Research on the Clinical Practical Use of Pivoxil-Conjugated Antibodies and the Risk of Carnitine Deficiency Using Real-World Data.

In Japan, pivoxil-conjugated antibodies (PVs) are commonly used to treat infections. However, carnitine deficiency is a known adverse drug reaction associated with PV treatment. This study aimed to research the practical use of PV and assess the risk of carnitine deficiency in patients receiving PV compared to their amoxicillin (AM)-treated counterparts. The Pediatric Medical Information Collection System (P-MICS) served as the data source for this study. The study cohort comprised patients aged 0-15 years prescribed PV between April 2016 and March 2021. Data on the actual PV prescriptions were extracted for each patient. To evaluate the risk of carnitine deficiency, adverse events (AEs) were defined as carnitine deficiency and its associated symptoms. Propensity score matching was employed to compare the AE incidence between the PV and AM groups. The number of cases of PV prescriptions decreased year-on-year between 2016 and 2021, and >80% of prescriptions were dispensed in the clinic. The propensity score matching analysis demonstrated no statistically significant difference in the incidence of carnitine deficiency and its associated symptoms between the PV and AM groups. Our findings suggest that the risk of carnitine deficiency in children treated with PV is not significantly higher than that associated with other antibiotics.

Quantitative Investigation on Exposure to Potentially Harmful Excipients by Injection Drug Administration in Children Under 2 Years of Age and Analysis of Association with Adverse Events: A Single-Center, Retrospective Observational Study.

INTRODUCTION: Potentially harmful excipients (PHEs) for children have been reported and the need for information collection has been advocated. However, studies on the actual occurrence of adverse events are limited. This study investigated the quantitative exposure of PHEs via injection and their association with adverse events in children under 2 years of age. MATERIALS AND METHODS: As a single-center observational study, children aged 0-23 months received injectable drugs from April 1, 2018, to March 31, 2023 were included. Information on PHE exposure and adverse events after administration were extracted from medical records. Sodium benzoate, benzyl alcohol, ethanol, glycerol, lactose, polyethylene glycol paraben, polysorbate, propylene glycol, sorbitol, sucrose, sulfite, and thimerosal were selected as PHEs. RESULTS AND DISCUSSION: 6265 cases, 333,694 prescriptions, and 368 drugs (264 ingredients) were analyzed. The median age was 0.63 years (interquartile range [IQR] 0.1-1.1). 72,133 prescriptions, 132 drugs and 99 ingredients contained PHE; 2,961 cases exposed to PHE and 1825 cases exceeding permitted daily exposure. The drug with the highest number of exposure cases was hydroxyzine, and the highest number of prescriptions was heparin (both drugs contain benzyl alcohol). In association between adverse events and PHE exposure, higher doses in cases of adverse event occurrence were found in benzyl alcohol, glycerol, polyethylene glycol, and polysorbate exposed cases. Among thimerosal-exposed cases, "developmental delay" was more frequent in exposed cases, but the causal relationship was unknown. Further investigation is needed to clarify the relationship between adverse events and PHE exposure. Additionally, more precise information on PDE for pediatrics including neonates is necessary.

Study on the Preparation Method of Quality-Assured In-Hospital Drug Formulation for Children-A Multi-Institutional Collaborative Study.

The quality-assured preparation of crushed and diluted preparations for children is a challenge. In this study, a multicenter study was conducted to validate the preparation method for the quality assurance of baclofen powder, clonidine powder, and hydrocortisone powder prepared from tablets according to a previously established method. In-hospital preparations were prepared at five medical facilities under different crushing and mixing conditions. After storage in closed bottles, in-use bottles, and laminated paper for 120 days, ingredients stability, drug elution, and content uniformity after packaging were evaluated. All three ingredients were maintained at between 90% and 110% of their initial content for 120 days under packaging conditions of 25 ± 2 °C and 60 ± 5% relative humidity, with no change in dissolution in all formulations made at all five facilities. The content uniformity was also acceptable. The established method may contribute to quality-assured pediatric dosage form modification.

Retrospective survey of compounded medications for children in Japan.

Compounding of medications, such as crushing tablets and dispersing the contents of capsules, is a common practice in pharmacies and hospitals worldwide and is often done to provide age-appropriate formulations for oral use in pediatric patients. In the present study, a retrospective, descriptive, questionnaire-based survey was conducted to clarify the current status of drug compounding for pediatric patients in Japan. An electronic questionnaire was distributed to 740 hospitals in Japan with pediatric beds, and 208 (28.1%) of these hospitals responded. The total instances of compounding numbered 14,864 (9.6% of the total pediatric oral prescriptions) and comprised 266 active pharmaceutical ingredients (APIs), one-third of which (98 APIs) were compounded even though flexible dosage forms were available. The three most frequently compounded drugs were dantrolene sodium capsules (1152 prescriptions), ramelteon tablets (726 prescriptions), and hydrocortisone tablets (652 prescriptions), all of which were prescribed and administered in powder form. Although compounding of medications frequently varied by the patients' age, steroids such as prednisolone, dexamethasone, and hydrocortisone were commonly compounded in all age groups. To ensure the quality and safety of these compounded medications, developing a standard protocol for compounding methods is urgently needed in Japan.

Age-Appropriate Pediatric Dosage Forms in Japan: Insights into End-User Perceptions From an Observational Cross-Sectional Survey Assessing the Acceptability of Oral Formulation.

BACKGROUND: The lack of appropriate pediatric formulations is a global issue and information on acceptability is urgently needed to develop standard pediatric formulations. This study aimed to assess perceptions of acceptability of several oral dosage forms among pediatric patients at a community and a pediatric hospital in Japan and collected information about age-appropriate pediatric formulations, aiming to contribute to drug development promotion worldwide. METHODS: A cross-sectional observational study was performed. A convenience sample of caregivers was recruited from available chain-owned retail pharmacies and inpatient pediatric units. The questionnaire was composed of 3 parts: (1) acceptability of the 5 dosage forms (tablets, capsules, powders, liquids, and orally disintegrating tablet) by age; (2) acceptability of dosage size, amount, and volume by age; and (3) the actual method of administration. Face-to-face interviews were conducted at 3 independent community pharmacies (324 parents) and tertiary care pediatric hospital wards (112 nursing staff). Acceptability scores and acceptable dosages were then determined. The survey was conducted from October 1 to December 1, 2017, for the hospital setting and November 1 to 30, 2017, for the outpatient setting. RESULTS: The acceptability of oral dosage forms was roughly similar to the matrix drafted by the European Medical Agency. Differences in perception of the powder forms between communities and hospitals were also observed, with the nursing staff perceiving powder as being acceptable from the neonatal period. CONCLUSIONS: The difference in caregivers' perception of the acceptability of oral formulations between Japan and Europe was small. The powder form was found to be more acceptable in Japan. Further intervention studies are needed to assess the preferred pediatric formulation worldwide.