What is the half-life of Pruvict?

Half-Life of Pruvict

Pruvict (vorapaxar) has a long half-life of 126 to 269 hours (approximately 5-11 days) and can inhibit platelet aggregation for up to 4 weeks. 1

Pharmacokinetic Properties of Vorapaxar

• Vorapaxar is a synthetic tricyclic 3-phenylpyridine analog that functions as a potent and specific competitive inhibitor of PAR-1 (Protease-Activated Receptor-1) 1
• The drug has excellent oral bioavailability and produces dose-dependent inhibition of thrombin or thrombin receptor agonist peptide (TRAP)-induced platelet aggregation 1
• The binding of vorapaxar to PAR-1 is reversible, but dissociation from the receptor is slow, which likely explains its exceptionally long half-life 1
• Vorapaxar is primarily metabolized by CYP3A4 1

Clinical Implications of Vorapaxar's Long Half-Life

• The extended half-life means that platelet function takes a significant time to normalize after discontinuation 1
• Inhibition of TRAP-induced platelet aggregation persists for up to 4 weeks after stopping the medication 1
• This prolonged antiplatelet effect has important implications for perioperative management and bleeding risk 1
• Unlike drugs with shorter half-lives that require more frequent dosing to maintain therapeutic levels, vorapaxar's long half-life allows for once-daily dosing 2

Comparison to Other Antiplatelet Agents

• Atopaxar, another PAR-1 antagonist, has a significantly shorter half-life of approximately 23 hours 1
• Most other antiplatelet agents have considerably shorter half-lives:
  • For example, the terminal half-life of dabigatran is 12-17 hours with repeated dosing 1
  • The half-life of rivaroxaban ranges from 7-17 hours 1

Clinical Considerations

• The extended half-life of vorapaxar requires careful planning when discontinuing therapy before invasive procedures 3
• Due to the prolonged antiplatelet effect, vorapaxar should be discontinued well in advance (likely several weeks) before elective surgery 1
• In cases of major bleeding, the long half-life presents challenges for reversal of antiplatelet effects 1
• Patients with hepatic or renal impairment may experience even longer half-lives, though specific data on these populations is limited 1

Monitoring Considerations

• Unlike some anticoagulants, there are no specific laboratory tests to monitor the antiplatelet effects of vorapaxar in routine clinical practice 1
• The prolonged half-life means that drug effects persist long after discontinuation, which is important when managing bleeding complications 1