What is the recommended dosing for Ticagrelor (antiplatelet agent)?

Ticagrelor Dosing Recommendations

The recommended dosing for ticagrelor is a 180 mg loading dose followed by 90 mg twice daily maintenance dose, always administered with low-dose aspirin (81 mg daily). 1

Standard Dosing Regimen

• Loading dose: 180 mg orally (Class I, Level of Evidence: B) 2
• Maintenance dose: 90 mg orally twice daily (Class I, Level of Evidence: B) 2
• Aspirin co-administration: Must be given with low-dose aspirin (81 mg daily) 1

Pharmacokinetic Considerations

Ticagrelor has several advantages over older P2Y12 inhibitors:

• Direct-acting, reversible P2Y12 receptor antagonist that doesn't require hepatic conversion to an active metabolite 1
• Rapid onset of action, achieving significant platelet inhibition within 30 minutes 2
• Peak inhibitory effect seen approximately 2 hours after loading dose 2
• Half-life of 6-12 hours for parent drug and 9 hours for active metabolite 1
• More consistent and potent inhibition of platelet aggregation compared to clopidogrel 3

Special Situations

Prior Clopidogrel Use

• Patients already receiving clopidogrel should still receive the full 180 mg loading dose of ticagrelor 2
• Ticagrelor's benefits were observed regardless of prior clopidogrel therapy (47% of patients in PLATO received clopidogrel at randomization) 2
• Pharmacokinetics of ticagrelor are not affected by prior clopidogrel exposure 3

Perioperative Management

• Discontinue ticagrelor at least 5 days before planned surgery to reduce bleeding risk 2, 1

Reloading Considerations

• In patients already on maintenance ticagrelor therapy who require coronary procedures, a 180 mg reloading dose provides more potent and prompt platelet inhibition compared to the standard 90 mg maintenance dose 4

Important Precautions

• Aspirin dose warning: Higher aspirin doses (>100 mg) reduce ticagrelor's effectiveness according to FDA's "Boxed Warning" 1, 5
• Bleeding risk: Ticagrelor increases risk of bleeding, including fatal intracranial hemorrhage compared with clopidogrel 2, 1
• Contraindications: Avoid in patients with history of intracranial hemorrhage 2, 1
• Caution: Use with careful consideration in patients with prior stroke or TIA due to possible increased risk of intracranial bleeding 2

Drug Interactions

• CYP3A4 interactions: Ticagrelor is metabolized by CYP3A4; avoid strong inhibitors or inducers 1
• Statin considerations:
  • No dosing restrictions with atorvastatin, pravastatin, fluvastatin, pitavastatin, and rosuvastatin 1
  • Simvastatin and lovastatin should not exceed 40 mg daily when used with ticagrelor 1

Adherence Considerations

• Twice-daily dosing regimen may present adherence challenges 1
• Consistent dosing is essential as trough plasma concentrations must be maintained for effective platelet inhibition 3

Ticagrelor has demonstrated superior efficacy compared to clopidogrel in reducing cardiovascular mortality, myocardial infarction, and stroke in patients with acute coronary syndrome 2, 1. The PLATO trial showed significant reductions in the primary composite endpoint (9.8% vs 11.7%, HR 0.84, p<0.001) and all-cause mortality (4.5% vs 5.9%, p<0.001) with ticagrelor compared to clopidogrel 2.