Certain neurologic drugs, such as deutetrabenazine, pitolisant, tetrabenazine, and valbenazine, are metabolized by the liver to inactive metabolites.  The protein in the liver responsible for 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 its ability to metabolize these neurologic drugs, along with other medications. The different alleles can produce four different metabolism phenotypes: ultrarapid, normal, intermediate, and poor metabolism.  The poor metabolism phenotype has been shown to decrease metabolism for these neurologic drugs, resulting in increased drug levels and a higher risk of side effects.

Patients who are CYP2D6 poor metabolizers have reduced metabolism of deutetrabenazine, pitolisant, tetrabenazine, and valbenazine, leading to higher drug levels. This may increase the risk of side effects and toxicity, meaning lower doses or alternative drugs may be needed. The FDA has provided dosing recommendations for CYP2D6 poor metabolizers being prescribed these drugs. Please see the links below for FDA recommendations.

Deutetrabenazine FDA dosing recommendations: https://www.pharmgkb.org/chemical/PA166169881/prescribingInfo 

Pitolisant FDA dosing recommendations: https://www.pharmgkb.org/chemical/PA166185163/prescribingInfo 

Tetrabenazine FDA dosing recommendations: https://www.pharmgkb.org/chemical/PA140222719/prescribingInfo 

Valbenazine FDA dosing recommendations: https://www.pharmgkb.org/chemical/PA166170051/prescribingInfo 

At UCHealth the use of pharmacogenetics when prescribing codeine or tramadol 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 deutetrabenazine, pitolisant, tetrabenazine, and valbenazine.

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.

For deutetrabenazine, pitolisant, and valbenazine: If you are a provider AND your patient is a CYP2D6 poor metabolizer, an in line medication warning will appear if you attempt to prescribe or refill deutetrabenazine, pitolisant, or valbenazine in UCHealth's EHR. 

For tetrabenazine: If you are a provider AND your patient has a CYP2D6 altered metabolizer phenotype, an inline medication warning will appear if you attempt to prescribe or refill tetrabenazine 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).