Aripiprazole is considered an atypical or second-generation antipsychotic agent.1, 2, 7, 28
Aripiprazole is commercially available in the US as aripiprazole and aripiprazole lauroxil.1, 118, 119, 139, 145, 147, 149, 150, 151
Aripiprazole conventional oral tablets, orally disintegrating tablets, oral solution, and oral film (Opipza®) are used for the treatment of schizophrenia in adults and pediatric patients 13 to 17 years of age.1, 145, 149, 150 Aripiprazole oral tablets with sensor (Abilify MyCite®) and extended-release IM injections (Abilify Maintena®, Abilify Asimtufii®) are used for the treatment of schizophrenia in adults.118, 139, 151 Aripiprazole lauroxil injection (Aristada®; available as prefilled syringes in 441-mg, 662-mg, 882-mg, and 1064-mg strengths) is used IM for the treatment of schizophrenia in adults.119 Aripiprazole lauroxil injection (Aristada Initio®; 675-mg strength) is used IM in combination with oral aripiprazole for the initiation of aripiprazole lauroxil for the treatment of schizophrenia in adults.147
The efficacy of oral aripiprazole for the treatment of schizophrenia in adults was evaluated in 5 placebo-controlled studies of 4 and 6 weeks' duration principally in acutely relapsed, hospitalized patients with schizophrenia.1, 2, 3, 9, 139, 145, 149, 150, 152, 153, 154 Four of the 5 studies identified an improvement in outcomes related to aripiprazole compared to placebo, but the smallest study did not.1, 139, 145, 149, 150 In these 4 studies, improvement in manifestations of schizophrenia was assessed based on results of psychiatric rating scales, including the Positive and Negative Syndrome Scale (PANSS), the PANSS positive subscale, the PANSS negative subscale, and the Clinical Global Impressions (CGI) scale.1, 2, 3, 9, 139, 145, 149, 150 Aripiprazole, at oral daily doses of 10 mg, 15 mg, 20 mg, and 30 mg, generally was found to be superior to placebo in improving both positive and negative manifestations of acute exacerbations of schizophrenia in these 4 studies.1, 2, 3, 9, 139, 145, 149, 150, 152, 153, 154 Active controls (haloperidol or risperidone) were used in addition to placebo controls in 3 of these studies, but study design did not allow for comparison between aripiprazole and the active controls.1, 2, 3, 9, 139, 145, 149, 150 An examination of population subgroups did not reveal any clear evidence of differential responsiveness to the medication based on age, gender, or race.1, 139, 145, 149, 150
In a longer-term study, adult inpatients or outpatients with schizophrenia who were, by history, symptomatically stable on other antipsychotic agents for at least 3 months were discontinued from those other agents and randomized to receive either oral aripiprazole 15 mg daily or placebo for up to 26 weeks of observation for relapse in the double-blind phase.1, 139, 145, 149, 150, 155 Relapse was based on results of the CGI-Improvement and PANSS psychiatric rating scales.1, 139, 145, 149, 150, 155 Patients receiving oral aripiprazole 15 mg daily experienced a substantially longer time to relapse over the subsequent 26 weeks compared with those receiving placebo.1, 139, 145, 149, 150, 155 In addition, pooled data from 2 double-blind, multicenter studies in acutely ill patients with schizophrenia in whom therapy with aripiprazole or haloperidol was continued for 52 weeks demonstrated a substantially higher rate of symptomatic remission across 52 weeks in the aripiprazole-treated patients compared with the haloperidol-treated patients; improved tolerability with aripiprazole may have contributed to the higher overall remission rates observed in this pooled analysis.93
The efficacy of oral aripiprazole in the acute treatment of schizophrenia in adolescents 13 to 17 years of age was evaluated in a double-blind, placebo-controlled trial of 6 weeks' duration in 302 outpatients with schizophrenia who had a PANSS total score of 70 or more at baseline.1, 91, 145, 149, 150 Patients were randomized to receive a fixed dosage of aripiprazole 10 mg daily or 30 mg daily or to receive placebo.1, 91, 145, 149, 150 Both dosages of aripiprazole were found to be superior to placebo in reducing the PANSS total score, which was the primary efficacy measure; the 10-mg daily dosage also demonstrated superiority over placebo on the PANSS negative subscale score at the study end point.1, 91, 145, 149 However, the 30-mg daily dosage failed to demonstrate superiority over the 10-mg daily dosage.1, 145, 149 The medication was generally well tolerated.91
The efficacy of the once-monthly extended-release IM formulation of aripiprazole (Abilify Maintena®) for the treatment of schizophrenia was established in a multicenter, double-blind, placebo-controlled study of 12 weeks' duration in acutely relapsed inpatients with schizophrenia who were experiencing an acute psychotic episode and in a longer-term, double-blind, placebo-controlled, randomized-withdrawal maintenance trial in adults.118, 120, 151 In the 12-week study, patients were randomized to receive IM injections of extended-release aripiprazole (400 mg) or placebo every 4 weeks.118, 120, 151 Patients receiving extended-release IM aripiprazole were also given oral aripiprazole (10-20 mg daily) for 14 days beginning on the day of the first injection to provide therapeutic plasma concentrations, which may take longer to achieve in some patients; patients who received placebo injections were given placebo tablets for the first 14 days.120 The IM dosage of extended-release aripiprazole could be adjusted down to 300 mg and increased back to 400 mg on a one-time basis.118, 120, 151 The primary efficacy measure in this study was the change in PANSS total score from baseline to end point (week 10).118, 120, 151 Patients treated with extended-release IM aripiprazole injection demonstrated substantially greater improvement in mean PANSS total scores compared with those receiving placebo.118, 120, 151
In the longer-term maintenance study, adults who met DSM-IV-TR criteria for schizophrenia and who were receiving at least one antipsychotic agent were treated with open-label oral aripiprazole for 4-6 weeks followed by extended-release aripiprazole (Abilify Maintena®) 400 mg IM once every 4 weeks with oral aripiprazole continued for the first 2 weeks after the initial injection.118, 121, 151 The IM extended-release aripiprazole dosage could be adjusted down to 300 mg based on tolerability and increased back to 400 mg on a one-time basis.118, 121, 151 Patients who remained stable on the extended-release IM injection for at least 12 weeks were then randomized either to continue receiving extended-release IM aripiprazole at the same dosage or to receive placebo injection IM every 4 weeks for up to 52 weeks and observed for relapse in the double-blind withdrawal phase.118, 121, 151 The primary efficacy measure was the time from randomization to relapse, and patients who received once-monthly extended-release IM aripiprazole had a substantially longer time to relapse than those who received placebo.118, 121, 151
Efficacy of the extended-release IM formulation of aripiprazole administered once every 2 months (Abilify Asimtufii®) was established based on the results of the studies with the once-monthly IM formulation (Abilify Maintena®).151
Efficacy of extended-release aripiprazole lauroxil IM injection (Aristada®) in the treatment of schizophrenia in adults was established, in part, based on extrapolation of efficacy data from clinical trials with oral aripiprazole.119 In addition, efficacy was established in a multicenter, double-blind, placebo-controlled, fixed-dose study of 12 weeks' duration in adults with schizophrenia who were experiencing an acute exacerbation or relapse.119, 122 Patients were randomized to receive extended-release aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg, or placebo by IM injection every 4 weeks.119, 122 After establishing tolerability to oral aripiprazole, patients concomitantly received oral aripiprazole 15 mg daily (if randomized to aripiprazole) or placebo for the first 3 weeks.119, 122 The primary efficacy measure in this study was the change in PANSS total score from baseline to end point (week 12).119, 122 At the study end point, both dosages of extended-release aripiprazole lauroxil injection resulted in substantially greater improvement in the PANSS total score compared with placebo.119, 122 Substantial improvements in the PANSS total score were evident as early as day 8 with extended-release aripiprazole lauroxil therapy and continued through the end of the treatment period.119, 122 The secondary efficacy end point was the CGI-Improvement score on day 85.119, 122 Both groups of patients receiving extended-release aripiprazole lauroxil therapy demonstrated substantially better CGI-Improvement scores compared with the placebo group.119, 122 An examination of population subgroups did not reveal any clear evidence of differential responsiveness to the drug based on age, gender, race, or body weight.119
Efficacy of the extended-release single-dose aripiprazole lauroxil IM injection formulation (Aristada Initio®), in combination with oral aripiprazole, for initiation of extended-release aripiprazole lauroxil IM injection (Aristada®) for the treatment of schizophrenia in adults was established by the controlled studies of oral aripiprazole and extended-release aripiprazole lauroxil IM injection (Aristada®), as well as a pharmacokinetic bridging study.147
Aripiprazole tablets with sensor (Abilify MyCite®) are part of a digital ingestion tracking system intended to provide objective data on drug ingestion.139, 146 The usability (i.e., ease of use, helpfulness) of this digital ingestion tracking system was evaluated in a multicenter, open-label study in 67 adults with a primary diagnosis of schizophrenia.144 Patients who had been stabilized on oral aripiprazole therapy were switched to the same dosage of aripiprazole tablets with sensor (Abilify MyCite®) for 8 weeks.144 Patients received training at baseline and weekly as needed for the first 3 weeks then were instructed to change the wearable sensor and pair it with their mobile device independently or with the assistance of a caregiver weekly for the next 5 weeks.144 The majority of patients in this study were male (74.6%) and black or African-American (76.1%), and 70.1% had mild disease (i.e., CGI-Severity score of 3) and a higher range of function (indicated by relatively high mean scores on the Instrumental Activities of Daily Living and Personal and Social Performance scales).144 Forty-nine patients (73.1%) completed the 8-week study; by the end of the study period or at the time of withdrawal from the study, 55.2% of patients were able to apply and pair a wearable sensor with their mobile device independently and 82.1% completed the tasks independently or with minimal assistance (as rated by a clinician using a standardized scale).144 Of the 60 patients who rated the ease of use and helpfulness of the digital ingestion tracking system at the end of study or at the time of withdrawal from the study, 78% reported that they were somewhat satisfied to extremely satisfied with the digital ingestion tracking system, 70% rated the system as at least somewhat helpful in management of their condition, 77% rated the system as at least somewhat helpful in improving discussions with their healthcare provider, and 65% rated the system as somewhat easy to extremely easy to use.144
