Pharmacogenetics
Loren Bonner
In August, FDA granted 23andMe clearance for its CYP2C19 pharmacogenetics report on clopidogrel and citalopram, allowing the company to offer more direct-to-consumer pharmacogenetics reports to patients.
According to a 23andMe spokesperson, the clearance will allow the genomics testing company to report interpretive drug information for these two medications without the need for confirmatory testing. “This means health care providers can use the 23andMe [report] as clinical decision support directly,” said David Kisor, PharmD, director of pharmacogenomics at Manchester University College of Pharmacy in Indiana.
To help health care providers, including pharmacists, navigate the CYP2C19 report as well as new reports on DPYD Drug Metabolism and SLCO1B1 Drug Transport, 23andMe launched a pharmacogenetics portal specifically for health care providers (https://medical.23andme.com/pgt-portal/). The portal is designed to help providers understand a patient’s results and possible next steps through educational information, including links to clinically established guidelines and FDA label information.
23andMe said the clearance allows the company to give patients information to share with their health care provider that is consistent with FDA-approved drug labels for both clopidogrel and citalopram.
Using the information
In 2018, FDA authorized 23andMe to report on variants in multiple genes that affect how well an individual metabolizes certain medications.
Currently, the company has the only FDA-approved direct-to-consumer pharmacogenomics product on the market. However, FDA made it clear that testing results information should not be used to “start, stop, or change any course of treatment.”
The CYP2C19 report provides potential drug response and toxicity risk information and can be used to alter drug or dose selection when a patient is taking clopidogrel and citalopram. For example, if a pharmacist has a patient who may be experiencing side effects from citalopram, the pharmacist may identify through the report that the patient is a CYP2C19 ‘poor metabolizer.’ “Meaning they have greater exposure to the drug and are at increased risk of side effects, thus potentially explaining the patient’s experience,” said Kisor.
In the context of clinical guidelines, such as those provided by the Clinical Pharmacogenetics Implementation Consortium, pharmacists can use the reported results and recommend a dose reduction or a switch to a medication not primarily metabolized by CYP2C19.
“Now that the 23andMe testing results report can be used for clinical decision making, specifically related to clopidogrel and citalopram, pharmacists must put this information into the overall data set used in optimizing pharmacotherapy. Ignoring this information if made available may impact professional liability,” said Kisor.
Caveats
Kisor said there are additional things pharmacists should consider about the new CYP2C19 report.
First, it includes test results considering the *2, *3, and *17 variants of CYP2C19. “These variants are the most common and highest frequency forms of CYP2C19 and are termed ‘tier 1’ variants,” said Kisor. “The variants have high-level evidence relative to no function (*2 and *3) or increased function (*17) and are seen at relatively high frequency in certain populations,” he said.
There are other “decrease function” or “no function” variants of CYP2C19 that are termed “tier 2.” They are not as frequently seen in certain populations, but in combination are still noted in greater than 1% of some populations. “Therefore, the 23andMe approach may miss important genetic-influenced CYP2C19 activity in patients of certain populations,” Kisor said.
Kisor added that it’s important for pharmacists to stress to their patients that they should not alter the use of their medications, specifically clopidogrel and citalopram, without consulting with their health care provider first.