events or stroke. Premature discontinuation of treatment should be avoided. If BRILINTA must be temporarily stopped due to an adverse event(s), it should be re-initiated as soon as possible when the benefits outweigh the risks of the adverse event or when the adverse event has come to resolution (see Dosage & Administration).
Effects on ability to drive and use machines: No studies on the effects of BRILINTA on the ability to drive and use machines have been performed. BRILINTA is expected to have no or negligible influence on the ability to drive and use machines. During treatment with BRILINTA, dizziness and confusion have been reported. Therefore, patients who experience these symptoms should be cautious while driving or using machines.