1. Dosage
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.
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
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 |
1.2. Pediatrics
Dipyridamole is FDA-approved for use in pediatric patients 12 years of age and older as adjunctive therapy to prevent thromboembolism following cardiac valve replacement. The maximum recommended dose is 100 mg four times daily in combination with warfarin. Dosages exceeding these recommendations will be reviewed.
Aspirin as Durlaza®, cilostazol, prasugrel, ticagrelor, vorapaxar, aspirin/omeprazole, and dipyridamole/aspirin are not recommended for use in pediatric patients as safety and efficacy have not been established for these agents in this patient population. Although not FDA-approved, clopidogrel has effectively been used in pediatric patients to reduce thrombosis risk in infants and children with select types of heart disease, or as an alternative in patients with Kawasaki disease or ischemic stroke when aspirin is not tolerated.2, 3, 14-17