Aripiprazole Lauroxil Long-Acting Injectable: The Latest Addition to Second-Generation Long-Acting Agents

Abstract

Antipsychotics have long been the mainstay for the treatment of schizophrenia and other psychotic disorders. Long-acting injectables (LAI) of antipsychotics-provided once every two weeks to once every three months-promise to reduce the incidence of nonadherence. ARISTADA(™) (aripiprazole lauroxil; ALLAI) extended-release injectable suspension was approved by the U.S. Food and Drug Administration in October 2015 for the treatment of schizophrenia, and is the newest entrant in the LAI market. ALLAI is available as a single-use, pre-filled syringe, can be started in three different dosages, and also has the option of every six-week dosing. Treatment with oral aripiprazole is recommended for the first twenty-one days after the first ALLAI injection, which is a potential disadvantage. Adverse effects include sensitivity to extrapyramidal symptoms, especially akathisia, which is well documented in other aripiprazole preparations. There is no available data comparing ALLAI to other antipsychotics, and more head-to-head trials comparing different LAI formulations are needed. Based on the available data, ALLAI is an effective and safe option for treatment of schizophrenia. Further studies and post-marketing data will provide better understanding of this formulation.

The Use of Long-Acting Injectable Antipsychotics in Schizophrenia

“…It can be initiated in three different dosages and has the option of 6-week dosing [43]. Oral aripiprazole supplementation is necessary for 3 weeks.…”

Prodrugs as empowering tools in drug discovery and development: recent strategic applications of drug delivery solutions to mitigate challenges associated with lead compounds and drug candidates

“…52). 76,77,238 After injection of 5ab to SD rats at 5.0 mg per kg equimolar dose of parent, 5aa , 5ab and 5ad were all detected in the systemic circulation, indicating conversion of 5ab to the N-CH 2 OH intermediate 5ad , which subsequently degrades to 5aa with the release of formaldehyde. 239 In phase I clinical trials, PK parameters were evaluated in adult patients with schizophrenia following injection of 5ab as an aqueous suspension into the gluteal muscle over 24 weeks based on a schedule of seven 441 mg injections [q4wk], five 882 mg injections [q6wk] or four 1064 mg injections [q8wk], with the last dose administered at the 24th week.…”

“…74,75 Prodrug design has also been exploited in the form of long-acting injectables (LAIs) where the physicochemical properties of successful prodrugs are often the inverse of those that facilitate dissolution in the GI tract. 76 LAIs, which minimize treatment burden, facilitate weekly or monthly administration that can reduce hospitalizations associated with symptom relapse due to poor adherence to therapy. LAIs are becoming especially popular for the treatment of schizophrenia.…”

An Update on the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved Pharmaceuticals (2013–2023)

“…Quinoline-2-one (#27). Three quinoline-2-one drugs are part of this dataset along with the reduced quinoline-2-one member aripiprazole lauroxil 124 (approved 10/2015), which is a prodrug derivative of the 2002-approved schizophrenia drug aripiprazole (Figure 20a). Brexpiprazole, presented in the piperazine section, is another member of this family of antipsychotics.…”