BackgroundThere is no standardized procedure or consensus to which tests should be performed to judge compatibility/incompatibility of intravenous drugs. The purpose of this study was to establish and evaluate a test program of methods suitable for detection of physical incompatibility in Y-site administration of total parenteral nutrition (TPN) and drugs.MethodsEight frequently used methods (dynamic light scattering, laser diffraction, light obscuration, turbidimetry, zeta potential, light microscopy, pH-measurements and visual examination using Tyndall beams), were scrutinized to elucidate strengths and weaknesses for compatibility testing. The responses of the methods were tested with samples containing precipitation of calcium phosphate and with heat destabilized TPN emulsions. A selection of drugs (acyclovir, ampicillin, ondansetron and paracetamol) was mixed with 3-in-1 TPN admixtures (Olimel® N5E, Kabiven® and SmofKabiven®) to assess compatibility (i.e. potential precipitates and emulsion stability). The obtained compatibility data was interpreted according to theory and compared to existing compatibility literature to further check the validity of the methods.ResultsLight obscuration together with turbidimetry, visual inspection and pH-measurements were able to capture signs of precipitations. For the analysis of emulsion stability, light obscuration and estimation of percent droplets above 5 μm (PFAT5) seemed to be the most sensitive method; however laser diffraction and monitoring changes in pH might be a useful support. Samples should always be compared to unmixed controls to reveal changes induced by the mixing. General acceptance criteria are difficult to define, although some limits are suggested based on current experience. The experimental compatibility data was supported by scattered reports in literature, further confirming the suitability of the test program. However, conflicting data are common, which complicates the comparison to existing literature.ConclusionsTesting of these complex blends should be based on a combination of several methods and accompanied by theoretical considerations.

Three drugs showed clear signs of precipitation when mixed with TPN and these products should not be co-administered in the same infusion line.

Manipulation of oral medication was regularly performed on paediatric wards. There is an urgent need for age-appropriate medicines, documented and standardised processes for manipulating medicines and staff training on the consequences of manipulation.

The acceptability of pediatric pharmaceutical products to patients and their caregivers can have a profound impact on the resulting therapeutic outcome. However, existing methodology and approaches used for acceptability assessments for pediatric products is fragmented, making robust and consistent product evaluations difficult. A pediatric formulation development workshop took place in Washington, DC in June 2016 through the University of Maryland's Center of Excellence in Regulatory Science and Innovation (M-CERSI). A session at the workshop was dedicated to acceptability assessments and focused on two major elements that affect the overall acceptability of oral medicines, namely swallowability and palatability. The session started with presentations to provide an overview of literature, background and current state on swallowability and palatability assessments. Five parallel breakout discussions followed the presentations on each element, focusing on three overarching themes, risk-based approaches, methodology and product factors. This article reports the key outcomes of the workshop related to swallowability and palatability assessments.

ObjectivesThe aim of this study was to investigate the use of off‐label (OL) and unlicensed (UL) medicines to hospitalised children in Norway, to add to the current knowledge on use of medicines in this vulnerable patient group.MethodsThe study was performed as a cross‐sectional prospective study. Medication was classified as on‐ or off‐label based on the comparison with the SmPC regarding age, indication, dosage, route of administration and handling of the product. UL products were classified as imported or pharmacy produced.Key findingsMore than 90% of children receiving medicines in our study were given OL or UL medicines. More patients received OL (83%) than UL (59%). Route of administration was the most frequently observed OL category. The vast majority of the OL prescriptions were for ‘off‐patent’ products. One‐third of products prescribed were UL.ConclusionsThe study confirms that medicines to children in hospital to a significant degree are being used outside or without authorisation, in spite of recent paediatric regulatory initiatives. More data are still needed on efficacy and safety of medicines used in children, data to be incorporated in the SmPC. In addition, suitable formulations are needed to ensure optimal dosing and adherence without risky manipulations.