ZONTIVITY- vorapaxar sulfate tablet, film coated
Merck Sharp & Dohme Corp.
WARNING: BLEEDING RISK
Do not use ZONTIVITY in patients with a history of stroke, transient ischemic attack (TIA), or intracranial hemorrhage (ICH); or active pathological bleeding [see CONTRAINDICATIONS (4.1, 4.2)].
Antiplatelet agents, including ZONTIVITY, increase the risk of bleeding, including ICH and fatal bleeding [see Warnings and Precautions
INDICATIONS AND USAGE
1.1 Patients with History of Myocardial Infarction (MI) or with Peripheral Arterial Disease (PAD)
ZONTIVITY � is indicated for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD). ZONTIVITY has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization (UCR).
2 DOSAGE AND ADMINISTRATION
2.1 General Dosing Information
Take one tablet of ZONTIVITY 2.08 mg orally once daily, with or without food.
2.2 Coadministration with Other Antiplatelet Drugs
There is no experience with use of ZONTIVITY alone as the only administered antiplatelet agent. ZONTIVITY has been studied only as an addition to aspirin and/or clopidogrel. Use ZONTIVITY with aspirin and/or clopidogrel according to their indications or standard of care [see Clinical Studies (14)]. There is limited clinical experience with other antiplatelet drugs.
3 DOSAGE FORMS AND STRENGTHS
ZONTIVITY tablets, 2.08 mg vorapaxar, are yellow, oval-shaped, film-coated tablets with "351″ on one side and the Merck logo on the other side.
4 CONTRAINDICATIONS
4.1 History of Stroke, Transient Ischemic Attack (TIA), or Intracranial Hemorrhage (ICH)
ZONTIVITY is contraindicated in patients with a history of stroke, TIA, or ICH because of an increased risk of ICH in this population [see Adverse Reactions (6)].
Discontinue ZONTIVITY in patients who experience a stroke, TIA, or ICH
ZONTIVITY contains vorapaxar sulfate, a tricyclic himbacine-derived selective inhibitor of platelet aggregation mediated by PAR-1.
The chemical name of vorapaxar sulfate is ethyl [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-{(1E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethen-1-yl}-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl]carbamate sulfate. The empirical formula is C29 H33 FN2 O4 ∙H2 SO4 , and its molecular weight is 590.7.
Mechanism of Action
Vorapaxar is a reversible antagonist of the protease-activated receptor-1 (PAR-1) expressed on platelets, but its long half-life makes it effectively irreversible. Vorapaxar inhibits thrombin-induced and thrombin receptor agonist peptide (TRAP)-induced platelet aggregation in in vitro studies. Vorapaxar does not inhibit platelet aggregation induced by adenosine diphosphate (ADP), collagen or a thromboxane mimetic and does not affect coagulation parameters ex vivo. PAR-1 receptors are also expressed in a wide variety of cell types, including endothelial cells, neurons, and smooth muscle cells, but the pharmacodynamic effects of vorapaxar in these cell types have not been assessed.