Devices for securing and administering pediatric compounded oral liquids: survey results from French university hospitals.

Oral liquid forms, either commercial or compounded, are preferred in pediatrics due to their suitability for weight-based dosing and acceptability for children. The choice of dosing delivery devices associated with oral liquid forms is important to ensure accurate dosing, ease of administration, and patient safety. Given the prevalence of compounding in pediatric settings, this study aimed to investigate the practices among French university hospitals concerning the selection of dosing delivery devices associated with compounding oral liquid forms for children. An online survey was distributed to pharmacists involved in compounding in French university hospitals. The survey covered aspects such as the presence of child-resistant caps, types of dosing devices, the presence of bottle adapters, and the type of bottle adapters used. Among the 36 hospital pharmacies contacted, 24 responded to the survey. One pharmacy employed child-resistant caps for compounded liquid forms. Enteral syringes emerged as the primary dosing device (71%), with a minority using luer/luer-lock syringes (21%). Spoon and measuring cup usage was reported by none. Approximately two-thirds of the pharmacies (67%) used a bottle adapter in conjunction with the sampling device.   Conclusion: The study highlighted diversity in the practices of French university hospitals regarding dosing delivery devices associated with compounding oral liquid forms for pediatric patients. The findings underscored the need for standardized guidelines to streamline practices and enhance safety and precision in compounded medication administration for children. What is Known: • Administration devices are important to ensure the correct administration of the required dose of oral liquids in pediatrics. • For compounded oral liquid forms, the selection and supply of administration devices are managed by compounding pharmacies from those available on the market. What is New: • The study highlighted the variability of administration devices associated with compounded liquids for oral use in French hospital pharmacies.

Development of an Oral Liquid Formulation of Nicardipine Hydrochloride Compounded with Simple Excipients for the Treatment of Pediatric Hypertension.

Nicardipine hydrochloride is an anti-hypertensive drug that is used off-label to treat hypertension in children. A previous oral formulation of nicardipine hydrochloride was developed using a commercial vehicle as an excipient. However, ready-to-use vehicles are prone to supply shortages, and their composition may undergo substantial modifications. The aim of this study was to propose a new oral formulation of nicardipine hydrochloride 2 mg/mL using simple excipients. The formulation included hydroxypropylmethylcellulose, simple syrup, polysorbate 80, sodium saccharin, citrate buffer, strawberry flavor and 0.2% potassium sorbate. The uniformity of content was maintained before and after agitation. Nicardipine hydrochloride concentration assessed by HPLC-MS/MS remained above 90% for 365 days before opening and for 28 days after opening. pH and osmolality were maintained throughout the study, and no microbial contamination was observed. The uniformity of mass of the delivered doses was evaluated using four different devices. A new oral formulation of nicardipine hydrochloride 2 mg/mL was developed using simple and safe excipients. Pharmacological and clinical parameters remain to be assessed and compared with those of the previous formulation.

Do generic drugs cause hypersensitivity?

Generic drugs may differ from brand-name drugs in nature and quantity of excipients. Hypersensitivity to generic drugs is a subject of growing importance given their key role in healthcare spending policies, however, a review of published data highlighted that relevant data is sparse. No scientific rationale has emerged for labelling patients allergic to all generic drugs, and hypersensitivity to generic drugs may rather be explored on a case-by-case basis. In the case of hypersensitivity without any change in medication, it is advisable to check for a switch from a brand-name to a generic drug, and if hypersensitivity to a generic drug is suspected, its composition must be checked.

Stability study of a compounded oral solution of nicardipine for the treatment of hypertension in children.

Nicardipine is an antihypertensive drug that may be used off-label by oral route to treat hypertension in children. Currently commercially available tablets are inappropriate for oral use in children and manufactured hard capsules are not suitable for easy dose individualization to achieve target blood pressure. We aimed to fulfill this lack of appropriate dose forms by developing an oral liquid formulation of nicardipine. We compounded an extemporaneous 2 mg/mL nicardipine solution in InOrpha® vehicle for oral use with 1% polysorbate 80. A HPLC-MS/MS stability-indicating method was developed and validated. The stability was assessed under room temperature and refrigerated storage conditions. Nicardipine concentration remained above 95% of the initial concentration for 90 days in both storage conditions, without apparition of degradation products. Organoleptic parameters, pH, osmolality, viscosity and density were assessed and remained stable throughout storage. A uniformity of content was maintained before and after agitation of the packaging bottles. Mass uniformity of delivered doses was also ensured. Finally, the formulation met the Pharmacopoeia specifications for microbiological contaminations. In this study we report a compounded formulation of nicardipine for oral use in pediatrics. This solution, which could be easily manufactured, is being used in our hospital. Pharmacological and clinical parameters including bioavailability, pharmacokinetics, efficacy and tolerance remain to be assessed.

