‘Acceptability’ of a new oral suspension formulation of mercaptopurine in children with acute lymphoblastic leukaemia

Mulla, Hussain; Buck, Helen; Price, L.; Parry, Annie; Bell, Geoff; Skinner, Roderick

doi:10.1177/1078155215577808

Cited by 17 publications

(18 citation statements)

References 23 publications

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“…Other methods used focused on a forced choice or preference between multiple products to rank order in terms of taste or a simple question as to whether the child would be prepared to take the medicine again (e.g. Refs [7,8]). One study evaluated the time taken for a nurse to administer the medicine as a measure of acceptability where it was stated that the average administration time was 60 s. [9] Although measures of acceptability and palatability are reported, there are very few studies that define the limits or criteria for 'acceptable' products.…”

Section: Resultsmentioning

confidence: 99%

“…The overall acceptability was good although there were reports of dispersion on the spoon being awkward for parents. [32] The acceptability criteria for taste varied between studies: a hedonic score greater than neutral was considered acceptable in one case, [8] whereas a hedonic score of 2.7/5 (which is beyond neutral) was reported for a product known to be unacceptable in another study. [12] Hedonic scores were also used to rank the smell of four antibiotic suspensions: cefdinir, amoxicillin/clavulanate, cefprozil and azithromycin.…”

Section: Liquid Dosage Forms Solutions Suspensionsmentioning

confidence: 99%

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Evidence of acceptability of oral paediatric medicines: a review

Mistry

Batchelor

2017

Journal of Pharmacy and Pharmacology

125

109

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Objectives The aim of this review was to map the currently available evidence on acceptability of oral paediatric medicines to aid in the selection of suitable platform formulations for the development of new acceptable paediatric products. Methods This process used a defined search strategy of indexed publications and included methods to assess the quality of the evidence retrieved. Key findings Taste/palatability was the most extensively studied area of paediatric medicine acceptability yet standard methods or criteria that define what is classed as acceptable to children is still to be defined. There have been many reports on the acceptability of medicines to paediatric populations yet major gaps in the acceptability knowledge base exist including the shape and dimensions of tablets, minitablets and capsules swallowed whole in infants and children; size and overall volume of multiparticulates; volume of liquids completely swallowed in infants and children; duration of retention within the oral cavity, size and taste of orodispersible tablets, lozenges and chewable tablets and the number of solid units dosed at each time point. Conclusions The review highlights where further information is required to support knowledge around acceptability of age-appropriate medicines. An algorithm to aid in selection of a formulation that is likely to be acceptable based on the age range to be treated by the medicine is presented as a result of this review. IntroductionThere is much evidence to support the need for age-appropriate medicines to treat paediatric patients. Pharmaceutical products for the paediatric population have a number of considerations that may not apply to adult products. In particular, the acceptability of a product needs to be clearly defined for paediatric populations and this is currently an area of great interest.The importance and incentive to study the acceptability, including palatability, of paediatric formulations was discussed in the reflection paper [1] and endorsed in the latest European Paediatric guideline on pharmaceutical development of formulations for paediatric use.[2] Before this regulatory change, there was no requirement for medicines to be demonstrated to be acceptable to children. Guidance issued by the European Medicines Agency (EMA) in 2013 states that patient acceptability must be an integral part of paediatric formulation development and described in the paediatric investigation plan (PIP).[3] Acceptability has previously been defined as 'an overall ability of the patient and caregiver (defined as "user") to use a medicinal product as intended (or authorised)'.[4] The palatability of paediatric medicines is one of the most important formulation factors in the acceptability of liquid medicines with potential to influence adherence to therapeutic regimens and outcomes.[5] Palatability has been defined as, 'the overall appreciation of a (often oral) medicine by organoleptic properties such as vision (appearance), smell, taste, aftertaste and mouth feel (e.g. texture, cooli...

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Section: Resultsmentioning

confidence: 99%

Section: Liquid Dosage Forms Solutions Suspensionsmentioning

confidence: 99%

Evidence of acceptability of oral paediatric medicines: a review

Mistry

Batchelor

2017

Journal of Pharmacy and Pharmacology

125

109

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“…A prática de manipulação desses quimioterápicos para ajuste de dose individual se torna comum 9 tendo em vista a falta de formulações adequadas disponíveis 21,22 . Órgãos regulatórios de alguns países já aprovaram a comercialização de uma suspensão oral de mercaptopurina 10,17,23 , porém ainda não está disponível amplamente, não sendo então uma realidade brasileira. A gravidade de leucemias agudas na infância e os problemas associados à dosagem correta de quimioterápicos exigem formulações pediátricas orais adequadas 10,24 , porque, apesar de ser uma doença grave, apresenta alta taxa de cura e sobrevida se o tratamento for realizado corretamente 4,5 .…”

Section: Discussionunclassified

“…A manipulação de medicamentos na pediatria para ajuste de dose individual, incluindo a partição de comprimidos, é algo comum e comprimidos divididos são frequentemente usados na prática clínica para atingir a dose prescrita [6][7][8] . A falta de disponibilidade de variadas formas farmacêuticas de quimioterápicos, utilizados para o tratamento de leucemias agudas de crianças e adolescentes, faz com que esses medicamentos sejam manipulados para atender às demandas pediátricas 9,10 .…”

