What are the details of Ticagrelor (antiplatelet medication) tablets?

Ticagrelor Tablet Details

Formulation and Dosing

Ticagrelor is administered as an oral tablet with a loading dose of 180 mg followed by a maintenance dose of 90 mg twice daily, achieving peak platelet inhibition within 2 hours of administration. 1

Loading Dose

• 180 mg loading dose is the standard for achieving potent and prompt platelet inhibition, not 90 mg 1
• Achieves platelet inhibition within 30 minutes that exceeds levels obtained with 300-600 mg clopidogrel loading doses 1
• Provides significantly more consistent platelet inhibition with less variability compared to clopidogrel 1

Maintenance Dose

• 90 mg twice daily after the initial loading dose 2, 1
• Peak inhibitory effect occurs approximately 2 hours after each maintenance dose 1
• A 60 mg twice daily dose is approved in many countries for extended treatment beyond 12 months in patients with prior myocardial infarction, as this lower dose is better tolerated 2

Pharmacological Properties

Ticagrelor is a reversible P2Y12 receptor antagonist with a plasma half-life of approximately 12 hours, requiring twice-daily dosing for sustained platelet inhibition. 1, 3

Mechanism of Action

• Reversible, direct-acting inhibitor of the adenosine diphosphate (ADP) receptor P2Y12 3, 4
• Binds to the receptor at a location distinct from the ADP binding site 5
• Does not require hepatic conversion to an active metabolite, providing more consistent platelet inhibition compared to clopidogrel 6, 5

Pharmacokinetics

• Faster onset of action than clopidogrel, with significant platelet inhibition within 30 minutes 1, 6
• Allows for faster platelet function recovery after discontinuation compared to irreversible agents 1
• Wait at least 5 days after the last dose before surgery to allow adequate recovery of platelet function 1, 6

Clinical Indications

Acute Coronary Syndromes

Ticagrelor is indicated for dual antiplatelet therapy in patients with acute coronary syndromes, both with and without ST-segment elevation, for up to 12 months. 2, 4

• For ACS without PCI: Ticagrelor 90 mg twice daily plus low-dose aspirin 75-100 mg daily is preferred over clopidogrel plus aspirin 2
• For ACS with PCI and stent placement: Ticagrelor 90 mg twice daily plus low-dose aspirin is recommended, with preference over clopidogrel plus aspirin 2
• Duration of dual antiplatelet therapy is 12 months unless contraindications such as excessive bleeding risk exist 2

Extended Treatment Beyond 12 Months

• In patients who have tolerated dual antiplatelet therapy without bleeding complications, prolonged treatment beyond 12 months should be considered in those with high thrombotic risk and without increased risk for major bleeding 2
• The 60 mg twice daily dose is approved for this extended indication and is better tolerated than the 90 mg dose 2

Concomitant Aspirin Dosing

The aspirin dose used with ticagrelor should not exceed 100 mg daily, as higher aspirin doses may reduce ticagrelor's efficacy. 1

• Loading dose: 162-325 mg aspirin (in aspirin-naïve patients) 6
• Maintenance dose: 75-100 mg daily, with 81 mg being the preferred dose 2, 1, 6
• After 325 mg loading dose administration, maintenance should be 75-100 mg daily 2

Safety Profile and Adverse Effects

Bleeding Risk

• No significant difference in overall major bleeding compared to clopidogrel (11.6% vs 11.2%) 4
• Higher rate of non-CABG-related major bleeding (4.5% vs 3.8% with clopidogrel) 4
• More instances of fatal intracranial bleeding but fewer fatal bleeding events of other types compared to clopidogrel 4

Non-Hemorrhagic Adverse Effects

• Dyspnea occurs in 10-15% of patients, typically within the first week of treatment, usually of mild or moderate severity 1, 3
• Ventricular pauses may occur but are largely asymptomatic 3

Drug Interactions

• Ticagrelor is a P-glycoprotein (P-gp) inhibitor that can increase levels of concomitant medications like dabigatran 1

Special Populations and Contraindications

Atrial Fibrillation Patients Undergoing PCI

• Clopidogrel is preferred over ticagrelor in most patients with atrial fibrillation undergoing PCI who require concomitant oral anticoagulation due to lower bleeding risk 2
• If ticagrelor is chosen in high ischemic/low bleeding risk patients, concomitant aspirin should not be given (avoid triple therapy) 2
• Ticagrelor may be reasonable in patients at high ischemic/thrombotic and low bleeding risks 2

Contraindications and Cautions

• Should be avoided in patients with prior history of intracranial hemorrhage 6
• Caution advised in patients with prior stroke or TIA due to possible increased risk of intracranial bleeding 6
• In the SOCRATES trial, ticagrelor was superior to aspirin in patients with acute ischemic stroke or TIA associated with ipsilateral atherosclerotic stenosis (6.7% vs 9.6% event rate, HR 0.68) 7

Switching Between Antiplatelet Agents

Switching from Clopidogrel to Ticagrelor

• A loading dose of 180 mg ticagrelor should still be administered when switching from clopidogrel 6

Switching from Ticagrelor to Clopidogrel (De-escalation)

• A loading dose of 600 mg clopidogrel should be administered after ticagrelor is discontinued, followed by 75 mg daily maintenance 5
• This de-escalation strategy may be considered as an alternative treatment regimen in NSTE-ACS patients 2