Zontivity (Vorapaxar) inhibits platelet aggregation by inhibiting thrombin, TRAP (Thrombin receptor agonist peptide), and PAR-1 (protease-activated receptor-1 ) that is expressed on the platelets. It is used to reduce the thrombotic cardiovascular events (myocardial infarction, stroke, cardiovascular death, and conditions requiring urgent coronary revascularization) in patients with a history of myocardial infarction or established peripheral arterial disease.

Zontivity Dose in Adults

Note: Vorapaxar (Zontivity) 2.08 mg is equivalent to 2.5 mg of vorapaxar sulfate.

Zontivity Dose in patients with a history of Myocardial infarction or established peripheral arterial disease (PAD):

• 2.08 mg orally once a day in combination with aspirin and/ or clopidogrel.
• It has not been studied as monotherapy or in combination with antiplatelets other than aspirin and/or clopidogrel.
• The role of vorapaxar as monotherapy or as an add-on therapy for the reduction of cardiovascular mortality is not established and should be used with caution.

Zontivity Dose in Childrens

It is not recommended for use in children.

Pregnancy Risk Factor B

• Although it has not been tested in pregnant women, animal studies have not shown an increase in the risk of adverse fetal outcomes.

Vorapaxar use during breastfeeding:

• Vorapaxar is not recommended for breastfeeding.It has not been tested in breastfeeding mothers.

Dose in patients with kidney disease:

• Adjustment in the dose is not necessary. It has not been studied in patients on hemodialysis. 

Zontivity dose in liver disease:

• Mild to moderate impairment:

  • Adjustment in the dose is not necessary.

• Severe impairment:

  • It is not recommended for use in severe liver disease.

Common Side Effects of Zontivity (Vorapaxar) Include:

• Hematologic and oncologic:

  • Hemorrhage
  • Major hemorrhage
  • Life-threatening

Less Common Side Effects of Vorapaxar Include:

• Central Nervous System:

  • Depression

• Dermatologic:

  • Skin Rash

• Endocrine & Metabolic:

  • Iron Deficiency

• Gastrointestinal:

  • Gastrointestinal Hemorrhage

• Hematologic And Oncologic:

  • Anemia
  • Major Hemorrhage

• Ophthalmic:

  • Retinopathy

Contraindication to Vorapaxar (ZOntivity) Include:

• Patients who have had a stroke, transient or chronic ischemic attack, and intracranial hemorhage in the past.
• Active bleeding, such as intracranial bleeding or peptic ulcer bleeding, is possible.
• Allergy to any component of the drug or the drug itself
• Grave liver disease.

Warnings and precautions

• Bleeding: [US Boxed Warning]

  • Patients with a history or TIA of stroke, ICH, or other serious health problems are advised not to use it.
  • Patients with active pathological bleeding should avoid it.
  • Patients who suffer a stroke, TIA or ICH should stop receiving therapy.
  • Patients at high risk of bleeding should not use it.Patients at high risk include:
    • Older age
    • Low body weight
    • Reduced renal or hepatic function
    • History of bleeding disorders
    • Concomitant use anticoagulants, or other medications, that could increase the risk for bleeding, such as NSAIDs and SSRIs.
    • It is not possible to reverse the effects of this drug. However, they may remain in effect for as long as 4 weeks.

• Hepatic impairment

  • You can use it in patients with mild or moderate hepatic impairment.
  • However, severe liver disease should not be treated with it due to the higher risk of bleeding.

• Renal impairment

  • Patients with kidney disease should use it with caution.

Vorapaxar: Drug Interaction

Monitor:

• Signs of bleeding
• Hemoglobin and hematocrit periodically

How to administer Vorapaxar (Zontivity)?

• Administer with or without food. 

Mechanism of action of Vorapaxar (Zontivity):

• Vorapaxar inhibits platelet aggregation through inhibition of thrombin (thrombin receptor agonist peptide) and TRAP (thrombin regulatory peptide). 
• It acts as an antagonist to the protease activated receptor-1 (PAR-1), which is found on platelets. It binds to PAR-1 receptor in a reversible manner with a half-life of approximately 20 hours. 
• Because of its long half life, it can maintain antiplatelet activity for as much as four weeks.
• Orally, more than 80% of platelet inhibition is achieved within one week. The duration is dose and concentration-dependent.

It is growing rapidlyabsorbedIt is almost completely bound to albumin. 

It is metabolized in the liver by CYP3A4 to CYP2J2 and M20 to M20 (which is a major metabolite with 20% activity).

It has been abioavailabilityA high percentage of around 100%, a half-life elimination time of 3 to 4 days and

a terminalHalf-lifeThe drug and its metabolites for approximately 8 days (ranging between 5 and 13 days).

It takes time to get there peak serum concentrationIt takes between 1 and 2 hours to

excrete and is mostly eliminated via its metabolites through feces (58%) and urine (25%).

International Brands of Vorapaxar:

• Cardimopaxar
• Zontivit
• Zontivity

Vorapaxar Brand Names in Pakistan:

It is not available in Pakistan.