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Vorapaxar

Vorapaxar is an antiplatelet medicine used to reduce the risk of serious cardiovascular events in people who have had a heart attack or have peripheral arterial disease (PAD).

Brand name Zontivity
Drug class Protease-activated Receptor-1 Antagonists
Rx
Dr. Brian Staiger, PharmD, BCPS
Reviewed by Last reviewed Jul 10, 2026 Content updated Oct 2, 2026
🧬 Where this information comes from Click to expand

The clinical label records used on this page are FDA-filed Structured Product Labeling (SPL) retrieved through openFDA. We identified 1 clinical label set within the page’s selected clinical scope after exact ingredient or ingredient-combination matching and applicable route/form matching. Forms, routes, brands, labelers, strengths, and NDC product-record counts are built separately from matching FDA National Drug Code Directory records. The linked DailyMed document is a representative official source for verification, not the page’s only clinical source. View the linked label on DailyMed →

✓No current FDA shortage listed · checked Oct 7, 2026
Dr. Brian Staiger, PharmD, BCPS
The Pharmacist’s Take By · Clinical pharmacist · Written

Vorapaxar (Zontivity) is an antiplatelet medicine that blocks PAR-1, the receptor thrombin (a clotting protein) uses to clump platelets, and is a less common add-on to aspirin and/or clopidogrel that helps prevent heart attack, stroke and cardiovascular death after a heart attack or in peripheral arterial disease (PAD). It is usually well tolerated, though easy bruising and minor bleeding are what most people notice. Its boxed warning covers serious and fatal bleeding, including in the brain, so it must never be used after a stroke, TIA (mini-stroke) or brain bleed. The effect lingers for weeks after the last dose, with no antidote, so bleeding cannot be quickly reversed.

Clinical pearls

  • Tell surgeons and dentists about vorapaxar well before any procedure, since stopping it a few days ahead will not clear it.
  • Avoid warfarin and other blood thinners with vorapaxar, and skip regular ibuprofen or naproxen, since both add to bleeding risk.
  • Ketoconazole, clarithromycin, ritonavir, rifampin, carbamazepine, phenytoin and St. John's Wort push vorapaxar levels too high or too low, so avoid them.
  • Report new depression or double vision to your prescriber, since both are listed side effects of vorapaxar that people rarely expect.
How we write & review this content — our editorial policy →
⚠️ FDA Boxed Warning — the FDA’s strongest safety alert ▾

Zontivity carries a serious FDA boxed warning about the risk of bleeding, including brain bleeding and fatal bleeding. This drug must NOT be used in anyone who has ever had a stroke, a TIA (mini-stroke), or bleeding inside the skull — because it significantly increases the chance of bleeding in the brain in these patients. It is also contraindicated in anyone who has active, serious bleeding right now (such as a bleeding stomach ulcer). Like all antiplatelet medicines, vorapaxar raises the risk of bleeding throughout the body, and some of those bleeding events can be life-threatening. If you have any of these conditions, do not take this medication.

Read the full warning on DailyMed →
How you get itPrescription only
Earliest FDA record2014
FDA label last updatedOct 18, 2022
FDA’s strongest warning (boxed)Yes, read the warning

Patient information guide A plain-language walkthrough of Vorapaxar, written from its FDA label.

What Vorapaxar is used for

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Vorapaxar is an antiplatelet medicine approved to reduce the risk of serious, potentially life-threatening cardiovascular events.

  • Zontivity (oral tablet) is indicated to reduce the risk of thrombotic cardiovascular events — including heart attack, stroke, cardiovascular death, and urgent coronary revascularization (procedures to restore blood flow) — in adults who have previously had a heart attack (myocardial infarction)
  • Zontivity (oral tablet) is also indicated for the same cardiovascular risk reduction in adults with peripheral arterial disease (PAD), a condition where arteries in the legs or other parts of the body outside the heart become narrowed
  • Zontivity is always used in combination with aspirin and/or clopidogrel; it has not been studied or approved as a stand-alone antiplatelet agent

How Vorapaxar works

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Vorapaxar targets a specific protein on platelets (the tiny blood cells that help form clots) called the PAR-1 receptor (protease-activated receptor-1). Thrombin — a clotting protein that spikes during a heart attack or arterial injury — normally latches onto PAR-1 and causes platelets to clump together, forming dangerous clots. Vorapaxar blocks PAR-1, preventing thrombin from triggering that clumping. The result is reduced platelet aggregation and a lower chance of a clot forming in a diseased artery.

