Vorapaxar

Uses

Vorapaxar is a platelet aggregation inhibitor used to reduce thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or peripheral arterial disease (PAD).

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.

Vorapaxar is also used to associated treatment for these conditions: Cardiovascular Events

How Vorapaxar works

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.

Toxicity

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.

Food Interaction

• Avoid herbs and supplements with anticoagulant/antiplatelet activity. Additive antiplatelet activity may increase the risk of bleeding. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
• Avoid St. John's Wort. This herb induces the CYP3A metabolism of vorapaxar and may reduce its serum concentration.
• Exercise caution with grapefruit products. Coadministration of vorapaxar with moderate CYP3A4 inhibitors does not require intervention, but coadministration with strong inhibitors should be avoided.
• Take with or without food.

Vorapaxar Drug Interaction

Major: bivalirudin, warfarin, ibuprofenUnknown: pseudoephedrine / triprolidine, fluticasone / salmeterol, calcium carbonate, multivitamin with minerals, docusate, misoprostol, metformin, chondroitin / glucosamine / methylsulfonylmethane, terazosin, sitagliptin, atorvastatin, metoprolol, nitroglycerin, amlodipine, acetaminophen, finasteride, pantoprazole

Vorapaxar Disease Interaction

Major: bleeding, history of stroke, liver disease

Volume of Distribution

424 L

Elimination Route

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%.

Half Life

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

Elimination Route

Vorapaxar is primarily eliminated as its metabolite M19 through the feces (91.5%), and partially eliminated in the urine (8.5%).

Innovators Monograph

You find simplified version here Vorapaxar