The prescriber's interaction problem, and a fluoroquinolone safety signal

The edition in brief

Physiologically based modelling clarified the interaction profile of zavegepant nasal spray, a CGRP antagonist for acute migraine. For the nasal route, CYP3A4 and P-glycoprotein inhibitors or inducers made little difference, but inhibitors of the liver-uptake transporters OATP1B3 and NTCP raised exposure substantially — single-dose rifampin by about 2.4-fold and cyclosporine by about 1.6-fold — so these should not be co-administered. A real-world analysis of the 100 most-prescribed drugs in sickle cell disease found 43 carried drug-interaction risk, dominated by CYP3A4 and by inhibition rather than induction; the frequent CYP3A4-substrate opioids oxycodone and fentanyl stand out as a serious interaction hazard in this population. The FDA issued supplemental approvals for tirzepatide (the GIP/GLP-1 agonist marketed as Mounjaro and Zepbound); the public record flags the supplements without detailing their content, so they are a prompt to check the updated labelling rather than news of a new indication. A clinic pearl: check interactions by mechanism — identify the enzyme or transporter and whether the other drug inhibits or induces it — rather than trusting a flat alert list. Finally, an unsupervised machine-learning analysis of 40,127 fluoroquinolone reports in the FDA's FAERS database identified a reproducible multi-system cluster (about 10% of reports) enriched for neuropsychiatric, musculoskeletal and sensory events and disproportionately disabling, and far more common than with macrolides or amoxicillin. Spontaneous-report data cannot prove causation, but the pattern supports the existing caution to reserve fluoroquinolones for when no safer alternative will do — a message that matters most where they are heavily overused.