CPIC Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update

The 2022 CPIC Guideline update for CYP2C19 Genotype and Clopidogrel Therapy is now published in Clinical Pharmacology and Therapeutics. The article can be accessed on the PharmGKB page for clopidogrel and on the CPIC website.

Clopidogrel is a commonly prescribed antiplatelet prodrug and CYP2C19 is a significant contributor in the two-step conversion of clopidogrel to its active metabolite. Response to clopidogrel varies widely and CYP2C19 intermediate and poor metabolizers experience reduced platelet inhibition and increased risk for major adverse cardiac and cerebrovascular events.

The 2022 update includes expanded indications for CYP2C19 genotype-guided antiplatelet therapy, increased strength of recommendation for CYP2C19 intermediate metabolizers, and evidence from an expanded literature review.

For therapeutic recommendations and further details, please refer to the Guideline for Clopidogrel and CYP2C19.

Update to PharmGKB Pediatric Drug Summaries

The second round of PharmGKB's pediatric drug summaries is now live on PharmGKB pediatric, adding over 25 more drugs beyond PharmGKB's initial release of CPIC guideline drugs and those on the Best Pharmaceuticals for Children Act (BPCA) priority list.

These manually-curated summaries include key information relevant to prenatal, postnatal, and pediatric populations from PharmGKB annotations and FDA-approved drug labels.

PharmGKB continues to add to the list of drugs with pediatric summaries.

Please help secure funding for PGx!!

The ability to predict ahead of time which drugs will be effective for a unique patient and determine which medications may cause patients serious issues, will save lives, improve health care outcomes, and decrease health care costs. Several genes in the human genome play a role in how people respond to medications, including how effective they will be, how quickly medication will be metabolized, and whether a person is likely to experience side effects from a particular drug. A person’s response to a medication, therefore, is impacted by the genetic variants in their those genes.

 

Pharmacogenomic testing evaluates an individual’s genetic makeup to help identify which medication and which dose is right for each patient and hopefully, prevent an adverse drug reaction. Adverse drug events (ADEs) are the most frequently cited significant cause of injury and death among hospitalized patients and can be the result of a drug-drug or drug-gene interaction. Pharmacogenomic testing can save lives by preventing ADEs. According to one estimation, there are more than 2,216,000 serious ADEs recorded in hospitalized patients every year, causing over 106,000 deaths annually, which makes ADEs the fourth leading cause of death ahead of pulmonary disease, diabetes, AIDS, pneumonia, accidents, and automobile deaths.

 

In addition, information about drug-gene interactions is not well integrated in patient care and tools that assist with patient care, like electronic alerting systems and electronic health records. Improving pharmacogenomic education and improved record keeping would drive down health care costs. In fact, one four-month long study predicted cost-savings of $1,132 per patient using pharmacogenomic testing and an accompanying alert system as a clinical decision support tool.

 

Congressional Representatives Eric Swalwell and Tom Emmer are introducing the Right Drug Dose Now Act, a bill to improve pharmacogenomics research and patient outcomes. The bill updates the National Action Plan for Adverse Drug Event Prevention; creates a public awareness campaign for adverse drug events and pharmacogenomic testing and a separate health care professional education campaign; creates a program to improve the reporting of adverse drug events through electronic health records; and provides additional funding for NIH to improve research and reporting of adverse drug events through the Genomic Community Resources program.

Please note as part of this bill is the intent is to support with dedicated funding to PGx resources such as PharmGKB, CPIC and PharmVar.

Please reach out to Sarah Shapiro (sarah.shapiro@mail.house.gov) in Representative Swalwell’s office if you or your organization would like to support the Right Drug Dose Now Act. 

Congress needs to hear from us as community. Please help. 

Thank you in advance.  Stay Safe. Be well.

Teri

Pediatric PharmGKB User Survey

Similar to our PharmGKB user survey in October-November, we have launched a user survey to gather feedback about the use of our Pediatric PharmGKB website. All user responses are greatly appreciated; no matter who you are, where you are in the world or how many times you have used Pediatric PharmGKB. Again, the survey is split into two parts. The first section takes about a minute to complete. If you have time to give us some more information, the second section will take an additional few minutes. Thank you for your contribution.

CPIC® Guideline for Potent Volatile Anesthetic Agents and Succinylcholine and RYR1 and CACNA1S update

The ClinGen Malignant Hyperthermia Susceptibility Variant Curation Expert Panel recently published recommendations for RYR1 pathogenicity classifications in malignant hyperthermia susceptibility (PMID: 33767344). These revised ACMG/AMP criteria were applied to the 44 variants originally included in the CPIC recommendations (PMID: 30499100) and 29 variants were classified as pathogenic, 13 as likely pathogenic, and 2 as variants of uncertain significance. Based on this classification, the assignment for the variants c.1589G>A p.(Arg530His) and c.1598G>A p.(Arg533His) has been changed from “malignant hyperthermia-associated” to “uncertain function” in the RYR1 allele functionality table.

Information about the update has been added to the CPIC RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine guideline page and the PharmGKB annotation for this guideline.

Pathways in progress, a way to accelerate the pathways visible to users

Thanks to user feedback regarding the PharmGKB pathways, we understand that many of our pathways are used for teaching and presentations, and that users love the detailed figures. We are also aware that many users are interested in the underlying data -- what's on the components tab, the papers supporting pathway arrows and the downloadable gpml file -- for doing further work with expression data or drug drug interactions. The detailed figures are a time consuming part of the life cycle of getting a pathway from first encounter of a paper with evidence to available on the PharmGKB website. Many pathways, including those from CPIC level A gene-drug pairs, do not yet have sufficient complexity for publication in peer reviewed journals. PharmGKB will continue to publish pathways with a lot of underlying data and those that people are willing to co-author and develop a rich text review in a peer reviewed journal with the detailed illustration. We are releasing a new feature for pathways that are in progress that will contain only the components tab and figure from the gpml. This will allow us to complete pathway updates more quickly as new candidates are published, and for users to see what's in progress. Some pathways will ultimately have the publication quality figures whereas others may not depending on demand or evidence. This will allow for more pathways to be available more quickly. We look forward to hearing back from the PharmGKB community at feedback@pharmgkb.org.

Some examples to check out ...

In Progress: Cilostazol Pathway, Pharmacokinetics

In Progress: Febuxostat Pathway, Pharmacokinetics

In Progress: Paclitaxel Pathway, Pharmacokinetics

In Progress: Tamsulosin Pathway, Pharmacokinetics

In Progress: Ziprasidone Pathway, Pharmacokinetics

Survey of PharmGKB API usage

PharmGKB is wholly supported by NIH (NHGRI and NICHD). As we prepare for grant renewal, we are asking users of our API to provide us with 3-4 brief pieces of information to help us demonstrate the importance of our API to the global PGx community. If you use our API, please spend 1 minute filling out this survey.