US-19233 ------------------------- DOSAGE AND ...

1 US-19233 ------------------------- DOSAGE AND ADMINISTRATION -------------------------- highlights OF prescribing information Initiate treatment with 180 mg oral loading dose following an ACS event. Continue treatment with 90 mg twice daily during the first year after an ACS. These highlights do not include all the information needed to use brilinta . event. After one year, administer 60 mg twice daily. ( ). safely and effectively. See full prescribing information for brilinta . Use brilinta with a daily maintenance dose of aspirin of 75-100 mg. brilinta (ticagrelor) tablets, for oral use ( , ). Initial Approval: 2011. ------------------------ DOSAGE FORMS AND STRENGTHS ------------------------ 60 mg and 90 mg tablets (3). WARNING: (A) BLEEDING RISK, and (B) ASPIRIN DOSE AND. brilinta EFFECTIVENESS -------------------------------- CONTRAINDICATIONS ------------------------------- See full prescribing information for complete boxed warning.

2 History of intracranial hemorrhage. ( ). BLEEDING RISK Active pathological bleeding. ( ). brilinta , like other antiplatelet agents, can cause significant, Hypersensitivity to ticagrelor or any component of the product. ( ). sometimes fatal bleeding. ( , ) -------------------------- WARNINGS AND PRECAUTIONS ------------------------- Do not use brilinta in patients with active pathological bleeding or Dyspnea was reported more frequently with brilinta than with control a history of intracranial hemorrhage. ( , ) agents in clinical trials. Dyspnea resulting from brilinta is self-limiting. Do not start brilinta in patients undergoing urgent coronary artery ( ). bypass graft surgery (CABG). ( , ) Severe Hepatic Impairment: Likely increase in exposure to ticagrelor. ( ). If possible, manage bleeding without discontinuing brilinta . Stopping brilinta increases the risk of subsequent cardiovascular ------------------------------- ADVERSE REACTIONS -------------------------------- events.

3 ( ) Most common adverse reactions are bleeding 12% and dyspnea 14%. ( , ASPIRIN DOSE AND brilinta EFFECTIVENESS , ). Maintenance doses of aspirin above 100 mg reduce the To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at effectiveness of brilinta and should be avoided. ( , , ) 1-800-236-9933 or FDA at 1-800-FDA-1088 or --------------------------------DRUG INTERACTIONS -------------------------------- ------------------------------ INDICATIONS AND USAGE ---------------------------- Avoid use with strong CYP3A inhibitors or CYP3A inducers. ( , ). brilinta is a P2Y12 platelet inhibitor indicated to reduce the rate of Opioids: Decreased exposure to ticagrelor. Consider use of parenteral cardiovascular death, myocardial infarction, and stroke in patients with acute anti-platelet agent. ( ). coronary syndrome (ACS) or a history of myocardial infarction (MI). For at Patients receiving more than 40 mg per day of simvastatin or lovastatin least the first 12 months following ACS, it is superior to clopidogrel.

4 brilinta may be at increased risk of statin-related adverse effects. ( ). also reduces the rate of stent thrombosis in patients who have been stented Monitor digoxin levels with initiation of or any change in brilinta . ( ). for treatment of ACS. (1). See 17 for PATIENT COUNSELING information and Medication Guide Revised: 03/2018. FULL prescribing information : CONTENTS*. WARNING: (A) BLEEDING RISK, (B) ASPIRIN DOSE AND 8 USE IN SPECIFIC POPULATIONS. brilinta EFFECTIVENESS Pregnancy 1 INDICATIONS AND USAGE Nursing Mothers 2 DOSAGE AND ADMINISTRATION Pediatric Use Dosing Geriatric Use Administration Hepatic Impairment 3 DOSAGE FORMS AND STRENGTHS Renal Impairment 4 CONTRAINDICATIONS 10 OVERDOSAGE. History of Intracranial Hemorrhage 11 DESCRIPTION. Active Bleeding 12 CLINICAL PHARMACOLOGY. Hypersensitivity Mechanism of Action 5 WARNINGS AND PRECAUTIONS Pharmacodynamics General Risk of Bleeding Pharmacokinetics Concomitant Aspirin Maintenance Dose Pharmacogenetics Dyspnea 13 NONCLINICAL TOXICOLOGY.

