Aripiprazole Lauroxil: A Review in Schizophrenia
Aripiprazole lauroxil long-acting injectable (LAI) [Aristada®] is an intramuscularly administered, extended-release prodrug of aripiprazole, an established atypical antipsychotic agent that, in terms of its relative position within the class, is at the low end of the risk spectrum for metabolic side effects. In the USA, aripiprazole lauroxil LAI is indicated for the treatment of schizophrenia; approved doses of the drug can be injected once-monthly (q4w), every 6 weeks (q6w) or every 2 months (q8w). The efficacy of the 441 and 882 mg q4w dosages in the treatment of acute exacerbations of schizophrenia and as long-term maintenance therapy in stable schizophrenia has been directly demonstrated in a phase III clinical trial and extension, while the efficacy of the 662 mg q4w, 882 mg q6w and 1064 mg q8w dosing regimens has been established on the basis of pharmacokinetic bridging studies. Aripiprazole lauroxil LAI therapy was generally well tolerated, with an adverse event profile consistent with that of oral aripiprazole (with the exception of injection-site reactions), including a low propensity to cause metabolic disturbances. Thus, aripiprazole lauroxil LAI extends the treatment regimen options for patients with schizophrenia; as with other LAI formulations of antipsychotic agents, it can be particularly recommended for patients with recurrent relapses related to nonadherence to oral preparations and for those who prefer this mode of administration. Moreover, unlike aripiprazole monohydrate LAI, the only other commercially available long-acting formulation of aripiprazole, aripiprazole lauroxil LAI offers more than one dosing interval option, which may be a potential advantage in terms of tailoring therapy to the needs of individual patients.
During the peer review process, the manufacturer of aripiprazole lauroxil LAI was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
Compliance with Ethical Standards
The preparation of this review was not supported by any external funding.
Conflicts of interest
James Frampton is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.
Additional information about this Adis Drug Review can be found at http://www.medengine.com/Redeem/8B4CF0607EB49AE7.
- 1.Patel KR, Cherian J, Gohil K, et al. Schizophrenia: overview and treatment options. PT. 2014;39(9):638–45.Google Scholar
- 5.Lehman AF, Lieberman JA, Dixon LB, et al. American Psychiatric Association Practice Guidelines; Work Group on Schizophrenia. Practice guideline for the treatment of patients with schizophrenia, 2nd edn. Am J Psychiatry. 2004;161(Suppl 2):1–56.Google Scholar
- 15.US FDA. ABILIFY MAINTENA® (aripiprazole) for extended-release injectable suspension, for intramuscular use: US prescribing information. 2016. https://www.accessdata.fda.gov. Accessed 4 Jul 2017.
- 16.Center for Drug Evaluation and Research. Application number: 207533Orig1s000. Summary review. https://www.accessdata.fda.gov. Accessed 30 Aug 2017.
- 18.Alkermes Inc. Aristada® (aripiprazole lauroxil) extended-release injectable suspension, for intramuscular use: US prescribing information. 2017. https://www.aristadahcp.com. Accessed 4 Jul 2017.
- 21.Turncliff R, Hard M, Du Y, et al. Relative bioavailability and safety of aripiprazole lauroxil, a novel once-monthly, long-acting injectable atypical antipsychotic, following deltoid and gluteal administration in adult subjects with schizophrenia. Schizophr Res. 2014;159(2–3):404–10.CrossRefPubMedGoogle Scholar
- 23.Center for Drug Evaluation and Research. Application number: 207533Orig1s000. Clinical Pharmacology and Biopharmaceutics Review(s). https://www.accessdata.fda.gov. Accessed 30 Aug 2017.
- 28.Citrome L, Risinger R, Cutler AJ, et al. Effect of aripiprazole lauroxil in patients with acute schizophrenia as assessed by the Positive and Negative Syndrome Scale-supportive analyses from a Phase 3 study. CNS Spectr. 2017;1–7.Google Scholar
- 29.US National Institutes of Health. ClinicalTrials.gov identifier NCT01626456. 2016. https://clinicaltrials.gov. Accessed 7 Aug 2017.
- 31.Risinger R, Stanford A, Du Y, et al. Long-term safety and durability of effect of aripiprazole lauroxil in a 1-year schizophrenia extension study [abstract no. T59 plus poster P51]. npj Schizophrenia (2016) 2, Article number: 16007. https://doi.org/10.1038/npjschz.2016.7.
- 32.Stanford A, Risinger R, Du Y, et al. Stability in a 52-week schizophrenia extension study of treatment with long-acting injectable aripiprazole lauroxil [abstract no. M61 plus poster no. P49]. npj Schizophrenia (2016) 2, Article number: 16008. https://doi.org/10.1038/npjschz.2016.8.
- 33.Weiden PJ, Risinger R, Stanford AD, et al. Switching stable schizophrenia patients from oral antipsychotics to monthly aripiprazole lauroxil: a post hoc analysis of a long-term outpatient study [poster no. #134]. In: US Psychiatric and Mental Health Congress; 2016.Google Scholar
- 35.Potkin SG, Du Y, Claxton A, et al. Switching patients with schizophrenia from paliperidone palmitate to aripiprazole lauroxil: a 6-month, prospective, open-label study [poster no. 259]. In: 30th US Psychiatric and Mental Health Congress; 2017.Google Scholar
- 37.Nasrallah HA, Aquila R, Stanford AD, et al. Metabolic and endocrine profiles during 1-year treatment of outpatients with schizophrenia with aripiprazole lauroxil [poster no. P5-009]. In: Poster Proceedings. American Psychiatric Association Annual Meeting; 2017.Google Scholar
- 38.Risinger R, Hard M, Weiden PJ. A phase 1 study comparing pharmacokinetic and safety profiles of three different dose intervals of aripiprazole lauroxil [poster no. P5-025]. In: Poster Proceedings. American Psychiatric Association Annual Meeting; 2017.Google Scholar
- 39.Alkermes plc. Alkermes to initiate new clinical study evaluating ARISTADA® and INVEGA SUSTENNA® for the treatment of schizophrenia [media release]. 26 Oct 2017. http://www.alkermes.com.