Background Valproic acid (VPA) is 90–95% protein bound to albumin; this binding can be saturated so other parameters that can modify the free fraction of VPA should be taken into account.
Purpose To identify areas for improvement in VPA use and monitoring in a tertiary hospital where the pharmacy service does not routinely send pharmacokinetic dose adjustment recommendations.
Materials and Methods A retrospective study was conducted from February to April 2012. All patients treated with VPA were included and grouped depending on whether VPA was part of their home treatment or not.
Variables collected were: dose, indication, total VPA serum concentration (C), drug interactions classified as ≥C by Lexi-Comp, glomerular filtration rate (GFR), Child-Pugh score, albumin and bilirubin.
Results 30 patients were treated with VPA, 24 of whom were on VPA before admission (15 epilepsy, 9 psychiatric disorders and 1 unknown reason).
Reasons for admission were: 5 convulsions, 12 psychiatric disorders and 13 causes unrelated to VPA. At discharge 27 patients continued on VPA with a mean dose similar to the dose at admission.
C was determined in 14 patients: 5 were within the reference range (50–100 mg/L); 2 above, achieving therapeutic levels before discharge and 7 below. In these latter cases, 3 had an albumin <4.2 g/dL, but none reached C > 50 mg/L after correcting it with the J. Hermida formula which is a theoretical method for normalising C in hypoalbumenic patients. GFR, Child-Pugh score and bilirubin were normal. Mean time between changes in dose and C determinations was 1.5 days (0–5 days).
21 drug interactions were detected in 15 patients, involving a total of 10 drugs. Only 2 interactions were reported: VPA meropenem and VPA lamotrigine.
Conclusions Changes in free fraction of VPA, due to hypoalbuminaemia, liver or kidney disease and hyperbilirubinaemia, must be detected.
C should be measured once a steady state has been achieved (3–5 days).
Drug interactions affecting VPA should be added to the pharmacy service’s interaction notification programme.
No conflict of interest.
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