Version July 2025
Do not use vorapaxar in patients with a history of stroke, transient ischemic attack, or intracranial hemorrhage; or active pathological bleeding. Antiplatelet agents, including vorapaxar, increase the risk of bleeding, including intracranial hemorrhage and fatal bleeding.
Note: Vorapaxar 2.08 mg is equivalent to vorapaxar sulfate 2.5 mg.
History of myocardial infarction or established peripheral arterial disease (PAD): Note: Role in therapy not well established. The overall clinical benefit of adding vorapaxar to other antiplatelet therapy is uncertain; must consider the risk-benefit of bleeding versus reduction in cardiovascular events. May use in combination with aspirin and/or clopidogrel, although some experts only recommend adding to aspirin therapy (Ref).
Oral: 2.08 mg once daily in combination with an appropriate antiplatelet regimen.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Hemodialysis: Unknown if dialyzable, but unlikely (Ref).
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: Use is not recommended.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Hematologic and oncologic: Hemorrhage (any GUSTO [Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries] bleeding [severe, moderate, mild]): 25%), major hemorrhage, life-threatening (13%; clinically significant bleeding, including any bleeding requiring medical attention such as intracranial hemorrhage, or clinically significant overt signs of hemorrhage associated with a drop in hemoglobin of ≥3 g/dL [or when hemoglobin is unavailable, an absolute drop in hematocrit of ≥15% or a fall in hematocrit of 9% to <15%])
1% to 10%:
Central nervous system: Depression (2%)
Dermatologic: Skin rash (2%, includes cutaneous eruptions and exanthemas)
Endocrine & metabolic: Iron deficiency (<2%)
Gastrointestinal: Gastrointestinal hemorrhage (4%)
Hematologic and oncologic: Anemia (5%), major hemorrhage (GUSTO bleeding category “moderate or severe”: 3%; GUSTO bleeding category “severe”: 1%)
Ophthalmic: Retinopathy (<2%)
<1%, postmarketing, and/or case reports: Diplopia (or oculomotor disturbance), hemorrhagic death, intracranial hemorrhage
History of stroke, transient ischemic attack (TIA), or intracranial hemorrhage (ICH); active pathological bleeding (eg, ICH, peptic ulcer bleeding)
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to vorapaxar or any ingredient in the formulation; severe hepatic impairment
Concerns related to adverse effects:
• Bleeding: [US Boxed Warning]: Use is contraindicated in patients with history of stroke, TIA, or ICH; or active pathological bleeding. Discontinue use in patients who experience a stroke, TIA, or ICH during therapy. Vorapaxar increases the risk of bleeding, including ICH and fatal bleeding. The risk of bleeding is proportional to the patient's underlying bleeding risk. General risk factors for bleeding include older age, low body weight, reduced renal or hepatic function, history of bleeding disorders, and concomitant use of medications known to increase the risk of bleeding (eg, anticoagulants, NSAIDS, SSRIs, SNRI); avoid use with anticoagulants. Note: No specific antidote exists for vorapaxar reversal. Significant inhibition of platelet aggregation remains 4 weeks after discontinuation.
Disease-related concerns:
• Hepatic impairment: Due to increased risk of bleeding, use is not recommended in patients with severe hepatic impairment; use with caution in patients with mild or moderate hepatic impairment.
• Renal impairment: Due to increased risk of bleeding, use with caution in patients with renal impairment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as sulfate:
Zontivity: 2.08 mg
No
Tablets (Zontivity Oral)
2.08 mg (per each): $18.43
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Administer with or without food.
An FDA-approved patient medication guide, which is available with the product information and at https://www.fda.gov/media/92207/download, must be dispensed with this medication.
