protease-activated receptor-1 (PAR-1) antagonists
To reduce thrombotic cardiovascular events in patients who have a history of MI or peripheral arterial disease (PAD); can be used with aspirin and/or clopidogrel.
Acts as an antagonist of the protease-activated receptor-1 (PAR-1) on platelet surfaces. Inhibits platelet aggregation.
Decreased cardiovascular events.
Absorption: Completely absorbed (100%) following oral administration.
Protein Binding: >99%.
Metabolism and Excretion: Extensively metabolized (CYP3A4 and CYP2J2); one metabolite (M20) has antiplatelet activity (20% of parent compound). Excreted mostly in feces (58%) and some in urine (25%) as metabolites.
Half-life: Effective half-life– 3–4 days, terminal elimination half-life– 8 days (range 5–13 days, similar for M20).
TIME/ACTION PROFILE (antiplatelet effect)
|PO||within 1 wk||unknown||4 wk|
- History of stroke, transient ischemic attack or intracranial hemorrhage;
- Active pathologic bleeding;
- Concurrent use of anticoagulants including warfarin;
- Concurrent use of strong inhibitors or inducers or CYP3A should be avoided;
- Severe hepatic impairment (↑ risk of bleeding);
- Lactation: Discontinue vorapaxar or discontinue breast feeding.
Use Cautiously in:
- Existing risk factors for bleeding including ↑ age, ↓ body weight, ↓ renal/hepatic function, concurrent chronic NSAIDs, other antiplatelet agents or history of bleeding disorders;
- Geri: Elderly patients may be at ↑ risk of bleeding;
- OB: use during pregnancy only if potential matenral benefit to justifies potential risk to the fetus;
- Pedi: Safe and effective use in children has not been established.
Adverse Reactions/Side Effects
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Blood levels and risk of bleeding may be ↑ by strong inhibitors of CYP3A including bocepravir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, or telapravir ; concurrent use should be avoided.
- Blood levels and effectiveness may be ↓ by strong inducers of CYP3A including carbamazepine, phenytoin or rifampin ; concurrent use should be avoided.
- ↑ risk of bleeding with anticoagulants, other antiplatelet agents, fibrinolytics, chronic NSAID use, SSRIs or SNRIs ; avoid concurrent use of warfarin or other anticoagulants.
Blood levels and effectiveness may be ↓ by St. John's wort ; concurrent use should be avoided.
PO (Adults): 2.08 mg (one tablet) once daily.
Tablets: 2.08 mg
- Assess for signs and symptoms of bleeding periodically during therapy.
- Decreased cardiac output (Indications)
- PO Administer once daily without regard to food.
- Administer with aspirin or clopidogrel according to directions.
- Instruct patient to take vorapaxar as directed. Do not stop therapy without consulting health care professional. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
- Caution patient to notify health care professional immediately if signs and symptoms of bleeding (bleeding that is severe or cannot be controlled, pink, red, or brown urine, vomiting blood or coffee ground-like vomit, red or black, tar-like stools, coughing up blood or blood clots) occur.
- Advise patient to notify health care professional of medication regimen before treatment or surgery.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Advise female patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.
Decrease in cardiac events.
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