Antiepileptic drugs for children: Availability, suitability and acceptability

Abstract

Background Effective treatment of epilepsy requires consistent plasma steady state concentration of the antiepileptic drug (AED). This calls for rational selection of the AED and an appropriate dosing regimen. A recent survey of medicines issued to the state sector indicated a shortfall in age-appropriate formulations of paediatric AEDs1. Unavailability of the suitable paediatric formulation is overcome by one of two ways; extemporaneous preparation (or compounding) of liquid formulations or manipulation of adult dosage-form. Such manipulation could reduce the bioavailability as many AEDs are sparingly soluble in aqueous solutions and sensitive to effects that alter solubility or dissolution. Further, compliance may be affected as the palatability of manipulated dosage-forms has not been studied. This study describes the availability of AEDs in suitable paediatric formulations at the Lady Ridgeway Hospital (LRH) for Children, methods of manipulation adapted by parents and palatability, acceptability and accuracy of dose of such manipulated dosage forms. Methods A prospective cross sectional study was conducted at the OPD pharmacy of the LRH. Study population comprised children aged 12 and below with epilepsy who regularly attend the clinic and collect their AEDs from the OPD pharmacy. A consecutive sample of 109 children was recruited in one week in the latter part of 2008. Children attending the clinic for the first time were excluded. The investigators visited the pharmacy, identified the children, explained the study to the parents, gave an information sheet and obtained consent. Data was collected from parents using a pre-tested, structured, interviewer administered questionnaire, analysed and presented using simple descriptive statistics. Study protocol was approved by both Ethics Review Committees of the Faculty of Medicine, University of Colombo and LRH. Results The mean age of study sample was 6.3 years (SD = 3.37), 15 children in 0-2 year, 38 in 2-6 year and 56 in 6 - 12 year age groups. They were on eight different AEDs with the majority (63%) on monotherapy. Sodium valproate (57%) was the most frequently prescribed AED followed by carbamazepine (16%). None of the prescribed AEDs were available in suitable paediatric formulations. Except a 2 year old for whom parents were buying sodium valproate syrup from private pharmacies, the others, irrespective of their ages, received adult strength AED tablets. Parents are instructed by pharmacists to segment the unscored adult tablet. Of the 53 children between 0 - 6 years, parents segmented the adult tablet: in 45% into half, in 7% into quarter, in 6% into three-quarter and in 3% into one-eighth. Parents used diverse methods to encourage children swallow the whole or segmented tablet. Majority in 2-6 (60.5%) and 6 -12 year (78.5%) age groups managed to swallow the tablet whole/part. A small minority (13.3%) of children in 0-2 year age group chewed the AED with the rest receiving it crushed and mixed with a variety of vehicles including water (54.5%), breast milk (17%), honey, sugar, co-prescribed syrup and food. On assessing the palatability of these medicines in the 5-12 year age group using a Likert scale (1-very tasty, 5 - very bitter), majority graded valproate (65%) and carbamazepine (64%) as of average taste. Approximately one-fifth of parents always encountered problems in administering valproate with half finding it hard to crush; when broken, the remaining half for the next dose often disappears (melts) and children refusing it claiming it was very bitter. This resulted in out of pocket purchasing till the next clinic date.