Voriconazole is 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"). Other cytochrome p450 enzymes CYP3A4 and CYP2C9 play a minor role in metabolism of voriconazole.  

Across populations, CYP2C19 protein alleles can have different genetic variants that impact its ability to metabolize voriconazole. The different alleles can produce five different metabolism phenotypes: ultrarapid, rapid, normal, intermediate and poor metabolism. Of these, the ultrarapid and rapid metabolism phenotypes have been shown in multiple studies to increase the risk of treatment failure due to sub-therapeutic voriconazole levels. The poor metabolism phenotype has been shown to increase the risk of voriconazole toxicity due to supra-therapeutic voriconazole levels. 

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 voriconazole, extensive guideline information can be found at: https://cpicpgx.org/guidelines/guideline-for-voriconazole-and-cyp2c19/ a reference maintained by CPIC.

Here is a video that reviews the CPIC guideline for voriconazole: https://www.youtube.com/watch?v=U1PKEF6M9oM 

 

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

1) Provided a blood or saliva sample to the CCPM 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 voriconazole.

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, or poor metabolizer, a best practice alert (BPA) will warn you if you attempt to prescribe voriconazole in UCHealth's EHR.  If the BPA alerts, 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.