Friday, December 19, 2014

CPIC Term Standardization

CPIC (Clinical Pharmacogenetics Implementation Consortium) is leading an effort to standardize terms for clinical pharmacogenetic tests.  The goal of the project is to create standardized terms to be used in CPIC guidelines (specifically Tables 1 and 2) and in the larger pharmacogenetics community.  A list of phenotype term options based on an extensive literature review and scanning of sample laboratory reports is being developed.  Refinement of the terms will be performed using a modified Delphi method in the context of expert opinions.

CPIC is actively engaging different constituencies including members of the PGRN, ClinGen, the CDC PGx nomenclature working group, clinical laboratories and the IOM PGx roundtable.  Further details about this project are described here. If you have questions or comments regarding this project, and/or if you are interested in participating in this process, please contact us at

Tuesday, December 2, 2014

Annotated PMDA drug labels now available on PharmGKB

PharmGKB now has annotated drug labels available from the Pharmaceutical and Medical Devices Agency (PMDA), Japan.

The PMDA is a regulatory agency responsible for scientific reviews for the approval of drugs or medical devices, as well as safety monitoring after approval. The PMDA website provides PDF copies of package inserts for approved drugs. However, these inserts are only available in Japanese, and until recently PharmGKB had been unable to search for or annotate PMDA package inserts containing relevant pharmacogenetic (PGx) information.

In a paper published in 2013 in the Journal of Clinical Pharmacy and Therapeutics, Shimazawa and Ikeda selected PMDA inserts to examine for PGx information based on the FDA's Table of Pharmacogenomic Biomarkers in Drug Labeling. In addition to a discussion of the differences in PGx biomarker information between labels from the United States, United Kingdom and Japan, the authors also provided a table in the supplementary information that gave translations of any PGx information present in the PMDA package inserts. Using these translations, PharmGKB was able to create annotated drug labels for the package inserts examined by Shimazawa and Ikeda that contained PGx information. As with the annotated FDA and EMA drug labels, PMDA labels are given a PGx level of evidence, and a PDF copy of the package insert with PGx information highlighted is available for each annotated label.

It is likely that there are other PMDA package inserts that contain PGx information, and PharmGKB welcomes any feedback regarding PGx information within PMDA package inserts or labels from other medicine agencies around the world.

See a list of drug labels available on PharmGKB:
PMDA labels on PharmGKB

Read the paper:
Differences in pharmacogenomic biomarker information in package inserts from the United States, the United Kingdom and Japan
Shimazawa R, Ikeda M. Journal of Clinical Pharmacy and Therapeutics 2013; 38(6): 468-75. PMID 23895776.

Wednesday, November 26, 2014

November SNPits Summary

The November issue of UF Health Personalized Medicine Program's e-newsletter, SNPits, is out.  This issue contains a summary of a recent paper by Nicholson and Formea in Clinical Chemistry that discusses implementing CPIC guidelines for CYP2D6 and codeine.  The authors highlight some of the difficulties that may arise in the clinic.  We are pleased that the larger clinical community is beginning to embrace PGx guidelines and practice.

Friday, November 21, 2014

PharmGKB VIP Summary for CYP4F2 published in Pharmacogenetics and Genomics

The PharmGKB Very Important Pharmacogene (VIP) summary describing important pharmacogenetic variants in CYP4F2 was recently published by Pharmacogenetics & Genomics. Cytochrome p450, family 2, subfamily F, polypeptide 2 (CYP4F2) catalyzes the oxidation of the terminal carbon of the side chains of vitamin K, vitamin E, arachidonic acid (AA), and leukotriene B4 (LTB 4). Thus, CYP4F2 plays a role in the regulation of the inflammation response, blood pressure as well as vitamin K and vitamin E bioavailability. A single genetic variant (rs2108622 C>T also known as CYP4F2 *3) has consistently demonstrated a small but significant effect on warfarin and acenocoumarol dosage and safety, particularly in Caucasian and Asian populations. 

View an interactive version: 

CYP4F2 VIP Summary on PharmGKB

Read the publication:

PharmGKB summary: very important pharmacogene information for CYP4F2 
Pharmacogenetics & Genomics. 2014 Nov 3. (Epub ahead of print)Alvarellos ML, Sangkuhl K, Daneshjou R, Whirl-Carrillo M, Altman RB, Klein TE.

Friday, October 31, 2014

Clinical evidence support for biomarkers on FDA-approved drug labels

A recent article by Wang et al. in JAMA Internal Medicine reviews the clinical evidence support found on FDA-approved drug labels that are listed on the FDA's Table of Pharmacogenomic Biomarkers in Drug Labeling.  The authors found that many labels on the list did not contain, or reference, "convincing evidence" of the biomarker's clinical validity or utility.  The authors used published guidelines from the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group to grade the evidence.

October's SNPits summary from the University of Florida's Personalized Medicine Program highlights this article and provides a discussion about the clinical implications and some limitations of the paper.  They note that post-market label updates regarding safety decisions will often depend on retrospective data that will fall short of proving clinical utility. Additionally, the clinical evidence provided on labels may not reflect the totality of the available evidence because it is difficult for label revisions to keep up with the pace of emerging literature.

Almost a year ago, PharmGKB blogged about lack of clarity regarding the actionability of pharmacogenomic information on FDA-approved drug labels.  This is a separate issue from that of clinical evidence support for biomarker information on the labels discussed in the JAMA Internal Medicine article.  Both issues suggest the need for clearer language and guidance for clinicians on labels. 

As the SNPits summary points out, resources do exist for clinicians to gather information outside of what is provided on the label.  "Prescribers frequently rely on data sources other than the package insert in clinical decision making, including drug databases, published information in guidelines, journal articles, and others." Though there is room for improvement on FDA-approved drug labels, the provided pharmacogenomic information can be integrated with other information clinicians use while making prescribing decisions.

Monday, October 27, 2014

ClinGen's GenomeConnect Patient Portal Launches

The NIH-funded Clinical Genome Resource (ClinGen) project has launched its patient portal at GenomeConnect.  This site provides a patient registry for those who have already had or are contemplating genetic testing, or have family members who have been tested.  It is open to the public for enrollment.  Once a personal account is created, participants are asked to provide health history information through a survey, and upload genetic test results if available.

De-identified health and genetic information from participants in GenomeConnect will be shared with researchers and clinicians studying genetic associations with health outcomes.  Participants will also be able to connect with other patients through the registry based on genetic variants and diagnosis.  Personal information such as name, address and other personal identifiers will NOT be shared without express permission from participants.  By freely sharing de-identified genetic and medical information, participants become a part of a potentially huge study to further understanding of the impact of genetics on health.  The more participants, the greater the chance of medical discoveries that can influence future health care.

Thursday, October 16, 2014

New pathway: Ibuprofen Pharmacodynamics

We have added a new pathway: ibuprofen PD pathway  to PharmGKB's pathway collections.

Ibuprofen is a traditional non-steroidal anti-inflammatory drug (NSAID) widely used for its analgesic, anti-inflammatory, and anti-pyretic properties. The main mechanism of action of  ibuprofen is the non-selective, reversible inhibition of the cyclooxygenase enzymes COX-1 and COX-2 (encoded by genes PTGS1 and PTGS2, respectively). The ibuprofen PD pathway depicts the mechanisms of action of the drug and highlights genes mediating the diverse biological effects triggered by ibuprofen.

View  ibuprofen PD pathway on PharmGKB.

View all pathways at PharmGKB.