Although vorapaxar technically binds reversibly to PAR-1, its half-life is so long — about 8 days — that the platelet-blocking effect is effectively irreversible in practical terms. Significant inhibition of platelet aggregation can last up to 4 weeks after the last dose, which is important to know before any surgery or procedure.

Vorapaxar dosage

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Zontivity is taken as one tablet by mouth once a day, with or without food — a high-fat meal does not meaningfully change how much of the drug gets into your system. It is always used alongside aspirin and/or clopidogrel; your prescriber will guide you on those additional medications.

  • Take it at the same time each day to stay consistent
  • There is no dose adjustment needed for most people based on age, sex, weight, or mild-to-moderate kidney or liver impairment — but Zontivity is not recommended if you have severe liver disease
  • Do not stop or change your dose without talking to your prescriber first

Dosing details from the FDA-approved label

From the Vorapaxar prescribing information (“Dosage and Administration”). Doses are set by your prescriber for your product, condition, kidney function and age — never change a dose on your own.

  • General dosing (all patients)
    • One tablet of ZONTIVITY 2.08 mg orally once daily, with or without food
  • Coadministration with other antiplatelet drugs
    • Use ZONTIVITY with aspirin and/or clopidogrel according to their indications or standard of care
    • No experience with ZONTIVITY alone as the only antiplatelet agent; studied only as an addition to aspirin and/or clopidogrel; limited clinical experience with other antiplatelet drugs
Read the label’s full dosing text

2 DOSAGE AND ADMINISTRATION One tablet of ZONTIVITY orally once daily. ( 2.1 ) Use with aspirin and/or clopidogrel according to their indications or standard of care. There is limited clinical experience with other antiplatelet drugs and none with ZONTIVITY as the only antiplatelet agent. ( 2.2 ) 2.1 General Dosing Information Take one tablet of ZONTIVITY 2.08 mg orally once daily, with or without food. 2.2 Coadministration with Other Antiplatelet Drugs There is no experience with use of ZONTIVITY alone as the only administered antiplatelet agent. ZONTIVITY has been studied only as an addition to aspirin and/or clopidogrel. Use ZONTIVITY with aspirin and/or clopidogrel according to their indications or standard of care [see Clinical Studies (14) ] . There is limited clinical experience with other antiplatelet drugs.

Read the full Dosage and Administration section on DailyMed →

Vorapaxar side effects

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The most important side effect to know about is bleeding — it is the most commonly reported concern with vorapaxar. Other side effects that occurred more often than with placebo include:

Common side effects

  • Bleeding (the most common concern — ranging from minor to serious)
  • Anemia (low red blood cell count)
  • Depression
  • Skin rash or skin eruptions
  • Iron deficiency
  • Gastrointestinal (stomach or intestinal) bleeding
  • Double vision or other eye/vision disturbances
  • Bleeding of any kind — from minor bruising to serious gastrointestinal or brain bleeding
  • Anemia (low red blood cell count), sometimes related to unrecognized bleeding
  • Double vision or other eye movement disturbances (less common but reported)

When to get medical help

  • Get emergency help right away for any sign of serious bleeding — coughing or vomiting blood, black or tarry stools, blood in the urine, or bleeding that won't stop
  • Seek immediate care for signs of bleeding in the brain — sudden severe headache, weakness on one side, trouble speaking or seeing
  • Call your doctor if you feel unusually lightheaded, faint, or notice a sudden drop in blood pressure, especially after a recent procedure
  • Tell your doctor if you develop new or worsening depression
  • Report any sudden or worsening vision changes or double vision to your doctor
  • If you become pregnant, stop Zontivity and contact your doctor right away

Seek emergency care immediately for any signs of serious bleeding — such as coughing blood, black or tarry stools, sudden severe headache, or weakness on one side of the body. These can be signs of internal or brain bleeding and require urgent attention.

