• Vorapoxar may interact with CYP3A4 enzyme inhibitors such as Ketoconazole, Itraconazole, Posaconazole, Clarithromycin, Nefazodone, Ritonavir, etc. • Vorapoxar may also interact with CYP3A4 enzyme inducers like Rifampin.

1. DRUG INTERACTIONS OF
ANTIPLATELETS (PART 6)
(DRUG INTERACTIONS OF VORAPAXAR)
Dr P.NAINA MOHAMED PhD
Pharmacologist

2. INTRODUCTION
• VORAPAXAR IS AN ANTIPLATELET DRUG AND IT IS THE ANTAGONIST OF
PROTEASE ACTIVATED RECEPTOR-1 (PAR-1) (THROMBIN RECEPTOR).
• VORAPAXAR IS USEFUL IN THE SECONDARY PREVENTION OF
ATHEROTHROMBOTIC EVENTS OCCURRING IN PATIENTS WITH A HISTORY
OF MYOCARDIAL INFARCTION OR PERIPHERAL ARTERIAL DISEASE.
• INTERACTION BETWEEN ONE OR MORE CO-ADMINISTERED MEDICATIONS
LEADING TO CHANGE IN THEIR EFFECTIVENESS OR TOXICITY, IS TERMED AS
“ADVERSE DRUG INTERACTION”.
• ANTIPLATELETS CAN INTERACT WITH PRESCRIPTION DRUGS, OVER-THE-
COUNTER (OTC) MEDICATIONS, HERBAL PRODUCTS, DIETARY SUPPLEMENTS,
VITAMINS, FOODS, DISEASES, AND GENETICS (FAMILY HISTORY).

3. ANTIPLATELETS
• IRREVERSIBLE CYCLOOXYGENASE (COX) INHIBITORS
 ASPIRIN
• ADENOSINE DIPHOSPHATE (ADP) RECEPTOR INHIBITORS
 CLOPIDOGREL
 PRASUGREL
 TICAGRELOR
 TICLOPIDINE
• ADENOSINE REUPTAKE INHIBITORS
 DIPYRIDAMOLE
• GLYCOPROTEIN IIB/IIIA INHIBITORS (IV USE ONLY)
 ABCIXIMAB
 EPTIFIBATIDE
 TIROFIBAN
• PHOSPHODIESTERASE INHIBITORS
 CILOSTAZOL
• PROTEASE ACTIVATED RECEPTOR-1 (PAR-1) ANTAGONISTS
 VORAPAXAR

4. MECHANISM OF ACTION OF VORAPAXAR
HTTP://CIRC.AHAJOURNALS.ORG/CONTENT/130/15/1287
Vorapaxar
Binds to Protease
activated receptor-1
(PAR-1) of platelets
Prevention of binding
of thrombin to PAR-
1
Inhibition of
thrombin-related
platelet aggregation

5. VORAPAXAR & CYP3A4
INHIBITORS
CONCOMITANT USE OF VORAPAXAR AND STRONG CYP3A4 ENZYME INHIBITORS
SHOULD BE AVOIDED.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC4913541/
HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC5318326/
Vorapaxar + CYP3A4 enzyme
inhibitors (Ketoconazole, Itraconazole,
Posaconazole, Clarithromycin,
Nefazodone, Ritonavir, etc.)
Inhibition of CYP3A4-mediated
metabolism of Vorapaxar
Elevated plasma concentrations and
risk of adverse effects of Vorapaxar

6. VORAPAXAR & CYP3A4 INDUCERS
• CONCOMITANT USE OF VORAPAXAR AND STRONG CYP3A4 ENZYME INDUCERS
SHOULD BE AVOIDED.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC4913541/
HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC5318326/
Vorapaxar + CYP3A4
enzyme inducers
(Rifampin)
Induction of
CYP3A4-mediated
vorapaxar
metabolism
Diminished
exposure and
efficacy of Vorapaxar