Agranulocytosis-complicated DRESS with medullar HHV-6 replication.

HHV-6B is the subtype most often involved in the systemic manifestations of the DRESS, but also in myelosuppression in bone marrow transplant. We report a new observation of its myelosuppressive effect: a case of DRESS complicated by agranulocytosis with detectable HHV-6 RNA in bone marrow.

Feedback on the use of three surgical sealants for preventing prolonged air leak after robot-assisted anatomical lung resection.

BACKGROUND: Prolonged air leak (PAL) is the most common complication after lung resection. Several surgical sealants have been developed to reduce PAL, including fibrin-based (FS), polyethylene glycol-based (PEGS) and polyglycolic acid-based (PGAS) sealants. In this work we report our experience of surgical sealant use after robot-assisted lung resection. METHODS: A 7-year retrospective study was conducted, including patients who had robot-assisted lobectomy or segmentectomy. Data were collected using a prospective national database. The use of surgical sealants was recorded in traceability sheets. RESULTS: PAL occurred in 60 of the 299 patients included. American Society of Anesthesiologists score (ASA) and index of prolonged air leak (IPAL) were higher for patients with sealants. In this group, operative time, chest drain duration and length of stay were significantly longer. PAL occurrence was significantly associated to sealant in univariate analysis (odds ratio =1.88, 95% CI: 1.07 to 3.36, P=0.03) but the association was slightly decreased when adjusting on IPAL and ASA score (Odds ratio =1.70, 95% CI: 0.94 to 3.10, P=0.08). Comparing sealants, more segmentectomies were performed in patients with PGAS (P=0.0013) and their operative time was shorter (P=0.0002). PAL occurrences were not different. Length of stay (P=0.0045) and operative time (P=0.0002) were longer in patients with PEGS who had more postoperative complications (P=0.024). CONCLUSIONS: This study did not identify a positive effect of surgical sealants for preventing PAL. However it highlighted the need to rationalize their use.

Biotin and high-sensitivity cardiac troponin T assay.

INTRODUCTION: The high-sensitivity cardiac troponin T assay of Roche Diagnostics is known to have interference with high concentrations of biotin as this assay uses biotin-streptavidin binding as detection method. As studies so far have not shown if different biotin concentrations could have diverse influence on various troponin concentrations and whether interference could be removed by available protocol within corresponding turnaround time we aimed to investigate it. MATERIALS AND METHODS: Plasma samples were spiked with different concentration of biotin solution. Troponin T concentrations were tested on a Roche Cobas® 8000 module 602 analyser. Final concentrations of biotin and troponin T were 50, 100, 500 and 1000 µg/L and 18, 59, 201 and 6423 ng/L, respectively. Impact of different incubation times following biotin neutralization protocol described by Piketty et al. was also tested. RESULTS: We observed a mean of negative biases of 24, 56, 97, and 98% of the troponin T expected value at biotin concentrations of 50, 100, 500, 1000 µg/L. Neutralization protocol was applied on the sample with initial concentration of TnT of 59 ng/L at a biotin concentration of 1000 µg/L. Same results across different incubation times from 60 to 0 minutes were obtained (mean value 56.8 ng/L, coefficient of variation of 1.31%). We demonstrated that neutralization process had a dilution effect of the troponin concentration (loss of 4.5% to 9.6% of initial troponin value). CONCLUSIONS: Biotin interference is not dependent of initial troponin value. Interference could be successfully neutralized within a time frame compatible with emergency but results still should be carefully interpreted due to possible dilution effect.

Physicochemical stability of oxycodone-ketamine solutions in polypropylene syringe and polyvinyl chloride bag for patient-controlled analgesia use.

OBJECTIVES: The study evaluated the stability of three combinations of oxycodone and ketamine diluted in normal saline (NS) after storage for 7 days at 23°C and exposed to light. METHODS: The stability of three mixtures of oxycodone and ketamine (oxycodone 0.4 mg/mL+ketamine 40 mg/mL, oxycodone 10 mg/mL+ketamine 0.1 mg/mL and oxycodone 10 mg/mL+ketamine 40 mg/mL) in NS stored in a polypropylene syringe and a polyvinyl chloride (PVC) bag was studied. The physical characteristics, including pH, colour and precipitation, were evaluated. The samples were analysed in triplicate by a stability-indicating high-performance liquid chromatography method. RESULTS: There was no significant change in the pH values of any solution. No precipitation or change in colour was observed. All formulations maintained more than 95% of the initial concentration of each drug on day 7. No trace of degradation products was detected. CONCLUSIONS: Ketamine (0.1-40 mg/mL) combined with oxycodone (0.4-10 mg/mL) is physically compatible and chemically stable for 7 days when diluted with NS, packaged in polypropylene syringe or PVC bag and stored at 23°C.