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2015-16
October 20, 2015
November 14, 2015
November 21, 2015
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Washington, DC
Sheraton Harborside
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Heart House
Washington, D.C.
WIC Section Advocacy
Roundtable
Northern New England
Chapter Annual Meeting 2015
Mid-Atlantic Capital
Cardiology Symposium 2015
trim: 8” X 10.5”
BRILINTA® (ticagrelor) tablets, for oral use
BRIEF SUMMARY of PRESCRIBING INFORMATION
For full Prescribing Information, see package insert.
WARNING: (A) BLEEDING RISK, (B) ASPIRIN DOSE AND BRILINTA EFFECTIVENESS
A. BLEEDING RISK
• BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal bleeding
(5.1, 6.1).
• Do not use BRILINTA in patients with active pathological bleeding or a history of
intracranial hemorrhage (4.1, 4.2).
• Do not start BRILINTA in patients undergoing urgent coronary artery bypass graft surgery
(CABG) (5.1, 6.1).
• If possible, manage bleeding without discontinuing BRILINTA. Stopping BRILINTA
increases the risk of subsequent cardiovascular events (5.4).
B. ASPIRIN DOSE AND BRILINTA EFFECTIVENESS
• Maintenance doses of aspirin above 100 mg reduce the effectiveness of BRILINTA and
should be avoided (2.1, 5.2, 14.1).
INDICATIONS AND USAGE
BRILINTA is indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke
in patients with acute coronary syndrome (ACS) or a history of myocardial infarction (MI). 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 [see Clinical Studies (14.1) in full Prescribing Information].
DOSAGE AND ADMINISTRATION
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.
Do not administer BRILINTA with another oral P2Y12 platelet inhibitor.
Use BRILINTA with a daily maintenance dose of aspirin of 75-100 mg [see Warnings (5.2) and
Clinical Studies (14.1) in full Prescribing Information]. A patient who misses a dose of BRILINTA
should take one tablet (their next dose) at its scheduled time.
Administration
For patients who are unable to swallow tablets whole, BRILINTA tablets can be crushed, mixed with
water and drunk. The mixture can also be administered via a nasogastric tube (CH8 or greater) [see
Clinical Pharmacology (12.3) in full Prescribing Information].
CONTRAINDICATIONS
History of Intracranial Hemorrhage
BRILINTA is contraindicated in patients with a history of intracranial hemorrhage (ICH) because of a
high risk of recurrent ICH in this population [see Clinical Studies (14.1) in full Prescribing Information].
Active Bleeding
BRILINTA is contraindicated in patients with active pathological bleeding such as peptic ulcer or
intracranial hemorrhage [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) in full
Prescribing Information].
Hypersensitivity
BRILINTA is contraindicated in patients with hypersensitivity (e.g., angioedema) to ticagrelor or
any component of the product.
WARNINGS AND PRECAUTIONS
General Risk of Bleeding
Drugs that inhibit platelet function including BRILINTA increase the risk of bleeding [see Adverse
Reactions (6.1) in full Prescribing Information].
If possible, manage bleeding without discontinuing BRILINTA. Stopping BRILINTA increases
the risk of subsequent cardiovascular events [see Warnings and Precautions (5.4) and Adverse
Reactions (6.1) in full Prescribing Information].
Concomitant Aspirin Maintenance Dose
In PLATO the use of BRILINTA with maintenance doses of aspirin above 100 mg decreased the
effectiveness of BRILINTA. Therefore, after the initial loading dose of aspirin, use BRILINTA with
a maintenance dose of aspirin o f 75-100 mg [see Dosage and Administration (2.1) and Clinical
Studies (14.1) in full Prescribing Information].
Dyspnea
In clinical trials, about 14% of patients treated with BRILINTA developed dyspnea. Dyspnea was
usually mild to moderate in intensity and often resolved during continued treatment, but led to
study drug discontinuation in 0.9% of BRILINTA and 0.1% of clopidogrel patients in PLATO and
4.3% of BRILINTA 60 mg and 0.7% on aspirin alone patients in PEGASUS.
In a substudy of PLATO, 199 subjects underwent pulmonary function testing irrespective of
whether they reported dyspnea. There was no indication of an adverse effect on pulmonary
function assessed after one month or after at least 6 months of chronic treatment.