Vorapaxar warnings and precautions

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  • Serious and potentially fatal bleeding: Vorapaxar raises the risk of all types of bleeding, including brain (intracranial) hemorrhage and fatal bleeds. There is no reversal agent, and the effect persists for weeks after stopping the drug.
  • Absolutely contraindicated in stroke or TIA history: People who have had a stroke, TIA (mini-stroke), or any bleeding in the brain must never take vorapaxar — it dramatically increases the risk of brain bleeding in this group.
  • No quick off-switch: Because of the long half-life, stopping vorapaxar before a surgery or procedure does not rapidly eliminate its antiplatelet effect. Platelet function may still be significantly impaired up to 4 weeks after the last dose.
  • Avoid anticoagulants: Using vorapaxar with warfarin or other blood thinners sharply raises bleeding risk and should be avoided.
  • Liver impairment: Vorapaxar is not recommended for people with severe liver disease due to the already elevated bleeding risk in that population.
  • Older adults: Elderly patients tend to have a higher baseline bleeding risk; prescribers should factor this in before starting treatment.

Vorapaxar interactions

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Vorapaxar is processed mainly by liver enzymes (particularly CYP3A4), so drugs that affect those enzymes — or that also affect bleeding — can significantly alter its safety or effectiveness:

  • Strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, posaconazole, nefazodone): raise vorapaxar blood levels — avoid combining
  • Strong CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort): lower vorapaxar blood levels, reducing its effectiveness — avoid combining
  • Warfarin and anticoagulants (blood thinners): greatly increase the risk of serious bleeding — avoid if possible
  • Regular NSAID use (e.g., ibuprofen, naproxen): further increases bleeding risk
  • SSRIs and SNRIs (certain antidepressants): also increase bleeding risk when combined with vorapaxar
  • Fibrinolytic (clot-busting) drugs: add significantly to bleeding risk
  • Aspirin and clopidogrel: intended co-medications, but the combination still raises overall bleeding risk and should be monitored

Interactions listed in the FDA-approved label

From the Vorapaxar prescribing information (“Drug Interactions”): what the manufacturer studied or reported to the FDA.

  • Strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan): Vorapaxar is eliminated primarily by metabolism, with contributions from CYP3A4 and CYP2J2, and strong CYP3A inhibitors are addressed under effects of other drugs on ZONTIVITY. Avoid concomitant use of ZONTIVITY with strong inhibitors of CYP3A.
  • Strong CYP3A inducers (e.g., rifampin, carbamazepine, St. John's Wort and phenytoin): Vorapaxar is eliminated primarily by metabolism, with contributions from CYP3A4 and CYP2J2, and strong CYP3A inducers are addressed under effects of other drugs on ZONTIVITY. Avoid concomitant use of ZONTIVITY with strong inducers of CYP3A.
Read the label’s full interactions text

7 DRUG INTERACTIONS 7.1 Effects of Other Drugs on ZONTIVITY Vorapaxar is eliminated primarily by metabolism, with contributions from CYP3A4 and CYP2J2. Strong CYP3A Inhibitors Avoid concomitant use of ZONTIVITY with strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan) [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ] . Strong CYP3A Inducers Avoid concomitant use of ZONTIVITY with strong inducers of CYP3A (e.g., rifampin, carbamazepine, St. John's Wort and phenytoin) [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ].

Read the full Drug Interactions section on DailyMed →

Not a complete list. The label covers the interactions the manufacturer studied or reported, and our own interaction database does not cover every medicine either. Bring your full medication list, including vitamins and herbal products, to your pharmacist.

