Key Characteristics of the Long-Acting Injectable Atypical Antipsychotic Aripiprazole Lauroxil for the Treatment of Adults with Schizophrenia

This work was sponsored by Alkermes, Inc. INTRODUCTION: Evidence-based practice involves consideration of best available data, clinical judgment, and patients’ values and preferences. Among available long-acting injectable (LAI) atypical antipsychotics for schizophrenia, aripiprazole lauroxil (AL) offers a range of dosing options intended to meet the medical and quality-of-care needs of individual patients. METHODS AND DESIGN: Key characteristics of AL are reviewed based on published data from studies examining efficacy, safety/tolerability, and pharmacokinetic profiles. RESULTS: AL was developed using an innovative prodrug technology that enabled predictable dissolution over time after intramuscular injection and resulted in a pharmacokinetic profile characterized by a long half-life with little variation between peak and trough aripiprazole concentrations across the dosing interval. This pharmacokinetic profile supports a range of dose strengths and injection intervals (1-month, 6-week, and 2-month) so that clinicians can recommend a regimen that best meets a patient’s needs. This prodrug technology was further refined to develop a nanocrystal dispersion formulation that allows AL treatment initiation in a single day. In phase 3 trials, 2 different monthly regimens of AL were efficacious vs placebo, and the efficacy of the AL every-2-months regimen was consistent with that of the monthly AL regimens. In randomized controlled trials and long-term safety studies, AL was safe and generally well tolerated at initiation, during acute treatment, and during maintenance treatment. CONCLUSION: Pharmacokinetic, efficacy, and safety characteristics support the use of AL across multiple approved dose strengths and dosing intervals, including treatment initiation in 1 day without further oral supplementation or loading doses, permitting versatility across treatment settings.