US FDA Approves Expanded Indication for AZ Medicine

WRITTEN BY

Meredith Hemler

On September 3, 2015, the US Food and Drug Administration (FDA) approved BRILINTA® (ticagrelor) tablets at a new 60mg dose to be used in patients with a history of heart attack beyond the first year. With this expanded indication, BRILINTA is now approved to reduce the rate of cardiovascular death, myocardial infarction (MI, also known as heart attack) and stroke in patients with acute coronary syndrome (ACS) or a history of MI.

The approval is based on the PEGASUS TIMI-54 study, a large-scale outcomes trial involving more than 21,000 patients. PEGASUS TIMI-54 investigated ticagrelor tablets plus low-dose aspirin, compared to placebo plus low-dose aspirin, for the long-term prevention of cardiovascular death, heart attack and stroke in patients ≥ 50 years old who had experienced a heart attack one to three years prior to study enrollment and had at least one risk factor for thrombotic cardiovascular events. The PEGASUS-TIMI 54 trial demonstrated that the addition of BRILINTA to low-dose aspirin in patients with a prior heart attack significantly reduced the risk of dying from cardiovascular causes, having another heart attack, or having a stroke.  In PEGASUS, TIMI Major and TIMI Major/Minor bleeding1 were higher for BRILINTA than for aspirin alone.

Paul Hudson, President, AstraZeneca US and Executive Vice President, North America, explains what this approval means for BRILINTA, healthcare practitioners and patients:

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.

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.

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
  • 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

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

Between PLATO and now PEGASUS, nearly 40,000 patients have been studied in clinical trials with BRILINTA. BRILINTA has been approved in over 100 countries for patients with ACS and is included in 12 major ACS treatment guidelines globally. In the American Heart Association (AHA)/American College of Cardiology (ACC) 2014 NSTE-ACS Guideline, BRILINTA is preferred over clopidogrel for the maintenance treatment in NSTE-ACS patients (Class IIa; Level of Evidence B) and is recommended as a treatment option in the management of NSTE-ACS patients (Class I; Level of Evidence B).2-4

The new BRILINTA 60mg tablet is expected to be available in pharmacies by the end of September 2015.

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

Patients can find out more information about BRILINTA at www.BRILINTAtouchpoints.com or by calling 1-888-412-7454.

AstraZeneca offers the AZ&MeTM Prescription Savings Program. To determine eligibility, patients can visit www.AZandMe.com or call 1-800-AZandMe (292-6363).

BRILINTA is a registered trademark of AstraZeneca group of companies.

1TIMI Major Bleeding Classification

  • Any intracranial bleeding, or
  • Clinically overt signs of hemorrhage associated with a drop in hemoglobin (Hgb) of ≥5 g/dL (or, when hemoglobin is not available, a fall in hematocrit of ≥15%), or
  • Fatal bleeding (a bleeding event that directly led to death within 7 days).

2Class IIa states that it is reasonable to perform procedure/administer treatment

3Class I recommends that the procedure/treatment should be performed/administered

4Level B is based on data derived from a single randomized clinical trial or nonrandomized studies

© AstraZeneca 2015

 

3150803 Last Updated 9/15