Dr. Michelle Whirl-Carrillo promoted to Associate Director of PharmGKB

PharmGKB is delighted to announce the promotion of Dr. Michelle Whirl-Carrillo to Associate Director.

Dr. Whirl-Carrillo joined PharmGKB in 2002 as the project's first Scientific Curator. After briefly leaving PharmGKB to join the DTC genotyping start-up 23andMe, she returned in 2009 as the Assistant Director.

We congratulate Michelle on her achievement.

New PharmGKB VIP Summary: SLC22A1 (OCT1)

Solute carrier family 22 (organic cation transporter), member 1 (SLC22A1, also called OCT1) is a polyspecific cationic transporter mediating the uptake of many organic cations from the blood into epithelial cells. It is predominantly expressed in the liver and plays a critical role in the hepatic uptake of many commonly used drugs.

Several SLC22A1 SNPs have functional consequences and have been associated with altered disposition and response for drugs such as metformin, imatinib, tropisetron, ondanesetron, morphine and tramadol. As a result, SLC22A1 is considered as an important pharmacogene.

 
For more information on this VIP gene and its important variants see the VIP tab for SLC22A1.

For all VIP gene summaries on pharmgkb, see here.

Canadian pharmacogenomics group recommends genetic testing for patients prescribed carbamazepine

In a recent article published online in the journal Epilepsia, the Canadian Pharmacogenomics Network for Drug Safety (CPNDS) has recommended genetic testing for the alleles HLA-B*15:02 and HLA-A*31:01 in all carbamazepine-naive patients before initiation of treatment. In patients who test positive for either of these alleles, alternative medications should be used.

Carbamazepine is an antiepileptic, and patients with the HLA-B*15:02 and HLA-A*31:01 alleles have been found to be at increased risk for carbamazepine-induced hypersensitivity reactions. These reactions can range from a mild rash to severe and even fatal adverse reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis. These hypersensitivity reactions usually occur within the first 3 months of treatment. The authors note that patients with no adverse effects after more than 3 months of carbamazepine treatment do not need to be screened, but that any patients who had a previous hypersensitivity reaction on carbamazepine should have genetic testing.

For more information about the CPNDS recommendation, please read the article:

Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions
Amstutz U, Shear NH, Rieder MJ, Hwang S, Fung V, Nakamura H, Connolly MB, Ito S, Carleton BC; the CPNDS clinical recommendation group. Epilepsia 2014 Mar 5. Epub ahead of print. [PMID: 24596466].


>Read more about HLA-B*15:02, HLA-A*31:01 and carbamazepine on PharmGKB

>Read the Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for HLA-B*15:02 and carbamazepine dosing

American Society of Health-System Pharmacists to host live webinar on CPIC

The American Society of Health-System Pharmacists (ASHP) will be hosting a live webinar on Tuesday, April 15th from 2:00 - 3:00 pm EST discussing the Clinical Pharmacogenetics Implementation Consortium (CPIC). The webinar will be presented by Kelly E. Caudle, CPIC coordinator at St. Jude Children's Research Hospital, and James M. Hoffman, Medication Outcomes & Safety Officer, also with St. Jude. The webinar will provide an overview of CPIC, as well as discussing how CPIC guidelines can be used in clinical practice, and how they have enabled the successful implementation of pharmacogenetics into a clinical electronic environment.

PharmGKB plays an integral role in the CPIC, and is involved in the creation of these drug dosing guidelines; online and interactive versions of the CPIC guidelines can be found on the PharmGKB website. Anyone interested in learning more about CPIC and clinical implementation of pharmacogenetics is encouraged to attend.

> Sign up for the webinar

> Read more about the CPIC

> See a list of all CPIC drug dosing guidelines on PharmGKB

Additional CFTR variants for ivacaftor treatment approved by FDA

The drug label for ivacaftor was recently amended and has been approved by the FDA.

Ivacaftor was originally indicated only for use in Cystic Fibrosis patients with one or two copies of the G551D variant within the CFTR gene. In the amended ivacaftor drug label, the indication has been changed to include 8 additional CFTR variants:

G1244E (rs267606723)                       S1251N (rs74503330)

G1349D (rs193922525)                      S1255P (rs121909041)

G178R (rs80282562)                           S549N (rs121908755)

G551S (rs121909013)                         S549R (rs121908757 and rs121909005). 

• View the FDA-approved ivacaftor drug label with relevant highlighted pgx information.
• View the CPIC dosing guidelines for ivacaftor based on CFTR genotype.
• View clinical annotations for ivacaftor.

CPIC guideline for ivacaftor therapy based on CFTR genotype of cystic fibrosis patients

Cystic fibrosis (CF) therapy has traditionally been based on the treatment of symptoms and infections, rather than targeting the underlying defect caused by variants in the CFTR gene. Ivacaftor is the first FDA-approved drug to specifically target a particular defect of the CFTR protein. It is indicated for use in patients who have at least one allele carrying the G551D variant (rs75527207 genotype AA or AG), which is present in around 4.4% of CF patients.

CPIC have published therapeutic guidelines for ivacaftor based on CFTR genotype in the Clinical Pharmacology & Therapeutics journal. Interactive versions of these guidelines are available on PharmGKB, along with the manuscript and supplement.

> View the guidelines

> Read the article:  

Clinical Pharmacogenetics ImplementationConsortium (CPIC) Guidelines for Ivacaftor Therapy in the context of CysticFibrosis Transmembrane Conductance Regulator (CFTR) Genotype.

John P. Clancy, Samuel G. Johnson, Sook Wah Yee, Ellen M. McDonagh, Kelly E. Caudle, Teri E. Klein, Matthew Cannavo, Kathleen M Giacomini.

Clinical Pharmacology & Therapeutics. (Accepted article preview).