NAPLEX Question of the Week: Drug Interaction Mechanisms

This week's question focuses on an important drug interaction mechanism.
NAPLEX Question of the Week: Drug Interaction Mechanisms

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A 65-year-old male patient presents to the emergency department with symptoms of a potential stroke. 

PMH: TIA, HTN, Hyperlipidemia, T2DM, GERD, and Osteoarthritis

Home meds: Lisinopril 40 mg PO QD, rosuvastatin 40 mg PO QD, omeprazole 40 mg PO QD, metformin 1000 mg PO BID, and empagliflozin 25 mg PO QD, acetaminophen 500mg PO TID PRN

Allergies: Aspirin (rash and hives)


Complete Blood Count (CBC):

    • Hemoglobin (Hb): 13.5 g/dL
    • Hematocrit (Hct): 40%
    • Platelet Count: 210,000/mm³
    • White Blood Cell Count (WBC): 7,800/mm³

Basic Metabolic Panel (BMP):

    • Sodium (Na): 140 mEq/L
    • Potassium (K): 4.0 mEq/L
    • Bicarbonate (HCO3-): 24 mEq/L
    • Blood Urea Nitrogen (BUN): 18 mg/dL
    • Creatinine (Cr): 1.0 mg/dL
    • Glucose (fasting): 130 mg/dL

Lipid Profile:

    • Total Cholesterol: 200 mg/dL
    • LDL Cholesterol: 120 mg/dL
    • HDL Cholesterol: 45 mg/dL
    • Triglycerides: 150 mg/dL

Coagulation Profile:

    • Prothrombin Time (PT): 12.5 seconds
    • International Normalized Ratio (INR): 1.1
    • Activated Partial Thromboplastin Time (aPTT): 32 seconds

Hemoglobin A1C 7.2%

Liver Function Tests:

    • Alanine Aminotransferase (ALT): 25 U/L
    • Aspartate Aminotransferase (AST): 30 U/L
    • Alkaline Phosphatase (ALP): 70 U/L
    • Total Bilirubin: 0.8 mg/dL

The medical resident asks your view on the potential for an interaction between clopidogrel and omeprazole inducing a stroke. What is the best pharmacologic mechanism for this potential interaction?

A. Omeprazole induces the metabolism of clopidogrel, resulting in potentially decreased activity of clopidogrel

B. Omeprazole inhibits the metabolism of clopidogrel, resulting in a potentially increased risk of bleeding by clopidogrel

C. Clopidogrel requires an acidic environment for optimal absorption; omeprazole would increase pH and therefore decrease clopidogrel absorption and potential effectiveness

D. Clopidogrel conversion to its active metabolite may be inhibited by omeprazole, resulting in potentially decreased clopidogrel effectiveness


    Drug interactions are a critical component of pharmacy practice no matter the area. This particular interaction between clopidogrel and proton pump inhibitors, such as omeprazole, is one of significant debate. Most of the studies evaluating this interaction have definitively shown an impact on platelet function via platelet reactivity index studies. However, the clinical relevance of this interaction is controversial, as most of the studies are of mixed quality and have found differing results. Most clinicians if using a PPI with clopidogrel will use pantoprazole albeit this is not without debate as well. 

    While the debate continues regarding the clinical significance of this interaction, what is not for debate is the mechanism of the interaction in question. Clopidogrel is a prodrug that requires bioactivation by the liver via CYP 2C19 to its active metabolite, which then exerts its antiplatelet effect via ADP. Omeprazole inhibits CYP 2C19 and therefore limits the potential biotransformation to the active metabolite which could potentially decrease the overall activity (answers A and B are incorrect). Clopidogrel does not require an acidic environment for absorption (answer C is incorrect). Certain drugs, like ketoconazole or itraconazole, do require an acidic environment for optimal absorption.

    For all of the above reasons, this makes Answer D the correct answer

    We will see you next week!

    Dr. B

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