WHO essential medicines for children 2011-2019: age-appropriateness of enteral formulations

INTRODUCTION: The WHO Essential Medicine List for children (EMLc) is used for promoting access to medicines. The age-appropriateness of enteral (oral and rectal) formulations for children depend on their adaptability/flexibility to allow age-related or weight-related doses to be administered/prescribed and the child's ability to swallow, as appropriate. There is scant information on the age-appropriateness of essential enteral medicines for children. OBJECTIVE: To evaluate the age-appropriateness of enteral essential medicines. MATERIALS AND METHODS: Age-appropriateness of all enteral formulations indicated and recommended in the EMLc 3rd to 7th (2011-2019) editions were determined by assessing swallowability and/or dose adaptability for children under 12 years, stratified into five age groups. RESULTS: Enteral formulations in the EMLc were more age-appropriate for older children aged 6-11 years than for younger children. In the 3rd edition, for older children, 77%, n=342, of formulations were age-appropriate. For younger children, age-appropriateness decreased with age group: 34% in those aged 3-5 years, 30% in those aged 1-2 years, 22% among those aged 28 days to 11 months and 15% in those aged 0-27 days. Overall, similar proportions were found for the 7th edition. In contrast, the majority of medicines in the 7th list were age-appropriate in targeted diseases like HIV and tuberculosis. CONCLUSION: Most recommended enteral essential medicines in EMLc 2011 and 2019 were not age-appropriate for children <6 years. Medicines which are not age-appropriate must be manipulated before administration, leading to potential issues of safety and efficacy. Evaluation of the age-appropriateness of formulations for medicines to be included in EMLc could improve access to better medicines for children in the future

Flexible Solid Oral Dosage (FSOD) forms as the preferred formulations for children

The lack of suitable formulations for children globally leads to manipulation of adult medicines that pose quality, safety, and efficacy concerns. In developing countries, poor access to medicines leads to deaths from treatable diseases. In 2008, the World Health Organisation (WHO) proposed Flexible Solid Oral Dosage (FSOD) forms, medicines which can either be swallowed intact as solids or dispersed in water at the point of administration, for example dispersible tablets, as the preferred formulations for children, especially in developing countries. If feasible, this would potentially improve access to age-appropriate medicines for children. This work examined the viability of the WHO’s proposal from the perspectives of needs, acceptability, and manufacturability using Nigeria as a model of a developing country. It surveyed selected countries to determine therapeutic needs; and end-users to identify issues with the use of the dispersible tablet. An assessment of the direct-compression manufacturability of oral essential medicines was performed; and a directly-compressible platform for the production of dispersible tablets was demonstrated using four model active pharmaceutical ingredients: caffeine citrate, furosemide, paracetamol and zinc sulfate. In a proof-of-concept study, milk was assessed as a novel excipient in dispersible tablets: and the taste-masking ability of infant formula was assessed in a human taste panel. The study found that, while there are challenges, capacity exists locally for the direct-compression (DC) production of dispersible tablets. Cardiovascular and anti-infective medicines were identified as priority needs. A platform suitable for the DC production of dispersible tablets was identified. Caregivers perceived the dispersible tablet as easy-to-use. The results suggested that the infant formula assessed may have weak taste-masking ability. Overall, these results suggest that the WHO proposal of FSOD forms as the preferred formulations for children is a viable modality to increase access to age-appropriate medicines for children under the age of 5 years