NYMC Faculty Publications

Aripiprazole Lauroxil: Development and Evidence-Based Review of a Long-Acting Injectable Atypical Antipsychotic for the Treatment of Schizophrenia

Author Type(s)

Faculty

DOI

10.2147/NDT.S499367

Journal Title

Neuropsychiatric Disease and Treatment

First Page

575

Last Page

596

Document Type

Article

Publication Date

1-1-2025

Department

Psychiatry and Behavioral Sciences

Keywords

dosing, pharmacokinetics, phase 3 clinical trials, safety, treatment efficacy, treatment initiation

Disciplines

Medicine and Health Sciences

Abstract

This review article describes why and how aripiprazole was formulated as aripiprazole lauroxil (AL), an extended-release antipsychotic agent that is delivered via a long-acting injectable formulation, and the clinical trials investigating its use. AL was formulated as an inactive prodrug of aripiprazole using LinkeRx® technology to provide a prolonged-release antipsychotic with predictable dissolution over time. The resulting AL pharmacokinetic profile is characterized by a long half-life and little peak-to-trough aripiprazole concentration variability across dosing intervals of every 1 month, every 6 weeks, and every 2 months. The prodrug technology was further refined to develop an AL initiation formulation with a somewhat faster release of aripiprazole, eliminating the need for a 21-day oral aripiprazole supplementation period. With this initiation formulation, AL treatment can be started in 1 day. Key AL characteristics, including pharmacokinetic profile and efficacy, safety, and tolerability data, are presented. In addition to the efficacy and safety established in clinical trials of oral aripiprazole, a placebo-controlled 12-week pivotal study investigated AL 441 mg and 882 mg monthly regimens in patients with acutely exacerbated schizophrenia and provided efficacy and safety information that led to US Food and Drug Administration approval in 2015. Thereafter, studies established the long-term safety profile and durability of the AL treatment effect. The 25-week, active-controlled ALPINE study evaluated the feasibility and effectiveness of AL 1064 mg every 2 months, initiated using the 1-day AL initiation regimen, without further oral supplementation beyond day 1, in patients hospitalized for acutely exacerbated schizophrenia with subsequent transition to outpatient care. In short-term and long-term studies, AL was generally well tolerated at initiation and during acute and maintenance treatment. Pharmacokinetic, efficacy, and safety characteristics support the use of AL across inpatient and outpatient treatment settings. with their first dose. The 1-day initiation regimen allows people with schizophrenia to start treatment during a doctor’s office visit or during a brief stay in the hospital. In short-term studies, aripiprazole lauroxil significantly reduced symptoms of acute schizophrenia. In longer-term studies, side effects were similar to those expected when using oral aripiprazole, and symptoms improved over extended durations of treatment lasting up to 3.5 years. Aripiprazole lauroxil’s safety and efficacy profile and multiple dosing and initiation options make it a treatment option for schizophrenia in inpatient and outpatient settings.

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