indication

For the prevention of thrombotic events (for example stroke or heart attack) in patients with acute coronary syndrome or myocardial infarction with ST elevation.

pharmacology

Plasma concentrations of ticagrelor are slightly increased (12–23%) in elderly patients, women, patients of Asian ethnicity, and patients with mild hepatic impairment. They are decreased in patients that described themselves as 'coloured' and such with severe renal impairment. These differences are considered clinically irrelevant. In Japanese people, concentrations are 40% higher than in Caucasians, or 20% after body weight correction. The drug has not been tested in patients with severe hepatic impairment.

mechanism of action

Like the thienopyridines prasugrel, clopidogrel and ticlopidine, ticagrelor blocks adenosine diphosphate (ADP) receptors of subtype P2Y12. In contrast to the other antiplatelet drugs, ticagrelor has a binding site different from ADP, making it an allosteric antagonist, and the blockage is reversible. Moreover, the drug does not need hepatic activation, which might work better for patients with genetic variants regarding the enzyme CYP2C19 (although it is not certain whether clopidogrel is significantly influenced by such variants).

toxicity

Bleeding is the expected pharmacologic effect of overdosing. If bleeding occurs, appropriate supportive measures should be taken. Other effects of overdose may include gastrointestinal effects (nausea, vomiting, diarrhea) or ventricular pauses.

biotransformation

The main metabolite, AR-C124910XX, is formed quickly via CYP3A4 by de-hydroxyethylation at position 5 of the cyclopentane ring. The metabolite reaches 30–40% of ticagrelor's plasma concentrations.

absorption

Absorbed quickly from the gut, the bioavailability being 36%.

route of elimination

The primary route of ticagrelor elimination is hepatic metabolism. When radiolabeled ticagrelor is administered, the mean recovery of radioactivity is approximately 84% (58% in feces, 26% in urine).

drug interactions

Conivaptan: CYP3A4 Inhibitors (Strong) such as conivaptan may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. Avoid use of ticagrelor in combination with strong CYP3A4 inhibitors.

Lovastatin: Patients receiving more than 40 mg per day of lovastatin may be at increased risk of statin-related adverse effects.

Simvastatin: Patients receiving more than 40 mg per day of simvastatin may be at increased risk of statin-related adverse effects.