DYSPNEA

DYSPNEA WAS USUALLY MILD TO MODERATE IN INTENSITY AND OFTEN RESOLVED DURING CONTINUED TREATMENT1

INCIDENCE OF DYSPNEA IN THE PLATO* TRIAL1-3

  BRILINTA 90 mg + ASPIRIN (N=9235) CLOPIDOGREL + ASPIRIN (N=9186)
OVERALL RATE OF DYSPNEA 14% 8%
MILD DYSPNEA 9.6% 5.5%
MODERATE DYSPNEA 4.5% 2.4%
SEVERE DYSPNEA 0.4% 0.2%
DISCONTINUATION DUE TO DYSPNEA 0.9% 0.1%

Patients may be counted in more than 1 event category. Patients with multiple events in the same category being tabulated are counted only once within that category.2
Dyspnea was prospectively evaluated in the PLATO trial. At enrollment, PLATO investigators were asked to record whether there was a history of dyspnea and/or current dyspnea and record occurrences of dyspnea as adverse events (AEs) or serious adverse events (SAEs) throughout the trial.3

  • If a patient develops new, prolonged, or worsened dyspnea that is determined to be related to BRILINTA, no specific treatment is required; continue BRILINTA without interruption if possible. In the case of intolerable dyspnea requiring discontinuation of BRILINTA, consider prescribing another antiplatelet agent1
  • In the PLATO trial, onset of dyspnea was more likely to occur within 7 days of initiation in the BRILINTA group (vs the clopidogrel group) and median time to onset of dyspnea in the BRILINTA group was 23 days (vs 43 days for the clopidogrel group)3
  • In a substudy of 199 patients from the PLATO trial who underwent pulmonary function testing irrespective of whether they reported dyspnea1:
    • No indication of an adverse effect on pulmonary function after 1 month or after at least 6 months of chronic treatment

HYPOTHESIZED MECHANISM FOR DYSPNEA

  • The mechanism of dyspnea reported by patients taking BRILINTA is not known, and further studies are necessary3
    • Adenosine receptors are found in the lungs, where adenosine has been shown to stimulate sensory nerve fibers that can produce dyspnea4
    • One hypothesis is that ticagrelor may increase endogenous levels of adenosine by interfering with adenosine uptake and degradation. There may be other possible mechanisms involved5,6

INCIDENCE OF DYSPNEA IN PEGASUS TRIAL1

  BRILINTA 60 mg + ASPIRIN (N=6958) ASPIRIN alone (N=6996)
OVERALL RATE OF DYSPNEA 14% 6%
DISCONTINUATION DUE TO DYSPNEA 4.3% 0.7%

Additional safety

See additional information for bleeding and other adverse reactions.

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
  • As with other oral P2Y12 inhibitors, co-administration of opioid agonists delay and reduce the absorption of ticagrelor. Consider use of a parenteral anti-platelet in ACS patients requiring co-administration
  • 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 Medication Guide and Prescribing Information, including Boxed WARNINGS, for BRILINTA.