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 agent.
Discontinuation of BRILINTA
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.
Severe Hepatic Impairment
Avoid use of BRILINTA in patients with severe hepatic impairment. Severe hepatic impairment
is likely to increase serum concentration of ticagrelor. There are no studies of BRILINTA patients
with severe hepatic impairment [see Clinical Pharmacology (12.3) in full Prescribing Information].
ADVERSE REACTIONS
The following adverse reactions are also discussed elsewhere in the labeling:
• Bleeding [see Warnings and Precautions (5.1) in full Prescribing Information]
• Dyspnea [see Warnings and Precautions (5.3) in full Prescribing Information]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed
in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another
drug and may not reflect the rates observed in practice.
BRILINTA has been evaluated for safety in more than 27000 patients, including more than 13000
patients treated for at least 1 year.
Bleeding in PLATO (Reduction in risk of thrombotic events in ACS)
Figure 1 is a plot of time to the first non-CABG major bleeding event.
Figure 1 - Kaplan-Meier estimate of time to first non-CABG PLATO-defined major bleeding event
(PLATO)
Frequency of bleeding in PLATO is summarized in Tables 1 and 2. About half of the Non-CABG major
bleeding events were in the first 30 days.
Table 1 – Non-CABG related bleeds (PLATO)
PLATO Major + Minor
Major
Fatal/Life-threatening
Fatal
Intracranial hemorrhage
(Fatal/Life-threatening)
BRILINTA*
N=9235
n (%) patients with event
713 (7.7)
362 (3.9)
171 (1.9)
15 (0.2)
Clopidogrel
N=9186
n (%) patients with event
567 (6.2)
306 (3.3)
151 (1.6)
16 (0.2)
26 (0.3)
15 (0.2)
PLATO Minor bleed: requires medical intervention to stop or treat bleeding.
PLATO Major bleed: any one of the following: fatal; intracranial; intrapericardial with cardiac tamponade;
hypovolemic shock or severe hypotension requiring intervention; significantly disabling (e.g., intraocular with
permanent vision loss); associated with a decrease in Hb of at least 3 g/dL (or a fall in hematocrit (Hct) of at
least 9%); transfusion of 2 or more units.
PLATO Major bleed, fatal/life-threatening: any major bleed as described above and associated with a decrease
in Hb of more than 5 g/dL (or a fall in hematocrit (Hct) of at least 15%); transfusion of 4 or more units.
Fatal: A bleeding event that directly led to death within 7 days.
*
90 mg BID
No baseline demographic factor altered the relative risk of bleeding with BRILINTA compared to
clopidogrel.
In PLATO, 1584 patients underwent CABG surgery. The percentages of those patients who bled are
shown in Figure 2 and Table 2.
Figure 2 – ‘Major fatal/life-threatening’ CABG-related bleeding by days from last dose of study
drug to CABG procedure (PLATO)
X-axis is days from last dose of study drug prior to CABG.
The PLATO protocol recommended a procedure for withholding study drug prior to CABG or other major surgery
without unblinding. If surgery was elective or non-urgent, study drug was interrupted temporarily, as follows: If local
practice was to allow antiplatelet effects to dissipate before surgery, capsules (blinded clopidogrel) were withheld
5 days before surgery and tablets (blinded ticagrelor) were withheld for a minimum of 24 hours and a maximum of
72 hours before surgery. If local practice was to perform surgery without waiting for dissipation of antiplatelet effects
capsules and tablets were withheld 24 hours prior to surgery and use of aprotinin or other haemostatic agents was
allowed. If local practice was to use IPA monitoring to determine when surgery could be performed both the capsules
and tablets were withheld at the same time and the usual monitoring procedures followed.
T Ticagrelor; C Clopidogrel.
Table – 2 CABG-related bleeding (PLATO)
PLATO Total Major
Fatal/Life-threatening
Fatal
BRILINTA*
N=770
n (%) patients with event
626 (81.3)
337 (43.8)
6 (0.8)
Clopidogrel
N=814
n (%) patients with event
666 (81.8)
350 (43.0)
7 (0.9)
PLATO Major bleed: any one of the following: fatal; intracranial; intrapericardial with cardiac tamponade;
hypovolemic shock or severe hypotension requiring intervention; significantly disabling (e.g., intraocular with