Title: CANONIC ANKI / ABOPM · Pharmacogenomics
Tags: cpic_pgx SILVER GOLD

Q: CYP2D6 poor metabolizer + tamoxifen — CPIC Level A
A: AI note — cites the primary sources.
CPIC Guideline for CYP2D6 and Tamoxifen 2018; PharmGKB CYP2D6-tamoxifen. Note: concurrent paroxetine/fluoxetine (strong CYP2D6 inhibitors) in a CYP2D6 PM effectively blocks residual endoxifen formation — always review concurrent meds.
Alexa Park · Fellow · Heme/Onc · breast focus
The evidence on tamoxifen CYP2D6 is less robust than SLCO1B1-statin or CYP2C19-clopidogrel, which is why the 2018 CPIC guideline is Level A but the recommendation is softer ("alternate therapy" rather than hard switch). Reference: Goetz MP et al Clin Pharmacol Ther 2018 (CPIC CYP2D6-tamoxifen).
Thread: @marcus_freeman · Contributors: @alexa_park, @canonic · Origin: https://onconex.ai/onconex/omicschat/community/omics-pgx-03

Q: CYP2C19 loss-of-function + clopidogrel — CPIC Level A guideline
A: AI note — cites the primary sources.
CPIC Guideline for CYP2C19 and Clopidogrel 2022 Update; ACC DAPT Guideline 2020. Key clinical pearl: ultrarapid metabolizers (*17/*17) have INCREASED bleeding risk on clopidogrel — the symmetry is often missed on boards.
Marcus Freeman · Attending · Genomic pathology · PharmGKB CPIC contributor
ACC 2020 DAPT guideline now explicitly recommends genotype-guided P2Y12 selection post-PCI when available (Class IIb). Cost-effectiveness data from TAILOR-PCI trial are mixed for universal PGx, but targeted CYP2C19 testing in high-ischemic-risk patients is more widely adopted. Reference: Levine GN et al Circulation 2020 DAPT Guideline.
Thread: @marcus_freeman · Contributors: @canonic, @marcus_freeman · Origin: https://onconex.ai/onconex/omicschat/community/omics-pgx-02

Q: SLCO1B1 c.521T>C + simvastatin myopathy — CPIC Level A
A: AI note — cites the primary sources.
CPIC Guideline for SLCO1B1 and Simvastatin-Induced Myopathy 2022 Update; PharmGKB SLCO1B1 drug-gene pair. Updated 2022 guideline now also covers atorvastatin + ABCG2 — broadens PGx statin framework beyond SLCO1B1-simvastatin alone.
Alexa Park · Fellow · Heme/Onc · breast focus
Action threshold: SLCO1B1*5 poor-function homozygote + simvastatin >20mg = CPIC strong recommendation to switch. For heterozygous (IM), reduce dose. Alternate statins: rosuvastatin preferred for IM, atorvastatin OK with caution. Reference: Ramsey LB et al Clin Pharmacol Ther 2014/2022 (CPIC SLCO1B1-statin guideline).
Thread: @marcus_freeman · Contributors: @alexa_park, @canonic · Origin: https://onconex.ai/onconex/omicschat/community/omics-pgx-01