7. CONCLUSION
• DRUG INTERACTIONS CAN RESULT IN SIGNIFICANT MORBIDITY AND
MORTALITY AND THUS MINIMIZING THE RISK FOR DRUG INTERACTIONS
SHOULD BE A GOAL IN DRUG THERAPY.
• THE PATIENTS ON ANTIPLATELET THERAPY SHOULD BRING A LIST OF ALL OF
THE DRUGS THEY ARE TAKING INCLUDING PRESCRIPTION DRUGS, OVER-THE-
COUNTER DRUGS, AND ANY SUPPLEMENTS, HERBAL OR OTHERWISE, DURING
THEIR VISIT TO THE DOCTOR OR PHARMACIST.
• THE RISK OF ADVERSE EFFECTS COULD BE REDUCED BY HEALTHCARE
PROFESSIONALS THROUGH THE SCREENING, EDUCATION, AND FOLLOW UP ON
SUSPECTED DRUG INTERACTIONS.
• IF POSSIBLE, THE PATIENTS ARE RECOMMENDED TO FILL ALL THEIR
PRESCRIPTIONS AT ONE PHARMACY.
• PHARMACISTS CAN PLAY A CRUCIAL ROLE IN IDENTIFYING POSSIBLE DRUG
INTERACTIONS BY ASKING PATIENTS ABOUT THEIR HERBAL AND OTHER
ALTERNATIVE MEDICINE PRODUCT USE.

8. REFERENCES
o STOCKLEY’S DRUG INTERACTIONS, 9E
KAREN BAXTER
o GOODMAN & GILMAN'S: THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, 12E
LAURENCE L. BRUNTON, BRUCE A. CHABNER, BJÖRN C. KNOLLMANN
o BASIC & CLINICAL PHARMACOLOGY, 12E
BERTRAM G. KATZUNG, SUSAN B. MASTERS, ANTHONY J. TREVOR
o A MANUAL OF ADVERSE DRUG INTERACTIONS
J.P. GRIFFIN, P.F. D'ARCY
o CLINICAL MANUAL OF DRUG INTERACTION PRINCIPLES FOR MEDICAL PRACTICE
GARY H. WYNN, JESSICA R. OESTERHELD, KELLY L. COZZA, SCOTT C.
ARMSTRONG
o HANDBOOK OF DRUG INTERACTIONS: A CLINICAL AND FORENSIC GUIDE

9. REFERENCES
• HTTP://WWW.MICROMEDEXSOLUTIONS.COM
• HTTPS://LINK.SPRINGER.COM/ARTICLE/10.2165%2F00003088-198917050-00003
• HTTP://ONLINELIBRARY.WILEY.COM/DOI/10.1111/J.1365-2796.2010.02299.X/FULL
• HTTPS://WWW.ACADEMIC.OUP.COM/EURHEARTJ/ARTICLE/24/19/1707/495173/DRUG-DRUG-
INTERACTIONS-INVOLVING-ANTIPLATELET
• HTTP://WWW.NATURE.COM/NRCARDIO/JOURNAL/V8/N10/FULL/NRCARDIO.2011.128.HTML
• HTTP://WWW.SCIENCEDIRECT.COM/SCIENCE/ARTICLE/PII/S2211594312000974
• HTTPS://WWW.RESEARCHGATE.NET/PUBLICATION/47788995_ANTIPLATELET_DRUG_INTERACTIONS
• HTTP://REFERENCE.MEDSCAPE.COM/DRUG-INTERACTIONCHECKER
• HTTPS://WWW.DRUGS.COM/DRUG_INTERACTIONS.HTML
• HTTP://WWW.WEBMD.COM/INTERACTION-CHECKER/
• HTTP://WWW.RXLIST.COM/DRUG-INTERACTION-CHECKER.HTM
• HTTPS://WWW.NPS.ORG.AU/AUSTRALIAN-PRESCRIBER/ARTICLES/WARFARIN-ANTIPLATELET-DRUGS-
AND-THEIR-INTERACTIONS