Friday, November 18, 2016
Wednesday, October 26, 2016
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.
Send a message to feedback if you have questions about this account update.
Tuesday, September 27, 2016
The Pharmacogenomics Clinical Annotation Tool (PharmCAT) is a software tool to extract all CPIC level-A variants from a genetic dataset (represented as a vcf), interpret the variant alleles, and generate a report. It is currently being developed in a collaboration between the PGRN Statistical Analysis Resource (P-STAR), the Pharmacogenomics Knowledgebase (PharmGKB), the Clinical Genome Resource (ClinGen), and CPIC.
For further coverage about PharmCAT, read the article by Julia Karow on September 26th in GenomeWeb: Researchers Hope PharmCAT Tool Will Help Improve ClinicalImplementation of Pharmacogenomics.
Monday, September 26, 2016
While we agree that the variability in patient response to codeine is important to consider, we feel that the AAP did not give enough credit to the power of CYP2D6 genotyping prior to treatment. The article devotes only two sentences to the possibility of pre-emptive genotyping, saying “although CYP2D6 genotyping that could identify patients at higher risk is available (although currently expensive), patients with normal metabolism are also at theoretical risk of high morphine levels. Therefore, further investigation is required to determine the value of such testing, which will depend on the population in whom it is applied.”
It is unclear what is intended by the claim that “patients with normal metabolism are also at theoretical risk of high morphine levels”, as no citation is provided. Patients who are CYP2D6 normal metabolizers are expected to have normal morphine formation. Furthermore, codeine is still an appropriate and effective drug choice in the majority of cases, regardless of the population. As the AAP statement points out, ~29% of African/Ethiopian, ~21% of Saudi Arabian and other Middle Eastern, and ~3.4 - 6.5% of African-American and Caucasian patients are expected to be ultrarapid metabolizers, with even lower frequencies of poor metabolizers, meaning that the majority of patients will receive the intended benefit from codeine treatment, contrary to what one doctor was quoted as saying in at least two media outlets (another article here).
While pharmacogenetics is still in the early stages of clinical adoption, it can be an effective tool for improving patient therapy, particularly when drug alternatives are not simple. In the case of codeine, the official AAP statement urges caution in using alternative analgesics, including oxycodone, hydrocodone, and tramadol, because they also are metabolized to some degree by CYP2D6 (though more than one public media article presented comments by one of the statement authors suggesting that hydrocodone or tramadol be used instead of codeine, without any caveats). Instead, AAP suggests NSAIDs for mild to moderate pain, and an IV drip for greater pain, though these therapies also require clinician education to avoid postoperative bleeding. If further education is required to deliver care, why does this curriculum not consider CYP2D6 pharmacogenetic information, which could make the effects of codeine more predictable and restore its value as an analgesic? As for an alternative to the antitussive properties of codeine, CBS and CBS local New York suggested that popsicles or honey be used.
We are concerned about the misinformation and creative interpretations related to the AAP statement that have been communicated in public media. Chicago Tonight reported that “children are among those considered to be ‘ultra-rapid metabolizers’ of codeine”, which implies to readers that all children are CYP2D6 ultra-rapid metabolizers; they are not. Similarly, a Huffington Post article stated that “children are specifically less capable of metabolizing codeine than adults because the enzyme changes as the body matures into adulthood.” While functional CYP2D6 activity is not appreciably expressed in fetal liver, it increases rapidly after birth, and CYP2D6 genotype is expected to be equally reliable for inferring phenotype in children as it is in adults.
CPIC has published a freely downloadable guideline for adjusting codeine therapy based on CYP2D6 genotype. The guideline recommends using alternative therapies -- specifically not hydrocodone or tramadol, which are also metabolized by CYP2D6 to some degree -- in patients with genotypes predicting poor and ultra-rapid metabolizer status. The “black box” warning on the FDA label for codeine can also be viewed at PharmGKB.
In the meantime, please pass the medical-grade popsicles.
Thursday, September 22, 2016
Wednesday, September 21, 2016
A stylized illustration of the PK/PD pathways of ivacaftor accompanies the publication, and can also be viewed on the PharmGKB website. The illustration and text also includes lumacaftor, a drug that is sometimes used in conjunction with ivacaftor to treat patients with CFTR variants that result in localization defects. The full text and pathway image can be found on the pharmgkb website at https://www.pharmgkb.org/pathway/PA166153178.
Tuesday, September 20, 2016
A full description of the RFI is available at: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-133.html
Responses are due by September 30, 2016.