Introduction
Ticagrelor is an oral antiplatelet medication belonging to the class of cyclopentyltriazolopyrimidines (CPTPs). It is a potent P2Y12 adenosine diphosphate (ADP) receptor antagonist approved by the FDA in 2011. Ticagrelor represents a significant advancement in antiplatelet therapy due to its reversible binding and more rapid onset/offset of action compared to clopidogrel.
Mechanism of Action
Ticagrelor inhibits platelet activation and aggregation by selectively and reversibly antagonizing the P2Y12 ADP receptor on platelets. Unlike thienopyridines (clopidogrel, prasugrel), ticagrelor does not require metabolic activation and binds directly to the P2Y12 receptor in a non-competitive manner. Additionally, ticagrelor increases extracellular adenosine levels by inhibiting adenosine reuptake, which may contribute to its pleiotropic effects including coronary vasodilation and anti-inflammatory properties.
Indications
- Acute coronary syndrome (ACS) to reduce rate of cardiovascular death, myocardial infarction, and stroke
- Unstable angina - Non-ST-elevation myocardial infarction (NSTEMI) - ST-elevation myocardial infarction (STEMI) managed medically or with percutaneous coronary intervention (PCI)
- Secondary prevention in patients with history of myocardial infarction
- With aspirin for reduction of stent thrombosis in patients who have undergone PCI
Dosage and Administration
Standard dosing:- Loading dose: 180 mg orally once
- Maintenance dose: 90 mg orally twice daily
- Renal impairment: No dose adjustment required
- Hepatic impairment: Avoid in severe hepatic impairment (Child-Pugh Class C)
- Elderly: No dose adjustment required
- Pediatric: Safety and effectiveness not established
- Can be taken with or without food
- Should be used with aspirin (75-100 mg daily maintenance dose)
- If a dose is missed, take next dose at scheduled time (do not double dose)
Pharmacokinetics
Absorption: Rapidly absorbed with mean bioavailability of 36% Distribution: Volume of distribution 88 L; 99.8% plasma protein bound Metabolism: Primarily via CYP3A4 to active metabolite AR-C124910XX Elimination: Half-life approximately 7 hours for ticagrelor and 9 hours for active metabolite; 58% excreted in feces and 26% in urineContraindications
- History of intracranial hemorrhage
- Active pathological bleeding
- Severe hepatic impairment
- Hypersensitivity to ticagrelor or any component of the formulation
- Concomitant use with strong CYP3A4 inhibitors (ketoconazole, clarithromycin, etc.)
Warnings and Precautions
Bleeding Risk: Significantly increases risk of serious and sometimes fatal bleeding Dyspnea: May cause usually mild dyspnea (20% incidence) typically resolving without intervention Bradyarrhythmias: May cause ventricular pauses, especially in ACS setting Aspirin Dose: Maintenance aspirin dose should not exceed 100 mg daily Discontinuation: Premature discontinuation increases risk of stent thrombosis, MI, and death Surgery: Discontinue 5 days prior to elective surgery if antiplatelet effect not desiredDrug Interactions
Strong CYP3A4 inhibitors: Contraindicated (ketoconazole, itraconazole, voriconazole, clarithromycin) Strong CYP3A4 inducers: Avoid coadministration (rifampin, phenytoin, carbamazepine) CYP3A4 substrates: May increase concentrations of simvastatin, lovastatin (>40 mg daily) Opioids: May delay and decrease ticagrelor absorption Other antiplatelets/anticoagulants: Increased bleeding risk with warfarin, NSAIDs, other antiplateletsAdverse Effects
Common (≥10%): Dyspnea, bleeding, headache Serious:- Major bleeding (TIMI major bleeding: 4.5-7.9%)
- Intracranial hemorrhage (0.3-0.6%)
- Fatal bleeding (0.2-0.3%)
- Ventricular pauses (6% in first week)
- Elevated uric acid
- Increased serum creatinine
Monitoring Parameters
- Signs and symptoms of bleeding
- Complete blood count (baseline and as clinically indicated)
- Renal function (baseline)
- Dyspnea assessment
- ECG monitoring in patients with bradycardia risk factors
- Compliance with twice-daily dosing
- Concomitant aspirin dose (should not exceed 100 mg daily)
Patient Education
- Take exactly as prescribed (twice daily dosing)
- Do not discontinue without consulting healthcare provider
- Report any signs of bleeding (unusual bruising, blood in urine/stool, prolonged bleeding)
- Report shortness of breath or difficulty breathing
- Inform all healthcare providers about ticagrelor use before any procedures
- Use caution with activities that may cause injury/bleeding
- Avoid grapefruit juice (may increase drug levels)
- Store at room temperature
- Keep out of reach of children
References
1. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057. 2. FDA Prescribing Information: Brilinta (ticagrelor). Revised 2023. 3. Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372(19):1791-1800. 4. Storey RF, Becker RC, Harrington RA, et al. Characterization of dyspnoea in PLATO study patients treated with ticagrelor or clopidogrel and its association with clinical outcomes. Eur Heart J. 2011;32(23):2945-2953. 5. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization. Circulation. 2022;145(3):e18-e114.