1.1. Adults

Platelet aggregation inhibitors (PAIs) are FDA-approved to reduce thrombotic cardiovascular events in patients with a history of ischemic stroke, or to prevent stroke in patients with predisposing factors for atherosclerosis or symptomatic cerebrovascular disease.1-12 PAIs work by interfering with pathways that promote normal platelet function: inhibiting cyclooxygenase-1 (e.g., aspirin); inhibiting adenosine uptake into platelets, resulting in increased cyclic-3’,5’-adenosine monophosphate (cAMP) and adenosine levels (e.g., dipyridamole); inhibiting the adenosine diphosphate (ADP) P2Y12 receptor on the platelet surface and blocking activation of the glycoprotein GPIIb/IIIa complex (e.g., clopidogrel, prasugrel, ticagrelor); antagonizing protease-activated receptor 1 (PAR-1), which inhibits thrombin and thrombin receptor agonist peptide activity (e.g., vorapaxar); or inhibiting phosphodiesterase lll (e.g., cilostazol).2-4, 13

Aspirin is available in combination with omeprazole, a proton pump inhibitor, to reduce the risk of aspirin-associated gastric ulcers in those patients requiring aspirin for secondary prevention of cardiovascular and cerebrovascular events.2-4, 10 Aspirin is also available as combination therapy with dipyridamole, pairing two antiplatelet agents with different mechanisms of action for secondary stroke prevention.2-4, 11 Maximum recommended adult dosages for PAIs are summarized in Tables 1 and 2 (1-3, 5-12). Medication profiles identifying patients prescribed dosages exceeding these recommendations will be reviewed.

Table 1. Maximum Daily Adult Dosages for PAIs – Monotherapy1-8
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage
cilostazol (generics) 50 mg, 100 mg tablets intermittent claudication 100 mg twice daily
clopidogrel (Plavix®, generics) 75 mg, 300 mg tablets ACS, including UA/NSTEMI and STEMI Initial: 300 mg or 600 mg loading dose, followed by 75 mg once daily for up to 12 months in combination with aspirin, followed by aspirin indefinitely
    thromboembolism prophylaxis in patients with recent MI or stroke, or established peripheral vascular disease 75 mg/day
dipyridamole (generics) 25 mg, 50 mg, 75 mg tablets prevention of postoperative thrombotic complications in patients with prosthetic heart valves 400 mg/day (divided doses, in combination with warfarin) or 400 mg/day (divided doses, in combination with aspirin)
prasugrel (Effient®, generics) 5 mg, 10 mg tablets ACS in patients to be managed with PCI following a 60 mg loading dose, 10 mg/day+ in combination with aspirin
ticagrelor (Brilinta®) 60 mg, 90 mg tablets reduce risk of death, MI, and stroke in patients with ACS, history of MI, or acute ischemic stroke/ high risk transient ischemic attack following a 180 mg loading dose, 90 mg twice daily^ in combination with aspirin
    reduce risk of first MI or stroke in patients with CAD at high risk of events 60 mg twice daily in combination with aspirin
vorapaxar (Zontivity®) 2.08 mg tablet MI, stroke, thrombosis prophylaxis in patients with a history of MI or PAD 2.08 mg/day in combination with aspirin or clopidogrel

Legend:

  • ACS = acute coronary syndrome
  • CAD = coronary artery disease
  • MI = myocardial infarction
  • NSTE-ACS = non-ST-elevation acute coronary syndrome
  • NSTEMI = non-ST-elevation myocardial infarction
  • PAD = peripheral arterial disease
  • PCI = percutaneous coronary intervention
  • STEMI = ST-elevation myocardial infarction
  • TIA = transient ischemic attack
  • UA = unstable angina
  • + patients 75 years or older or weigh less than 60 kg may use prasugrel 5 mg/day as maintenance therapy in combination with aspirin to reduce bleeding risk
  • ^ ticagrelor dosages are decreased to 60 mg twice daily after 12 months
Table 2. Maximum Daily Adult Dosages for PAIs – Combination Therapy1,2,9,10
Drug Name Dosage Form/ Strength Treatment Indication Maximum Recommended Dosage
aspirin/ omeprazole (Yosprala®) 81 mg/40 mg, 325 mg/40 mg delayed-release tablets secondary prevention of cardiovascular and cerebrovascular events in patients predisposed to gastric ulcers 325 mg/40 mg once daily
dipyridamole/aspirin (generics) 200 mg/25 mg extended-release capsule secondary stroke prevention 200 mg/25 mg twice daily