Bricor Special Precautions

Bleeding risk: As with other antiplatelet agents, the use of Ticagrelor in patients at known increased risk for bleeding should be balanced against the benefit in terms of prevention of thrombotic events.
If clinically indicated, Ticagrelor should be used with caution in the following patient groups: Consideration should be given to following: Patients with a propensity to bleed (e.g. due to recent trauma, recent surgery, active or recent gastrointestinal bleeding or moderate hepatic impairment). The use of Ticagrelor is contraindicated in patients with active pathological bleeding and in those with history of intracranial haemorrhage, and severe hepatic impairment.
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 Ticagrelor dosing).
No data exist with Ticagrelor regarding a haemostatic benefit of platelet transfusions; circulating Ticagrelor may inhibit transfused platelets. Since co-administration of Ticagrelor with desmopressin did not increase platelet 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 may augment haemostasis. Ticagrelor 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 Ticagrelor treatment should occur.
Because of the reversible binding of Ticagrelor, restoration of platelet aggregation occurs faster with Ticagrelor compared to clopidogrel. In the OFFSET study, mean Inhibition of Platelet Aggregation (IPA) for Ticagrelor 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, Ticagrelor had a similar rate of major bleeds compared to clopidogrel at all days after stopping therapy except Day 1 where Ticagrelor had a higher rate of major bleeding.
If a patient is to undergo elective surgery and antiplatelet effect is not desired, Ticagrelor should be discontinued 5 days prior to surgery.
Patients with moderate hepatic treatment: Caution is advised in patients with moderate hepatic impairment because Ticagrelor has not been studied in these patients. Use of Ticagrelor is contraindicated in patients with severe hepatic impairment.
Patients at risk for bradycardic events: Due to observation of mostly asymptomatic ventricular pauses in an earlier clinical study, patients with an increased risk of bradycardic events (e.g. patients without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree AV block or bradycardic-related syncope) were excluded from the main study evaluating the safety and efficacy of Ticagrelor. Therefore due to the limited clinical experience in these patients, caution is advised.
Dyspnoea: Dyspnoea, usually mild to moderate in intensity and often resolving without need for treatment discontinuation, is reported in patients treated with Ticagrelor (approximately 13.8%). 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 Ticagrelor should be stopped.
Others: Based on a relationship observed in PLATO 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.
Co-administration of Ticagrelor with strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir) would be expected to have similar effects and should not be given concomitantly with Ticagrelor.
Discontinuations: Patients who require discontinuation of Ticagrelor are at increased risk for cardiac events. Premature discontinuation of treatment should be avoided. If Ticagrelor 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.