Premium
Was it necessary to change the therapeutic range of topiramate?
Author(s) -
Koristkova Blanka,
Grundmann Milan,
Brozmanova Hana,
Kacirova Ivana
Publication year - 2022
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14985
Subject(s) - topiramate , bonferroni correction , medicine , anticonvulsant , therapeutic index , adverse effect , therapeutic drug monitoring , analysis of variance , cohort , pharmacokinetics , anesthesia , epilepsy , pharmacology , drug , statistics , mathematics , psychiatry
Aims The Norwegian Association for Clinical Pharmacology in their National Guidelines decreased the therapeutic range (TR) of topiramate (TPM) from 5–20 mg/L to 2–10 mg/L. The objective of this study is to ascertain which TR produces better clinical outcomes. Methods The data sources were request forms for routine therapeutic drug monitoring (TDM) of TPM. Concentration dependent adverse drug reactions (ADRs) were evaluated in 1721 samples taken pre‐dose. Seizure frequency analysis was performed in 294 samples of monotherapy. Statistical analysis was performed using Prism 5.0, GraphPad Instatt: One‐way ANOVA with Bonferroni correction for median plasma level (PL) and χ 2 ‐test with Bonferroni correction for seizure frequency and for distribution of PL according to TR 5–20 mg/L and intervals <2, 2–5, 5–10, 10–20, >20 mg/L. Results Better seizure control was found in children both in the whole cohort (without seizure 49% vs 37% adults), as well as in monotherapy (56% vs 44%), in children with PL 5–20 mg/L vs <5 mg/L (65% vs 44%) and in children with PL 5–10 mg/L vs <2 mg/L (63 vs 14%). PL in seizure‐free patients did not differ from those with seizure. Seizure control was poorer in the period 2003–2005 compared to 2006–2011. ADRs reported in 38 samples (2.8%) were not related to PL. Conclusions Change of TR is not recommended.