Section: Introductionunclassified

“…Isso pode ser problemático, considerando que grande parte dos antineoplásicos são citotóxicos e agentes perigosos, podendo causar danos às pessoas que estão envolvidas na preparação, na administração de medicamentos e no cuidado de quem está em quimioterapia 11-14 , já que a partição de comprimidos em um ambiente não controlado as expõe à poeira citotóxica 10 . Além disso, a manipulação também é preocupante por conta de questões que incluem estabilidade, biodisponibilidade e precisão da dosagem do medicamento, podendo ser administradas doses tóxicas ou subterapêuticas para a criança/adolescente 6,8 .…”

Section: Introductionunclassified

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Partição de Comprimidos Antineoplásicos Utilizados no Tratamento de Leucemias Agudas em Crianças e Adolescentes

Tessmann

Souza

Córdoba

et al. 2020

Rev. Brasileira.De.Cancerologia

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Introdução: A manipulação de antineoplásicos para ajuste de dose, como partição de comprimidos, e comum no tratamento de leucemias agudas de crianças e adolescentes. Objetivo: Identificar a frequência e descrever a pratica da partição domiciliar de comprimidos antineoplásicos utilizados no tratamento oral de crianças e adolescentes com leucemias agudas na fase de manutenção. Método: Trata-se de um estudo transversal descritivo, realizado em um hospital pertencente a rede de saúde publica do Distrito Federal com assistência especializada em pediatria. Foram incluídos no estudo crianças e adolescentes entre 1 e 18 anos, diagnosticados com leucemias agudas e em fase de manutenção do tratamento no período de estudo. Foi aplicado um questionário semiestruturado ao responsável principal pela administração dos medicamentos quimioterápicos via oral, podendo ser o cuidador ou a própria criança/adolescente. Foram coletadas variáveis sociodemográficas dos pacientes e cuidadores e variáveis sobre a pratica de partição de medicamentos antineoplásicos no domicilio. Resultados: Todos os 48 entrevistados no período do estudo relataram ter partido comprimidos antineoplásicos ao longo do tratamento de leucemias agudas, sendo estes mercaptopurina (n=45 [93,75%]) e tioguanina (n=3 [6,25%]). Conclusão: A partição de comprimidos antineoplásicos foi uma pratica unanime em virtude da necessidade referida de ajuste de dose individual para o tratamento de leucemias agudas de crianças e adolescentes, considerando a indisponibilidade de formulações adequadas. Os resultados reforçam a necessidade de a partição ser uniformizada e realizada de maneira a minimizar os riscos e a garantir a segurança para as crianças e adolescentes e seus cuidadores.

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Bioequivalence study followed by model‐informed dose optimization of a powder for oral suspension of 6‐mercaptopurine

Arun,

Joshi,

Kakkar

et al. 2023

Pediatric Blood & Cancer

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Background6‐Mercaptopurine (6MP) is the mainstay chemotherapy for acute lymphoblastic leukemia (ALL) and is conventionally available as 50 mg tablets. A new 6MP powder for oral suspension (PFOS 10 mg/mL) was developed recently by IDRS Labs, India, intended for pediatric use. A comparative pharmacokinetics of PFOS with T. mercaptopurine was conducted to determine the dose equivalence.MethodsAn open‐label, randomized, two‐treatment, two‐period, two‐sequence, single oral dose, crossover, bioequivalence study was conducted on 51 healthy adult subjects. Post hoc, a population pharmacokinetic (PopPK) model was developed using the healthy volunteer data to perform simulations with various PFOS doses and select a bioequivalent dose. Further, to confirm the safety of PFOS in pediatrics, a simulation of 6MP and 6‐thioguanine exposures was performed by incorporating the formulation‐specific parameters derived from the healthy volunteer study into the PopPK model in childhood ALL available in literature.ResultsThe 6MP PFOS had 47% higher oral bioavailability compared to the reference product. Simulations using a two‐compartmental PopPK model with dissolution and transit compartments showed that 40 mg of PFOS was found to be equivalent to 50 mg tablets. The simulated 6‐thioguanine nucleotide concentrations in children using the dose adjusted for PFOS were between 114 and 703.6 pmol/8 × 108 RBC, which was within the range reported in pediatric ALL studies.Conclusion6MP PFOS 10 mg/mL should be administered at a 20% lower dose than the tablet to achieve comparable exposure. 6MP PFOS addresses an unmet medical need for a liquid formulation of 6MP in the Indian subcontinent.

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‘Acceptability’ of a new oral suspension formulation of mercaptopurine in children with acute lymphoblastic leukaemia

Abstract: The results of this survey show that Xaluprine® has good overall acceptability in the paediatric population and suggests that Xaluprine® is an important, alternative, age-appropriate formulation of mercaptopurine.

Cited by 17 publications

References 23 publications

Evidence of acceptability of oral paediatric medicines: a review

Evidence of acceptability of oral paediatric medicines: a review

Partição de Comprimidos Antineoplásicos Utilizados no Tratamento de Leucemias Agudas em Crianças e Adolescentes

Bioequivalence study followed by model‐informed dose optimization of a powder for oral suspension of 6‐mercaptopurine

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