Low albumin and liver disease threw vancomycin AUC estimates off; check levels early

The edition in brief

In patients with liver disease, creatinine is low because less is made, so renal function and vancomycin clearance can be overestimated. A Japanese multicentre study of 157 adults found hepatic dysfunction with albumin below 2 g/dL more than doubled the odds that population-model AUC estimates differed by 30% or more from Bayesian estimates using measured troughs (adjusted OR 2.26). Exposure was higher than predicted. The practical step is early therapeutic drug monitoring rather than relying on dosing software alone. Six phase 1 studies characterised drug interactions for orforglipron, an oral non-peptide GLP-1 receptor agonist: clarithromycin and ciclosporin raised its exposure, carbamazepine lowered it, and orforglipron itself had no meaningful effect on midazolam, digoxin or atorvastatin, with a weak rise in rosuvastatin. A national analysis of English primary care found benzodiazepine prescribing fell 4.3% a year from 2020 to 2025, while clobazam use rose. Reported fatality ratios were highest for oxazepam, lorazepam and alprazolam, though spontaneous-report data cannot give true risk. The FDA recorded a supplemental approval for pirtobrutinib on 2 October; the record does not specify the change. The pearl covers why creatinine misleads in cirrhosis.