Omeprazole, pantoprazole, lansoprazole, and deslansoprazole are metabolized by the liver to inactive metabolites. The protein in the liver responsible for the majority of this metabolism is the cytochrome p450 enzyme CYP2C19 (pronounced "sip two see nineteen").  

Across populations, CYP2C19 protein alleles can have different genetic variants that impact its ability to metabolize PPIs and other medications. The different alleles can produce five different metabolism phenotypes: ultrarapid, rapid, normal, intermediate and poor metabolism. Of these, the ultrarapid and rapid metabolizer phenotypes have been shown to have lower drug levels and therefore, risk of treatment failure. The intermediate and poor metabolizer phenotypes have been shown to have higher drug levels and risk of dose-related adverse effects with long-term use.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) is a group who evaluates the evidence for the use of pharmacogenetics and then develops clinical practice guidelines. For omeprazole, pantoprazole, lansoprazole, and deslansoprazole, extensive guideline information can be found at: https://cpicpgx.org/guidelines/cpic-guideline-for-proton-pump-inhibitors-and-cyp2c19/ a reference maintained by CPIC.  

Here is a video that reviews the CPIC guideline for PPIs: https://www.youtube.com/watch?v=KgRrti8dIRs 

 

At UCHealth the use of pharmacogenetics when prescribing irinotecan will occur in patients who meet the following conditions:

1) Provided a blood or saliva sample to the Colorado Biobank, consented for the return of their results, and this sample has undergone genotyping OR the patient is being seen in a clinic which is currently using pharmacogenetic testing as part of standard care (e.g., the UCHealth GI Oncology Clinic). 
2) Are prescribed dexlansoprazole, lansoprazole, omeeprazole, or pantoprazole.

For patients enrolled in the Biobank, this process takes a minimum of 4-6 weeks but may take several years. Therefore, results will not be available at initial presentation if a patient has not previously enrolled in the Biobank.

 

If you are a provider AND your patient is a CYP2C19 ultrarapid, rapid, intermediate or poor metabolizer, an inline medication warning will appear if you attempt to prescribe or refill omeprazole, pantoprazole, lansoprazole, or dexlansoprazole in UCHealth's EHR.  If the inline medication warning is visible, links to resources will be listed for your reference.  There is patient education text available for UCHealth providers to use in discharge paperwork or the after visit summary (AVS).

Visit our Provider FAQs page here.  For immediate questions, secure chat Groups: Pharmacogenomics Service in UCHealth's EHR.