🌿282 supplements and herbs with documented Vorapaxar interactions, ranked by severity Check Vorapaxar against a supplement or herb →

Before taking Vorapaxar

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  • History of stroke, TIA, or brain bleeding: Vorapaxar is absolutely contraindicated — do not take it
  • Active serious bleeding (e.g., bleeding ulcer, active hemorrhage): do not take vorapaxar until resolved
  • Pregnancy: Stop vorapaxar as soon as pregnancy is detected and contact your doctor immediately — the drug's long-lasting platelet effects pose a serious bleeding risk
  • Breastfeeding: Not recommended — the drug may be present in breast milk and could harm the infant
  • Children: Safety and effectiveness have not been established in pediatric patients
  • Older adults: Eligible for use, but age raises baseline bleeding risk — prescribers should weigh this carefully
  • Severe liver (hepatic) impairment: Vorapaxar is not recommended due to inherent elevated bleeding risk
  • Kidney (renal) impairment: No dose adjustment needed, but kidney disease is a general risk factor for bleeding
  • Upcoming surgery or procedures: Tell every member of your care team you take vorapaxar — stopping it does not quickly restore normal platelet function

Vorapaxar overdose

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There is no known antidote or treatment to reverse vorapaxar's antiplatelet effect after an overdose. Neither dialysis nor platelet transfusion is expected to be helpful if serious bleeding occurs. Because significant platelet inhibition can persist for weeks, a vorapaxar overdose situation requires emergency medical care and close monitoring for bleeding.

What Vorapaxar does in the body

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At the recommended once-daily dose, Zontivity achieves at least 80% inhibition of thrombin-triggered platelet clumping within the first week of treatment. This antiplatelet effect is dose- and concentration-dependent. Even four weeks after stopping the daily dose, platelet clumping is still inhibited by roughly 50% — reflecting just how long the drug's effect lingers in the body. Vorapaxar does not affect standard coagulation tests (like PT or aPTT) or markers of inflammation.

How your body processes Vorapaxar

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Vorapaxar is nearly completely absorbed when taken by mouth, reaching peak blood levels within 1 to 2 hours, and food does not meaningfully affect the total amount absorbed. It is extensively bound (99% or more) to plasma proteins and is broken down mainly by liver enzymes (CYP3A4 and CYP2J2) into active and inactive metabolites, with the majority leaving the body through the stool. The drug has an effective half-life of 3 to 4 days and a terminal half-life of about 8 days — meaning it takes weeks to fully clear the system — and reaches stable blood levels after about 3 weeks of daily dosing.

How to store Vorapaxar

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of bottles Store at 20-25°C (68-77°F), excursions permitted between 15-30°C (between 59-86°F). Store tablets in the original package with the bottle tightly closed. protect from moisture.

Written from the FDA-approved label with AI and reviewed by our pharmacy team. How we use AI →

282

Supplements & herbs that interact with Vorapaxar

282 supplements and herbal products have documented interactions with Vorapaxar in the licensed clinical database we use. Most are manageable — but your pharmacist should know about everything you take, including vitamins and herbals.

Severity mix
  • Major · 5
  • Moderate · 236
  • Minor · 41
ACTIVATED CHARCOAL Major DANSHEN Major GRAPEFRUIT Major PIRACETAM Major ST. JOHN'S WORT Major ACACIA RIGIDULA Moderate ACONITE Moderate ADRAFINIL Moderate +274 more
Every supplement checked against Vorapaxar — ranked by severity The full interaction hub: 5 major · 236 moderate · 41 minor · every one linked to its full report. Check Vorapaxar against your exact supplements

Educational information from a licensed clinical database (Natural Medicines) — see our data sources & update cadence. Not medical advice: an interaction being documented does not mean it will happen to you; do not start or stop medications or supplements without professional guidance.

Vorapaxar: pharmacist answers to common questions

Quick, plain-English answers to the questions patients ask most about Vorapaxar — the kind of thing our pharmacy team would talk through with you at the counter.

Why was I prescribed Zontivity? What exactly does it do?

