Ticagrelor
Generic: TICAGRELOR
Basic Information
Manufacturer
Hisun Pharmaceuticals USA, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
c4c1ca82-99bd-451a-ad77-7fe28c4ae3e8
Indications & Usage
1 INDICATIONS AND USAGE Ticagrelor is a P2Y 12 platelet inhibitor indicated to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events.
While use is not limited to this setting, the efficacy of Ticagrelor was established in a population with type 2 diabetes mellitus (T2DM).
( 1.2 ) to reduce the risk of stroke in patients with acute ischemic stroke (NIH Stroke Scale score ≤5) or high-risk transient ischemic attack (TIA).
( 1.3 ) 1.2 Coronary Artery Disease but No Prior Stroke or Myocardial Infarction Ticagrelor is indicated to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events [see Clinical Studies ( 14.2 )] .
While use is not limited to this setting, the efficacy of Ticagrelor was established in a population with type 2 diabetes mellitus (T2DM).
1.3 Acute Ischemic Stroke or Transient Ischemic Attack (TIA) Ticagrelor is indicated to reduce the risk of stroke in patients with acute ischemic stroke (NIH Stroke Scale score ≤5) or high-risk transient ischemic attack (TIA) [see Clinical Studies ( 14.3 )] .
1.2 Coronary Artery Disease but No Prior Stroke or Myocardial Infarction Ticagrelor is indicated to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events [see Clinical Studies ( 14.2 )] .
While use is not limited to this setting, the efficacy of Ticagrelor was established in a population with type 2 diabetes mellitus (T2DM).
1.3 Acute Ischemic Stroke or Transient Ischemic Attack (TIA) Ticagrelor is indicated to reduce the risk of stroke in patients with acute ischemic stroke (NIH Stroke Scale score ≤5) or high-risk transient ischemic attack (TIA) [see Clinical Studies ( 14.3 )] .
While use is not limited to this setting, the efficacy of Ticagrelor was established in a population with type 2 diabetes mellitus (T2DM).
( 1.2 ) to reduce the risk of stroke in patients with acute ischemic stroke (NIH Stroke Scale score ≤5) or high-risk transient ischemic attack (TIA).
( 1.3 ) 1.2 Coronary Artery Disease but No Prior Stroke or Myocardial Infarction Ticagrelor is indicated to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events [see Clinical Studies ( 14.2 )] .
While use is not limited to this setting, the efficacy of Ticagrelor was established in a population with type 2 diabetes mellitus (T2DM).
1.3 Acute Ischemic Stroke or Transient Ischemic Attack (TIA) Ticagrelor is indicated to reduce the risk of stroke in patients with acute ischemic stroke (NIH Stroke Scale score ≤5) or high-risk transient ischemic attack (TIA) [see Clinical Studies ( 14.3 )] .
1.2 Coronary Artery Disease but No Prior Stroke or Myocardial Infarction Ticagrelor is indicated to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events [see Clinical Studies ( 14.2 )] .
While use is not limited to this setting, the efficacy of Ticagrelor was established in a population with type 2 diabetes mellitus (T2DM).
1.3 Acute Ischemic Stroke or Transient Ischemic Attack (TIA) Ticagrelor is indicated to reduce the risk of stroke in patients with acute ischemic stroke (NIH Stroke Scale score ≤5) or high-risk transient ischemic attack (TIA) [see Clinical Studies ( 14.3 )] .
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are also discussed elsewhere in the labeling: Bleeding [see Warnings and Precautions ( 5.1 )] Dyspnea [see Warnings and Precautions ( 5.3 )] Most common adverse reactions (>5%) are bleeding and dyspnea.
( 5.1 , 5.3 , 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hisun Pharmaceuticals USA, Inc.
at 1-855-554-4786 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 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.
Ticagrelor has been evaluated for safety in more than 58,000 patients.
Bleeding in THEMIS (Prevention of major CV events in patients with CAD and Type 2 Diabetes Mellitus) The Kaplan-Meier curve of time to first TIMI Major bleeding event is presented in Figure 3.
Figure 3 - Time to first TIMI Major bleeding event (THEMIS) T = Ticagrelor; P = Placebo; N = Number of patients The bleeding events in THEMIS are shown below in Table 6.
Table 6 – Bleeding events (THEMIS) Ticagrelor N=9562 Placebo N=9531 Events / 1000 patient years Events / 1000 patient years TIMI Major 9 4 TIMI Major or Minor 12 5 TIMI Major or Minor or Requiring medical attention 46 18 Fatal bleeding 1 0 Intracranial hemorrhage 3 2 Bleeding in THALES (Reduction in risk of stroke in patients with acute ischemic stroke or TIA) The Kaplan-Meier curve of time course of GUSTO severe bleeding events is presented in Figure 4.
