Implementation of CYP2C19 genotyping to guide proton pump inhibitor use at an academic health center

Purpose: To describe the implementation of CYP2C19 testing into clinical practice at University of Florida (UF) Health Gainesville hospital to guide proton pump inhibitor (PPI) dosing and the lessons learned from this experience.

Summary: Different CYP2C19 genotypes are associated with variability in PPI plasma concentrations and intragastric pH, which may contribute to the risk of treatment failure due to subtherapeutic concentrations and adverse effects (eg, infection, bone fracture, renal dysfunction) with sustained supratherapeutic concentrations. Based on evidence available prior to the availability of pertinent Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, the UF Health Precision Medicine Program (PMP) developed clinical recommendations, provided through automated alerts at the time of a PPI order, to (1) increase the PPI dose for individuals with genotypes linked to increased CYP2C19 enzyme activity (ie, rapid and ultrarapid metabolizers) to improve the likelihood of drug effectiveness and (2) decrease the dose for individuals with decreased CYP2C19 activity (ie, intermediate and poor metabolizers) to reduce the risk of harm. The CYP2C19-PPI implementation was an iterative process that taught us key implementation lessons. Most notably, physician engagement is essential, problem lists in the medical record are unreliable, and special populations (eg, pediatric patients) need to be considered.

Conclusion: Guiding PPI prescribing based on CYP2C19 genotype is a practical approach to potentially improve the benefit-risk ratio with PPI therapy. Physician engagement is key for successful implementation. A CPIC guideline on CYP2C19 genotype-guided PPI dosing is now available, and automated alerts may be instituted to facilitate implementation.