The edition · Clinical Pharmacology
No sign that levetiracetam raises or lowers apixaban levels in hospital patients
Measured apixaban concentrations did not differ with levetiracetam, supporting the absence of a label warning; saturable caffeine metabolism can stretch toxic exposure over days; and anti-HER2 cardiotoxicity reports with other cardiovascular events carried more than double the rate of severe outcomes.
The edition in brief
In 77 hospital patients on apixaban, trough and peak apixaban concentrations measured from salvaged blood samples showed no apparent difference between those also taking levetiracetam and those who were not, despite advice from some professional bodies to use caution with the combination. A single-patient pharmacokinetic analysis of severe caffeine intoxication showed Michaelis–Menten elimination, with the apparent half-life falling from 43 hours at high concentrations to 11 hours later; simulations predicted more than 10 days to fall below 50 mcg/mL from 300 mcg/mL. A FAERS analysis confirmed a strong reporting signal for echocardiographic cardiac dysfunction with anti-HER2 therapies (ROR 26.6), and reports that also carried other cardiovascular events had severe outcomes in 41.7% versus 17.5%. A children's hospital's first year of model-informed precision dosing for cefepime changed the regimen in half of 20 consultations, half of them in patients on extracorporeal support. The FDA recorded a supplement to Eli Lilly's abemaciclib (Verzenio) application, with no detail on its content.
Anti-HER2 cardiotoxicity reports with other cardiovascular events carried much worse outcomes
During anti-HER2 therapy, a fall in ejection fraction accompanied by any other cardiovascular event signals a much higher risk of severe outcome and warrants prompt cardiology input.
Severe caffeine poisoning: saturable elimination can keep levels toxic for days
In severe caffeine overdose, elimination is saturable and toxic levels can persist for days — plan monitoring and consider haemodialysis accordingly.
A cefepime precision-dosing service changed the regimen in half of consultations
Model-informed dosing of cefepime changed therapy in half of complex paediatric patients, especially those on extracorporeal support.
FDA records a supplement to the abemaciclib (Verzenio) application
An FDA supplement to the abemaciclib application has been recorded without detail; prescribing is unchanged until a revised label appears.
When a small dose increase causes a large rise in level
For drugs with saturable elimination such as phenytoin, raise doses in small steps and wait longer before rechecking levels.
Levetiracetam did not appear to change apixaban concentrations
Levetiracetam and apixaban can be co-prescribed; the drugs to avoid with apixaban are enzyme-inducing anticonvulsants, not levetiracetam.
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