Friday, January 24, 2014

CPIC guidelines for CYP2D6 genotypes and codeine therapy: 2014 Update

The Clinical Pharmacogenetics Implementation Consortium (CPIC) has published updates to the guidelines for the use of genetic test results for cytochrome P450-2D6 (CYP2D6) in codeine dosing. The 2014 update is now available online, as an accepted article preview.

Alternate analgesics are recommended for CYP2D6 ultrarapid and poor metabolizers. Label recommended age- or weight-specific codeine dosing is warranted for CYP2D6 extensive and intermediate metabolizers. However, patients with the intermediate metabolizer phenotype should be monitored closely for less than optimal response and should be offered an alternative analgesic if required.

This updated guideline extended Table 2, which summarizes codeine therapy recommendations based on CYP2D6 phenotype, to include considerations regarding the use of alternative opioids. 

The guideline supplements include updates on the literature review, the CYP2D6 genetic testing interpretation, the frequencies of CYP2D6 alleles in major race/ethnic groups, and evidence linking CYP2D6 genotype to phenotype.

For other CPIC guidelines see the list of CPIC publications and guidelines in progress.

The Genetics/Genomics Competency Center (G2C2) adds a new PGx section

The Genetics/Genomics Competency Center (G2C2) is a free, online resource that provides a collection of high quality educational materials for self-directed learning in genetics or genomics. It is targeted toward health care professionals such as genetic counselors, nurses, physician assistants and pharmacists. The educational information presented consists of journal articles, websites and textbooks, among other types of resources. 

The National Human Genome Resource Institute (NHGRI) announced on Tuesday that G2C2 now provides educational materials on pharmacogenetics and pharmacogenomics (PGx). This comprehensive collection of PGx information available on the website was created with the needs of pharmacists in mind, though given the broad reach of PGx, the materials presented are relevant to anyone within the health care field. The materials provided range from basic introductions to PGx to in-depth discussions on the subject; both PharmGKB and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are featured on the G2C2 site. 

PharmGKB encourages anyone who is interested in learning more about PGx to explore the information available on the G2C2 website. More information about this new section of G2C2 can be found in the NHGRI news release; please see the links below.


PGx materials
G2C2 homepage
NHGRI news release

Thursday, January 16, 2014

Pharmacodynamic pathways for drugs that lower uric acid levels

Unlike other animals, humans and apes have lost the ability to break down uric acid. High uric acid levels (hyperuricemia) can result in gout and kidney failure, and are a symptom of Tumor Lysis Syndrome experienced by some cancer patients.

Two new PharmGKB pathways describe the mechanism of action of drugs that lower uric acid levels to treat or prevent hyperuricemia, and outline the underlying genes involved. The pharmacogenetic associations behind adverse reactions to allopurinol (HLA-B*5801) and rasburicase (G6PD) are detailed.

Three treatment strategies for hyperuricemia/ gout exist:

1. Reduce the generation of uric acid: Allopurinol, Febuxostat

2. Increase the removal of uric acid: Rasburicase, Pegloticase

-> Covered in the PharmGKB Uric Acid-Lowering Drugs Pathway

3. Reduce the reabsorption of uric acid: Probenecid, Benzbromarone, Sulfinpyrazone

-> Covered in the PharmGKB Uricosurics Pathway