The American Psychiatric Association (APA) recommends that patients with schizophrenia be treated with an antipsychotic medication.156 The APA states that, with the possible exception of clozapine, there currently is no definitive evidence that one atypical antipsychotic agent will have superior efficacy compared with another medication in the class, although meaningful differences in response may be observed in individual patients.156 The choice of an antipsychotic agent should be individualized, considering patient preference, past response to therapy, concurrent medical conditions, and drug-specific factors (e.g., adverse effect profile, available formulations, potential drug interactions, receptor binding profiles, pharmacokinetic considerations).156 Patients whose symptoms improve on an antipsychotic agent should continue treatment with an antipsychotic agent long-term; in most patients, it is appropriate to continue the same antipsychotic agent rather than switch to another antipsychotic agent for maintenance therapy.156
Guidelines from the Department of Veterans Affairs and Department of Defense similarly recommend the use of antipsychotic medication for acute and maintenance treatment of schizophrenia.157 Choice of antipsychotic medication should be based on patient-specific factors and the side effect profiles of the different antipsychotic medications.157 Clozapine should generally be reserved for individuals with treatment-resistant schizophrenia.157
A practice parameter from the American Academy of Child and Adolescent Psychiatry (AACAP) recommends antipsychotic drugs as a primary treatment for schizophrenia spectrum disorders in children and adolescents.158 The AACAP states that most atypical and typical antipsychotic agent, with the exception of clozapine, can be used as primary treatment in early-onset schizophrenia (i.e., onset of schizophrenia before 18 years of age).158 Depot antipsychotics (i.e., IM formulations) have not been studied in pediatric patients.158 Choice of antipsychotic agent in pediatric patients should be individualized based on FDA-labeling, side effect profiles, patient and family preferences, cost, and clinician familiarity.158
Aripiprazole conventional oral tablets, orally disintegrating tablets, and oral solution are used for the acute treatment of manic and mixed episodes associated with bipolar I disorder in adults and adolescents 10 to 17 years of age.1, 145, 149 Aripiprazole oral tablets with sensor (Abilify MyCite®) are used in adults for the acute treatment of manic and mixed episodes associated with bipolar I disorder (as monotherapy or as an adjunct to lithium or valproate) and for the maintenance treatment of bipolar I disorder (as monotherapy or as an adjunct to lithium or valproate).139 Aripiprazole extended-release IM injections (Abilify Maintena®, Abilify Asimtufii®) are used for maintenance monotherapy treatment of bipolar I disorder in adults.118, 151
Efficacy of oral aripiprazole monotherapy in the treatment of acute manic and mixed episodes has been demonstrated in 4 short-term (i.e., 3 weeks' duration), placebo-controlled trials in hospitalized adults who met DSM-IV criteria for bipolar I disorder with manic or mixed episodes.1, 67, 139, 145, 149, 159 These studies included patients with or without psychotic features and 2 of the studies also included patients with or without a rapid cycling course.1, 67, 139, 145, 149, 159 The main efficacy endpoint used for assessing manic symptoms in these trials was the Young Mania Rating Scale (Y-MRS), an 11-item clinician-rated scale traditionally used to assess the degree of manic symptomatology in a range from 0 (no manic features) to 60 (maximum score).1, 67, 139, 145, 149, 159 A key secondary endpoint used in these trials was the CGI-Bipolar scale.1, 67, 139, 145, 149, 159 In these trials, aripiprazole 15-30 mg once daily (with an initial dosage of 15 mg daily in 2 studies and an initial dosage of 30 mg daily in the other 2 studies) was found to be superior to placebo in the reduction of the Y-MRS total score and the CGI-Bipolar Severity of Illness score (mania).1, 67, 139, 145, 149, 159 In the 2 studies with an initial aripiprazole dosage of 15 mg daily, 48 and 44% of patients were receiving 15 mg daily at the study end point; in the 2 studies with an initial dosage of 30 mg daily, 86 and 85% of patients were receiving 30 mg daily at end point.1, 67, 139, 145, 149, 159
Efficacy of aripiprazole in the acute treatment of manic and mixed episodes in pediatric patients 10 to 17 years of age has been demonstrated in a double-blind, placebo-controlled study of 4 weeks' duration in pediatric outpatients with bipolar I disorder manic or mixed episodes (with or without psychotic features) who had Y-MRS scores of 20 or greater at baseline.1, 145, 149, 160 Patients in this study received aripiprazole 10 mg daily, aripiprazole 30 mg daily, or placebo.1, 145, 149, 160 Aripiprazole was initiated at a dosage of 2 mg daily, then titrated to 5 mg daily after 2 days, and to the target dosage of 10 mg daily in 5 days or 30 mg daily in 13 days.1, 145, 149, 160 Both dosages of aripiprazole (10 mg daily and 30 mg daily) were found to be superior to placebo in the reduction of the Y-MRS total score from baseline to week 4.1, 145, 149, 160
Efficacy of oral aripiprazole as an adjunct to lithium or valproate in the treatment of acute manic and mixed episodes has been demonstrated in a placebo-controlled study of 6 weeks' duration in adult outpatients who met DSM-IV criteria for bipolar I disorder manic or mixed type (with or without psychotic features).1, 90, 139, 145, 149, 160 Patients initially received open-label lithium (dosage producing a serum lithium concentration of 0.6-1 mEq/L) or valproate (dosage producing a serum valproic acid concentration of 50-125 mcg/mL) monotherapy for 2 weeks during the lead-in phase.1, 90, 139, 145, 149 At the end of 2 weeks, patients demonstrating an inadequate response to lithium or valproate were randomized to receive either aripiprazole (15 mg daily or increased to 30 mg daily as early as day 7) or placebo as adjunctive therapy with open-label lithium or valproate during the 6-week, placebo-controlled phase.1, 90, 139, 145, 149 Patients who received adjunctive aripiprazole with lithium or valproate demonstrated greater reductions in the Y-MRS total score and the CGI-Bipolar Severity of Illness score (mania) compared with patients who received adjunctive placebo with lithium or valproate.1, 90, 139, 145, 149
Efficacy of oral aripiprazole as monotherapy for the maintenance treatment of bipolar I disorder was evaluated in a 26-week, double-blind, placebo-controlled trial in patients with a recent manic or mixed episode who had been stabilized on open-label aripiprazole monotherapy (15-30 mg daily); patients who maintained clinical response with the drug for at least 6 weeks were randomized to either continue aripiprazole at the same dosage or be switched to placebo and monitored for manic or depressive relapse.1, 125, 139, 145, 149 In this study, time to relapse to any mood episode, particularly manic episode, was substantially longer and there were fewer manic relapses among patients receiving aripiprazole than in those receiving placebo.1, 125, 127, 139, 145, 149 There were no differences between aripiprazole and placebo in time to relapse to depressive or mixed episodes125, 127 , or in the number of depressive episodes.1, 139, 145, 149 A 74-week extension of the study also found that time to relapse to any mood episode, particularly manic episode, was substantially longer with aripiprazole than placebo at 100 weeks of treatment;126, 127 however, time to relapse to depressive episode was not substantially different between treatment groups during the 74-week extension phase.126, 127
Oral aripiprazole as adjunctive maintenance therapy in adults with bipolar I disorder was evaluated in a double-blind, placebo-controlled trial in patients with a recent manic or mixed episode.1, 112, 139, 145, 149 Patients in this study had received lithium or valproate therapy for at least 2 weeks, and those with an inadequate response to the mood stabilizer also received adjunctive aripiprazole therapy (10-30 mg daily) and were maintained on the combined regimen for at least 12 weeks.1, 112, 139, 145, 149 Patients who maintained clinical response with aripiprazole and a mood stabilizer during this period were randomized to either continue aripiprazole or be switched to placebo (combined with lithium or valproate therapy) and monitored for manic, mixed, or depressive relapse for a maximum of 52 weeks.1, 112, 139, 145, 149 Patients receiving adjunctive aripiprazole therapy with lithium or valproate experienced a significant delay in time to relapse to any mood episode compared with those receiving placebo plus lithium or valproate, particularly for relapse to manic episode; no difference between the treatment groups was observed for time to relapse to depressive episode.1, 112, 139, 145, 149
Efficacy of extended-release IM aripiprazole injections (Abilify Maintena®; Abilify Asimtufii®) as monotherapy for the maintenance treatment of bipolar I disorder has been established in a randomized, double-blind, placebo-controlled withdrawal study of 52 weeks' duration in adults with bipolar I disorder.118, 140, 151 This study included patients currently experiencing a manic episode and who had experienced at least 1 prior manic or mixed episode with manic symptoms necessitating treatment (e.g., hospitalization, mood stabilizer, antipsychotic agent); patients were converted to oral aripiprazole monotherapy over 4-6 weeks.118, 140, 151 Patients successfully converted to oral aripiprazole monotherapy or patients already receiving oral aripiprazole monotherapy continued receiving the drug orally for a stabilization phase of 2-8 weeks at a target dosage of 15-30 mg daily, and those who remained stable were subsequently converted to extended-release aripiprazole 400 mg IM once every 4 weeks for 12-28 weeks.118, 140, 151 Oral aripiprazole was continued for the first 2 weeks after the initial injection during the stabilization phase.118, 140, 151 Patients who remained stable on the extended-release IM injection for at least 8 consecutive weeks were then randomized either to continue receiving extended-release IM aripiprazole at the same dosage or placebo for up to 52 weeks during the double-blind withdrawal phase.118, 140, 151 The monthly IM aripiprazole dosage could be adjusted down to 300 mg based on tolerability and increased back to 400 mg on a one-time basis.118, 140, 151 The primary efficacy measure was the time from randomization to recurrence of any mood episode, which was defined as hospitalization for any mood episode; Y-MRS total score 15 or higher; Montgomery-Asberg Depression Rating Scale (MADRS) total score 15 or higher; CGI-Bipolar scale overall score over 4; worsening of bipolar I disorder; withdrawal from the study because of lack of efficacy, adverse event, or worsening disease; clinical worsening with the need for addition of a mood stabilizer, antidepressant, or antipsychotic agent, and/or increase in benzodiazepine dosage above the highest permitted dosage (i.e., exceeding 2 mg of lorazepam or equivalent per day); or active suicidality.118, 140, 151 Patients who received extended-release IM aripiprazole had a substantially longer time to recurrence of any mood episode than those who received placebo.118, 140, 151 Time to recurrence of manic or mixed episodes was substantially longer in patients receiving extended-release IM aripiprazole compared with those receiving placebo; no difference between the treatment groups was observed for time to relapse to depressive episodes.118, 151
Legacy practice guidelines from APA recommend lithium plus an antipsychotic or valproate plus an antipsychotic for first-line treatment of patients with severe manic or mixed episodes associated with bipolar I disorder; patients with less severe symptoms may be treated with lithium, valproate, or antipsychotic monotherapy.69 Selection of a specific treatment should be based on clinical factors such as illness severity, associated features (e.g., rapid cycling, psychosis), and patient preference, with particular attention to side effect profiles.69 Manic or mixed episodes with psychotic features usually require treatment with an antipsychotic.69 Atypical antipsychotics are generally preferred over typical antipsychotics because of their more benign side effect profile.69 Following remission of an acute episode, maintenance pharmacologic treatment is recommended; first-line options for maintenance therapy include lithium and valproate.69 The guideline states that, for patients treated with an antipsychotic medication during the acute episode, the need for ongoing antipsychotic therapy should be reassessed upon entering the maintenance phase; antipsychotics should generally be discontinued, unless they are required to control persistent psychosis or prevent recurrence.69 The role of aripiprazole is not specifically addressed.69
Guidelines from the Department of Veterans Affairs and Department of Defense suggest lithium or quetiapine monotherapy for the treatment of acute mania in patients with bipolar disorder.161 If lithium or quetiapine is not selected based on patient preference or characteristics, olanzapine, paliperidone, and risperidone are recommended as alternative treatments.161 If none of these therapies are considered suitable based on patient preference or characteristics, other suggested options include aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, valproate, or ziprasidone.161 For patients who experience breakthrough episodes of mania or unsatisfactory response to initial treatment, lithium or valproate in combination with an antipsychotic (haloperidol, asenapine, quetiapine, olanzapine, or risperidone) is recommended.161 For prevention of mania recurrence, lithium or quetiapine is recommended; alternatives include olanzapine, paliperidone, or risperidone.161
A practice parameter from the AACAP recommends pharmacotherapy as primary treatment for mania in bipolar I disorder in children and adolescents.162 Standard therapies include lithium, valproate, and/or atypical antipsychotic agents, based on adult literature.162 Choice of medication in pediatric patients should be based on evidence for efficacy, phase of illness, presence of confounding symptoms, side effect profiles, patient history of response to medication, and patient and family preferences.162
Aripiprazole conventional oral tablets, oral tablets with sensor (Abilify MyCite®), orally disintegrating tablets, and oral film (Opipza®) are used as an adjunct to antidepressants for the treatment of major depressive disorder in adults.1, 139, 145, 150
The efficacy of oral aripiprazole as an adjunctive treatment in major depressive disorder in adults has been demonstrated in 2 short-term, double-blind, placebo-controlled trials of 6 weeks' duration in adults with major depressive disorder who had an inadequate response to previous antidepressant therapy (1-3 courses) in the current episode and who had also demonstrated an inadequate response during a prospective treatment period to 8 weeks of antidepressant therapy with extended-release paroxetine, extended-release venlafaxine, fluoxetine, escitalopram, or sertraline.1, 139, 145, 150, 163 Patients in both trials initially received an aripiprazole dosage of 5 mg daily; subsequent dosage adjustments, based on efficacy and tolerability, could be made in 5-mg increments 1 week apart.1, 139, 145, 150, 163 Allowable aripiprazole dosages were 2, 5, 10, and 15 mg daily; patients who were not receiving the potent cytochrome P-450 (CYP) isoenzyme 2D6 inhibitors fluoxetine and paroxetine could also receive 20 mg daily.1, 139, 145, 150, 163 The primary efficacy endpoint was the mean change in the MADRS total score, a 10-item clinician-rated scale used to assess the degree of depressive symptomatology.1, 139, 145, 150, 163 A secondary endpoint used was the Sheehan Disability Scale (SDS), a 3-item self-rated instrument used to assess the impact of depression on three domains of functioning (work/school, social life, and family life), with each item scored from 0 (not at all) to 10 (extreme).1, 139, 145, 150, 163 In both of these trials, aripiprazole was found to be superior to placebo in reducing mean MADRS total scores; aripiprazole was also superior to placebo in reducing the mean SDS score in one study.1, 139, 145, 150, 163
An analysis of population subgroups did not reveal evidence of differential response based on age, choice of prospective antidepressant, or race.1, 139, 145, 150 With regard to gender, a smaller mean reduction in the MADRS total score was observed in males than in females.1, 139, 145, 150
Treatment options for major depressive disorder include pharmacologic and nonpharmacologic (e.g., psychotherapy) approaches.164, 165, 166, 167, 168 Several classes of antidepressant drugs are available for the treatment of major depressive disorder.164, 165, 166, 167, 168 In general, antidepressants have shown similar effectiveness; therefore, initial treatment is guided by specific patient- and drug-related factors.164, 165, 166, 167, 168 For patients who do not respond or have an inadequate response to initial treatment with an antidepressant, approaches to therapy may include changing to a different antidepressant or psychotherapy, or augmentation with psychotherapy or another pharmacological agent.164, 165, 166, 167, 168
The Department of Veterans Affairs and Department of Defense have developed guidelines for the management of major depressive disorder.165 Treatment of major depressive disorder can be initiated with either psychotherapy (e.g., cognitive behavioral therapy) or pharmacotherapy, depending on patient preference; for patients with severe, persistent, or recurrent major depressive disorder, a combination of pharmacotherapy and psychotherapy is suggested.165 When pharmacotherapy is used as initial therapy, either bupropion, mirtazapine, a selective serotonin reuptake inhibitor (SSRI), a serotonin-norepinephrine reuptake inhibitor (SNRI), trazodone, vilazodone, or vortioxetine is suggested.165 No evidence is available to suggest superiority of one agent over another.165 The guidelines recommend against using esketamine, ketamine, monoamine oxidase inhibitors (MAOIs), nefazodone, or tricyclic antidepressants (TCAs) as initial therapy.165 For patients not responding to initial therapy, recommendations include switching to another antidepressant (including MAOIs or TCAs), switching to or augmenting with psychotherapy, or augmenting with a second-generation antipsychotic (e.g., aripiprazole, brexpiprazole).165
A guideline from the American College of Physicians (ACP) provides recommendations for initial and second-line treatment of the acute phase of major depressive disorder.168 For initial pharmacotherapy, ACP recommends the use of a second-generation antidepressant (e.g., SSRI, SNRI).168 For patients in the acute phase of moderate to severe major depressive disorder who do not respond to initial treatment with an adequate dose of a second-generation antidepressant, ACP suggests switching to or augmenting with cognitive behavioral therapy, switching to a different second-generation antidepressant, or augmenting with a second pharmacologic agent.168 Suggested second-line augmentation agents include mirtazapine, bupropion, or buspirone.168 The ACP states that there is insufficient evidence to draw conclusions about the comparative effectiveness and risk for harms of augmentation treatment with aripiprazole versus bupropion.168
Irritability Associated with Autistic Disorder
Aripiprazole conventional oral tablets, orally disintegrating tablets, oral solution, and oral film (Opipza®) are is used for the acute treatment of irritability associated with autistic disorder in pediatric patients 6 to 17 years of age.1, 145, 149, 150
Efficacy of aripiprazole was established in 2 double-blind, placebo-controlled trials of 8 weeks' duration in pediatric patients 6 to 17 years of age who met DSM-IV criteria with autistic disorder and demonstrated behaviors such as aggression towards others, self-injurious behavior, quickly changing moods, or a combination of these behaviors.1, 145, 149, 150 Over 75% of the enrolled patients were under 13 years of age.1, 109, 110, 145, 149, 150 The primary instruments used for assessing clinical efficacy were the Aberrant Behavior Checklist (ABC) and the CGI-Improvement scale.1, 109, 110, 145, 149, 150 The primary outcome measure in both trials was the change from baseline to end point in the irritability subscale of the ABC (ABC-I).1, 109, 110, 145, 149, 150 In one of the trials, 98 children and adolescents with autistic disorder received flexible daily dosages of aripiprazole ranging from 2-15 mg daily, starting at 2 mg daily with increases allowed up to 15 mg daily based on clinical response, or placebo.1, 110, 145, 149, 150 In this trial, aripiprazole substantially improved scores on both the ABC-I subscale and on the CGI-Improvement scale compared with placebo.1, 110, 145, 149, 150 The mean daily dosage of aripiprazole at the end of the 8-week treatment period was approximately 9 mg daily.1, 145, 149, 150
In the other trial, 218 children and adolescents with autistic disorder received one of 3 fixed dosages of aripiprazole (5, 10, or 15 mg daily) or placebo.1, 109, 110, 145, 149, 150 Aripiprazole therapy was started at 2 mg daily and was increased to 5 mg daily after 1 week.1, 109 After the second week, the dosage was increased to 10 mg daily for patients in the 10- and 15-mg daily dosage arms; after the third week, the dosage was increased to 15 mg daily in the 15-mg daily treatment arm.1, 109, 145, 149, 150 Patients receiving all 3 aripiprazole dosages in this study demonstrated improved ABC-I subscale and CGI-I scores compared with placebo.1, 109, 145, 149, 150
The American Academy of Pediatrics (AAP) and the AACAP have developed guidelines for children and adolescents with autism spectrum disorder.169, 170 While there are no medications that correct core social and communication symptoms in patients with ASD, there are medications that may be used to help manage behavioral and psychiatric symptoms.169 For symptoms of irritability and severe disruptive behavior, the AAP suggests the use of aripiprazole or risperidone.169 These atypical antipsychotics may also improve repetitive behaviors, decrease hyperactivity, and may help with mood dysregulation disorders.169 The AACAP states that pharmacotherapy may be offered to pediatric patients with autism spectrum disorder when there is a specific target symptom or comorbid condition.170 The AACAP also lists risperidone and aripiprazole as options for the treatment of irritability associated with autism.170
Aripiprazole conventional oral tablets, orally disintegrating tablets, oral solution, and oral film (Opipza®) are used orally for the treatment of Tourette's disorder in pediatric patients 6 to 18 years of age.1, 124, 145, 149, 150
Efficacy of aripiprazole was established in 2 controlled trials (one 8-week and one 10-week) in pediatric patients who met DSM-IV criteria for Tourette's disorder and who had a total tic score (TTS) of at least 20-22 on the Yale Global Tic Severity Scale (YGTSS).1, 124, 145, 149, 150, 171 The YGTSS is a fully validated scale that measures current tic severity.1, 145, 149, 150 The primary outcome measure in both trials was the change from baseline to end point in the TTS on the YGTSS (YGTSS TTS).1, 124, 145, 149, 150, 171 Over 65% of the enrolled patients were under 13 years of age.1, 145, 149, 150
In the 8-week, placebo-controlled, fixed-dose trial, 133 patients 7 to 17 years of age were randomized to receive high-dose aripiprazole (target daily dosage of 10 mg for patients weighing less than 50 kg and 20 mg for those weighing 50 kg or more), low-dose aripiprazole (target daily dosage of 5 mg for those weighing less than 50 kg and 10 mg for those weighing 50 kg or more), or placebo.1, 145, 149, 150, 171 Aripiprazole was initiated at 2 mg daily and increased to 5 mg after 2 days with subsequent increases of 5 mg on day 7 and weekly thereafter when the target dosage was 10 mg daily or higher.1, 145, 149, 150, 171 ] Patients receiving aripiprazole in both the high-dose and low-dose groups demonstrated substantially improved scores on the YGTSS TTS compared with patients receiving placebo.1, 124, 149, 150, 171
In the 10-week, placebo-controlled, flexible-dose study, which was conducted in Korea, 61 patients 6 to 18 years of age with Tourette's syndrome were randomized to receive flexible daily dosages of aripiprazole, starting at 2 mg daily with increases allowed up to 20 mg daily based on clinical response, or placebo.1, 124, 145, 149, 150 The aripiprazole-treated patients in this study demonstrated substantially improved scores on the YGTSS TTS compared with patients receiving placebo.1, 124, 145, 149, 150 The mean daily dosage of aripiprazole at the end of the 10-week treatment period was approximately 6.5 mg daily.1, 145, 149, 150
The AACAP has developed a practice parameter for children and adolescents with tic disorders, including Tourette's disorder.172 According to the AACAP, behavioral interventions for chronic tic disorders should be considered when tics cause impairment, are moderate in severity, or if behavioral-responsive psychiatric comorbidities are present.172 Medications should be considered for patients with chronic tic disorders if they have moderate to severe tics causing severe impairment in quality of life or medication-responsive psychiatric comorbidities.172 Atypical antipsychotics such as aripiprazole and risperidone are listed as options to treat tic disorders.172 Haloperidol, pimozide, clonidine, and guanfacine are also listed as having been used for the treatment of tic disorders.172
Behavioral and Psychological Symptoms with Dementia
Aripiprazole has been used orally for the management of behavioral and psychological symptoms associated with dementia (BPSD)†.173, 174, 175 The APA recommends that antipsychotic medication be used only for the treatment of agitation or psychosis in patients with dementia when symptoms are severe, are dangerous, and/or cause significant distress to the patient.173 Prior to nonemergency treatment with an antipsychotic, review of clinical response to nonpharmacological interventions is recommended; a discussion of the risks and benefits of antipsychotic treatment with the patient and caregivers is also recommended.173 Another treatment algorithm includes oral aripiprazole and risperidone as first-line pharmacotherapy options for urgent BPSD associated with dementia.174 For emergent BPSD when IM administration is necessary, IM injections of olanzapine, haloperidol or benzodiazepines are recommended.174 For non-emergent BPSD, initial treatment should include decreasing the anticholinergic load and optimizing pain control, followed by sleep optimization with consideration of the use of trazodone.174 If there is an inadequate response, donepezil and memantine can be initiated.174 The addition of escitalopram or sertraline can then be considered if there is still an inadequate response.174 Use of second-generation antipsychotics such as aripiprazole for non-emergent BPSD should be reserved for patients with inadequate response to the maximum doses of escitalopram or sertraline.174 The American Geriatrics Society (AGS) 2023 Beers Criteria for potentially inappropriate medication use in older adults state that antipsychotics should be avoided for behavioral problems of dementia and delirium as their use is associated with harm (increased risk of stroke and greater rate of cognitive decline and mortality).175 Antipsychotics should be avoided unless documented nonpharmacologic options have failed and/or the patient is threatening substantial harm to self and others; if used, use the lowest effective dosage and consider periodic deprescribing attempts.175
Aripiprazole has been used as adjunctive treatment for obsessive-compulsive disorder (OCD)† in adults.177 Legacy practice guidelines from the APA list cognitive-behavioral therapy and pharmacotherapy as safe and effective first-line treatments for OCD.176 For pharmacotherapy, SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) are considered the first-line drugs of choice.176 If a patient does not respond to one SSRI, they may switch to a different SSRI, switch to clomipramine, augment their current SSRI with a second-generation antipsychotic, switch to venlafaxine, or switch to mirtazapine.176 Updated guidelines from international experts state that escitalopram, fluvoxamine, fluoxetine, paroxetine, and sertraline are first-line treatments for OCD.177 For treatment-resistant patients, augmentation with antipsychotics (e.g., aripiprazole or risperidone) or other drugs (e.g., memantine, ondansetron, lamotrigine) may be considered.177
Dispensing and Administration Precautions
Aripiprazole is administered orally1, 139, 145, 149, 150 or by IM injection.118, 151 Aripiprazole lauroxil is administered only by IM injection.119, 147
Aripiprazole conventional tablets, tablets with sensor (Abilify MyCite®), orally disintegrating tablets, oral solution, and oral film are administered orally once daily without regard to meals.1, 139, 145, 149, 150
Aripiprazole conventional tablets can be stored at 25°C (excursions permitted between 15-30°C).1
Aripiprazole is available as part of a digital ingestion tracking system comprised of the following components: aripiprazole tablets embedded with an ingestible event marker sensor (IEM; Abilify MyCite®); a wearable sensor (MyCite® patch), which detects the signal from the IEM sensor after ingestion and transmits data to a compatible mobile device (i.e., a smart phone); a software application (app) for compatible mobile devices (e.g., smart phones; MyCite® App), which displays information for the patient; and a web-based portal for healthcare professionals and caregivers.139
Prior to initial patient use of the Abilify MyCite® system, use of the combination product and its components (patch, app, portal) should be facilitated.139 Clinicians should ensure that patients are capable and willing to use a mobile device (e.g., smart phone) and the software application (app).139 Before using any component of the system, clinicians should instruct patients to download the mobile software application and follow all the instructions for use and to ensure that the software is compatible with their specific mobile device and paired with the patch prior to use.139
Aripiprazole tablets with sensor are administered orally once daily without regard to meals; tablets with sensor should be swallowed whole and not divided, crushed, or chewed.139
Prior to use of the software application, the patient's mobile device should be powered on and Bluetooth® enabled.139 The accompanying wearable sensor should be applied when prompted by the mobile software application; the application will instruct patients to apply and remove the sensor correctly.139 Patients should confirm that their mobile device is paired with the wearable sensor prior to use; the mobile software application will display a status icon on the mobile device to indicate that the wearable sensor is properly adhered and functioning.139 For further information, clinicians and patients may refer to the information provided in the product packaging as well as the instructions for use within the mobile software application.139
Most ingestions of aripiprazole tablets with sensor will be detected within 30 minutes following ingestion; however, it may take up to 2 hours for the smart phone application and web portal to detect the ingestion of the tablet with sensor.139 In some cases, ingestion of the tablet with sensor may not be detected.139 If the tablet with sensor is not detected following ingestion, the dose should not be repeated.139
The wearable sensor should be applied topically to the right or left side of the body just above the lower edge of the rib cage.139 Application to areas where the skin is scraped, cracked, inflamed, or irritated or areas overlapping the area of the most recently removed wearable sensor should be avoided.139 The wearable sensor should be changed weekly or sooner as needed; the mobile software application will remind patients when to change the sensor.139 Patients should be instructed keep the sensor in place while showering, swimming, or exercising.139 However, the sensor should be removed before undergoing magnetic resonance imaging (MRI) and replaced with a new sensor as soon as possible following the procedure.139 If skin irritation occurs, the wearable sensor should be removed.139
Store tablet bottle at 20-25°C (excursions permitted between 15-30°C).139 Avoid exposure to humid conditions.139
Store wearable sensors (i.e., MyCite® Patch) at 5-27°C and 15-93% relative humidity.139
Instruct patients receiving aripiprazole orally disintegrating tablets not to remove a tablet from the blister package until just prior to dosing.145 Do not push the tablet through the foil, since this may damage the tablet.145 With dry hands, peel open the blister package to expose a tablet.145 Remove the tablet and place it on the tongue, where it rapidly disintegrates in saliva.145 The manufacturer recommends that the orally disintegrating tablets be taken without liquid; however, they may be taken with liquid, if necessary.145 Aripiprazole orally disintegrating tablets should not be split.145
Store at 25°C (excursions permitted between 15-30°C).145
Aripiprazole oral solution is commercially available as a 1 mg/mL solution in child-resistant bottles with calibrated oral dosing cup.149
Store at 25°C (excursions permitted between 15-30°C).145 The solution may be used for up to 6 months after opening, but not beyond the expiration date on the bottle.149
Instruct patients receiving the aripiprazole oral film (Opipza®) to apply the oral film to the top of the tongue; the film will dissolve in saliva and can be swallowed in a normal manner without drinking liquids or water.150 Do not chew or swallow the oral film until it is fully dissolved.150 Administer only 1 oral film at a time; if >1 oral film is needed to complete the dosage, the next oral film may be administered after the previous film has completely dissolved.150 Aripiprazole oral film must not be split or cut prior to administration.150
Store at 20-25°C in the unopened pouch (excursions permitted between 15-30°C).150
Clinicians should be aware that there are several different extended-release IM formulations of aripiprazole with different indications, dosages, and dosing frequencies.118, 119, 147, 151 The extended-release IM formulation of aripiprazole (Abilify Maintena®) that is given once monthly is available in 300- and 400-mg vials and prefilled syringes and is used for the treatment of schizophrenia and maintenance monotherapy of bipolar I disorder.118 The extended-release IM formulation of aripiprazole (Abilify Asimtufii®) that is given once every 2 months is available in 720- and 960-mg prefilled syringes and is used for the treatment of schizophrenia and maintenance monotherapy of bipolar I disorder.151 The extended-release IM formulation of aripiprazole lauroxil (Aristada®) is available in 441-, 662-, 882-, and 1064-mg prefilled syringes and is used for the treatment of schizophrenia.119
Extended-release aripiprazole lauroxil injection also is available in 675-mg prefilled syringes (Aristada Initio®), which are used IM as a single dose to initiate treatment of schizophrenia or to re-initiate therapy following a missed dose; this formulation is not intended for repeated dosing.147
Aristada Initio® is not interchangeable with Aristada® because of their different pharmacokinetic profiles.147
Extended-release aripiprazole injection and extended-release aripiprazole lauroxil injection are administered only by IM injection by a healthcare professional.118, 119, 147, 151 Extended-release aripiprazole injection (Abilify Maintena®) is administered monthly.118 Extended-release aripiprazole injection (Abilify Asimtufii®) is administered every 2 months.151 The 441- and 662-mg doses of extended-release aripiprazole lauroxil injection (Aristada®) are administered monthly, the 882-mg dose may be administered every month or every 6 weeks, and the 1064-mg dose is administered every 2 months.119 Extended-release aripiprazole lauroxil injection available in 675-mg prefilled syringes (Aristada Initio®) is used as a single dose only and is not intended for repeated dosing.147
The manufacturers state that tolerability with oral aripiprazole therapy should be established prior to initiating IM therapy with extended-release formulations of the drug.118, 119, 147, 151
Extended-release Aripiprazole Injection (Abilify Maintena®)
Extended-release aripiprazole injection (Abilify Maintena®) is administered by deep IM injection monthly into the deltoid or gluteal muscle using the appropriate length needle (based on body type and injection site) supplied by the manufacturer.118 Injection sites should be rotated between the 2 deltoid or gluteal muscles.118 Following IM administration, the injection site should not be massaged.118 The manufacturer states that at least 26 days should elapse between doses.118 Each injection should be administered only by IM injection by a healthcare professional.118
Aripiprazole extended-release IM injection (Abilify Maintena®) must be reconstituted with sterile water for injection prior to administration.118 The drug is commercially available in 2 types of kits that contain aripiprazole lyophilized powder in either single-use vials or prefilled dual-chamber syringes with all the components required for reconstitution and administration (e.g., sterile water for injection diluent, needles, syringes).118 Because the entire contents of the prefilled syringe should be administered following reconstitution, only vials of the drug should be used for dosages smaller than 300 mg (e.g., for the 160- and 200-mg dosage adjustments recommended in patients concurrently receiving certain cytochrome P-450 (CYP) isoenzyme inhibitors or inducers.118 Kits containing prefilled dual-chamber syringes should be stored below 30°C and not frozen; the syringe should be protected from light by storing in the original package until the time of use.118 Kits containing single-use vials should be stored at 25°C, but may be exposed to temperatures ranging from 15-30°C.118 The manufacturer's instructions for use should be consulted for specific information on the preparation, reconstitution, and administration of aripiprazole extended-release injection (Abilify Maintena®) using these single-use kits.118
Following reconstitution, the prefilled syringe or vial should be shaken vigorously for 20 or 30 seconds, respectively, to ensure a uniform suspension.118 The reconstituted suspension should be inspected visually for particulate matter and discoloration prior to administration; the suspension should appear to be a uniform, homogeneous suspension that is opaque and milky-white in color.118 If using vials, the appropriate dose of aripiprazole should be drawn from the vial into the syringe supplied by the manufacturer and injected immediately.118 If a vial of reconstituted suspension is not administered immediately, the vial should be shaken vigorously for at least 60 seconds to resuspend the drug; reconstituted suspension should not be stored in a syringe.118 If using prefilled syringes, the entire contents of the prefilled syringe should be injected immediately following reconstitution; the manufacturer states that the contents of the prefilled syringe should be administered within 30 minutes of reconstitution.118
To maintain therapeutic antipsychotic concentrations during initiation of therapy with extended-release aripiprazole injection, oral aripiprazole at a dosage of 10-20 mg daily or another oral antipsychotic agent (for patients already stable on another oral antipsychotic agent and known to tolerate aripiprazole) should be given after the first IM injection of extended-release aripiprazole and continued for 14 days.118
If a dose of extended-release aripiprazole injection is missed, the next dose should be administered as soon as possible.118 Supplementation with oral aripiprazole may be required depending on the time elapsed.118 If the second or third doses are missed, supplementation with oral aripiprazole is not required if the time elapsed since the last injection is <5 weeks; however, if the time elapsed since the last injection is >5 weeks, supplementation with oral aripiprazole should be given for 14 days with the next administered injection.118 If the fourth or subsequent doses are missed, supplementation with oral aripiprazole is not required if the time elapsed since the last injection is <6 weeks; however, if the time elapsed since the last injection is >6 weeks, supplementation with oral aripiprazole should be given for 14 days with the next administered injection.118
Extended-release Aripiprazole Injection (Abilify Asimtufii®).
Extended-release aripiprazole injection (Abilify Asimtufii®) is administered by deep IM injection every 2 months into the gluteal muscle and should not be administered by any other route.151 The manufacturer states that at least 56 days should elapse between doses.151 Each injection should be administered only by IM injection by a healthcare professional.151
Aripiprazole extended-release IM injection (Abilify Asimtufii®) is commercially available as a kit that includes a prefilled syringe of aripiprazole extended-release suspension.151 The prefilled syringes are available in 2 strengths: 960 mg/3.2 mL and 720 mg/2.4 mL.151 Prior to use, the prefilled syringe should be tapped ≥10 times and then shaken for ≥10 seconds to ensure a uniform suspension.151 Kits containing single-use prefilled syringes should be stored at 25°C, but may be exposed to temperatures ranging from 15-30°C.151 The manufacturer's instructions for use should be consulted for specific information on the administration of aripiprazole extended-release injection (Abilify Asimtufii®) using these single-use kits.151 Extended-release aripiprazole (Abilify Asimtufii®) should be administered slowly by deep IM injection into the gluteal muscle using the appropriate length needle (based on body type) supplied by the manufacturer.151 Following IM administration, the injection site should not be massaged.151
To maintain therapeutic antipsychotic concentrations during initiation of therapy with extended-release aripiprazole injection, oral aripiprazole at a dosage of 10-20 mg daily or another oral antipsychotic agent (for patients already stable on another oral antipsychotic agent and known to tolerate aripiprazole) should be given after the first IM injection of extended-release aripiprazole and continued for 14 days.151
When switching from once monthly Abilify Maintena® injections to extended-release aripiprazole injection (Abilify Asimtufii®) administer the first IM injection of Abilify Asimtufil® in place of the next scheduled injection of Abilify Maintena®.151
If a dose of extended-release aripiprazole injection is missed by >8 weeks but <14 weeks, the next dose should be administered as soon as possible.151 The every 2-month schedule may be resumed.151 If >14 weeks have elapsed since the last dose, then supplementation with oral aripiprazole is recommended for 14 days with the next injection of extended-release aripiprazole injection (Abilify Asimtufii®).151
Extended-release Aripiprazole Lauroxil Injection
Both formulations of extended-release aripiprazole lauroxil injectable suspension (Aristada® and Aristada Initio®) are administered by IM injection.119, 147 The 441-, 662-, and 882-mg doses are administered monthly; the 882-mg dose also may be administered every 6 weeks; and the 1064-mg dose is administered every 2 months.119 The manufacturer states that if a dose of Aristada® is given earlier than the scheduled time, at least 14 days should elapse between doses.119 Each injection should be administered only by IM injection by a healthcare professional.119, 147
Extended-release aripiprazole lauroxil injection in 675-mg prefilled syringes (Aristada Initio®) is used only as a single dose to initiate treatment of schizophrenia or to re-initiate therapy following a missed dose; this formulation is not intended for repeated dosing.147 Aristada Initio® is not interchangeable with Aristada® because of their different pharmacokinetic profiles.147
Aripiprazole lauroxil injectable suspension (Aristada® and Aristada Initio®) is commercially available in a kit containing the drug in a prefilled syringe and safety needles for IM injection.119, 147 The kit should be stored at room temperature from 20-25°C, but may be exposed to temperatures ranging from 15-30°C.119, 147 Prior to use, the prefilled syringe should be tapped at least 10 times to dislodge any material that may have settled.119, 147 The syringe should then be shaken vigorously for at least 30 seconds to ensure a uniform suspension.119, 147 If the drug is not administered within 15 minutes, the syringe should be shaken again for 30 seconds.119, 147
The entire contents of the syringe should be administered rapidly and continuously by IM injection into either the deltoid (for 441- and 675-mg doses only) or gluteal muscle (for 441-, 662-, 675-, 882-, and 1064-mg doses) using the appropriate length needle supplied by the manufacturer.119, 147 The manufacturer states that the longer needles provided should be used in patients with a larger amount of subcutaneous tissue over the injection site muscle.119, 147
Treatment with aripiprazole lauroxil injection can be initiated using 1 of 2 methods.119 The first method requires administration of one 30 mg dose of oral aripiprazole in conjunction with one 675 mg IM injection of aripiprazole lauroxil injection (Aristada Initio®).119, 147 The first aripiprazole lauroxil injection (Aristada®) injection may also be administered the same day as the Aristada Initio® injection or up to 10 days after; however, concurrent administration of the 2 different aripiprazole lauroxil injection formulations (Aristada Initio® and Aristada®) in the same muscle should be avoided.119, 147 The second method requires oral administration of aripiprazole for 21 days starting on the same day as the first aripiprazole lauroxil injection (Aristada®) IM injection.119
If a dose of aripiprazole lauroxil injection is missed, the next dose should be administered as soon as possible.119 Supplementation with oral aripiprazole and/or a 675-mg IM dose of extended-release aripiprazole lauroxil (Aristada Initio®) may be required depending on the dosage and the time elapsed (See Table 1).119, 147 Dosage of oral aripiprazole supplementation should be same as when patient began extended-release aripiprazole lauroxil therapy.119
Dosage of Patient's Last Injection | No Oral Supplementation Required | Supplement with a Single Dose of Aristada Initio® OR Oral Aripiprazole for 7 Days | Re-initiate with a Single Dose of Aristada Initio® and a 30-mg Dose of Oral Aripiprazole OR Supplement with Oral Aripiprazole for 21 Days |
|---|---|---|---|
441 mg | ≤6 weeks since last injection | >6 and ≤7 weeks since last injection | >7 weeks since last injection |
662 mg | ≤8 weeks since last injection | >8 and ≤12 weeks since last injection | >12 weeks since last injection |
882 mg | ≤8 weeks since last injection | >8 and ≤12 weeks since last injection | >12 weeks since last injection |
1064 mg | ≤10 weeks since last injection | >10 and ≤12 weeks since last injection | >12 weeks since last injection |
Aripiprazole oral solution may be given at the same dose on a mg-per-mg basis as the tablet strengths of the medication up to a dose of 25 mg.149 However, if the oral solution is used in patients who were receiving aripiprazole 30 mg as tablets, a dose of 25 mg of the oral solution should be used.149
Conventional tablets and orally disintegrating tablets of aripiprazole are bioequivalent; therefore, dosing for the orally disintegrating tablets is the same as for the conventional tablets.1, 145
Dosage of aripiprazole lauroxil is expressed in terms of aripiprazole lauroxil.119, 147
Extended-release aripiprazole lauroxil (Aristada®) doses of 441, 662, 882, and 1064 mg correspond to aripiprazole doses of 300, 450, 600, and 724 mg, respectively.119
Of the available oral dosage forms of aripiprazole, aripiprazole oral film (Opipza®) is not indicated for use in pediatric or adult patients with manic and mixed episodes associated with bipolar I disorder.150
For the management of schizophrenia in adolescents ≥13 years of age, the recommended target dosage of aripiprazole is 10 mg orally once daily and maximum recommended dosage is 30 mg daily.1, 145, 149, 150 In clinical studies, therapy was initiated at a dosage of 2 mg once daily in these patients, with subsequent titration to 5 mg once daily after 2 days and to the target dosage of 10 mg once daily after 2 additional days.1, 145, 149, 150 The manufacturer recommends that any subsequent dosage increases be made in 5-mg, once-daily increments.1, 145, 149, 150 Although aripiprazole dosages of 10 and 30 mg orally once daily have been studied in adolescents, the 30-mg daily dosage was not found to be more effective than the 10-mg daily dosage.1, 145, 149, 150
Although the efficacy of oral aripiprazole as maintenance therapy in pediatric patients with schizophrenia has not been systematically evaluated, the manufacturers state that such efficacy can be extrapolated from adult data in addition to comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients.1, 145, 149, 150
For the acute management of manic and mixed episodes associated with bipolar I disorder in pediatric patients 10 to 17 years of age, the recommended initial aripiprazole dosage when given as monotherapy is 2 mg orally once daily, with subsequent titration to 5 mg once daily after 2 days and to the target dosage of 10 mg once daily after 2 additional days.1, 145, 149 The maximum recommended dosage is 30 mg daily.1 The recommended dosage when aripiprazole is given as adjunctive therapy with lithium or valproate is the same as that for monotherapy.1, 145, 149 Subsequent increases in the daily dosage of aripiprazole, if necessary, should be made in 5-mg increments.1, 145, 149 In pediatric clinical studies, oral aripiprazole dosages of 10 and 30 mg daily were effective.1, 145, 149
Irritability Associated with Autistic Disorder
For the treatment of irritability associated with autistic disorder in pediatric patients 6 to 17 years of age, efficacy of oral aripiprazole was established within a dosage range of 5-15 mg daily in clinical studies.1, 145, 149, 150 Dosing should be initiated at 2 mg daily, then increased to 5 mg daily, with subsequent increases to 10 mg daily or 15 mg daily, if necessary.1, 145, 149, 150 Dosage increases should be gradual, at intervals of at least 1 week.1, 145, 149, 150
The manufacturers state that the need for continued therapy with aripiprazole should be reassessed periodically.1, 145, 149, 150
For the treatment of Tourette's syndrome in pediatric patients 6 to 18 years of age, the recommended dosage range of oral aripiprazole is 5-20 mg once daily.1, 145, 149, 150 In pediatric patients weighing <50 kg, therapy should be initiated at 2 mg once daily, then increased to the recommended target dosage of 5 mg once daily after 2 days.1, 145, 149, 150 In patients who do not achieve optimal control of tics, the dosage may be increased to 10 mg once daily.1, 145, 149, 150 Dosage adjustments should be made gradually at intervals of at least 1 week.1, 145, 149, 150
In pediatric patients weighing ≥50 kg, therapy should be initiated at 2 mg once daily for 2 days and then increased to 5 mg once daily for 5 days, with a recommended target dosage of 10 mg once daily on day 8.1, 145, 149, 150 In patients who do not achieve optimal control of tics, the dosage may be increased up to 20 mg once daily.1, 145, 149, 150 Dosage adjustments should be made gradually in increments of 5 mg daily at intervals of at least 1 week.1, 145, 149, 150
The manufacturer states that the need for continued maintenance therapy with aripiprazole should be reassessed periodically.1, 145, 149, 150
For the management of schizophrenia in adults, the recommended initial and target dosage of aripiprazole is 10 or 15 mg orally once daily.1, 139, 145, 149, 150 Although dosages ranging from 10-30 mg daily administered as conventional tablets were effective in clinical trials, the manufacturers state that dosages exceeding 10-15 mg daily did not result in greater efficacy.1, 139, 145, 149, 150 The maximum recommended dosage is 30 mg daily.1, 139, 145, 149, 150 Because steady-state plasma concentrations of aripiprazole and dehydro-aripiprazole, its active metabolite, may not be attained for 2 weeks, dosage adjustments generally should be made at intervals of not less than 2 weeks.1, 139, 145, 149, 150
The optimum duration of oral aripiprazole therapy in patients with schizophrenia currently is not known, but maintenance therapy with aripiprazole 15 mg once daily as conventional tablets has been shown to be effective in preventing relapse for up to 26 weeks in adults.1, 139, 145, 149, 150
The manufacturers state that the need for continued therapy with the drug should be reassessed periodically.1, 139, 145, 149, 150
IM Dosage of Aripiprazole (Abilify Maintena®)
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole be established prior to initiating IM therapy with extended-release aripiprazole injection (Abilify Maintena®).118 Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.118
For the treatment of schizophrenia in adults, the recommended dosage of extended-release aripiprazole injection (Abilify Maintena®) is 400 mg administered by IM injection every month (no sooner than 26 days following the previous injection).118 In patients experiencing adverse effects, a reduction in dosage to 300 mg every month may be considered.118
To maintain therapeutic antipsychotic concentrations during initiation of therapy with extended-release aripiprazole injection, oral aripiprazole at a dosage of 10-20 mg daily or another oral antipsychotic agent (for patients already stable on another oral antipsychotic agent and known to tolerate aripiprazole) should be given after the first IM injection of extended-release aripiprazole and continued for 14 days.118
IM Dosage of Aripiprazole (Abilify Asimtufii®)
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole be established prior to initiating IM therapy with extended-release aripiprazole injection (Abilify Asimtufii®).151 Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.151
For the treatment of schizophrenia in adults, the recommended dosage of extended-release aripiprazole injection (Abilify Asimtufii®) is 960 mg administered by IM injection every 2 months (56 days following the previous injection).151 In patients experiencing adverse effects, a reduction in dosage to 720 mg every 2 months may be considered.151 The manufacturer states that dosages of Abilify Asimtufii® may be administered as early as 2 weeks before or 2 weeks following the scheduled 2-month dosage.151
To maintain therapeutic antipsychotic concentrations during initiation of therapy with extended-release aripiprazole injection, oral aripiprazole at a dosage of 10-20 mg daily or another oral antipsychotic agent (for patients already stable on another oral antipsychotic agent and known to tolerate aripiprazole) should be given after the first IM injection of extended-release aripiprazole and continued for 14 days.151
When switching from once monthly Abilify Maintena® injections to extended-release aripiprazole injection (Abilify Asimtufii®) administer the first IM injection of Abilify Asimtufil® in place of the next scheduled injection of Abilify Maintena®.151
IM Dosage of Aripiprazole Lauroxil (Aristada®)
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole therapy be established prior to initiating IM therapy with extended-release aripiprazole lauroxil (Aristada®).119 Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.119
For the treatment of schizophrenia in adults, extended-release aripiprazole lauroxil injection (Aristada®) may be initiated at a dosage of 441, 662, or 882 mg every month; 882 mg every 6 weeks; or 1064 mg every 2 months by IM injection.119 Extended-release aripiprazole lauroxil injection (Aristada®) may be initiated using 1 of 2 methods.119 The first method requires administration of one 30 mg dose of oral aripiprazole with a single 675 mg IM injection of aripiprazole lauroxil injection (Aristada Initio®) in conjunction with the first Aristada® injection.119, 147 The first Aristada® injection may be given within 10 days (as early as the same day) of the first Aristada Initio® injection, but IM injections must be administered into different muscles.119 The second method requires oral administration of aripiprazole with the first IM injection of Aristada® and continued for 21 days.119
For patients established on oral aripiprazole 10 mg daily, the recommended IM dosage of extended-release aripiprazole lauroxil is 441 mg every month.119
For patients established on oral aripiprazole 15 mg daily, the recommended IM dosage of extended-release aripiprazole lauroxil is 662 mg every month, 882 mg every 6 weeks, or 1064 mg every 2 months.119
For patients established on oral aripiprazole 20 mg or higher daily, the recommended IM dosage of extended-release aripiprazole lauroxil is 882 mg every month.119
Subsequent dosage adjustments may be made if needed.119 If dosage adjustments are required, the manufacturer states that the pharmacokinetics and prolonged-release characteristics of extended-release aripiprazole lauroxil injection should be considered when making dosage and dosing interval adjustments.119
IM Dosage of Aripiprazole Lauroxil (Aristada Initio®)
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole therapy be established prior to initiating IM therapy with extended-release aripiprazole lauroxil (Aristada Initio®).147 Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.147
The 675-mg strength of extended-release aripiprazole lauroxil injection (Aristada Initio®) is only used as a single dose to initiate aripiprazole lauroxil therapy or as a single dose to reinitiate therapy following a missed dose of extended-release aripiprazole lauroxil injection (Aristada®).147 The 675-mg strength of extended-release aripiprazole lauroxil injection (Aristada Initio®) is not used for repeated dosing of the drug.147
For the initiation of aripiprazole lauroxil therapy for the treatment of schizophrenia in adults and after establishing tolerability with oral aripiprazole, the first IM injection of aripiprazole lauroxil (Aristada®; 441 mg, 662 mg, 882 mg, or 1064 mg) may be administered in conjunction with both one 675-mg IM injection of aripiprazole lauroxil (Aristada Initio®) into the deltoid or gluteal muscle (this dosage is equivalent to 459 mg of aripiprazole) and one 30-mg dose of oral aripiprazole.147
The first dose of aripiprazole lauroxil (Aristada®) may be administered on the same day as Aristada Initio® or up to 10 days thereafter.147 Clinicians should avoid injecting both IM formulations of aripiprazole lauroxil concurrently into the same deltoid or gluteal muscle.147
For re-initiation of aripiprazole lauroxil (Aristada®) therapy following a missed dose, the next injection of aripiprazole lauroxil (Aristada®) should be administered as soon as possible.147 Depending on the time elapsed since the last Aristada® injection, the next Aristada® injection may be supplemented (see Table 1 under Dosage and Administration).147
Adult Dosage (Bipolar Disorder)
For the acute management of manic and mixed episodes associated with bipolar I disorder in adults, the recommended initial aripiprazole dosage is 15 mg given orally once daily as monotherapy or 10-15 mg given orally once daily as adjunctive therapy with lithium or valproate.1, 139, 145, 149 The recommended target dosage of aripiprazole is 15 mg daily whether the drug is given as monotherapy or as adjunctive therapy with lithium or valproate.1, 139, 145, 149 Based on clinical response, the dosage can be increased to the maximum recommended dosage of 30 mg daily.1, 139, 145, 149 Safety of aripiprazole dosages exceeding 30 mg daily has not been established in clinical trials.1, 145, 149
IM Dosage of Aripiprazole (Abilify Maintena®)
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole be established prior to initiating IM therapy with extended-release aripiprazole injection (Abilify Maintena®).118 Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.118
For the maintenance treatment of bipolar I disorder in adults, the recommended dosage of extended-release aripiprazole injection (Abilify Maintena®) is 400 mg administered by IM injection every month (no sooner than 26 days following the previous injection).118 In patients experiencing adverse effects, a reduction in dosage to 300 mg every month may be considered.
