The edition · Clinical Pharmacology
Cenobamate raised brivaracetam levels by 32% at low doses and lowered them by 21% at high doses
A biphasic antiseizure drug interaction, five years of HIV interaction-checker queries, a machine-learning view of fluoroquinolone disability in FAERS, and an FDA sterility recall of compounded semaglutide.
The edition in brief
A retrospective German study of 891 serum samples from 213 patients found that cenobamate, which inhibits CYP2C19, raised brivaracetam concentrations by 32% at 12.5–50 mg a day but lowered them by 21% at 250–450 mg a day, consistent with inhibition at low doses and net induction at high doses. Clinical outcomes were not measured. Queries to the Liverpool HIV drug interaction checker rose 441% between 2020 and 2024, to 7.3 million from 48 countries; dolutegravir and bictegravir led, antibacterials, lipid-lowering drugs and supplements were the commonest co-medications, and the share of red and amber interactions fell as unboosted integrase inhibitors spread. Unsupervised clustering of 40,127 fluoroquinolone reports in FAERS identified a multi-system cluster of neuropsychiatric, musculoskeletal and sensory events in 10% of reports, of which 43% were disabling; the signature matched 14.9% of fluoroquinolone reports against 5.3% for macrolides and 3.9% for amoxicillin. Spontaneous reports cannot give incidence, so this is hypothesis-generating. The FDA lists a Class II recall of compounded semaglutide with cyanocobalamin from Carolina Infusion for lack of assurance of sterility.
HIV interaction-checker queries rose 441%, while severe interactions became less common
Interactions with modern integrase inhibitors are fewer but not absent; check supplements and cations every time.
A multi-system fluoroquinolone signature in FAERS, found without prior clinical input
Keep fluoroquinolones for infections that need them, and warn patients about early multi-system symptoms.
FDA Class II recall: compounded semaglutide with cyanocobalamin, sterility not assured
Ask what incretin product each patient is injecting; compounded supplies carry sterility and dose risks.
Some drugs inhibit at low doses and induce at high doses
Re-measure interacting drug levels as doses change; the direction of an interaction can reverse.
Cenobamate and brivaracetam: the interaction flips direction with dose
Monitor patients on brivaracetam through cenobamate titration; exposure may rise early and fall later.
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