Metoprolol 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 CYP2D6 (pronounced "sip two dee six").  

Across populations, CYP2D6 protein alleles can have different genetic variants that impact their ability to metabolize metoprolol and other medications. The different alleles can produce four different metabolism phenotypes: ultrarapid, normal, intermediate, and poor metabolizers. The ultrarapid metabolism phenotype has been shown to increase metoprolol metabolism, resulting in decreased metoprolol levels and a higher risk of therapeutic failure.

The Dutch Pharmacogenetics Working Group (DPWG) is a group who evaluates the evidence for the use of pharmacogenetics and then develops clinical practice guidelines. For metoprolol, extensive guideline information can be found at: https://www.g-standaard.nl/risicoanalyse/B0001556.PDF a reference maintained by DPWG. 

Patients who are CYP2D6 ultrarapid metabolizers have increased metabolism of metoprolol leading to lower drug levels. This may increase the risk of therapeutic failure and higher doses may be needed. For CYP2D6 ultrarapid metabolizers, the DPWG recommends to use the maximum dose for the relevant indication as the target dose and, if insufficient, to increase the dose by 1.5 to 2 times standard dose or use an alternative beta-blocker.

At UCHealth the use of pharmacogenetics when prescribing metoprolol 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 metoprolol.

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 CYP2D6 ultrarapid metabolizer, an inline medication warning will appear if you attempt to prescribe or refill metoprolol 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).