Pharmacological Class:
Protease-activated receptor-1 (PAR-1) antagonist.
Active Ingredient(s):
Vorapaxar 2.08mg (equivalent to 2.5mg of vorapaxar sulfate); tablets.
Company
Merck & Co., Inc.
Indication(s):
To reduce thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD).
Pharmacology:
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.
Clinical Trials:
The efficacy of Zontivity was established in the TRA 2°P-TIMI 50 clinical trial. TRA 2°P was a multicenter, randomized, double-blind, placebo-controlled study conducted in patients who had evidence or a history of atherosclerosis involving the coronary (spontaneous MI ≥2 weeks but ≤12 months prior), cerebral (ischemic stroke), or peripheral vascular (documented peripheral arterial disease [PAD]) systems.
Patients were randomized to receive daily treatment with Zontivity (n=13,225) or placebo (n=13,224) in addition to standard of care. The primary endpoint was the composite of cardiovascular death, MI, stroke, and urgent coronary revascularization (UCR). The composite of cardiovascular death, MI, and stroke was assessed as a key secondary endpoint. The median follow-up was 2.5 years (up to 4 years).
Results for the primary endpoint in all randomized patients showed a 3-year Kaplan-Meier (K-M) event rate of 11.2% in the Zontivity group vs. 12.4% in the placebo group (HR: 0.88, 95% CI: 0.82–0.95; P=0.001). Results for the secondary endpoint showed a 3-year K-M event rate of 9.3% in the Zontivity group vs. 10.5% in the placebo group (HR: 0.87, 95% CI: 0.80–0.94; P<0.001).
In post-MI or PAD patients without a history of stroke or TIA, the 3-year K-M event rate for the primary endpoint was 10.1% in the Zontivity group vs. 11.8% in the placebo group (HR: 0.83, 95% CI: 0.76–0.90; P<0.001). Results for the secondary endpoint showed a 3-year K-M event rate of 7.9% in the Zontivity group vs. 9.5% in the placebo group (HR: 0.80, 95% CI: 0.73–0.89; P<0.001).
For more clinical trial data, see full labeling.
Legal Classification:
Rx
Adults:
2.08mg once daily. Use with aspirin and/or clopidogrel according to their indications or standard of care.
Children:
Not established.
Contraindication(s):
History of stroke, transient ischemic attack (TIA), or intracranial hemorrhage (ICH). Active pathological bleeding (eg, peptic ulcer, ICH).
Warnings/Precautions:
Discontinue if stroke, TIA, or ICH occurs. Increased risk of bleeding (may be fatal). Consider underlying risk of bleeding before initiating (eg, older age, low body wt., reduced renal or hepatic function, history of bleeding disorders, concomitant certain medications). Hypotensive and has recently undergone coronary angiography, PCI, CABG or other surgeries: suspect bleeding and monitor. Severe hepatic impairment: not recommended. Elderly. Pregnancy (Category B). Nursing mothers: not recommended.
Interaction(s)
Avoid concomitant strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin, conivaptan). Avoid concomitant strong CYP3A4 inducers (eg, rifampin, carbamazepine, St. John’s wort, phenytoin). Avoid concomitant warfarin or other anticoagulants. Increased risk of bleeding with concomitant fibrinolytics, chronic NSAIDs, SSRIs, SNRIs.
Adverse Reaction(s)
Bleeding (may be fatal), anemia, depression, rashes, eruptions, exanthemas, iron deficiency, retinopathy or retinal disorder, diplopia/oculomotor disturbances.
How Supplied:
Tabs—30, 90
LAST UPDATED:
8/1/2014
