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.