Beta-blockers with SSRIs: bradycardia signals point to CYP2D6

The edition in brief

A scoping review of 48 articles on beta-blockers taken with SSRIs found bradycardia was the most reported adverse event, mostly in case reports of metoprolol with fluoxetine, paroxetine or sertraline, or propranolol with fluoxetine. Blood pressure changes appeared in half the studies that looked, and most authors proposed CYP2D6 inhibition as the mechanism. The evidence is a set of signals, not measured risks. An Italian algorithm that matches one drug's listed adverse reactions with another drug's indication identified known prescribing-cascade pairs with 85.5% sensitivity and over 99% specificity in internal validation, a possible aid to structured medication review. A model-informed precision dosing service for cefepime in a children's hospital changed the dosing strategy in half of 20 consultations, though results took a median of 28 hours. The FDA approved a supplement to the application for pirtobrutinib on 2 October; the notice does not state what it changes. The pearl: cefepime neurotoxicity is a dosing problem in renal impairment, and confusion or myoclonus on cefepime should prompt a dose check.