Please see Important Safety Information, including Boxed Warning, below.
Extension Study: Exploring Safety and Therapeutic Effect of ARISTADA Over 52 Weeks
52-week extension study design1
Those who completed the 12-week study, as well as new adults with chronic stable schizophrenia, were eligible to participate in the 52-week extension study. Patients in this study received up to 13 doses of ARISTADA® (aripiprazole lauroxil) 441 mg or 882 mg administered by gluteal intramuscular injection every 4 weeks
The following patients were included in the study:
Those who had been previously receiving monthly ARISTADA 441 mg (n = 81) or 882 mg (n = 100) continued on their assigned dose
Those who had been receiving placebo in the 12-week study started monthly ARISTADA at a dose of 441 mg (n = 29) or 882 mg (n = 26) based on the volume of their prior placebo injection
De novo patients (n = 242) started ARISTADA 882 mg every 4 weeks as they entered the study
Those on prior placebo and de novo patients received active oral aripiprazole 21-day supplementation, whereas patients who had received prior active ARISTADA received placebo
The primary objective was to assess the long-term safety and tolerability of ARISTADA in patients with stable schizophrenia. The durability of the therapeutic effect of ARISTADA was also assessed (secondary outcome)
Adverse events during the extension period1
Adverse Events (AEs) Occurring in ≥2% of Patients During the 52-Week Study1
ARISTADA 441 mg monthly N = 110
ARISTADA 882 mg monthly N = 368
All ARISTADA doses N = 478
aMajority reported in de novo patients (16 patients).
Adverse events leading to discontinuation were reported in 5.9% (n = 28) of the total population1
Adverse events were generally consistent with what is established and known of the safety of aripiprazole
Continued therapeutic benefit of ARISTADA was observed over the 52-week extension period1
Decreases in PANSS total score from baseline to week 64 were observed in both treatment groups: 441 mg monthly and 882 mg monthly1
Long-term efficacy was evaluated in a post hoc analysis*
This post hoc analysis assessed long-term outcomes for a subgroup of patients who entered the 52-week extension study after being successfully stabilized with one of 2 doses of ARISTADA (441 mg or 882 mg monthly) in the 12-week study2,3
In this post hoc analysis, patients from the acute-phase study who continued in the 52-week study were observed to have sustained and gradual improvements in PANSS total score for both dose groups through week 64 (least squares mean [standard error] change from week 12 was -8.1 [1.3] and -7.2 [1.2] for the 441 mg and 882 mg cohorts, respectively)3
*This post hoc analysis of active rollover patients from the 12-week acute-phase study was not designed to prospectively assess, nor was it powered to examine, the efficacy of ARISTADA in this subgroup of patients. No definitive conclusions of efficacy can be drawn from these results.
In addition to the inherent limitations of post hoc analyses, limitations of this analysis include the preferential selection of study participants and differing assessment intervals between the 12-week study and the 52-week extension study.
References: 1. Data on file. Alkermes, Inc. 2. Meltzer HY, Risinger R, Nasrallah HA, et al. A randomized, double-blind, placebo-controlled trial of aripiprazole lauroxil in acute exacerbation of schizophrenia. J Clin Psychiatry. 2015;76(8):1085-1090. 3. McEvoy JP, Risinger R, Mykhnyak S, et al. Durability of therapeutic response with long-term aripiprazole lauroxil treatment following successful resolution of an acute episode of schizophrenia. J Clin Psychiatry. 2017;78(8):1103-1109.
Please read the Indication and Important Safety Information for ARISTADA® (aripiprazole lauroxil)
ARISTADA® (aripiprazole lauroxil) is indicated for the treatment of schizophrenia.
Important Safety Information
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ARISTADA is not approved for the treatment of patients with dementia-related psychosis.
Contraindication: Known hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis.
Cerebrovascular Adverse Reactions, Including Stroke: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatalities, have been reported in placebo-controlled trials of elderly patients with dementia-related psychosis treated with risperidone, aripiprazole, and olanzapine. ARISTADA is not approved for the treatment of patients with dementia-related psychosis.
Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex sometimes referred to as NMS may occur with administration of antipsychotic drugs, including ARISTADA. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available.
Tardive Dyskinesia (TD): The risk of developing TD (a syndrome of abnormal, involuntary movements) and the potential for it to become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. Prescribing should be consistent with the need to minimize TD. Discontinue ARISTADA if clinically appropriate. TD may remit, partially or completely, if antipsychotic treatment is withdrawn.
Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include:
Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics. There have been reports of hyperglycemia in patients treated with oral aripiprazole. Patients with diabetes should be regularly monitored for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia, including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients require continuation of antidiabetic treatment despite discontinuation of the suspect drug.
Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.
Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.
Pathological Gambling and Other Compulsive Behaviors: Compulsive or uncontrollable urges to gamble have been reported with use of aripiprazole. Other compulsive urges less frequently reported include sexual urges, shopping, binge eating and other impulsive or compulsive behaviors which may result in harm for the patient and others if not recognized. Closely monitor patients and consider dose reduction or stopping ARISTADA if a patient develops such urges.
Orthostatic Hypotension: Aripiprazole may cause orthostatic hypotension which can be associated with dizziness, lightheadedness, and tachycardia. Monitor heart rate and blood pressure, and warn patients with known cardiovascular or cerebrovascular disease and risk of dehydration and syncope.
Falls: Antipsychotics including ARISTADA may cause somnolence, postural hypotension, or motor and sensory instability, which may lead to falls and subsequent injury. Upon initiating treatment and recurrently, complete fall risk assessments as appropriate.
Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia, neutropenia, and agranulocytosis have been reported. Patients with a history of clinically significant low white blood cell count (WBC)/absolute neutrophil count (ANC) and history of drug-induced leukopenia/neutropenia should have frequent complete blood count (CBC) during the first few months of receiving ARISTADA. Consider discontinuation of ARISTADA at the first sign of a clinically significant decline in WBC count in the absence of other causative factors. Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur. Discontinue ARISTADA in patients with severe neutropenia (absolute neutrophil count <1000/mm3) and follow their WBC until recovery.
Seizures: ARISTADA should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.
Potential for Cognitive and Motor Impairment: ARISTADA may impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are certain ARISTADA does not affect them adversely.
Body Temperature Regulation: Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents. Advise patients regarding appropriate care in avoiding overheating and dehydration. Appropriate care is advised for patients who may exercise strenuously, may be exposed to extreme heat, receive concomitant medication with anticholinergic activity, or are subject to dehydration.
Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use; use caution in patients at risk for aspiration pneumonia.
Concomitant Medication: Decreasing the ARISTADA dosage is recommended in patients taking strong CYP3A4 inhibitors and/or strong CYP2D6 inhibitors for longer than 2 weeks. Increasing the ARISTADA dosage from 441 mg to 662 mg is recommended in patients taking CYP3A4 inducers for longer than 2 weeks. No ARISTADA dosage changes are recommended for patients taking CYP450 modulators for less than 2 weeks.
Most Commonly Observed Adverse Reaction: The most common adverse reaction (≥5% incidence and at least twice the rate of placebo reported by patients treated with ARISTADA 441 mg and 882 mg monthly) was akathisia.
Injection-Site Reactions: Injection-site reactions were reported by 4%, 5%, and 2% of patients treated with 441 mg ARISTADA (monthly), 882 mg ARISTADA (monthly), and placebo, respectively. Most of these were injection-site pain and associated with the first injection and decreased with each subsequent injection. Other injection-site reactions (induration, swelling, and redness) occurred at less than 1%.
Dystonia: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first days of treatment and at low doses.
Pregnancy/Nursing: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. Advise patients to notify their healthcare provider of a known or suspected pregnancy. Inform patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ARISTADA during pregnancy. Aripiprazole is present in human breast milk. The benefits of breastfeeding should be considered along with the mother’s clinical need for ARISTADA and any potential adverse effects on the infant from ARISTADA or from the underlying maternal condition.