The edition · Clinical Pharmacology
Pharmacogenomic-guided antidepressant choice gave modest short-term gains, and orforglipron's interaction profile is mapped
A platform-aware meta-analysis found one combinatorial pharmacogenomic test raised response and remission at 8 to 12 weeks, while other panels gave imprecise results. Phase 1 studies show which CYP3A4 and OATP1B drugs move orforglipron exposure, and Baxter premixed vancomycin bags are under an FDA Class II recall.
The edition in brief
A meta-analysis of eight randomised trials in adult depression found care guided by the GeneSight combinatorial pharmacogenomic test increased response (RR 1.30, 1.09 to 1.56) and remission (RR 1.53, 1.19 to 1.97) at 8 to 12 weeks across three trials, while five trials of other multigene panels gave heterogeneous, non-significant results; the authors caution this does not show one platform is superior. Six phase 1 studies found exposure to orforglipron, an oral small-molecule GLP-1 receptor agonist in development, rose with clarithromycin and ciclosporin and fell with carbamazepine; orforglipron did not meaningfully change midazolam, digoxin or atorvastatin and weakly raised rosuvastatin. In 78 cefepime courses in critically ill children, prolonged infusion gave higher target attainment than intermittent infusion when the pathogen MIC was 1 mg/L or more. The FDA lists an ongoing Class II recall of Baxter vancomycin 1 g in 200 mL premixed containers for manufacturing practice deviations. None of the studies is a large outcome trial; the pharmacogenomic result is short term and from few trials.
Class II recall: Baxter premixed vancomycin 1 g in 200 mL
Check stock for recalled Baxter premixed vancomycin bags; the recall is about manufacturing practice, not a new vancomycin safety finding.
Orforglipron levels rise with strong CYP3A4 or OATP1B inhibitors and fall with carbamazepine
Treat orforglipron as a CYP3A4 and OATP1B substrate: review strong inhibitors and inducers before co-prescribing.
Prolonged cefepime infusion reached targets more often in children when the MIC was 1 mg/L or higher
Consider prolonged cefepime infusion for less susceptible organisms in critically ill children, with level monitoring to avoid overexposure.
Pause simvastatin while a patient takes clarithromycin
Pause simvastatin or lovastatin during clarithromycin, or choose an antibiotic that does not inhibit CYP3A4.
Pharmacogenomic-guided antidepressant choice raised short-term remission with one test, but not across panels
Consider pharmacogenomic-guided prescribing after antidepressant failure or intolerance, acting first on CYP2D6 and CYP2C19 results, and expect a modest short-term gain at best.
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