Vorapaxar
Antiplatelet drugs
Antiplatelet drugs
An oral PAR-1 (thrombin receptor) antagonist added to aspirin or clopidogrel after MI or in peripheral artery disease; it has been discontinued in the US.
Quick facts
- Group
- Antiplatelet drugs
- Target
- Protease-activated receptor 1 (PAR-1), the platelet thrombin receptor
- Used for
- Reduction of thrombotic events
- Key effects
- Bleeding · Anaemia
- Monitor
- Signs of bleeding · Haemoglobin
- ATC
- B01AC26
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows vorapaxar bound to human PAR-1 (the crystal uses a lysozyme insert to stabilise the receptor).
Thrombin activates platelets by cutting PAR-1. Vorapaxar is a competitive PAR-1 antagonist that blocks thrombin-induced platelet activation and aggregation. It binds so tightly that its effect can last up to 4 weeks after the last dose.
- Thrombin normally activates platelets through PAR-1
- Vorapaxar occupies PAR-1
- Thrombin-induced aggregation is blocked
- Tight binding keeps the effect for weeks
Indications
- Reduction of thrombotic events after myocardial infarction, with aspirin and/or clopidogrel Myocardial Infarction (Heart Attack) →
- Reduction of thrombotic events in peripheral artery disease Peripheral artery disease →
Adverse effects
Common
- Bleeding, including nosebleeds
- Anaemia (tiredness, weakness, pallor)
Contraindications
- History of stroke, transient ischaemic attack or intracranial bleeding
- Active pathological bleeding, such as a bleeding ulcer
Key interactions
- Anticoagulants (warfarin, heparins, fondaparinux, rivaroxaban, dabigatran)
- Add to the bleeding risk
- NSAIDs, SSRIs and SNRIs
- Add to the bleeding risk
- St John's wort and drugs that strongly change CYP3A4 activity
- Can change vorapaxar levels
What is monitored
- Signs of bleeding
- Haemoglobin
- Neurological symptoms (headache, weakness)
Administration and safety
- Oral tablet, always together with aspirin and/or clopidogrel
- Before surgery or dental work, the team is told: the effect lasts weeks after stopping
- Discontinued in the US; availability elsewhere varies
Pregnancy and breastfeeding
A pregnancy, plans for it or breastfeeding are reported to the doctor; the label information is limited.
Nursing care
- Screen for previous stroke, TIA or brain bleeding before the first dose
- Teach signs of bleeding and to seek help at once
- Review all medicines, including NSAIDs, antidepressants and herbal products
- Explain that bleeding risk continues for at least 4 weeks after stopping
Pharmacokinetics
- Absorption
- Oral; about 90% bioavailable, rapid onset
- Metabolism
- Liver, by CYP3A4
- Half-life
- About 3–4 days; the effect on platelets can last up to 4 weeks
Test yourself
Think of the answer, then tap the question to see it.
Which receptor does vorapaxar block?
PAR-1, the thrombin receptor on platelets.
Which history rules it out?
Stroke, TIA or intracranial bleeding.
Why does its effect last weeks after stopping?
It binds PAR-1 very tightly and has a long half-life.
Connections
← Back to the class: Antiplatelet drugs
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Vorapaxar: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); 3VW7: Crystal structure of human protease-activated receptor 1 (PAR1) bound with antagonist vorapaxar at 2.2 angstrom (RCSB Protein Data Bank, 2012).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.