Tacrolimus is metabolized by the liver to inactive metabolites.  The protein in the liver responsible for this activation is the cytochrome p450 enzyme CYP3A5 (pronounced "sip three a five").

Across populations, CYP3A5 protein alleles can have different genetic variants that impact its ability to metabolize tacrolimus. The different alleles can produce three different metabolism phenotypes: normal, intermediate, and poor metabolism. The normal and intermediate metabolism phenotypes are associated with decreased response to tacrolimus. 

 

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 tacrolimus, extensive guideline information can be found at: https://www.pharmgkb.org/chemical/PA451578/guidelineAnnotation/PA166124619 a reference maintained by CPIC. 

Here is a video that reviews the CPIC guideline for tacrolimus: https://youtu.be/OGP4_sQsnBE 

 

At UCHealth the use of pharmacogenetics when prescribing tacrolimus 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.
2) Are prescribed tacrolimus for the first time in the inpatient setting (heart and kidney transplants only).

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 CYP3A5 normal or intermediate metabolizer, a best practice alert will warn you if you attempt to prescribe tacrolimus for the first time in the inpatient setting for kidney and heart transplants only (in UCHealth's EHR).  The BPA recommends increasing the dose of tacrolimus to avoid treatment failure. 

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.