Figure 4 - Time course of GUSTO severe bleeding events KM%: Kaplan-Meier percentage evaluated at Day 30; T = Ticagrelor; P = placebo; N = Number of patients GUSTO Severe : Any one of the following: fatal bleeding, intracranial bleeding (excluding asymptomatic hemorrhagic transformations of ischemic brain infarctions and excluding microhemorrhages < 10 mm evident only on gradient-echo magnetic resonance imaging), bleeding that caused hemodynamic compromise requiring intervention (eg, systolic blood pressure <90 mmg Hg that required blood or fluid replacement, or vasopressor/inotropic support, or surgical intervention).
Intracranial bleeding and fatal bleeding in THALES: In total, there were 21 intracranial hemorrhages (ICHs) for ticagrelor and 6 ICHs for placebo.
Fatal bleedings, almost all ICH, occurred in 11 for ticagrelor and in 2 for placebo.
Bradycardia THEMIS and THALES excluded patients at increased risk of bradycardic events (e.g., patients who have sick sinus syndrome, 2 nd or 3 rd degree AV block, or bradycardic-related syncope and not protected with a pacemaker).
15 16 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of ticagrelor.
Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and lymphatic system disorders: Thrombotic Thrombocytopenic Purpura (TTP) has been rarely reported with the use of ticagrelor.
TTP is a serious condition which can occur after a brief exposure (<2 weeks) and requires prompt treatment.
Immune system disorders: Hypersensitivity reactions including angioedema [see Contraindications ( 4.3 )].
Respiratory Disorders: Central sleep apnea, Cheyne-Stokes respiration Skin and subcutaneous tissue disorders: Rash
( 5.1 , 5.3 , 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hisun Pharmaceuticals USA, Inc.
at 1-855-554-4786 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 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.
Ticagrelor has been evaluated for safety in more than 58,000 patients.
Bleeding in THEMIS (Prevention of major CV events in patients with CAD and Type 2 Diabetes Mellitus) The Kaplan-Meier curve of time to first TIMI Major bleeding event is presented in Figure 3.
Figure 3 - Time to first TIMI Major bleeding event (THEMIS) T = Ticagrelor; P = Placebo; N = Number of patients The bleeding events in THEMIS are shown below in Table 6.
Table 6 – Bleeding events (THEMIS) Ticagrelor N=9562 Placebo N=9531 Events / 1000 patient years Events / 1000 patient years TIMI Major 9 4 TIMI Major or Minor 12 5 TIMI Major or Minor or Requiring medical attention 46 18 Fatal bleeding 1 0 Intracranial hemorrhage 3 2 Bleeding in THALES (Reduction in risk of stroke in patients with acute ischemic stroke or TIA) The Kaplan-Meier curve of time course of GUSTO severe bleeding events is presented in Figure 4.
Figure 4 - Time course of GUSTO severe bleeding events KM%: Kaplan-Meier percentage evaluated at Day 30; T = Ticagrelor; P = placebo; N = Number of patients GUSTO Severe : Any one of the following: fatal bleeding, intracranial bleeding (excluding asymptomatic hemorrhagic transformations of ischemic brain infarctions and excluding microhemorrhages < 10 mm evident only on gradient-echo magnetic resonance imaging), bleeding that caused hemodynamic compromise requiring intervention (eg, systolic blood pressure <90 mmg Hg that required blood or fluid replacement, or vasopressor/inotropic support, or surgical intervention).
Intracranial bleeding and fatal bleeding in THALES: In total, there were 21 intracranial hemorrhages (ICHs) for ticagrelor and 6 ICHs for placebo.
Fatal bleedings, almost all ICH, occurred in 11 for ticagrelor and in 2 for placebo.
Bradycardia THEMIS and THALES excluded patients at increased risk of bradycardic events (e.g., patients who have sick sinus syndrome, 2 nd or 3 rd degree AV block, or bradycardic-related syncope and not protected with a pacemaker).
15 16 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of ticagrelor.
Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and lymphatic system disorders: Thrombotic Thrombocytopenic Purpura (TTP) has been rarely reported with the use of ticagrelor.
TTP is a serious condition which can occur after a brief exposure (<2 weeks) and requires prompt treatment.
Immune system disorders: Hypersensitivity reactions including angioedema [see Contraindications ( 4.3 )].
Respiratory Disorders: Central sleep apnea, Cheyne-Stokes respiration Skin and subcutaneous tissue disorders: Rash