Common drugs: Ticagrelor profile

Ticagrelor is an antagonist of the P2Y ₁₂ receptor on the surface of platelets. The natural agonist of this receptor is adenosine diphosphate (ADP), which is one of the platelet activators. When ADP binds to the P2Y ₁₂ receptor, it causes platelet activation and aggregation, forming a white thrombus.

Unlike its precursor drugs, clopidogrel and prasugrel, ticagrelor blocks the _P2Y12 receptor competitively rather than irreversibly. Its duration of action is therefore limited by the half-lives of ticagrelor and its main active metabolite; it lasts up to 24 hours. This makes the drug more controllable. However, it also means that ticagrelor must be taken twice daily, whereas clopidogrel and prasugrel require a single daily dose. Another difference from clopidogrel and prasugrel is that ticagrelor is not a prodrug. Its effect begins after 30 minutes.

In which indications is ticagrelor used?

Ticagrelor acts synergistically with low-dose acetylsalicylic acid (ASA) (75 to 150 mg) and is therefore combined with it for platelet aggregation inhibition. The combination is indicated for the prevention of atherothrombotic events in adult patients with acute coronary syndrome (ACS) or a history of myocardial infarction.

How is ticagrelor dosed?

Patients with ACS begin treatment with ticagrelor with a single initial dose of 180 mg, followed by 90 mg twice daily with or without food. Combination therapy with aspirin should be continued for 12 months. Under certain circumstances, in patients with an increased risk of bleeding, aspirin can be discontinued after three months, allowing ticagrelor to be continued alone for nine months.

If a heart attack occurred at least one year ago, ticagrelor is administered as immediate follow-up treatment at 60 mg twice daily. Aspirin should continue to be administered at 75 to 150 mg daily, unless specifically contraindicated.

When should ticagrelor not be used?

Ticagrelor is contraindicated in patients with active pathological bleeding, a history of intracranial bleeding, severe liver impairment, and during breastfeeding. Relative contraindications include bleeding tendencies and an increased risk of bradycardic events, as well as renal disorders (uric acid nephropathy, dialysis requirements), moderate liver impairment, gout, asthma/COPD, and pregnancy. Patients of childbearing potential treated with ticagrelor should use effective contraception.

What side effects can ticagrelor have?

Very common side effects of ticagrelor are bleeding, increased uric acid levels and gout, dyspnea, dizziness, hypotension, gastrointestinal disturbances and increased serum creatinine levels.

What interactions are possible?

Ticagrelor is metabolized in the liver primarily via CYP3A4. Concomitant use with strong CYP3A4 inhibitors is contraindicated; concomitant use with potent CYP3A4 inducers is discouraged. Since the active ingredient also slightly inhibits CYP3A4, concomitant use with substrates of this enzyme can be problematic. For this reason, the two statins simvastatin and lovastatin should not be dosed higher than 40 mg daily when administered concomitantly with ticagrelor.

What should be taken into account when moving and weaning?

If a patient is switching from another antiplatelet agent to ticagrelor, the first dose of ticagrelor should be taken 24 hours after the last dose of the previous drug. Before scheduled surgery, patients taking ticagrelor should inform their doctor or dentist. If advised by the surgeon, ticagrelor may be discontinued five days before the procedure.

Which ADP antagonist is the best?