07/16/2026
One of the most consequential — and least discussed — gaps in everyday prescribing practice is pharmacogenomics.
Not because it's new. Not because the evidence is weak. But because most clinicians were never taught to apply it at the point of prescribing, and most health systems haven't yet embedded genetic screening into routine workflows.
The result: patients labelled as non-compliant who are actually poor metabolisers. Patients experiencing toxicity on standard doses who are actually ultrarapid metabolisers. Preventable harm that looks like clinical failure.
Three gene-drug relationships every prescriber should have working knowledge of:
CYP2D6 — governs the metabolism of codeine, tramadol, most SSRIs, and many antipsychotics. Poor metabolisers receive no therapeutic benefit from codeine. Ultrarapid metabolisers face overdose risk from tramadol. Prevalence of poor metaboliser status: approximately 7% of the population.
CYP2C19 — governs clopidogrel activation and the metabolism of PPIs and several antidepressants. Poor metabolisers on clopidogrel following coronary stenting have significantly higher rates of major adverse cardiovascular events.
TPMT / NUDT15 — governs thiopurine metabolism. Deficiency leads to life-threatening myelosuppression at standard doses of azathioprine or 6-mercaptopurine. Testing is now recommended before initiating therapy in many guidelines.
Pharmacogenomic testing is increasingly accessible. More importantly, awareness of these relationships costs nothing and changes how you interpret drug failure.
Drug failure is not always non-compliance. Sometimes it is biology.
