Vorapaxar

492.58200

492.58

612-523-7

ZCE93644N2

B01|B - Blood and blood forming organs

77.52000

6.02040

1.25 g/cm3

676ºC at 760 mmHg

362.632ºC

1.594

|Warning|H371 (100%): May cause damage to organs [Warning Specific target organ toxicity, single exposure]|P260, P264, P270, P273, P309+P311, P314, P391, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

There is an increased risk of bleeding and intracranial hemorrhage (ICH), which is why the use of vorapaxar is contraindicated in patients with a history of stroke, trans-ischemic attack (TIA), ICH, or active pathological bleeding such as peptic ulcer. Animal studies have suggested that there is a low probability of embryo/fetal toxicities, however there are no adequate and well-controlled studies describing use in pregnant women. Vorapaxar should also be avoided during breastfeeding as it is unknown whether vorapaxar or its metabolites are excreted in human milk, however it has been shown to be actively secreted in the milk of rats.

Vorapaxar is associated with a low rate of serum enzyme elevations during therapy that was similar to the rate that occurred with placebo or comparator therapies. In a large controlled trial in over 10,000 patients monitored over a 2 year period, ALT elevations above 5 times the upper limit of normal occurred in 1% of vorapaxar vs 1.4% of placebo patients. In pooled analyses of laboratory studies from more than 39,000 patients receiving vorapaxar or placebo, GGT was the only liver test that was abnormal in a higher proportion of patients receiving vorapaxar (3.8%) than placebo (3.3%), and there were no reports of liver related serious adverse events or clinically apparent liver injury. Thus, liver injury from vorapaxar must be rare, if it occurs at all.

Vorapaxar is extensively bound (>99%) to human plasma proteins, such as human serum albumin.

Vorapaxar is indicated for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or peripheral arterial disease (PAD). It is usually co-administered with acetylsalicylic acid (ASA) and/or clopidogrel, and should therefore be administered as an addition to these medications as it has not been studied alone.|FDA Label|Zontivityis indicated for the reduction of atherothrombotic events in adult patients with- a history of myocardial infarction (MI), ,co-administered with acetylsalicylic acid (ASA) and, where appropriate, clopidogrel; or- symptomatic peripheral arterial disease(PAD), co-administered with acetylsalicylic acid (ASA) or, where appropriate, clopidogrel.|Prevention of arterial thromboembolism

Vorapaxar is an inhibitor of platelet aggregation that is used to decrease the risk of further cardiovascular thrombotic events in patients with a history of myocardial infarction or peripheral vascular disease. Vorapaxar therapy is associated with a low rate of serum aminotransferase elevations, but has not been linked to instances of clinically apparent acute liver injury.

Antithrombotic Agents

Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. (See all compounds classified as Platelet Aggregation Inhibitors.)

After oral administration, vorapaxar is rapidly absorbed and peak concentrations occur at a median tmax of 1 hour under faster conditions. Vorapaxar may be taken with or without food as ingestion with a high-fat meal did not result in meaningful changes in AUC. The mean absolute bioavailability is 100%.|Vorapaxar is primarily eliminated as its metabolite M19 through the feces (91.5%), and partially eliminated in the urine (8.5%).|424 L

Vorapaxar is metabolized to its major circulating metabolite, M20, and its predominant metabolite excreted into feces, M19, by CYP3A4 and CYP 2J2.

Vorapaxar has an effective half life of 3-4 days and an apparent terminal half life of 8 days.

Vorapaxar inhibits platelet aggregation through the reversible antagonism of protease-activated receptor 1 (PAR-1), also known as thrombin receptor. PARs are a family of G-protein coupled receptors highly expressed on platelets and activated by serine protease activity of thrombin to mediate thrombotic response. By blocking PAR-1 activating, vorapaxar inhibits thrombin-induced platelet aggregation and thrombin receptor agonist peptide (TRAP)-induced platelet aggregation. Vorapaxar does not inhibit platelet aggregation induced by other agonists such as adenosine diphosphate (ADP), collagen or a thromboxane mimetic.

SCH 530348

Human drugs -> Zontivity -> EMA Drug Category|Antithrombotic agents -> Human pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients