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Prescribing Information
For ARISTADA For ARISTADA INITIO
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Pivotal Trial:

Pivotal Trial

ARISTADA 1064 mg, 662 mg, and 882 mg every 6 weeks were not evaluated in the pivotal trial1,2

Study design

A 12-week, phase 3, randomized, double-blind, placebo-controlled, fixed-dose study evaluating the efficacy and safety of ARISTADA® in adults with schizophrenia1,2

ARISTADA PIVOTAL TRIAL DESIGN (N=622)1,2

Pivotal trial design chartPivotal trial design chart

KEY INCLUSION CRITERIA1,2

  • Experiencing acute exacerbation or relapse
  • Ages 18 to 70 years
  • Positive and Negative Syndrome Scale (PANSS) total score of 70 to 120
  • Score of ≥4 for at least 2 of the selected Positive Scale items
  • Clinical Global Impression-Severity of Illness (CGI-S) score ≥4

STUDY ENDPOINTS1,2

  • Change in PANSS total score from baseline to day 85 (primary)
  • Clinical Global Impression-Improvement (CGI-I) score at day 85 (secondary)

ARISTADA® (aripiprazole lauroxil) was studied in 622 adult patients with schizophrenia meeting DSM-IV TR criteria and experiencing acute exacerbation.1,2

Abbreviation: IM, intramuscular.

Vertical dotted line indicates end of oral supplementation.

The Positive and Negative Syndrome Scale (PANSS) was used to evaluate efficacy1,3

POSITIVE SCALE

  • Delusions
  • Conceptual disorientation
  • Hallucinations
  • Excitement
  • Grandiosity
  • Suspiciousness
  • Hostility

NEGATIVE SCALE

  • Blunted affect
  • Emotional withdrawal
  • Poor rapport
  • Passive/apathetic social withdrawal
  • Difficulty in abstract thinking
  • Lack of spontaneity and flow of conversation
  • Stereotyped thinking

THE GENERAL PSYCHOPATHOLOGY SCALE

  • Mannerisms and posturing
  • Motor skills hindrance
  • Somatic concern
  • Guilt feelings
  • Unusual thought content
  • Poor attention
  • Preoccupation
  • Poor impulse control
  • Lack of judgment and insight
  • Uncooperativeness
  • Anxiety
  • Tension
  • Active social avoidance
  • Depression
  • Disorientation
  • Disturbance of volition

This 12-week trial included patients who were considered markedly ill1,4

Patients enrolled in the 12-week clinical trial were considered markedly ill, with mean baseline PANSS total scores of 93.9 (placebo), 92.6 (ARISTADA 441 mg monthly), and 92.0 (ARISTADA 882 mg monthly).1,4

MEAN BASELINE PANSS TOTAL SCORES1,4

Baseline PANSS chartBaseline PANSS chart

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Learn more from a representative about the efficacy of ARISTADA

Clinically proven efficacy

ARISTADA was shown to reduce the symptoms of schizophrenia in adults in a phase 3 study1,2

2X GREATER MEAN REDUCTION IN PANSS TOTAL SCORE VS PLACEBO AT DAY 85 (PRIMARY ENDPOINT)1,2

PANSS total score chart PANSS total score chart
PANSS total score chartPANSS total score chart

Twice as many patients receiving ARISTADA had CGI-I scores that were very much improved or much improved at day 85 vs placebo (secondary endpoint)1,2,5

CGI-I SCORE AT DAY 85 (SECONDARY ENDPOINT)1,2,5

CG-I score chart that presents Placebo (n= 196), ARISTADA 441 mg monthly (n=196), and ARISTADA 882 mg monthly (n=204)CG-I score chart that presents Placebo (n= 196), ARISTADA 441 mg monthly (n=196), and ARISTADA 882 mg monthly (n=204)
  • The CGI-I scale allows the clinician to assess and rate improvement in schizophrenia on a scale of 1 (very much improved) to 7 (very much worse) based on the change in clinical condition from baseline1
  • In an exploratory analysis,* improvement in CGI-I was seen for both ARISTADA groups vs the placebo group at each post-baseline visit5

*Exploratory analysis: Analysis of all exploratory endpoints was supportive of the prespecified key primary and secondary endpoints. However, these analyses do not allow definitive efficacy conclusions regarding treatment effects of ARISTADA to be drawn.

  • In a post hoc analysis† of the 12-week phase 3 clinical trial, improvement was seen in a subgroup of patients with more severe symptoms. Patients with PANSS total score >92 at baseline showed a mean reduction in PANSS total score from baseline to day 85. Those receiving placebo (n=99), ARISTADA 441 mg monthly (n=95), and ARISTADA 882 mg monthly (n=100) experienced a mean decrease in PANSS total scores of 7.44, 22.14, and 24.05, respectively6

†Post hoc analysis: The 12-week phase 3 study was not designed to prospectively assess, nor was it adequately powered to examine, the efficacy of ARISTADA in the treatment of this subgroup of patients. Therefore, there are limitations to these data, and no conclusions can be drawn from this post hoc analysis.

Efficacy of the 2-month Dose

The efficacy of ARISTADA 441 mg monthly and 882 mg monthly was established in the phase 3 clinical trial. The efficacy of ARISTADA 662 mg monthly, 882 mg every 6 weeks, and 1064 mg every 2 months was established by pharmacokinetic bridging, which demonstrated that these dosing regimens resulted in plasma aripiprazole concentrations that are within the range provided by doses of 441 mg monthly and 882 mg monthly.1

Safety and tolerability

ARISTADA has been evaluated for safety in 1180 adult patients in clinical trials in schizophrenia1

ADVERSE REACTIONS IN ≥2% OF ARISTADA-TREATED PATIENTS AND THAT OCCURRED AT GREATER INCIDENCE THAN IN PLACEBO-TREATED PATIENTS IN THE 12-WEEK CLINICAL TRIAL1

Adverse reaction table presenting placebo (n=207), ARISTADA 441 mg monthly (n=207), and ARISTADA 882 mg monthly (n=208) Adverse reaction table presenting placebo (n=207), ARISTADA 441 mg monthly (n=207), and ARISTADA 882 mg monthly (n=208)
  • In an open-label pharmacokinetic study, adverse reactions associated with the use of ARISTADA® were similar across the 441 mg monthly, 882 every 6 weeks, and 1064 mg every 2 months groups1

Discontinuations

  • In the 12-week clinical trial, discontinuations due to adverse events in patients receiving ARISTADA were lower than for placebo: 6.8% for the 441 mg dose, 2.9% for the 882 mg dose, and 17.9% for placebo2
  • In the placebo group, the majority of adverse events leading to discontinuation were related to exacerbation of psychosis/schizophrenia. Otherwise, adverse events leading to discontinuation were similar between the 3 treatment groups2,5

Akathisia

AKATHISIA ONSET RELATIVE TO INJECTION NUMBER AND STUDY DAY5

Akathisia chart that presents placebo (n=207), ARISTADA 441 mg monthly (n=207), and ARISTADA 882 mg monthly (n=208) Akathisia chart that presents placebo (n=207), ARISTADA 441 mg monthly (n=207), and ARISTADA 882 mg monthly (n=208)
  • Akathisia was the most common adverse reaction—incidence ≥5% and at least twice the rate of placebo in patients treated with ARISTADA (aripiprazole lauroxil) in the 12-week clinical trial1
  • Two out of 415 patients discontinued ARISTADA due to akathisia, which was not dose-related5
  • Benzodiazepines and short term use of beta-blockers were permitted for treatment-emergent akathisia as needed5

Prolactin

PROLACTIN LEVELS AT BASELINE AND LAST POST-BASELINE VISIT7

Prolactin chart that presents placebo (n=207), ARISTADA 441 mg monthly (n=207), and ARISTADA 882 mg monthly (n=208) Prolactin chart that presents placebo (n=207), ARISTADA 441 mg monthly (n=207), and ARISTADA 882 mg monthly (n=208)

aMean baseline prolactin: placebo: 10.1 (men), 28.8 (women); ARISTADA 441 mg monthly: 10.3 (men), 27.1 (women); ARISTADA 882 mg monthly: 10.2 (men), 25.7 (women). Values used to define changes in prolactin levels were <4.0 and ≥15.2 ng/mL in men; <4.8 and ≥23.3 ng/mL in women.7

  • In the 12-week clinical trial, mean prolactin levels decreased below baseline measurements starting at Day 29 through Day 85 in both ARISTADA groups compared with placebo7
  • Baseline prolactin levels may have been affected by previous antipsychotic medication use prior to starting the study2
  • Patients in the clinical trial had previously established tolerability to aripiprazole, which may affect prolactin measurements2

Weight gain

MEAN INCREASE IN BODY WEIGHT FROM BASELINE TO LAST BASELINE ASSESSMENT7

Weight gain chart that presents placebo (0.02 lb), ARISTADA 441 mg monthly (1.16 lb), and ARISTADA 882 mg monthly (1.19 lb) Weight gain chart that presents placebo (0.02 lb), ARISTADA 441 mg monthly (1.16 lb), and ARISTADA 882 mg monthly (1.19 lb)
  • In the 12-week clinical trial, mean increase in body weight from baseline to last post-baseline assessment was 0.02 lbs for placebo (n=207), 1.6 lbs for ARISTADA 441 mg monthly (n=207), and 1.9 lbs for ARISTADA 882 mg monthly (n=208)7
  • The percentage of patients with ≥7% increase in weight noted at the last post-baseline visit during the treatment period was 6% for placebo, 10% for ARISTADA 441 mg monthly, and 9% for ARISTADA 882 mg monthly1

Injection site reactions

  • In the phase 3 clinical trial, overall injection-site reactions were reported in 2% (placebo), 4% (441 mg monthly), and 5% (882 mg monthly) of patients1
    • Of these, the incidence of pain was 2%, 3%, and 4%, respectively, and ≤1% with each subsequent injection. Other injection-site reactions (induration, swelling, and redness) were reported in <1% of patients1
  • In an open-label pharmacokinetic study evaluating 441 mg monthly, 882 mg every 6 weeks, and 1064 mg every 2 months, injection-site reactions were similar across the dose groups1

Safety of ARISTADA INITIO®

  • In pharmacokinetic studies, the safety profile of ARISTADA INITIO® (aripiprazole lauroxil) was generally consistent with that observed for ARISTADA8
  • The most commonly observed adverse reaction was akathisia in the 12-week clinical trial for ARISTADA1,8
  • In pharmacokinetic studies evaluating ARISTADA INITIO, the incidences of injection-site reactions with ARISTADA INITIO were similar to the incidence observed for ARISTADA8
  • A phase 1 study evaluating the safety, tolerability, and pharmacokinetics of the 2 initiation regimens was conducted (N=161). In this study, patients received 21 days of oral aripiprazole (15 mg daily dose) and one ARISTADA dose (n=81) or one injection of ARISTADA INITIO plus a single dose of 30 mg oral aripiprazole and one ARISTADA dose (n=80). Patients were randomized 1:1:1:1 to receive an ARISTADA dose of either 441 mg or 882 mg9
    • There were 2 cases of akathisia in the 21-day oral aripiprazole arms (2 mild cases)
    • There were 4 cases of akathisia in the ARISTADA INITIO arms (3 mild cases, 1 moderate case)
    • None of the patients experienced serious adverse events or discontinued participation in the trial due to akathisia

For a full list of adverse events, please refer to the full Prescribing Information for ARISTADA INITIO and ARISTADA.

52-Week Open-Label Safety Study
Explore the ALPINE* Active-Controlled Study

*Abbreviation: ALPINE, Aripiprazole Lauroxil and Paliperidone palmitate: INitiation Effectiveness. This was not a head-to-head study. This study was not powered to provide comparative efficacy or safety results and should not be interpreted as suggesting ARISTADA is superior or noninferior to paliperidone palmitate.10

References: 1. ARISTADA. Package insert. 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. Kay SR, Fiszbein A, Opler LA. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261-276. 4. Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel RR. What does the PANSS mean? Schizophr Res. 2005;79(2-3):231-238. 5. Data on file. Alkermes, Inc. 6. Potkin SG, Risinger R, Du Y, et al. Efficacy and safety of aripiprazole lauroxil in schizophrenic patients presenting with severe psychotic symptoms during an acute exacerbation. Schizophr Res. 2017;190:115-120. 7. Nasrallah HA, Newcomer JW, Risinger R, et al. Effect of aripiprazole lauroxil on metabolic and endocrine profiles and related safety considerations among patients with acute schizophrenia. J Clin Psychiatry. 2016;77(11):1519-1525. 8. ARISTADA INITIO. Package insert. Alkermes, Inc. 9. Hard ML, Wehr AY, Du Y, Weiden PJ, Walling D, von Moltke L. Pharmacokinetic evaluation of a 1-day treatment initiation option for starting long-acting aripiprazole lauroxil for schizophrenia. J Clin Psychopharmacol. 2018;38(5):435-441. 10. Weiden PJ, Claxton A, Kunovac J, et al. Efficacy and safety of a 2-month formulation of aripiprazole lauroxil with 1-day initiation in patients hospitalized for acute schizophrenia transitioned to outpatient care: phase 3, randomized, double-blind, active control ALPINE study. J Clin Psychiatry. 2020;81(3):19m13207. doi:10.4088/JCP.19m13207

INDICATION AND IMPORTANT SAFETY INFORMATION FOR ARISTADA INITIO AND ARISTADA

INDICATION

ARISTADA INITIO® (aripiprazole lauroxil), in combination with oral aripiprazole, is indicated for the initiation of ARISTADA® (aripiprazole lauroxil) when used for the treatment of schizophrenia in adults.

ARISTADA is indicated for the treatment of schizophrenia in adults.

SCROLL FOR IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION

BOXED 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 INITIO and ARISTADA are 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 INITIO and ARISTADA are not approved for the treatment of patients with dementia-related psychosis.

Potential for Dosing and Medication Errors: Medication errors, including substitution and dispensing errors, between ARISTADA INITIO and ARISTADA could occur. ARISTADA INITIO is intended for single administration in contrast to ARISTADA which is administered monthly, every 6 weeks, or every 8 weeks. Do not substitute ARISTADA INITIO for ARISTADA because of differing pharmacokinetic profiles.

Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex may occur with administration of antipsychotic drugs, including ARISTADA INITIO and 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 antipsychotics 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 aripiprazole 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 INITIO and 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 with antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue ARISTADA INITIO and/or ARISTADA at the first sign of a clinically significant decline in WBC and in severely neutropenic patients.

Seizures: Use with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment: ARISTADA INITIO and ARISTADA may impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are certain therapy with ARISTADA INITIO and/or 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: ARISTADA INITIO is only available at a single strength as a single-dose pre-filled syringe, so dosage adjustments are not possible. Avoid use in patients who are known CYP2D6 poor metabolizers or taking strong CYP3A4 inhibitors, strong CYP2D6 inhibitors, or strong CYP3A4 inducers, antihypertensive drugs or benzodiazepines.

Depending on the ARISTADA dose, adjustments may be recommended if patients are 1) known as CYP2D6 poor metabolizers and/or 2) taking strong CYP3A4 inhibitors, strong CYP2D6 inhibitors, or strong CYP3A4 inducers for greater than 2 weeks. Avoid use of ARISTADA 662 mg, 882 mg, or 1064 mg for patients taking both strong CYP3A4 inhibitors and strong CYP2D6 inhibitors. (See Table 4 in the ARISTADA full Prescribing Information.)

Commonly Observed Adverse Reactions: In pharmacokinetic studies the safety profile of ARISTADA INITIO was generally consistent with that observed for ARISTADA. 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: In pharmacokinetic studies evaluating ARISTADA INITIO, the incidences of injection site reactions with ARISTADA INITIO were similar to the incidence observed with ARISTADA. 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 INITIO and/or 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 INITIO and/or ARISTADA and any potential adverse effects on the infant from ARISTADA INITIO and/or ARISTADA or from the underlying maternal condition.

To report SUSPECTED ADVERSE REACTIONS, contact Alkermes at 1-888-238-8008 or FDA at 1-800-FDA-1088 or https://www.fda.gov/medwatch.

Please see full Prescribing Information, including Boxed Warning, for ARISTADA INITIO and ARISTADA.

INDICATION

INDICATION AND IMPORTANT SAFETY INFORMATION FOR ARISTADA INITIO AND ARISTADA

INDICATION

ARISTADA INITIO® (aripiprazole lauroxil), in combination with oral aripiprazole, is indicated for the initiation of ARISTADA® (aripiprazole lauroxil) when used for the treatment of schizophrenia in adults.

ARISTADA is indicated for the treatment of schizophrenia in adults.

SCROLL FOR IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION

BOXED 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 INITIO and ARISTADA are 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 INITIO and ARISTADA are not approved for the treatment of patients with dementia-related psychosis.

Potential for Dosing and Medication Errors: Medication errors, including substitution and dispensing errors, between ARISTADA INITIO and ARISTADA could occur. ARISTADA INITIO is intended for single administration in contrast to ARISTADA which is administered monthly, every 6 weeks, or every 8 weeks. Do not substitute ARISTADA INITIO for ARISTADA because of differing pharmacokinetic profiles.

Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex may occur with administration of antipsychotic drugs, including ARISTADA INITIO and 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 antipsychotics 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 aripiprazole 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 INITIO and 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 with antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue ARISTADA INITIO and/or ARISTADA at the first sign of a clinically significant decline in WBC and in severely neutropenic patients.

Seizures: Use with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment: ARISTADA INITIO and ARISTADA may impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are certain therapy with ARISTADA INITIO and/or 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: ARISTADA INITIO is only available at a single strength as a single-dose pre-filled syringe, so dosage adjustments are not possible. Avoid use in patients who are known CYP2D6 poor metabolizers or taking strong CYP3A4 inhibitors, strong CYP2D6 inhibitors, or strong CYP3A4 inducers, antihypertensive drugs or benzodiazepines.

Depending on the ARISTADA dose, adjustments may be recommended if patients are 1) known as CYP2D6 poor metabolizers and/or 2) taking strong CYP3A4 inhibitors, strong CYP2D6 inhibitors, or strong CYP3A4 inducers for greater than 2 weeks. Avoid use of ARISTADA 662 mg, 882 mg, or 1064 mg for patients taking both strong CYP3A4 inhibitors and strong CYP2D6 inhibitors. (See Table 4 in the ARISTADA full Prescribing Information.)

Commonly Observed Adverse Reactions: In pharmacokinetic studies the safety profile of ARISTADA INITIO was generally consistent with that observed for ARISTADA. 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: In pharmacokinetic studies evaluating ARISTADA INITIO, the incidences of injection site reactions with ARISTADA INITIO were similar to the incidence observed with ARISTADA. 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 INITIO and/or 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 INITIO and/or ARISTADA and any potential adverse effects on the infant from ARISTADA INITIO and/or ARISTADA or from the underlying maternal condition.

To report SUSPECTED ADVERSE REACTIONS, contact Alkermes at 1-888-238-8008 or FDA at 1-800-FDA-1088 or https://www.fda.gov/medwatch.

Please see full Prescribing Information, including Boxed Warning, for ARISTADA INITIO and ARISTADA.

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