Click below to learn more about the use of CYP2D6 genetics in the prescribing of metoclopramide.
Metoclopramide 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 metoclopramide and other medications. The different alleles can produce four different metabolism phenotypes: ultrarapid, normal, intermediate, and poor metabolizers. The poor metabolism phenotype has been shown to decrease metoclopramide metabolism, resulting in increased metoclopramide levels and a higher risk of side effects.
Patients who are CYP2D6 poor metabolizers have reduced metabolism of metoclopramide leading to higher drug levels. This may increase the risk of side effects and toxicity (e.g., dystonic and other adverse events) and lower doses may be needed. The FDA has provided dosing recommendations for CYP2D6 poor metabolizers being prescribed metoclopramide. Please see the associated tip sheet for specific dosing recommendations.
At UCHealth the use of pharmacogenetics when prescribing metoclopramide 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 metoclopramide.
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 poor metabolizer, an inline medication warning will appear if you attempt to prescribe or refill metoclopramide 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.
