Long-Acting Injectable Aripiprazole Lauroxil for Schizophrenia: Administered IM Every 4 to 6 Weeks Aripiprazole Lauroxil Is an Option for Patients Who Need a Longer-Acting Antipsychotic (2016)

Approximately 80% of patients with schizophrenia relapse within 5 years (1) despite the availability and increased use of second-generation antipsychotics. Long-acting depot formulations are a proven, effective treatment option for patients with schizophrenia. In October 2015, another long-acting injectable antipsychotic, aripiprazole lauroxil, was FDA-approved for schizophrenia. (2) Aripiprazole lauroxil is administered IM every 4 to 6 weeks in the deltoid or gluteal region and is available in multiple dosages (Table I). Mechanism of action Aripiprazole lauroxil is a prodrug of aripiprazole. Prodrugs are chemical compounds that exert their pharmacological effects after they undergo a biologic transformation and transform into a more active metabolite. (3) The development of prodrugs is an established method used to improve physiochemical or pharmacokinetic properties of the pharmacologically active compound. After IM injection, aripiprazole lauroxil is most likely converted by an enzyme-mediated hydrolysis to N-hydroxymethyl aripiprazole, which is then hydrolyzed to aripiprazole. Aripiprazole's mechanism of action is mediated through a combination of partial agonist activity at D2 and 5-HT1A receptors and antagonistic activity at 5-HT2A receptors. (2,4) Dosing and administration If your patient has never taken aripiprazole, ensure that she (he) will tolerate the drug by initiating a trial of oral aripiprazole before beginning treatment with aripiprazole lauroxil; establishing tolerability might take as long as 2 weeks because of the half-life of aripiprazole. Aripiprazole lauroxil can be started at 441 mg, 662 mg, or 882 mg administered monthly; these dosages correspond to 300 mg, 450 mg, and 600 mg of aripiprazole, or 10 mg/d, 15 mg/d, [greater than or equal to] 20 mg/d of oral aripiprazole, respectively (Table 2). (2) Aripiprazole lauroxil can be administered either in the deltoid muscle (441 mg only) or gluteal muscle (441 mg, 662 mg, or 882 mg). (2,4,5) Treatment with the 441-mg, 662-mg, or 882-mg dosages can be given every 4 weeks but the 882-mg dosage can be given every 6 weeks and only in the gluteal muscle, which provides greater dosing flexibility compared with extended-release injectable aripiprazole. (2,4,5) Supplementation with oral aripiprazole is required for 21 days before the first aripiprazole lauroxil injection. (2,4) The next injection should not be given earlier than 14 days after the previous dose. When a dose is missed, follow the guidelines outlined in Table 3. (2) After a single injection, aripiprazole starts to appear in the systemic circulation at Day 5 or Day 6 and continues to be released for another 36 days. (2) Steady-state concentration will be reached after the fourth monthly injection. The termination half-life of aripiprazole lauroxil ranged from 29 to 35 days after each monthly injection. (2) Packaging. Aripiprazole lauroxil is available as single-dose, pre-filled, color-coded syringes for IM injection at 441 mg (light blue), 662 mg (green), and 882 mg (burgundy); syringes do not require refrigeration (Table 2). (2) The syringe needs to be tapped at least 10 times to dislodge any material that might have settled. Shake the syringe vigorously for at least 30 seconds to ensure a uniform suspension. Shake it again for 30 seconds if the syringe is not used within 15 minutes. (2) Efficacy The efficacy of aripiprazole lauroxil for treating patients with schizophrenia has been established, in part, on the basis of efficacy data from clinical trials of oral aripiprazole. In addition, efficacy has been established in a 12-week, multicenter, randomized, placebo-controlled, double-blind, fixed-dose study of 622 individuals age 18 to 70 with schizophrenia. (4,5) All eligible patients were diagnosed with schizophrenia as defined by DSM-IV-TR criteria and confirmed by the Structured Clinical Interview for DSM-IV Disorders, Clinical Trial Version and were experiencing an acute exacerbation of their illness at the time of the study. …