Friday, May 17, 2019

Pharmacogenomics for dermatologists


An introduction to pharmacogenomics in dermatology has been published in Seminars in Cutaneous Medicine and Surgery by Stanford Medicine dermatology resident Dr. Roxana Daneshjou, PharmGKB curator Dr. Rachel Huddart and PharmGKB co-PIs Dr. Teri Klein and Dr. Russ Altman.

After introducing the field of pharmacogenomics, the paper highlights some of the features of PharmGKB, including our search functionality, curated pathways and drug label annotations. The work of CPIC is also introduced with examples of dermatology-relevant guidelines such as carbamazepine and HLA-A/HLA-B. The article concludes with a discussion of the current state of pharmacogenomics implementation in the clinic.

Although the article has a focus on dermatology, it is relevant to anyone who wants to learn more about pharmacogenomic resources and implementation, regardless of their clinical field. The paper can be accessed here.

Tuesday, May 14, 2019

Pharmacogenomics in the clinic

In 2018, Stanford Medicine launched a pilot project, Humanwide, using precision health approaches to predict, prevent and treat disease based on the individual patient in primary care. Over the past year, the Humanwide project provided care to a diverse group of 50 patients based on their individual factors, from lifestyle to DNA data. In addition to disease screening, the patients also underwent pharmacogenomic screening and patients with unusual drug responses received consultation from the Stanford Pharmacogenomics Clinic, led by Dr. Russ Altman.

In this video, Dr. Altman gives an introduction to pharmacogenomics and explains to the patients how their genetic information can be used to guide prescribing decisions to lower the side effects and improve the efficacy of the drugs they are using now and in the future.



“If we can bring pharmacogenomics to the frontlines of medicine, I think we have a better chance of managing health instead of disease," said Dr. Altman. "This is where Precision Health is a powerful idea, where we’re trying to keep people out of the system by giving them the minimum medication at the right time and not having their disease progress, get worse and become chronic diseases”.

To learn more about Stanford Pharmacogenomics Clinic:

To learn more about Stanford Precision Health Initiative:



Wednesday, May 1, 2019

New CPIC Guideline: CYP2B6 and efavirenz

The CPIC Guideline for CYP2B6 and efavirenz is now published in Clinical Pharmacology and Therapeutics. The accepted article can be viewed on the PharmGKB pages for efavirenz, CYP2B6, and on the CPIC website.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor widely used worldwide to treat HIV-1 infection. It is predominantly metabolized into inactive metabolites by cytochrome P450-2B6 (CYP2B6). Genetic variants in CYP2B6 (eg. CYP2B6*6 and *18), along with other genetic and non-genetic factors, are known to influence variability in efavirenz response. Patients with certain CYP2B6 genetic polymorphisms may be at increased risk for adverse effects, particularly central nervous system toxicity and treatment discontinuation. 

The CPIC guideline and supplement summarize evidence from the literature and provide therapeutic recommendations for efavirenz based on CYP2B6 genotype. For therapeutic recommendations and further details, please refer to the CPIC Guideline for CYP2B6 and efavirenz-containing antiretroviral therapy.

Wednesday, April 17, 2019

PharmGKB opinion piece on pharmacogenomic RCTs published in Clinical Pharmacology and Therapeutics

Is supporting evidence from a randomized controlled trial (RCT) always necessary when implementing pharmacogenomics in the clinic? In an opinion piece authored by members of the PharmGKB team and published in Clinical Pharmacology and Therapeutics, we argue that an overreliance on evidence from RCTs is not beneficial to pharmacogenomic implementation.

An insistence that RCT evidence is made available prior to implementation assumes that RCTs will eventually be carried out for every actionable gene-drug pair. This is an unrealistic assumption, especially in the case of generic drugs. We also question why other factors which can influence drug clearance in a patient, such as hepatic or renal impairment, are easily incorporated into clinical care without RCT evidence while pharmacogenomics is held, seemingly arbitrarily, to a different standard.

There are also significant issues with pharmacogenomic RCTs, in terms of cohort diversity, adequate allele representation and statistical power; all of which can have serious, even fatal, consequences for patients. Furthermore, a reliance on evidence from RCTs overlooks the substantial evidence base from other studies, much of which is curated in PharmGKB. Evidence from non-RCT studies already informs clinical guidelines from international consortia, including CPIC and the DPWG.

The paper is available online and will be included in an upcoming special issue of Clinical Pharmacology and Therapeutics. Dr. Andrea Gaedigk of Children’s Mercy Kansas City, and leader of the PharmVar consortium, will be the guest editor of this issue.