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Zontivity is prescribed to lower your chances of having another heart attack, a stroke, or a procedure to unblock arteries — especially if you've already had a heart attack or have been diagnosed with peripheral arterial disease (PAD). It works by blocking a receptor on your platelets called PAR-1, which prevents a clotting protein called thrombin from making your platelets clump together and form dangerous clots in your arteries. Think of it as a targeted 'clot brake' for one specific pathway.

Do I have to take other blood thinners with it, or can I take Zontivity on its own?

▾
Zontivity should not be taken alone. It has only been studied alongside aspirin and/or clopidogrel, and your doctor will prescribe it as part of that combination. The three medications work through different pathways, so they complement each other. Just be aware that combining antiplatelet medicines does increase your overall bleeding risk, which is something your care team will monitor.

I'm nervous about the bleeding risk — what should I watch for?

▾
That's a completely reasonable concern, and it's the most important thing to stay alert to. Seek emergency care right away if you notice any of these: coughing or vomiting blood, black or tarry stools, blood in your urine, a cut that won't stop bleeding, a sudden severe headache, or weakness or numbness on one side of your body. Everyday minor bruising is less alarming but worth mentioning to your doctor. Make sure every healthcare provider — including your dentist — knows you take Zontivity before any procedure.

What happens if I need surgery? Can I just stop taking it a few days before?

▾
Unfortunately, stopping Zontivity a few days early won't fully protect you — the drug's antiplatelet effect can linger in your body for up to four weeks after the last dose. There is also no medication that can reverse it quickly. So if you have a planned or emergency surgery, it's critical to tell your surgical team about Zontivity as early as possible so they can plan accordingly and manage any bleeding risk.

Are there any medications or supplements I need to avoid while taking Zontivity?

▾
Yes, a few important ones. You should avoid strong antifungals like ketoconazole or itraconazole, certain antibiotics like clarithromycin, and HIV medications like ritonavir — these can raise vorapaxar levels in your blood to potentially unsafe amounts. On the flip side, rifampin, carbamazepine, phenytoin, and St. John's Wort (an herbal supplement) can lower the drug's effectiveness. Warfarin and other blood thinners should also be avoided because together they significantly raise the risk of serious bleeding. Always check with your pharmacist before starting any new medication or supplement.

I'm thinking about getting pregnant. Is it safe to take Zontivity during pregnancy?

▾
No — if you find out you're pregnant, you should stop Zontivity immediately and contact your doctor right away. One of the biggest concerns is the risk of serious bleeding for both you and the baby, and the drug stays in your system for weeks after stopping. Your doctor will switch you to an alternative treatment with a shorter-acting effect. Breastfeeding is also not recommended while taking Zontivity, as the drug could potentially pass into breast milk.

Is Vorapaxar available over the counter?

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No. Vorapaxar is a prescription medicine: every Vorapaxar product listed with the FDA is prescription only, so it is not sold over the counter. Your prescriber decides whether it is appropriate for you, and your pharmacist dispenses it.

When was Vorapaxar first available?

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The earliest FDA record we hold for Vorapaxar is from 2014: its first approval in Drugs@FDA or its earliest product listing in the NDC Directory, whichever is older. Many older medicines were in use before their first formal FDA approval, so this is the earliest date on record, not necessarily when Vorapaxar was first used.

Answers drafted from the FDA-approved label with AI and reviewed by our pharmacy team. How we use AI →

More about Vorapaxar on HelloPharmacist

📊Vorapaxar supplement interactions282 checked — ranked by severity 🌿Drug & Supplement CheckerVorapaxar vs. vitamins & herbs 💬Ask a PharmacistFree answer, usually < 24h 🔎NDC & pricing lookupFind Vorapaxar NDCs & costs 🅰️Browse Drugs A–ZLook up any medication
Detailed data & references for Vorapaxar Forms & strengths, pricing, billing codes, manufacturers, safety reports and sourcing — the data behind the page. Most people can stop here. Each section below opens on a tap.

