Paliperidone Palmitate

Objectives: There are currently no long-acting injectable antipsychotics (LAIAs) that are approved by the Food and Drug Administration for use in child and adolescent patients, however these agents are used off-label for the treatment of various psychiatric disorders. This study aims to describe the initiation and maintenance dosing strategies of LAIAs in child and adolescent psychiatry inpatients. Methods: This was a single-site retrospective chart review of patients less than 18 years of age initiated on an LAIA during an acute psychiatric hospitalization between October 1, 2015, and October 31, 2022. Patient demographics and hospital encounter information were collected and analyzed using descriptive statistics. Results: Of the 6402 unique pediatric patients discharged from the acute psychiatric hospital within the specified timeframe, 45 (0.7%) were newly initiated on an LAIA. The average age was 15.6 years (range 10-17), with a greater proportion of male (n = 26, 57.8%) and Black or African American (n = 27, 60%) patients. The LAIA agents prescribed included paliperidone palmitate (n = 21, 46.7%), aripiprazole monohydrate (n = 15, 33.3%), aripiprazole lauroxil (n = 7, 15.6%), haloperidol decanoate (n = 1, 2.2%), and risperidone microspheres (n = 1, 2.2%). Primary diagnosis via International Classification of Diseases-10 code at discharge included schizophrenia spectrum and other psychotic disorders (n = 19, 42.2%); bipolar disorder (n = 14, 31.1%); disruptive, impulse control, and conduct disorders (n = 6, 13.3%); autistic disorder (n = 5, 11.1%); and attention-deficit/hyperactivity disorder (n = 1, 2.2%). Seventeen patients (37.8%) received a loading dose regimen and/or a maintenance dose regimen that differed from adult package-insert dosing. The mean length of stay was 23.7 days, and 14 patients (31.1%) were readmitted to the psychiatric hospital within 6 months of discharge. The mean number of days to readmission was 71.9 days. Conclusions: This retrospective study is the first to focus on LAIA initiation and maintenance dosing strategies of multiple agents in both a child and adolescent patient population. Further research is required to evaluate the impact of LAIAs on clinical outcomes in this patient population.

The aim of this study was to comprehensively characterize paliperidone palmitate (PP) long-acting suspension (Invega Sustenna®) through reverse engineering. We developed a series of analytical methods to assess critical quality attributes of four batches of Invega Sustenna®. The size distributions of the four batches of suspensions were measured using laser diffraction, and variations in the D50 and D90 parameters were observed. The morphology of suspension was determined through scanning electron microscope (SEM), which exhibited irregular granular shape across all batches. The size distributions determined by SEM images were similar to the laser diffraction results. Thermal characteristics were detected using differential scanning calorimetry (DSC) and crystalline properties were assessed by powder X-ray diffraction (PXRD), displaying consistency among the four batches in these two aspects. In vitro dissolution methods (sample separation and dialysis bag methods) were developed to evaluate the release behaviors of Invega Sustenna® and four lots showed a similar dissolution pattern. Furthermore, following a single-dose intramuscular administration to rats, two batches of Invega Sustenna® with the largest size differences demonstrated comparable plasma concentration-time profiles and pharmacokinetics parameters, indicative of one month long-acting release. In summary, we established a systematic quality characteristics assessment for Invega Sustenna®, including particle size distribution, particle morphology, thermal characteristics, crystalline properties, in vitro dissolution kinetics and in vivo pharmacokinetics. Our work will assist pharmaceutical companies and regulatory agencies in the development and regulatory assessment of novel or generic products of long-acting injectable suspension.