Pharmacokinetics of the novel PAR-1 antagonist vorapaxar in patients with hepatic impairment

Statkevich, Paul; Kosoglou, Teddy; Preston, Richard A.; Kumar, Bharath; Xuan, Fengjuan; Trusley, Craig; Schiller, James E.; Langdon, Ronald B.; Cutler, David L.

doi:10.1007/s00228-012-1269-7

Cited by 26 publications

(21 citation statements)

References 25 publications

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“…No dose adjustment is required for age, gender, renal function 6 and mild to moderate hepatic impairment. 7 Ethnic differences in pharmacokinetics and pharmacodynamics were not observed in healthy Japanese and Caucasian subjects. 8 There is no known antidote for vorapaxar overdose.…”

Section: Pharmacokinetics and Dosagementioning

confidence: 96%

Vorapaxar, a novel oral antiplatelet drug

Tekulapally¹

2015

Int J Basic Clin Pharmacol

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Section: Pharmacokinetics and Dosagementioning

confidence: 96%

Vorapaxar, a novel oral antiplatelet drug

Tekulapally¹

2015

Int J Basic Clin Pharmacol

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“…Vorapaxar is not recommended in patients with severe hepatic impairment (Child-Pugh score of >10) due to the increased risk of bleeding. 25 In an open-label study of eight patients with end-stage renal disease, no pharmacokinetic changes were observed; therefore, dosage adjustments in this population are not required. 26…”

Section: Dose Evaluationmentioning

confidence: 98%

“…Vorapaxar is not recommended in patients with severe hepatic dysfunction due to its inherent bleeding risk in this population. 25 Bleeding should be suspected in patients with hypotension after undergoing recent coronary angiography, PCI, CABG, or other surgical procedures. 10 Vorapaxar is contraindicated in patients with a history of stroke, transient ischemic attack (TIA), or ICH due to the increased risk of ICH in this population.…”

Section: Safety Concernsmentioning

confidence: 99%

Vorapaxar for reduction of thrombotic cardiovascular events in myocardial infarction and peripheral artery disease

Arif

D’Souza

Gil

et al. 2015

American Journal of Health-System Pharmacy

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“…In addition, exposure to vorapaxar or its active metabolite M20 and half-life values did not seem to correlate with the severity of hepatic impairment. 29 Furthermore, end-stage renal disease had no clinically significant effects on the pharmacokinetics or pharmacodynamics of a single oral dose of vorapaxar 10 mg in an open-label study in 8 patients on hemodialysis and 7 matched healthy volunteers. 30 In a large randomized clinical trial, 33% of patients were 65 years or older and 9% were 75 years or older.…”

Section: Drug Interactionsmentioning

confidence: 99%

Vorapaxar

Lam

Tran

2015

Cardiology in Review

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Antiplatelet therapy reduces the risks for cardiovascular morbidity and mortality in patients with atherosclerotic disease, and it is also beneficial in managing peripheral arterial disease (PAD). These agents work through various therapeutic pathways to achieve antithrombotic effects. Although single- or two-drug regimens have been deployed to prevent vascular events, approximately 10% of the patients with acute coronary syndrome remain at risk for recurrent thrombotic events and may need a more aggressive preventative strategy. Vorapaxar offers a unique mechanism for platelet inhibition via the antagonism of protease-activated receptor-1. It is approved for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or PAD. This new drug approval was mainly based on the results from subgroup analyses from a large landmark trial (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50), which found that vorapaxar reduces the rate of the combined end point of cardiovascular death, MI, stroke, and urgent coronary revascularization when used in addition to aspirin and/or clopidogrel in patients without a history of stroke. In this study, vorapaxar was discontinued in patients with a history of stroke due to excessive risk for intracranial hemorrhage after 2 years of therapy. As an adjunctive therapy to standard regimens, vorapaxar provides a greater net clinical benefit in MI patients who are at a lower risk for bleeding. In patients with PAD, it reduces the rates of recurrent acute limb ischemia with rehospitalization or peripheral revascularization. The most concerning adverse effect is bleeding. Vorapaxar should not be used in patients with a history of stroke, transient ischemic attack, intracranial hemorrhage, or active pathological bleeding. The risks and benefits of adding vorapaxar to intensify antiplatelet regimens should be assessed in individual patients to aim for additional therapeutic outcomes with minimal bleeding risks.

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Pharmacokinetics of the novel PAR-1 antagonist vorapaxar in patients with hepatic impairment

Cited by 26 publications

References 25 publications

Vorapaxar, a novel oral antiplatelet drug

Vorapaxar, a novel oral antiplatelet drug

Vorapaxar for reduction of thrombotic cardiovascular events in myocardial infarction and peripheral artery disease

Vorapaxar

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