Update to individual statin pathways to support release of new CPIC guidelines for statins

To coincide with the release of the updated CPIC guidelines for SLCO1B1, ABCG2 and CYP2C9 and statin-associated musculoskeletal symptoms, we have updated the statin pharmacokinetic (PK) pathways. We now have one PK pathway for each individual drug in the guideline and have added details of the specific metabolites as well as the candidate genes and references. 

Atorvastatin Pathway, Pharmacokinetics

Fluvastatin Pathway, Pharmacokinetics

Lovastatin Pathway, Pharmacokinetics

Pitavastatin Pathway, Pharmacokinetics

Pravastatin Pathway, Pharmacokinetics

Rosuvastatin Pathway, Pharmacokinetics

Simvastatin Pathway, Pharmacokinetics

Note: If you have visited pathways recently you may need to refresh your browser or empty cookies to see the updated versions. Plus the history log at the bottom of the pathway lets you know if you are seeing the most updated version. 

CPIC Publishes Guideline for SLCO1B1, ABCG2, CYP2C9 and Statin Therapy

The CPIC guideline for SLCO1B1, ABCG2, and CYP2C9 and statin-associated musculoskeletal symptoms (SAMS) has been published in the journal Clinical Pharmacology and Therapeutics. This guideline is an update to the CPIC guideline for simvastatin and SLCO1B1, but now includes expanded literature review on four additional genes, ABCG2, CYP2C9, HMGCR and CYP3A4/5 and all statins. 

The guideline gives specific prescribing recommendations for: 

• simvastatin, atorvastatin, lovastatin, pravastatin and pitavastatin based on SLCO1B1 phenotype
• rosuvastatin based on SLCO1B1 and ABCG2 phenotypes 
• fluvastatin based on SLCO1B1 and CYP2C9 phenotypes 

It also provides a figure illustrating statin recommendations with preferred statin intensity and statin dose stratified by SLCO1B1 phenotype (i.e., decreased or poor function):

For therapeutic recommendations and further details, please refer to the guideline and supplemental materials on the CPIC website. Annotations of the guideline, including interactive genotype picker tool for each statin, is available on the PharmGKB website.

Registration opens for CPIC-PGRN 2022 meeting in Denver, Colorado

We are excited to announce that registration is open for the 2022 CPIC-PGRN meeting: Diversifying PGx Science to Improve Implementation. The meeting will be held at the University of Colorado on May 10^th, 11^th, and 12^th in Denver, CO. Registration, agenda, and hotel information available at the meeting website. Early bird registration is now open and is $250.00.  The deadline for early bird registration is April 1, 2022. Regular registration will open April 2, 2022 and is $350.00.  The deadline to register is May 1, 2022. 

We are keeping an eye on the COVID status and will abide by the restrictions and guidelines set by the University of Colorado at the time of the meeting. We are planning a COVID “rain date” in case we need to reschedule the meeting. If the meeting is cancelled due to COVID, registration fees will be refunded. No virtual option will be available.

 

The draft agenda can be found on the meeting website. We are still finalizing final titles and speakers and we will post the final agenda once complete.

 

Participants are invited to submit abstracts for the poster sessions.  Please send your abstract to CPIC-PGRN2022@pgrn.org. Acceptance notifications and guidelines will be sent prior to the early registration deadline (April 1^st). 

 

Abstract Submission guidelines:

Final Submission Deadline: March 18th, 2022 

Required Sections:  Authors, Institutions, Background, Methods, Results, Conclusions

1 figure or table may be included

Word limit: 500 words

Please note that submitting an abstract does not register you for this meeting. 

 

Hope to see you there! If you have any questions about registration, please email kelly.caudle@stjude.org. 

 

Best wishes,

Kelly Caudle and Teri Klein (CPIC co-PIs)

PharmGKB Heparin-Induced Thrombocytopenia Pathway published

A PharmGKB pathway of heparin-induced thrombocytopenia (HIT) has been published in Pharmacogenetics and Genomics.

Heparin is a commonly used anticoagulant. The pathway, written by Elise Miller along with other members of the Karnes lab at the University of Arizona as well as members of the PharmGKB team, outlines the atypical immune response which can occur in some patients receiving heparin. HIT can have a mortality rate of up to 30% and shares some similarities with COVID-19 while patients with COVID-19 have been found to be at an increased risk of HIT. Pharmacogenomics research has identified some candidate biomarkers, particularly in immune system receptors, which may affect a patient’s risk of experiencing HIT, however further work is needed to validate these and discover other candidates.

 

An interactive version of the pathway can be found on the PharmGKB website.

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