Research Article: Co-administration of Paediatric Medicines with Food and Drinks in the Context of Their Physicochemical Properties—a Global Perspective on Practices and Recommendations

Date Published: March 4, 2020

Publisher: Springer International Publishing

Author(s): Joana Martir, Talia Flanagan, James Mann, Nikoletta Fotaki.

http://doi.org/10.1208/s12248-020-0432-9

Abstract

Medicine co-administration with food or drink vehicles is a common administration practice in paediatrics. The aims of this review were (i) to describe the current recommended strategies for co-administration of paediatric medicines with food and drinks (vehicles); (ii) to compare current administration recommendations from different countries; and (iii) to obtain a global perspective on the rationale behind the choice of recommended vehicle, in the context of the physicochemical properties of the drug and formulation. This study used a defined search strategy on the practices of paediatric medicine co-administration with vehicles, recommended in a commonly used paediatric and neonatal handbook, in addition to the information previously gathered from UK formularies. Logistic regression analysis was performed to further understand the biopharmaceutical basis of the choice of recommended vehicle for medicine co-administration. Differences were identified in the type of vehicles globally recommended for medicine co-administration. Ultimately, a statistical model was developed which provided an understanding on which vehicle is recommended for use with drugs/formulations, with basis on their biopharmaceutical properties. Overall, this review highlights the areas where further information is needed to support standardised procedures and guide the recommendation of age-appropriate and acceptable vehicles for use in the co-administration of paediatric medicines. Unified requirements are needed for harmonisation of the practice of medicine co-administration with vehicles. In vitro and/or in silico tools should be developed to evaluate the potential clinical outcomes of this practice during paediatric drug development.

Partial Text

A shift has been observed towards the development of user-friendly, preservative-free, taste-masked formulations (e.g. multiparticulate single-use solid dosage forms) for the paediatric population [1–4]. However, several factors hinder paediatric drug product development, such as the heterogeneity of the paediatric population, the knowledge gaps in the understanding of developmental changes in physiology and organ maturation, the need for outcome measures for paediatric patients, the parental involvement, the ethical and economic constraints and the adaptations of required research procedures and settings to accommodate paediatric anatomic/cognitive development [2, 3]. Consequently, lack of medicines designed and studied for use in paediatrics is still an issue, and in many therapeutic areas the need for authorised paediatric formulations remains [2]. When age-appropriate licensed formulations are not available, there are several options for providing paediatric patients with suitable treatments. These include: (i) seeking a licensed therapeutic alternative, (ii) importing products authorised in other countries (which can be costly, time-consuming, and often subject to strict regulations), (iii) compounding medicines within the pharmacy (i.e. preparing an unlicensed medicine to meet specific patient needs) or (iv) manipulating licensed dosage forms [5–7].

In this study, a focused search was performed on the vehicles that are globally used for mixing with dosage forms for paediatric administration. When gathering data, it was identified that the formularies previously consulted (British National Formulary for Children [BNF-C] [22] and Hospital Formulary [23]) do not differ from the formularies used in several other countries such as Australia, New Zealand, and the Netherlands. The Lexicomp Neonatal and Paediatric Dosage Handbook [24] (referred to as Lexicomp Handbook in this paper) was identified as a second source of information. In clinic, it is a valuable point-of-care dosing resource, designed to support medical professionals managing paediatric and neonatal patients. For the purpose of this study, the drug monographs included in this handbook were screened, with emphasis on the ‘mode of administration’ section. Drugs were included in the analysis if co-administration of the dosage forms with food, drinks or meals was suggested. Drugs for which recommendations were to take the formulations ‘with or without food/meals’ or ‘without regards to food/meals’ were also included. As this review focuses on a specific type of medicine manipulation (i.e. mixing the drug with vehicles), drugs for which only manipulation techniques were referred and/or drugs for which only water was noted as an administration vehicle were not taken into account. The information gathered from this new source was combined with information previously gathered, for a global evaluation of practices and vehicle recommendations [7, 22, 23].

In view of the prevalence of the practice of medicine co-administration with food and drinks in paediatrics, and of the challenges still faced in the development of age-appropriate medicines, efforts should be made to reconcile the information available and provide clear, easily accessible information on vehicle suitability. Regulatory guidance indicates that clear instructions should be included on which vehicles have been demonstrated to be suitable for mixing with medicines. However, this study has shown that information on the appropriate vehicle to use is still not available for many medicines, and no clear rationale seems to guide vehicle recommendations. The absence of standard methods and criteria defining which vehicles are widely acceptable and available for the paediatric age groups, and of standard protocols for administration, complicate the compatibility studies needed to provide informed recommendations regarding this administration practice. Moreover, the absence of mandatory status leads to differences between practice and recommendations, further hindering the establishment of uniform, acceptable administration techniques. A statistical model was developed to provide an understanding on which vehicle is recommended for use in medicine co-administration practices, with the information gathered from available paediatric formularies, based on the physicochemical and biopharmaceutical properties of the drug/formulation. This could serve as a starting point towards the development of unified guidelines, where selection of a vehicle can be made based on drug/formulation characteristics. In the future, this could also be combined with information regarding the physicochemical properties and composition of the vehicles. It is evident that further information is required for the elucidation of current practices on a global perspective.

 

Source:

http://doi.org/10.1208/s12248-020-0432-9

 

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