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 artery disease (PAD). Zontivity has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization.
Important Safety Information
Indications and Usage
ZONTIVITY is indicated for the reduction of thrombotic cardiovascular (CV) 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 CV death, MI, stroke, and urgent coronary revascularization (UCR).
Warning: Bleeding Risk
- Do not use ZONTIVITY in patients with a history of stroke, transient ischemic attack (TIA), or intracranial hemorrhage (ICH), or with active pathological bleeding (eg, ICH or peptic ulcer).
- Antiplatelet agents, including ZONTIVITY, increase the risk of bleeding, including ICH and fatal bleeding.
Additional Selected Safety Information
ZONTIVITY is contraindicated in patients with a history of stroke, TIA, or ICH and in patients with active pathological bleeding such as ICH or peptic ulcer. Discontinue ZONTIVITY in patients who experience a stroke, TIA, or ICH.
Warnings and Precautions
Antiplatelet agents, including ZONTIVITY, increase the risk of bleeding, including ICH and fatal bleeding. ZONTIVITY increases the risk of bleeding in proportion to the patient’s underlying bleeding risk. Consider the underlying risk of bleeding before initiating ZONTIVITY.
General risk factors for bleeding include older age, low body weight, reduced renal or hepatic function, and history of bleeding disorders. Use of certain concomitant medications (eg, anticoagulants, fibrinolytic therapy, chronic nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors) also increases the risk of bleeding. Avoid concomitant use of warfarin or other anticoagulants.
Withholding ZONTIVITY for a brief period will not be useful in managing an acute bleeding event because, due to its long half-life, significant inhibition of platelet aggregation remains 4 weeks after discontinuation. There is no known treatment to reverse the antiplatelet effect of ZONTIVITY.
Strong CYP3A inhibitors increase and inducers decrease ZONTIVITY exposure. Avoid concomitant use of ZONTIVITY with strong CYP3A inhibitors or inducers.
Use in Special Populations
Based on the increased inherent risk of bleeding in patients with severe hepatic impairment, ZONTIVITY is not recommended in these patients.
Bleeding, including life-threatening and fatal bleeding, is the most commonly reported adverse reaction with ZONTIVITY. Among post-MI or PAD patients with no history of stroke or TIA, three-year bleeding rates (shown with hazard ratios and 95% confidence intervals) in patients who added ZONTIVITY or placebo, respectively, to aspirin and/or clopidogrel were:
- GUSTO moderate or severe bleeding,a 7% vs 2.4%, HR 1.55 (1.30-1.86)
- GUSTO severe bleeding,a 3% vs 1.0%, HR 1.24 (0.92-1.66)
- Any GUSTO bleeding (severe/moderate/mild),a 7% vs 19.8%, HR 1.52 (1.43-1.61)
- ICH, 0.6% vs 0.4%, HR 1.46 (0.92-2.31)
- Fatal bleeding, 0.2% vs 0.2%, HR 1.15 (0.56-2.36)
- Clinically significant bleeding,b 5% vs 10.9%, HR 1.47 (1.35-1.60)
a. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) severe bleeding: fatal, intracranial, or bleeding with hemodynamic compromise requiring intervention; GUSTO moderate bleeding: bleeding requiring transfusion of whole blood or packed red blood cells without hemodynamic compromise.
b. Clinically significant bleeding: bleeding requiring medical attention including ICH, or clinically significant overt signs of hemorrhage with a drop in Hgb ≥3 g/dL (or, when Hgb is not available, an absolute drop in Hct ≥9%).
Dosage and Administration
ZONTIVITY, taken as one 2.08-mg tablet daily, was studied only as an addition to aspirin and/or clopidogrel and should be used with aspirin and/or clopidogrel according to their indications or standard of care. There is no experience with use of ZONTIVITY alone as the only administered antiplatelet agent.
This product information is intended only for residents of the United States.