Acceptability of compounded preparations – A Romanian pediatric hospital perspective

Abstract

Compounded medicines are widely used, especially for pediatric patients. The aim of this study was to evaluate children’s acceptability of compounded preparations and to provide information regarding compounding practices’ characteristics in a Romanian hospital setting. An observational, cross-sectional, and retrospective study was conducted in three Clinical Pediatric Departments (Emergency Clinical Hospital for Children, Cluj-Napoca). The study population comprised patients under 18 years old taking at least one compounded medication. Study data was collected mainly through an interviewer-administered questionnaire and medicine acceptability was assessed based on the children’s first reaction to the preparations using a 3-point facial hedonic scale. A total of 162 compounded medications were evaluated. A positive/negative reaction was reported for 20.83%/58.33%, 20.63%/49.21%, and 66.67%/7.41% of oral, oromucosal and cutaneous dosage forms. Although patient disapproval was recorded for various reasons, medication administration was successful in over 75% of cases. Factors such as fewer steps required for intake of a dose, capsule dosage form, no additional food/drink immediately after drug intake, medication perceived as “easy/very easy” to swallow, were correlated with a better acceptability of oral preparations. This study highlights the importance of identifying factors that can improve the acceptability of compounded preparations and, subsequently, treatment outcomes in pediatric patients.

Introduction

Pediatric patients have specific needs that require age-appropriate formulations, including personalized strengths, child-friendly dosage forms, and adequate palatability [1]. The formulation of pediatric medicines can be challenging since it is necessary to consider the diversity of this patient population in terms of age alongside compliance challenges and potential safety concerns associated with excipients [2].

In Europe, more than 70 % of marketed drugs do not include a pediatric authorization and have not been adequately tested on children [3]. For this reason, The European Pediatric Regulation that came into force on 26th January 2007 aimed to stimulate the research and development of medicines for children. Several key regulatory changes were introduced to achieve this objective, and several rewards and incentives were offered to the industry. For example, an application for marketing authorization requires a Pediatric Investigational Plan (PIP) to ensure that the necessary data are obtained through studies in children and the Pediatric Use Marketing Authorization (PUMA) was introduced for medicines developed exclusively for use in the pediatric population [3]. As reported by Petkova V et al. (2023), ten years after The Pediatric Regulation was introduced, a total of 273 new medicines and 43 additional pharmaceutical forms appropriate for use in children were authorized in the European Union (EU). Although this is a step forward, it must be acknowledged that not all medications that are needed to treat the pediatric population were developed after 2007 and benefited from those incentives [4]. In addition, when it comes to older drugs, Summaries of Product Characteristics (SmPC) are based on studies conducted at the time of drug development, and most of them are not updated based on current clinical practice [5]. Therefore, pediatric labeling and dosage forms are still not available for many medicines [1], [6]. Consequently, healthcare professionals often have no choice but to treat children with off-label or compounded drugs to fill this gap [7], [8], [9].

According to the European Pharmacopeia (EP), pharmaceutical preparations may be licensed by the competent authority or unlicensed and compounded to meet patientsʹ specific needs. The latter category includes extemporaneous preparations (i.e., pharmaceutical preparations individually prepared for a specific patient or patient group, supplied after preparation) and stock preparations (i.e., pharmaceutical preparations prepared in advance and stored until a request for a supply is received) [10]. The technical guidelines developed by The International Pharmaceutical Federation (FIP) – World Health Organization (WHO) in 2016 define compounding as “preparation under the supervision of a pharmacist following national legislation of an unlicensed medicine to meet the specific needs of a patient when no suitable authorized dosage form is available; this may involve preparation from the authorized dosage form or the active pharmaceutical ingredient (API) and usually requires addition of excipients to produce an acceptable product” [11].

Currently, there is an increased interest in documenting pediatric compounding practices all over the world. For example, in 2022, The FIP Pediatric Formulations Focus Group (PFFG) undertook a global survey to identify current oral extemporaneous preparation practices, challenges and needs in different geographic regions across the globe [12]. Compounded formulations for pediatric patients can provide tailored and effective medication options, but questions surrounding their acceptability and safety persist [13]. Acceptability, which is defined by the European Medicines Agency (EMA) as the “overall ability and willingness of the patient to use and its caregiver to administer the medicine as intended”, is a key factor in drug administration in children [14]. Acceptability may significantly affect adherence and efficacy and safety secondarily [14], [15], [16]. Evolving regulatory guidelines recommend routine assessment of the acceptability of pediatric medicines throughout clinical development processes [2], [14], [15].

As to the authorsʹ best knowledge, up to date, there are no published papers that cover compounding practices in Eastern European countries, and very few papers address the acceptability of compounded pediatric medicines. Therefore, we aimed to explore the acceptability of different compounded preparations in pediatric patients and to gain insights into the practice of compounding medications in a Romanian hospital setting.

Acceptability of compounded preparations – A Romanian pediatric hospital perspective

Abstract

Introduction

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