Vorapaxar

Indications

Vorapaxar is used for: Thromboembolism

Adult Dose

Oral Thromboembolism Indicated to reduce thrombotic cardiovascular events in patients with a history of MI or with peripheral arterial disease 2.08 mg PO qDay in combination with either aspirin and/or clopidogrel (according to their indications or standard of care); there is limited clinical experience with other antiplatelet drugs and none with vorapaxar as the only antiplatelet agent Mild-to-moderate hepatic impairment: No dose adjustment required Severe hepatic impairment: Not recommended; based on the increased inherent risk of bleeding in patients with severe hepatic impairment

Child Dose

Renal Dose

Renal impairment: No dose adjustment required

Administration

May take with or without food

Contra Indications

History of stroke, TIA, or ICH because of an increased risk of ICH in this population (see Black Box Warnings) Active pathologic bleeding

Precautions

Discontinue in patients who experience a stroke, TIA, or ICH Antiplatelet agents, including vorapaxar, increase the risk of bleeding, including ICH and fatal bleeding (see Black Box Warnings) Strong CYP3A inhibitors increase and inducers decrease vorapaxar exposure; avoid coadministration

Pregnancy-Lactation

Pregnancy Based on potential for serious adverse reactions (such as maternal bleeding/hemorrhage) and long half-life which makes it effectively irreversible, discontinue therapy when pregnancy is detected and initiate alternative therapy with a shorter duration of action Available data from postmarketing experience with use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes Animal data In animal reproduction studies, no embryo/fetal toxicities, malformations or maternal toxicities were observed in rats and rabbits exposed during period of organogenesis at exposures 56 times and 26 times, respectively, human systemic exposure at recommended human dose (RHD) Lactation There are no data on presence of drug or metabolites in human milk, effects on breastfed infant, or on milk production; when drug was administered to lactating rats, drug was actively secreted in milk of rats; when a drug is present in animal milk, it is likely the drug will be present in human milk; because of potential for serious adverse reactions in breastfed infant, such as bleeding, advise patients that breastfeeding is not recommended during treatment

Interactions

Adverse Effects

Side effects of Vorapaxar : Bleeding Non-CABG-Related Bleeds in Post-MI or PAD Patients without a History of Stroke or TIA Severe (1%) Moderate or severe (3%) Any bleeding (25%) Fatal bleeding (0.2%) Intracranial hemorrhage (0.4%) Clinically significant bleeding (15.5%) GI bleeding (4.7%) 1-10% Anemia (5%) Depression (2.4%) Rashes, eruptions, exanthemas (2.2%) <1% Diplopia (0.2%)

Mechanism of Action

Reversible antagonist of the protease-activated receptor-1 (PAR-1) expressed on platelets, but its long half-life makes it effectively irreversible; inhibits thrombin-induced and thrombin receptor agonist peptide (TRAP)-induced platelet aggregation in in vitro studies