ZONTIVITY™
Warnings
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Description
| Description: 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 C29H33FN2O4·H2SO4, and its molecular weight is 590.7. Vorapaxar sulfate is a white to off-white solid. Vorapaxar sulfate is freely soluble in methanol and slightly soluble in ethanol, acetone, 2-propanol, and acetonitrile. In aqueous solution, it is slightly soluble in pH 1; its solubility decreases with increasing pH. ZONTIVITY tablets are formulated with vorapaxar sulfate, but during manufacture and storage, partial conversion from vorapaxar sulfate to vorapaxar free base may occur. ZONTIVITY is available for oral use as tablets containing 2.08 mg of vorapaxar, which is equivalent to 2.5 mg of vorapaxar sulfate. Each film-coated tablet of ZONTIVITY contains the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, povidone, and magnesium stearate. In addition, the film coating contains the following inactive ingredients: lactose monohydrate, hypromellose, titanium dioxide, triacetin (glycerol triacetate), and iron oxide yellow. |
Clinical pharmacology
| 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. |
Indications and usage
| INDICATIONS AND USAGE: ZONTIVITY is a protease-activated receptor-1 (PAR-1) antagonist 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. |
Precautions
WARNINGS AND PRECAUTIONS:
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Adverse reactions
| ADVERSE REACTIONS: Bleeding, including life-threatening and fatal bleeding, is the most commonly reported adverse reaction. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide. |
Dosage and administration
| DOSAGE AND ADMINISTRATION: General Dosing Information Take one tablet of ZONTIVITY 2.08 mg orally once daily, with or without food. ----------------------------------------------------------------------- |
Reference(s)
National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
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