Ondansetron

Ondansetron & CYP2D6

Click below to learn more about the use of CYP2D6 genetics in the prescribing of ondansetron.

Ondansetron 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 ondansetron 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 ondansetron metabolism, resulting in decreased ondansetron levels and a higher risk of therapeutic failure.

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 ondansetron, extensive guideline information can be found at https://cpicpgx.org/guidelines/guideline-for-ondansetron-and-tropisetron-and-cyp2d6-genotype/ a reference maintained by CPIC.

Here is a video that reviews the CPIC guideline for ondansetron: https://www.youtube.com/watch?v=OHD9LFRlJ4g

At UCHealth the use of pharmacogenetics when prescribing ondansetron 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 ondansetron.

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 ondansetron 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).

Webpage updated as of: 7/26/2022

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Ondansetron & CYP2D6

Click below to learn more about the use of CYP2D6 genetics in the prescribing of ondansetron.

Colorado Center for Personalized Medicine

Ondansetron & CYP2D6

Click below to learn more about the use of CYP2D6 genetics in the prescribing of ondansetron.

Ondansetron Metabolism and Pharmacogenetics

Clinical Evidence

Clinical Implementation

Further Questions

Colorado Center for Personalized Medicine