History of MI or established peripheral arterial disease: To reduce thrombotic cardiovascular events (cardiovascular death, MI, stroke, urgent coronary revascularization) in patients with a history of MI or with peripheral arterial disease (PAD)
Substrate of CYP2J2 (Minor), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: Therapeutic Antiplatelets may increase antiplatelet effects of Abrocitinib. Management: Do not use antiplatelet drugs with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. This does not apply to low dose aspirin (81 mg/day or less). Risk X: Avoid
Acalabrutinib: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Aducanumab: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Agents with Antiplatelet Effects: May increase antiplatelet effects of Miscellaneous Antiplatelets. Risk C: Monitor
Anagrelide: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Anticoagulants: Vorapaxar may increase adverse/toxic effects of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Risk X: Avoid
Antiplatelet Agents (P2Y12 Inhibitors): Therapeutic Antiplatelets may increase antiplatelet effects of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor
Caplacizumab: May increase antiplatelet effects of Therapeutic Antiplatelets. Management: Avoid this combination if possible. If coadministration is required, monitor closely for bleeding. Interrupt caplacizumab if clinically significant bleeding occurs and administer von Willebrand factor concentrate to rapidly correct hemostasis, if needed. Risk D: Consider Therapy Modification
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
Collagenase (Systemic): Therapeutic Antiplatelets may increase adverse/toxic effects of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Vorapaxar. Risk X: Avoid
CYP3A4 Inducers (Strong): May decrease serum concentration of Vorapaxar. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Vorapaxar. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Vorapaxar. Risk X: Avoid
Dasatinib: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Deoxycholic Acid: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Donanemab: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Glycoprotein IIb/IIIa Inhibitors: Therapeutic Antiplatelets may increase anticoagulant effects of Glycoprotein IIb/IIIa Inhibitors. Risk C: Monitor
Grapefruit Juice: May increase serum concentration of Vorapaxar. Risk C: Monitor
Herbal Products with Anticoagulant/Antiplatelet Effects: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Ibritumomab Tiuxetan: Therapeutic Antiplatelets may increase antiplatelet effects of Ibritumomab Tiuxetan. Risk C: Monitor
Ibrutinib: Therapeutic Antiplatelets may increase adverse/toxic effects of Ibrutinib. Specifically, the risks of bleeding and hemorrhage may be increased. Risk C: Monitor
Icosapent Ethyl: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Inotersen: Therapeutic Antiplatelets may increase adverse/toxic effects of Inotersen. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Lecanemab: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Limaprost: May increase adverse/toxic effects of Therapeutic Antiplatelets. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Lipid Emulsion (Fish Oil Based): May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Miscellaneous Antiplatelets: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Multivitamins/Fluoride (with ADE): May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Multivitamins/Minerals (with ADEK, Folate, Iron): May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Multivitamins/Minerals (with AE, No Iron): May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Obinutuzumab: Therapeutic Antiplatelets may increase adverse/toxic effects of Obinutuzumab. Specifically, the risk of bleeding may be increased. Management: Consider avoiding coadministration of obinutuzumab and therapeutic antiplatelets, especially during the first cycle of obinutuzumab therapy. Risk D: Consider Therapy Modification
Omega-3 Fatty Acids: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Pentosan Polysulfate Sodium: Therapeutic Antiplatelets may increase adverse/toxic effects of Pentosan Polysulfate Sodium. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor
Pirtobrutinib: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Selumetinib: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
St John's Wort: May decrease serum concentration of Vorapaxar. Risk X: Avoid
Therapeutic Antiplatelets: Miscellaneous Antiplatelets may increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Thrombolytic Agents: Therapeutic Antiplatelets may increase adverse/toxic effects of Thrombolytic Agents. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Tipranavir: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Vitamin E (Systemic): May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Volanesorsen: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Zanubrutinib: May increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Due to the potential for serious adverse events (eg, maternal bleeding, hemorrhage) and the long half-life of vorapaxar, alternate agents may be preferred in pregnant patients. Discontinue use if pregnancy is detected.
It is not known if vorapaxar is present in breast milk.
Due to the potential for adverse events in a breastfed infant (eg, bleeding), breastfeeding is not recommended by the manufacturer.
Signs of bleeding; hemoglobin and hematocrit periodically
Vorapaxar, an antagonist of the protease-activated receptor-1 (PAR-1) expressed on platelets, inhibits thrombin-induced and thrombin receptor agonist peptide (TRAP)-induced platelet aggregation. Due to the very long half-life, vorapaxar is effectively irreversible. Vorapaxar reversibly binds to the PAR-1 receptor with a long receptor dissociation half-life of approximately 20 hours; additionally, vorapaxar displays significant inhibition of platelet aggregation that remains for up to 4 weeks after discontinuation due to the very long elimination half-life (Ueno 2010).
Onset of action: ≥80% inhibition of TRAP-induced platelet aggregation within 1 week
Duration: Dose and concentration dependent; with the recommended dosing, inhibition of TRAP-induced platelet aggregation at a level of 50% can be expected 4 weeks after discontinuation
Absorption: Rapidly absorbed (Kosoglou 2012)
Distribution: ~424 L
Protein binding: ≥99% to albumin
Metabolism: Hepatic via CYP3A4 and CYP2J2. Major active metabolite: M20 (accounts for ~20% of exposure to vorapaxar)
Bioavailability: ~100%
Half-life elimination: Effective half-life: 3 to 4 days; Terminal elimination half-life (vorapaxar and active metabolite): ~8 days (range: 5 to 13 days)
Time to peak: 1 to 2 hours
Excretion: Primarily in the form of metabolites through feces (58%); urine (25%)
