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ZONTIVITY™ - vorapaxar

DESCRIPTION CLINICAL PHARMACOLOGY INDICATIONS AND USAGE
CONTRAINDICATIONS PRECAUTIONS ADVERSE REACTIONS
DOSAGE AND ADMINISTRATION HOW SUPPLIED WARNINGS
PRESCRIBING HIGHLIGHTS:  Please see package insert for additional information and possible updates to ensure safe and effective use of this medication. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. Please read the disclaimer carefully BEFORE accessing or using this site. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.  
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Updates:

Drug:  ZONTIVITY ® (vorapaxar) Tablets
[Drug information  /  PDF]  
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

Initial U.S. Approval:  2014

WARNINGS  top of page


WARNING:   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 ].
Antiplatelet agents, including ZONTIVITY, increase the risk of bleeding, including ICH and fatal bleeding [see Warnings and Precautions]

DESCRIPTION  top of page

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: top of page

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  top of page

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.

CONTRAINDICATIONS top of page

Contraindications:
History of stroke, TIA, or ICH.
Active pathologic bleeding.

PRECAUTIONS top of page

WARNINGS AND PRECAUTIONS:
  1. Like other antiplatelet agents, ZONTIVITY increases the risk of bleeding.
  2. Avoid use with strong CYP3A inhibitors or inducers.

ADVERSE REACTIONS top of page

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  top of page

DOSAGE AND ADMINISTRATION:
General Dosing Information

Take one tablet of ZONTIVITY 2.08 mg orally once daily, with or without food.

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Coadministration with Other Antiplatelet Drugs:
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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. There is limited clinical experience with other antiplatelet drugs.

HOW SUPPLIED top of page

DOSAGE FORMS AND STRENGTHS:
Tablets: 2.08 mg vorapaxar.

REFERENCE

Reference(s):
Package insert data:   [Accessed: June 2014]
Manufactured for: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

Manufactured by: MSD International GmbH (Singapore Branch),
Singapore 638414, Singapore

Issued: 05/2014

For patent information: www.merck.com/product/patent/home.html
Copyright © 2013 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved.

Updates:
Drug:  ZONTIVITY ® (vorapaxar) Tablets
[Drug information  /  PDF]  
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

Initial U.S. Approval:  2014
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