5 Discontinuation of brilinta Carcinogenesis, Mutagenesis, Impairment of Fertility Bradyarrhythmias 14 CLINICAL STUDIES. Severe Hepatic Impairment Acute Coronary Syndromes and Secondary Prevention after 6 ADVERSE REACTIONS Myocardial Infarction Clinical Trials Experience 16 HOW SUPPLIED/STORAGE AND HANDLING. Postmarketing Experience 17 PATIENT COUNSELING information . 7 DRUG INTERACTIONS. Strong CYP3A Inhibitors * Sections or subsections omitted from the full prescribing information are Strong CYP3A Inducers not listed. Aspirin Opioids Simvastatin, Lovastatin Digoxin brilinta (ticagrelor) tablets, for oral use 2. FULL prescribing information Dyspnea In clinical trials, about 14% of patients treated with brilinta developed WARNING: (A) BLEEDING RISK, (B) ASPIRIN DOSE dyspnea. Dyspnea was usually mild to moderate in intensity and often AND brilinta EFFECTIVENESS resolved during continued treatment, but led to study drug discontinuation in of brilinta and of clopidogrel patients in PLATO and of A.

6 BLEEDING RISK brilinta 60 mg and on aspirin alone patients in PEGASUS. brilinta , like other antiplatelet agents, can cause significant, In a substudy of PLATO, 199 subjects underwent pulmonary function testing sometimes fatal bleeding ( , ). irrespective of whether they reported dyspnea. There was no indication of an Do not use brilinta in patients with active pathological bleeding or adverse effect on pulmonary function assessed after one month or after at a history of intracranial hemorrhage ( , ). least 6 months of chronic treatment. Do not start brilinta in patients undergoing urgent coronary artery If a patient develops new, prolonged, or worsened dyspnea that is determined bypass graft surgery (CABG) ( , ). to be related to brilinta , no specific treatment is required; continue brilinta . If possible, manage bleeding without discontinuing brilinta . without interruption if possible. In the case of intolerable dyspnea requiring Stopping brilinta increases the risk of subsequent cardiovascular discontinuation of brilinta , consider prescribing another antiplatelet agent.

7 Events ( ). Discontinuation of brilinta . B. ASPIRIN DOSE AND brilinta EFFECTIVENESS Discontinuation of brilinta will increase the risk of myocardial infarction, Maintenance doses of aspirin above 100 mg reduce the stroke, and death. If brilinta must be temporarily discontinued ( , to effectiveness of brilinta and should be avoided ( , , ). 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 1 INDICATIONS AND USAGE achieved. brilinta is indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ACS) or a Bradyarrhythmias history of myocardial infarction (MI). For at least the first 12 months following Ticagrelor can cause ventricular pauses [see Adverse Reactions ( )].

8 ACS, it is superior to clopidogrel. Bradyarrhythmias including AV block have been reported in the postmarketing setting. Patients with a history of sick sinus syndrome, 2nd or 3rd degree brilinta also reduces the rate of stent thrombosis in patients who have been AV block or bradycardia-related syncope not protected by a pacemaker stented for treatment of ACS [see Clinical Studies ( )]. were excluded from PLATO and PEGASUS and may be at increased risk of 2 DOSAGE AND ADMINISTRATION developing bradyarrhythmias with ticagrelor. Dosing Severe Hepatic Impairment In the management of ACS, initiate brilinta treatment with a 180 mg loading Avoid use of brilinta in patients with severe hepatic impairment. Severe dose. Administer 90 mg twice daily during the first year after an ACS event. hepatic impairment is likely to increase serum concentration of ticagrelor. After one year administer 60 mg twice daily. There are no studies of brilinta patients with severe hepatic impairment Do not administer brilinta with another oral P2Y12 platelet inhibitor.

9 [see Clinical Pharmacology ( )]. Use brilinta with a daily maintenance dose of aspirin of 75-100 mg [see 6 ADVERSE REACTIONS. Warnings and Precautions ( ) and Clinical Studies ( )]. A patient who The following adverse reactions are also discussed elsewhere in the labeling: misses a dose of brilinta should take one tablet (their next dose) at its Bleeding [see Warnings and Precautions ( )]. scheduled time. Dyspnea [see Warnings and Precautions ( )]. Administration Clinical Trials Experience 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 Because clinical trials are conducted under widely varying conditions, adverse via a nasogastric tube (CH8 or greater) [see Clinical Pharmacology ( )]. 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 3 DOSAGE FORMS AND STRENGTHS rates observed in practice.

10 brilinta (ticagrelor) 90 mg is supplied as a round, biconvex, yellow, brilinta has been evaluated for safety in more than 27000 patients, including film-coated tablet marked with a 90 above T on one side. more than 13000 patients treated for at least 1 year. brilinta (ticagrelor) 60 mg is supplied as a round, biconvex, pink, Bleeding in PLATO (Reduction in risk of thrombotic events in ACS). film-coated tablet marked with 60 above T on one side. Figure 1 is a plot of time to the first non-CABG major bleeding event. 4 CONTRAINDICATIONS Figure 1 - Kaplan-Meier estimate of time to first non-CABG PLATO-defined History of Intracranial Hemorrhage major bleeding event (PLATO). 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 ( )]. Active Bleeding brilinta is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage [see Warnings and Precautions ( ) and Adverse Reactions ( )].