Platelet Inhibition of BRILINTA

Review platelet inhibition data for BRILINTA.

BRILINTA provided rapid onset and high inhibition of platelet aggregation (IPA)1,2

In a multicenter, randomized, double-blind study, patients with stable coronary artery disease (CAD) who were taking aspirin therapy (75 mg to 100 mg per day) received BRILINTA (180-mg loading dose, 90-mg twice daily maintenance dose), clopidogrel (600-mg loading dose, 75-mg once daily maintenance dose), or placebo for 6 weeks.1

Assessment of IPA over 8 hours after 180-mg loading dose2,3

Assessment of inhibition of Platelet Aggregation for BRILINTA® (ticagrelor) tablets

ADP=adenosine diphosphate.

  • It is not known how bleeding risk or thrombotic risk track with IPA for either BRILINTA or clopidogrel3
  • The maximum IPA effect of BRILINTA was 88% at around 2 hours and was maintained for at least 8 hours2,3
  • IPA was higher in the BRILINTA group at all time points3
  • Patients can be transitioned from clopidogrel to BRILINTA without interruption of antiplatelet effect3
    • The transition from clopidogrel to BRILINTA resulted in an absolute IPA increase of 26.4%, and the transition from BRILINTA to clopidogrel resulted in an absolute IPA decrease of 24.5%

IMPORTANT SAFETY INFORMATION FOR BRILINTA® (ticagrelor) 60-mg AND 90-mg TABLETS
WARNING: (A) BLEEDING RISK, (B) ASPIRIN DOSE AND BRILINTA EFFECTIVENESS

A. BLEEDING RISK
  • BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal bleeding
  • Do not use BRILINTA in patients with active pathological bleeding or a history of intracranial hemorrhage
  • Do not start BRILINTA in patients undergoing urgent coronary artery bypass graft surgery

BRILINTA offset of Platelet Aggregation Inhibition3

Assessment of IPA after the last dose following 6 weeks on placebo, ticagrelor 90 mg twice daily, or clopidogrel 75 mg daily

Offset of Platelet Aggregation Inhibition for BRILINTA® (ticagrelor) tablets

BID=twice daily.

QD=once daily.

Demonstrated in patients with stable CAD.

  • It is not known how either bleeding risk or thrombotic risk track with IPA for either BRILINTA or clopidogrel3
  • Do not start BRILINTA in patients undergoing urgent coronary artery bypass graft surgery3
  • Discontinuation of BRILINTA will increase the risk of myocardial infarction, stroke, and death. If BRILINTA must be temporarily discontinued (e.g., to treat bleeding or for significant surgery), restart it as soon as possible. When possible, interrupt therapy with BRILINTA for five days prior to surgery that has a major risk of bleeding. Resume BRILINTA as soon as hemostasis is achieved
1975408-3218312 Last Updated 10/16

IMPORTANT SAFETY INFORMATION FOR BRILINTA® (ticagrelor) 60-mg AND 90-mg TABLETS

WARNING: (A) BLEEDING RISK, (B) ASPIRIN DOSE AND BRILINTA EFFECTIVENESS A. BLEEDING RISK

  • BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal bleeding
  • Do not use BRILINTA in patients with active pathological bleeding or a history of intracranial hemorrhage
  • Do not start BRILINTA in patients undergoing urgent coronary artery bypass graft surgery 
  • If possible, manage bleeding without discontinuing BRILINTA. Stopping BRILINTA increases the risk of subsequent cardiovascular events

B. ASPIRIN DOSE AND BRILINTA EFFECTIVENESS

  • Maintenance doses of aspirin above 100 mg reduce the effectiveness of BRILINTA and should be avoided

CONTRAINDICATIONS

  • BRILINTA is contraindicated in patients with a history of intracranial hemorrhage or active pathological bleeding such as peptic ulcer or intracranial hemorrhage. BRILINTA is also contraindicated in patients with hypersensitivity (eg, angioedema) to ticagrelor or any component of the product

WARNINGS AND PRECAUTIONS

  • Dyspnea was reported in about 14% of patients treated with BRILINTA, more frequently than in patients treated with control agents. Dyspnea resulting from BRILINTA is often self-limiting
  • Discontinuation of BRILINTA will increase the risk of MI, stroke, and death. When possible, interrupt therapy with BRILINTA for 5 days prior to surgery that has a major risk of bleeding. If BRILINTA must be temporarily discontinued, restart as soon as possible
  • Ticagrelor can cause ventricular pauses. Bradyarrhythmias including AV block have been reported in the post-marketing setting. PLATO and PEGASUS excluded patients at increased risk of bradyarrhythmias not protected by a pacemaker, and they may be at increased risk of developing bradyarrhythmias with ticagrelor
  • Avoid use of BRILINTA in patients with severe hepatic impairment. Severe hepatic impairment is likely to increase serum concentration of ticagrelor and there are no studies of BRILINTA in these patients

ADVERSE REACTIONS

  • The most common adverse reactions associated with the use of BRILINTA included bleeding and dyspnea: In PLATO, for BRILINTA vs clopidogrel, non-CABG PLATO-defined major bleeding (3.9% vs 3.3%) and dyspnea (14% vs 8%); in PEGASUS, BRILINTA vs aspirin alone, TIMI Total Major bleeding (1.7% vs 0.8%) and dyspnea (14% vs 6%)

DRUG INTERACTIONS

  • Avoid use with strong CYP3A inhibitors and strong CYP3A inducers. BRILINTA is metabolized by CYP3A4/5. Strong inhibitors substantially increase ticagrelor exposure and so increase the risk of adverse events. Strong inducers substantially reduce ticagrelor exposure and so decrease the efficacy of ticagrelor
  • Patients receiving more than 40 mg per day of simvastatin or lovastatin may be at increased risk of statin-related adverse events
  • Monitor digoxin levels with initiation of, or change in, BRILINTA therapy

INDICATIONS

BRILINTA is indicated to reduce the rate of cardiovascular death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction. For at least the first 12 months following ACS, it is superior to clopidogrel.

BRILINTA also reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS.

DOSING

In the management of ACS, initiate BRILINTA treatment with a 180-mg loading dose. Administer 90 mg twice daily during the first year after an ACS event. After one year administer 60 mg twice daily. Use BRILINTA with a daily maintenance dose of aspirin of 75-100 mg.

Please read full Prescribing Information , including Boxed WARNINGS, and Medication Guide  .

REFERENCES:

  1. Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009;120(25):2577-2585.
  2. Data on file, 1766201. AstraZeneca Pharmaceuticals LP.
  3. BRILINTA [package insert]. Wilmington, DE: AstraZeneca LP; 2016.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.