Vorapaxar on the U.S. market: products, makers and brands

How Vorapaxar appears in the FDA’s National Drug Code Directory — including its dosage forms, strengths, brand names, manufacturers, and FDA-listed product records. These are directory records, not sales or prescription volume.

The FDA lists Vorapaxar products; the earliest marketing or approval year on record is 2014. Brand names on the directory include Zontivity; the rest are generics.

2014
Earliest FDA record ⓘ

Vorapaxar recall history

A recall is when a specific batch of a medicine is pulled from the market — usually a manufacturing issue, not a problem with the drug itself. Class I is most serious, Class III least.

The FDA’s enforcement reports list no Vorapaxar recalls since July 2021.

✅No Vorapaxar recalls on record since July 2021

Source: FDA enforcement (recall) reports, via openFDA; our copy was last updated Sep 24, 2026.

RxNorm Concept Web — From Ingredient to Every Form and Strength

This page starts with one ingredient concept (IN). The branches below show its dose-form concepts (SCDF), then the available clinical drug and strength concepts (SCD). Combination products remain separate concepts with their own pages.

Ingredient (IN) Vorapaxar RxCUI 1537034 1 dose form · 1 strength
  1. Dose form (SCDF) Oral Tablet RxCUI 1537038 No current FDA listing
    Clinical drug / strength (SCD) 2.08 MG RxCUI 1537039

Look up RxCUI 1537034 in the RxCUI Atlas →

RxNorm is the U.S. National Library of Medicine’s normalized drug vocabulary. Its concept hierarchy can include forms that are not currently marketed; the status on each branch compares that concept with current FDA listings. RxCUIs identify vocabulary concepts, not individual packages or manufacturers.

Vorapaxar brand names

Vorapaxar is sold under one brand name in the FDA directory — Zontivity. A brand and its generic contain the same active ingredient; the brand name belongs to one company's product.

Zontivity

Vorapaxar drug class (RxNorm)

Vorapaxar belongs to the Protease-activated Receptor-1 Antagonist class.

Pharmacologic class Protease-activated Receptor-1 Antagonist
Drug family (ATC) Platelet aggregation inhibitors excl. heparin
How it works Protease-activated Receptor-1 Antagonists

Classified by RxNorm RxClass — the U.S. National Library of Medicine's standardized drug-classification service (Established Pharmacologic Class from the FDA, the ATC drug family from the WHO, and mechanism of action). Reference only, not medical advice.

Sources for this Vorapaxar page

Core label, product, RxNorm, safety, and utilization data on this page come from the sources identified below. AI-written, editorial, and licensed sections are labeled separately.

📄
FDA-filed drug labels (SPL) Uses, dosing, warnings & side effects from SPL records retrieved through openFDA; the linked representative set can be verified on DailyMed. ✓ Linked label effective Oct 18, 2022
🏭
Forms, brands & labelersAggregated from ingredient-matched FDA National Drug Code Directory product records for Vorapaxar.
📈
Real-world reportsThe FDA Adverse Event Reporting System (FAERS), served through openFDA.
🚨
Recalls & shortagesopenFDA drug-enforcement reports and the FDA drug-shortage database.
🧾 Clinical label set — FDA-filed SPL labels retained for Vorapaxar after exact ingredient or ingredient-combination matching and applicable route/form matching
Clinical labels in scope
1
Linked representative label ⓘ
WraSer Pharmaceuticals, LLC
Linked label effective
Oct 18, 2022
Composite sections available
24
Linked SPL Set ID
f2abe3ed-ed3d-4215-a489-b18341ce85bc
Linked SPL Document ID
eb55583e-2701-6426-e053-2a95a90abb4f
Open the linked representative label on DailyMed ↗

How this page is built

HelloPharmacist combines public FDA and NLM records and does not author the underlying clinical facts. The plain-language sections are written with AI from the FDA-approved label text and reviewed by our pharmacy team before publication. WraSer Pharmaceuticals, LLC is the representative DailyMed label linked for verification and dates. This is general education, not medical advice: always talk to your doctor or pharmacist about your own medicines. How we build and review drug pages →