The edition · Clinical Pharmacology
Vancomycin in liver disease: measure early, not by formula
A multicentre study finds population models misjudge vancomycin exposure far more often in patients with hepatic dysfunction, where creatinine flatters renal function. Plus semaglutide and depression, topical diclofenac under heat, benzodiazepine prescribing trends, and an FDA supplement for baricitinib.
The edition in brief
Vancomycin: in 157 adults whose vancomycin was monitored by trough levels, hepatic dysfunction with albumin below 2 g/dL more than doubled the odds that the Bayesian AUC estimate differed from the population-model prediction by 30% or more (aOR 2.26, 1.10–4.62). Exposures and trough ratios were higher in these patients, consistent with creatinine overestimating renal function. Semaglutide and depression: a meta-analysis combining trials, observational studies and pharmacovigilance found pooled risk ratios of 1.25 for depression, 1.22 for anxiety and 1.20 for suicidal ideation or attempt, none statistically significant, with extreme heterogeneity. Topical diclofenac: in 36 adults over 50, systemic exposure from the 1% sodium gel and 1.16% diethylamine gel was comparable, and urinary recovery was about 0.5% of the applied dose; moderate exercise did not change absorption and heat produced a wider, inconclusive range. Benzodiazepines in England: prescribing fell by 4.3% a year from 2020 to 2025, while clobazam rose; among spontaneous adverse reaction reports, fatality ratios were highest for oxazepam, lorazepam and alprazolam. Regulatory: the FDA recorded a supplement to the baricitinib (Olumiant) new drug application on 25 September; the record does not state its content.
Semaglutide and depression: no significant increase detected, in very mixed evidence
Continue semaglutide where indicated, but ask about mood in patients with a psychiatric history and report new symptoms.
Topical diclofenac: about 0.5% reaches the urine, and exercise did not raise it
Use topical diclofenac rather than oral NSAIDs for localised pain in older adults, while still reviewing renal and bleeding risk.
FDA: supplement to the baricitinib (Olumiant) application
Note the filing, but keep prescribing baricitinib according to the current label and class warnings.
Benzodiazepine prescribing in England fell 4% a year, while clobazam rose
Review long-term benzodiazepine use for a gradual taper, and avoid new long-term prescriptions where alternatives exist.
Creatinine flatters renal function in cirrhosis and low muscle mass
Do not trust creatinine-based clearance in cirrhosis or low muscle mass; use drug levels or cystatin C for narrow-margin drugs.
Population models misjudged vancomycin exposure more often with hepatic dysfunction
In patients with liver disease and low albumin, consider checking vancomycin levels early rather than trusting the calculated dose.
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