Ticagrelor, when used together with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with acute coronary syndromes (ACS) or in those with a prior history of myocardial infarction (MI) who are at increased risk of developing atherothrombotic complications.

Ticagrelor is a P2Y₁₂ receptor antagonist that inhibits platelet activation and aggregation. The P2Y₁₂ receptor interacts with Gi proteins, which normally suppress adenylyl cyclase activity. Through Gi-mediated pathways, signaling molecules such as PI3K, Akt, Rap1b, and potassium channels are activated, contributing to platelet aggregation. By blocking the P2Y₁₂ receptor, Ticagrelor prevents these signaling processes, thereby reducing thrombus formation and lowering the risk of myocardial infarction and ischemic stroke.

Patients taking Ticagrelor should also take a daily low maintenance dose of acetylsalicylic acid (ASA) 75-150 mg unless specifically contraindicated.

Acute coronary syndrome: Ticagrelor treatment should be initiated with a single 180 mg loading dose (two tablets of 90 mg) and then continued at 90 mg twice daily. Treatment with Ticagrelor twice daily is recommended for 12 months in ACS patients unless discontinuation is clinically indicated.

History of myocardial infarction: Ticagrelor 60 mg twice daily is the recommended dose when an extended treatment is required for patients with a history of MI of at least one year and a high risk of an atherothrombotic event. Treatment may be started without interruption as continuation therapy after the initial one-year treatment with ticagrelor or another adenosine diphosphate (ADP) receptor inhibitor therapy in ACS patients with a high risk of an atherothrombotic event. Treatment can also be initiated up to 2 years from the MI, or within one year after stopping previous ADP receptor inhibitor treatment. There are limited data on the efficacy and safety of ticagrelor beyond 3 years of extended treatment.

Switch therapy: If a switch is needed, the first dose of ticagrelor should be administered 24 hours following the last dose of the other antiplatelet medication.

Missed dose: A patient who misses a dose of ticagrelor should take only one tablet (their next dose) at its scheduled time.

Elderly: No dose adjustment is required in the elderly.

Renal impairment: No dose adjustment is necessary for patients with renal impairment. No information is available concerning the treatment of patients on renal dialysis and therefore ticagrelor is not recommended in these patients.

Hepatic impairment: Ticagrelor has not been studied in patients with severe hepatic impairment and its use in these patients is therefore contraindicated. Only limited information is available in patients with moderate hepatic impairment. Dose adjustment is not recommended, but ticagrelor should be used with caution. No dose adjustment is necessary for patients with mild hepatic impairment.

Pediatric population: The safety and efficacy of ticagrelor in children below the age of 18 years have not been established. No data are available. Ticagrelor can be administered with or without food. Contra-indications, warnings etc.

Effects of Other Drugs on Ticagrelor:

CYP3A4 inhibitors: Strong CYP3A4 inhibitors (such as clarithromycin, nefazodone, ritonavir, and atazanavir) significantly increase ticagrelor exposure; therefore, their concomitant use is contraindicated.

CYP3A inducers: Potent CYP3A inducers (e.g., rifampicin) may reduce ticagrelor plasma levels and effectiveness; concurrent use is not recommended.

Cyclosporine (P-gp and CYP3A inhibitor): Co-administration with strong P-gp inhibitors or moderate CYP3A inhibitors (e.g., verapamil, quinidine) may increase ticagrelor exposure. Use with caution if unavoidable.

Effects of Ticagrelor on Other Drugs:

CYP3A4 substrates: Ticagrelor may increase exposure of drugs metabolized by CYP3A4. High doses of simvastatin or lovastatin (>40 mg) are not recommended. Increased levels of atorvastatin and its metabolites have been observed but are not clinically significant. Use with drugs having a narrow therapeutic index (e.g., cisapride, ergot alkaloids) should be avoided.

P-gp substrates (e.g., digoxin, cyclosporine): Monitoring is recommended when used together with drugs having a narrow therapeutic range.

CYP2C9 substrates: Ticagrelor has minimal effect on CYP2C9; no significant interaction is expected with drugs like warfarin or tolbutamide.

Oral contraceptives: No clinically relevant interaction has been observed.

Drugs inducing bradycardia: No major adverse interactions noted, but caution is advised with drugs that may lower heart rate.

Other concomitant therapy: No significant interactions with aspirin, PPIs, statins, beta-blockers, ACE inhibitors, or ARBs. However, caution is advised with anticoagulants, fibrinolytics, and SSRIs due to increased bleeding risk.

Ticagrelor is contraindicated in patients with hypersensitivity to the drug or its components, active pathological bleeding, history of intracranial hemorrhage, and severe hepatic impairment.

Very Common: Bleeding events, hyperuricemia, dyspnea.

Common: Gout, dizziness, syncope, headache, vertigo, hypotension, respiratory bleeding, gastrointestinal bleeding, diarrhea, nausea, dyspepsia, constipation, subcutaneous bleeding, rash, pruritus, urinary tract bleeding, increased creatinine, post-procedural bleeding, traumatic bleeding.

Uncommon: Tumor-related bleeding, hypersensitivity (including angioedema), confusion, intracranial hemorrhage, eye bleeding, ear bleeding, retroperitoneal bleeding, muscular bleeding.

Ticagrelor is not recommended during pregnancy. Animal studies indicate that ticagrelor and its metabolites are excreted in milk, and potential risk to the infant cannot be excluded. A decision should be made whether to discontinue breastfeeding or stop the drug, considering the benefits of both.

Bleeding risk: Use with caution in patients at increased risk of bleeding (e.g., recent trauma, surgery, or gastrointestinal bleeding). Combination with fibrinolytics or anticoagulants may further increase bleeding risk.

Surgery: Patients should inform healthcare providers before surgery. Ticagrelor should be discontinued at least 5 days prior to elective surgery.

Special populations: Use with caution in patients with a history of stroke, asthma/COPD (due to dyspnea risk), and renal impairment. Monitor renal function and uric acid levels.

Ticagrelor is generally well tolerated at single doses up to 900 mg. Overdose may lead to gastrointestinal toxicity, dyspnea, and ventricular pauses.

Antiplatelet agent.

Store in a cool and dry place, protected from light.