Zontivity | vorapaxar 

Medication Class: Protease-activated receptor-1 (PAR-1) antagonist 
Similar Drugs: None, Zontivity is the first medication in this new class, PAR-1 antagonists
Manufactured by: Merck
Approval Date: May 8, 2014

What is Zontivity and its mechanism of action?                                            

Zontivity (vorapaxar) is a novel antiplatelet medication for people who have had a heart attack or who have reduced blood flow in their legs. The medication can be used to decrease risk of heart attack, stroke, and cardiovascular death.

Zontivity is a reversible antagonist of the protease-activated receptor-1 (PAR-1) found on platelets. It blocks PAR-1 which is the primary receptor for thrombin (an enzyme that causes blood clotting). By blocking this receptor Zontivity prevents aggregation of platelets and prevents formation of blood clots. The long half-life of Zontivity (3 to 4 days) essentially makes the antiplatelet effect irreversible.  

What does Zontivity treat?

Zontivity is FDA approved for the reduction of thrombotic cardiovascular events (clot formation causing blockage) in patients with a history of heart attacks or with peripheral arterial disease (PAD), a disease where plaque builds up in the arteries that carry blood to your head, organs, and limbs.

How to take Zontivity

Zontivity is available as 2.08 mg tablets. Take 1 tablet (2.08mg) daily with or without food. Zontivity may be used with aspirin and/or clopidogrel (Plavix) according to standard of care.  There is limited data about use of Zontivity with other antiplatelet therapy or as monotherapy (by itself). If patients have liver or renal impairment there is no need for adjusting the dose of Zontivity.

How effective is Zontivity?

Zontivity reduced the risk of heart attack, stroke, cardiovascular death, and urgent coronary revascularization (restoring blood flow to the heart) in patients with prior heart attacks or peripheral arterial disease (PAD). A double-blind randomized control study of 26,449 patients showed an overall reduction in primary events after 36 months was 11.2% in the Zontivity group versus 12.4% in the placebo group. The occurrence of moderate to severe bleeding in the placebo group was 17.6% and 27.7% in the Zontivity group. The study also showed patients with previous ischemic stroke were at greater risk of developing intracranial hemorrhage (ICH) (bleeding within the brain) while on Zontivity. Patients enrolled in the study were also on standard therapy for post heart attack or PAD.  

What are interesting Zontivity facts?

• Its effect can last for several days to weeks
• There is no reversible agent for Zontivity and dialysis or platelet infusion is not effective in reversing its effect.
• Zontivity is the first medication in this new class, PAR-1 antagonists antiplatelet drug. 

Who should not use Zontivity?

Zontivity is not recommended in patients with prior stroke, transient ischemic stroke (TIA), intracranial hemorrhage (bleeding within the brain), or active pathological bleeding. Active pathological bleeding is categorized as having ulcers or hemorrhages.

What are side effects of Zontivity?

The major side effect of Zontivity is bleeding, including fatal bleeding, especially since Zontivity is used together with another anti-clotting drugs. Patients may bleed and bruise more easily. Patients should report any unanticipated, prolonged, or excessive bleeding, or blood in the stool or urine. Other side effects include anemia (5%), depression (2.4%), and rashes (2.2%). 

Can Zontivity be used in pregnancy?

Zontivity is a pregnancy category B. There is insufficient data on use of Zontivity in pregnant women.

What are Zontivity drug interactions?

Zontivity is eliminated and metabolized by liver enzymes ( CYP3A4 enzymes). St. John’s Wort, phenytoin, rifampin, carbamazepine increase the breakdown of Zontivity in the liver. Ketoconazole, clarithromycin, nefazodone, itraconazole, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telithromycin, and conivaptan all increase blood levels of Zontivity by reducing its breakdown in the liver. Avoid the use of Zontivity with drugs that affect its breakdown in the liver. Notify your pharmacist or doctor if you are prescribed any of these medications in addition to Zontivity.

What is the cost of Zontivity

Average wholesale price is $320.76 for a 30 tablet bottle, $962.28 for the 90 tablet bottle, and $1069.20 for a 100 tablet bottle. Average unit price is $10.69 per tablet.

How to obtain prescription assistance for Zontivity

For prescription assistance for Zontivity please visit the Merck website for updates on Merck assistance programs or call Merck at 1-800-727-5400. 

References

RED BOOK Online Zontivity. Truven Health Analytics, Inc. 2014

Zontivity (vorapaxar) Prescribing Information (package insert)

Zontivity (vorapaxar) Med Guide- Clinical Pharmacology