CPIC Guideline Summary Videos Available on PharmGKB

A new resource is available on PharmGKB to help researchers and clinicians more easily and quickly understand CPIC recommendations and how to find supporting information on the PharmGKB website. Short ~5 minute videos describe the role of the gene(s) and the impact of genetic variation on drug response, provide an overview of the genotype-phenotype terminology and classification, and summarize the CPIC recommendations for changing drug dose or drug choice based on patient diplotypes. By distilling information from the guidelines themselves and by integrating the illustrated pathways and extended dosing guidelines that are available on the PharmGKB website, these videos communicate the important relationships between each gene/drug combination. We hope the videos will help CPIC guidelines reach new audiences by providing information in a new format and that, ultimately, they will increase the use of pharmacogenetics in the clinic.

The first videos have been released and can be found on the CPIC guideline pages for codeine, clopidogrel, simvastatin, phenytoin, carbamazepine, allopurinol, and abacavir on the PharmGKB website. Over the coming weeks, summary videos describing each of the CPIC guidelines will be available through the PharmGKB YouTube channel and on each CPIC guideline page on the PharmGKB website.  We encourage you to watch and share them.

Early Registration for Precision Medicine Conference ends Sunday

Early registration for the University of Florida Precision Medicine Conference, held from March 8-10 in Orlando, Florida, ends this Sunday, January 22 at midnight. Earn continuing education credit and learn how to translate pharmacogenomics into practice. The program, which includes speakers, case studies, and participant genotyping, will provide practical information on how to individualize drug therapy, how to perform genetic testing, and how to navigate reimbursement, in addition to providing information about other emerging topics in precision medicine. The conference is open to practitioners, faculty, students, residents, and fellows.

CPIC Guideline Update: CYP2D6, CYP2C19 and tricyclic antidepressants (TCAs)

The 2016 update of the guidelines by the Clinical Pharmacogenetics Implementation Consortium (CPIC) regarding the use of pharmacogenetic tests for CYP2D6 and CYP2C19 in dosing tricyclic antidepressants (TCAs) have been accepted for publication in Clinical Pharmacology and Therapeutics. The accepted article can currently be viewed on the PharmGKB and CPIC websites. 

TCAs are mixed serotonin and norepinephrine reuptake inhibitors used to treat depression and several other disease states.

The 2016 guideline update provides dosing recommendations:

• for TCAs based on CYP2D6 phenotype
• for TCAs based on CYP2C19 phenotype
• for amitriptyline based on both CYP2D6 and CYP2C19 phenotype.

Amitriptyline and nortriptyline are used as representative TCAs because the majority of pharmacogenomics studies have been published on these drugs. However, TCAs have comparable pharmacokinetic properties and it it may be reasonable to apply the recommendations to other TCAs.

For further details see the guidelines and supplement at PharmGKB and CPIC.

New CPIC Guideline - CYP2C19 and voriconazole

Guidelines by the Clinical Pharmacogenetics Implementation Consortium (CPIC) regarding the use of pharmacogenetic tests of CYP2C19 for voriconazole prescribing decisions have been accepted for publication in Clinical Pharmacology and Therapeutics. The accepted article can currently be viewed on the PharmGKB or CPIC websites.

Voriconazole is a triazole antifungal agent active against a variety of fungi and molds, such as Candida, Aspergillus, Fusarium and Cryptococcous. However, it is particularly recommended for pulmonary invasive aspergillosis, an infection that primarily occurs in immunocompromised patients. CYP2C19 is the primary enzyme responsible for the metabolism of voriconazole, and variations within the CYP2C19 gene have been shown to affect exposure to voriconazole. CYP2C19 ultrarapid or rapid metabolizers may have decreased voriconazole exposure, affecting the ability to achieve therapeutic concentrations, while poor metabolizers may have increased exposure, affecting the risk for adverse effects.

For therapeutic recommendations and further details, please refer to the CPIC Guideline for CYP2C19 and Voriconazole Therapy on the PharmGKB or CPIC websites.

New and Updated PMDA label translations now available

New translations of package inserts from the Pharmaceutical and Medical Devices Agency (PMDA), Japan, as well as updated translations of existing package inserts, are now available on PharmGKB.

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, though these inserts are only available in Japanese. Previously, PharmGKB had used a 2013 paper by Shimazawa and Ikeda that selected PMDA inserts to examine for PGx information based on the FDA's Table of Pharmacogenomic Biomarkers in Drug Labeling as it existed on October 2012, and then provided translations of any PGx information present in the PMDA package inserts. Though this paper was useful, additional drug labels with PGx information have been added to the FDA table in the past 4 years, and PharmGKB has also identified drug labels with PGx information independently. 

Now, through a collaboration with the Japanese Society of Pharmacogenomics, as well as Silicon Valley Tech KK, PharmGKB is able to provide translations of a wider set of PMDA labels, as well as more extensive translations of some labels. 

Some of the new labels available include:

Allopurinol
Carbamazepine
Efavirenz
Fesoterodine
Methylene Blue

An overview of all the drug labels on PharmGKB can be viewed here. 

PharmGKB thanks the Japanese Society of Pharmacogenomics for its diligent work in translating these labels, and helping to make them available to the public.

Very Important Pharmacogene (VIP) summary for MT-RNR1 published in Pharmacogenetics and Genomics

The PharmGKB review of the MT-RNR1 gene has been published in the December issue of Pharmacogenetics and Genomics. MT-RNR1 is a mitochondrial gene that codes for ribosomal RNA (rRNA). Variations within this gene, particularly rs267606617 (1555A>G), are strongly associated with the development of hearing loss following administration of aminoglycoside antibiotics. Indeed, over 40 studies have found that 100% of individuals with the G allele at this variant developed hearing loss after receiving aminoglycosides, a class of antibiotics that includes streptomycin and gentamicin, among others. Several other variations in this gene are also associated with hearing loss following aminoglycoside treatment.

The full Very Important Pharmacogene (VIP) review can also be viewed on the PharmGKB website. In addition to discussing the pharmacogenetics of MT-RNR1, it also provides a brief overview of the mitochondrial genetic system as well as the anatomy of the ear and types of hearing loss.

Upcoming change to user accounts

We will be making a small change to user accounts this weekend that should make our users’ lives a little easier. Registered PharmGKB users will no longer be required to have a username as part of their profile. Instead, users will be able to log into the site and manage their profile using their registered email address.

Existing users, you will be able to sign in using your existing username or your email address (along with your password, of course). Please make sure your email address in your profile is current and active. Usernames will be completely phased out in a later update and we will notify you before it happens.

New users, you will no longer be asked to come up with a unique username when registering for an account. That’s one less thing to remember.

Registering as a user of PharmGKB and accepting our data usage agreement enables you to view all the information in our curated Clinical Annotations and Variant Annotations on the site.

Send a message to feedback if you have questions about this account update.