The edition · Clinical Pharmacology
Cenobamate raises brivaracetam levels at low doses and lowers them at high doses
A biphasic antiseizure interaction worth monitoring, an NRTI-free HIV switch built to avoid interactions, steroid exposure and low vancomycin troughs in children, and a generic exenatide licence supplement.
The edition in brief
A retrospective study of 891 serum samples from 213 patients found cenobamate altered brivaracetam concentrations in a dose-dependent, biphasic way: brivaracetam levels were 32% higher with cenobamate 12.5–50 mg/day and 21% lower with 250–450 mg/day, consistent with CYP2C19 inhibition at low doses and induction of other pathways at high doses. In the DORAL phase 2 trial, 114 long-suppressed adults with HIV switched to once-daily doravirine plus raltegravir; one virological failure occurred by week 48 and none further to week 96, supporting the regimen where avoiding NRTIs or interactions matters. Among 245 hospitalised children on vancomycin, prior glucocorticoid exposure was associated with higher odds of a subtherapeutic trough (OR 1.45), though not independently with clearance after adjustment. FDA recorded a supplement to Amneal's abbreviated application for synthetic exenatide on 2 October, an administrative licence change rather than a safety finding.
Doravirine plus raltegravir held viral suppression in an NRTI-free switch
Doravirine with raltegravir is a reasonable low-interaction switch for selected stable patients, on phase 2 evidence.
Children with prior steroid exposure more often had low vancomycin troughs
Check vancomycin levels early in children with recent steroid exposure, who more often start below target.
FDA records a supplement to a generic synthetic exenatide licence
This is an administrative supplement to a generic exenatide licence, not a safety finding.
Separate levothyroxine from calcium, iron and binding agents by four hours
Before increasing levothyroxine for a rising TSH, check for absorption interactions.
Cenobamate shifts brivaracetam levels in opposite directions depending on its dose
Consider monitoring brivaracetam levels through cenobamate titration, as the interaction reverses with dose.
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