To maintain therapeutic antipsychotic concentrations during initiation of therapy with extended-release aripiprazole injection, oral aripiprazole at a dosage of 10-20 mg daily or another oral antipsychotic agent (for patients already stable on another oral antipsychotic agent and known to tolerate aripiprazole) should be given after the first IM injection of extended-release aripiprazole and continued for 14 days.118
IM Dosage of Aripiprazole (Abilify Asimtufii®)
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole be established prior to initiating IM therapy with extended-release aripiprazole injection (Abilify Asimtufii®).151 Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.151
For the maintenance treatment of bipolar I disorder in adults, the recommended dosage of extended-release aripiprazole injection (Abilify Asimtufii®) is 960 mg administered by IM injection every 2 months (56 days following the previous injection).151 In patients experiencing adverse effects, a reduction in dosage to 720 mg every 2 months may be considered.151 The manufacturer states that dosages of Abilify Asimtufii® may be administered as early as 2 weeks before or 2 weeks following the scheduled 2-month dosage.151
To maintain therapeutic antipsychotic concentrations during initiation of therapy with extended-release aripiprazole injection, oral aripiprazole at a dosage of 10-20 mg daily or another oral antipsychotic agent (for patients already stable on another oral antipsychotic agent and known to tolerate aripiprazole) should be given after the first IM injection of extended-release aripiprazole and continued for 14 days.151
When switching from once monthly Abilify Maintena® injections to extended-release aripiprazole injection (Abilify Asimtufii®) administer the first IM injection of Abilify Asimtufil® in place of the next scheduled injection of Abilify Maintena®.151
Adult Dosage (Major Depressive Disorder)
For adjunctive management of major depressive disorder in adults already receiving an antidepressant, the manufacturer recommends an initial aripiprazole dosage of 2-5 mg orally once daily for acute treatment.1, 139, 145, 149, 150 Subsequent dosage adjustments of up to 5 mg daily should occur gradually at intervals of at least 1 week; the recommended dosage range is 2-15 mg once daily.1, 139, 145, 149, 150 The maximum recommended dosage is 15 mg daily.139 Efficacy of the drug was established within a dosage range of 2-15 mg daily in clinical studies; mean maintenance dosage in these studies was approximately 11 mg daily.1, 139
The manufacturer states that if aripiprazole is used for maintenance therapy, the need for continued therapy with the drug should be reassessed periodically.1, 139, 145, 149, 150
Dosage Modification for Use with Drugs Affecting Hepatic Microsomal Enzymes
Potent CYP3A4 or CYP2D6 inhibitors: In patients receiving concomitant therapy with potent cytochrome P-450 (CYP) 3A4 inhibitors (e.g., clarithromycin, itraconazole, ketoconazole) or potent CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine), dosage of oral aripiprazole should be reduced to 50% of the usual dosage, except when oral aripiprazole is used in the adjunctive treatment of major depressive disorder.1, 139, 145, 149, 150 Dosage adjustment is not necessary when oral aripiprazole is used as adjunctive treatment of major depressive disorder.1, 139, 145, 149, 150
In patients receiving concomitant therapy with potent CYP3A4 or CYP2D6 inhibitors for >14 days, dosage of extended-release aripiprazole injection (Abilify Maintena®) should be reduced from 400 mg to 300 mg every month, or from 300 mg to 200 mg every month.118 In such patients, dosage of extended-release aripiprazole lauroxil injection (Aristada®) should be reduced to the next available lower strength; in patients tolerating the 441-mg dosage, dosage reduction is not necessary.119 A dosage of 882 mg every 6 weeks or 1064 mg every 2 months should be reduced to 441 mg every 4 weeks.119 Dosage of extended-release aripiprazole injection (Abilify Asimtufii®) should be reduced from 960 mg every 2 months to 720 mg every 2 months.151 If the potent CYP3A4 or 2D6 inhibitor is used for <14 days, dosage adjustment of extended-release aripiprazole (Abilify Maintena®, Abilify Asimtufii®) or aripiprazole lauroxil injection is not necessary.118, 119, 151
Potent CYP3A4 and CYP2D6 inhibitors: In patients receiving concomitant therapy with potent CYP3A4 inhibitors and potent CYP2D6 inhibitors, oral aripiprazole dosage should be reduced to 25% of the usual dosage, except when aripiprazole is used in the adjunctive treatment of major depressive disorder.1, 139, 145, 149, 150 Dosage adjustment is not necessary when oral aripiprazole is used as adjunctive treatment of major depressive disorder.1, 139, 145, 150
In patients receiving concomitant therapy with potent CYP3A4 inhibitors and potent CYP2D6 inhibitors for >14 days, dosage of extended-release aripiprazole injection (Abilify Maintena®) should be reduced from 400 mg to 200 mg every month, or from 300 mg to 160 mg every month.118 In such patients tolerating the 441-mg dosage of extended-release aripiprazole lauroxil injection (Aristada®) , dosage adjustment is not necessary; however, the manufacturer states that concomitant therapy with potent CYP3A4 inhibitors and potent CYP2D6 inhibitors for >2 weeks should be avoided in patients receiving 662-, 882-, or 1064-mg dosages of extended-release aripiprazole lauroxil injection.119 If such therapy is used for <14 days, dosage adjustment of extended-release aripiprazole (Abilify Maintena®, Abilify Asimtufii®) or aripiprazole lauroxil injection is not necessary.118, 119, 151 Concomitant therapy with potent CYP3A4 inhibitors and potent CYP2D6 inhibitors for >2 weeks should be avoided in patients receiving Abilify Asimtufii®.151
Combination of potent, moderate, or weak CYP3A4 and CYP2D6 inhibitors: Dosage of oral aripiprazole should be reduced to 25% of the usual dosage in patients receiving aripiprazole concurrently with a combination of potent, moderate, or weak inhibitors of CYP3A4 and CYP2D6 (e.g., a potent CYP3A4 inhibitor and a moderate CYP2D6 inhibitor or a moderate CYP3A4 inhibitor and a moderate CYP2D6 inhibitor).1, 145, 149, 150 The oral aripiprazole dosage may then be adjusted based on clinical response.1, 145, 149, 150
Aripiprazole dosages should be increased back to the original dosage when the CYP3A4 inhibitor and/or CYP2D6 inhibitor is discontinued.1, 118, 145, 149, 150
Potent CYP3A4 inducers: In patients receiving potent CYP3A4 inducers (e.g., carbamazepine, rifampin), dosage of oral aripiprazole should be doubled over 1-2 weeks of concomitant therapy.1, 145, 149, 150 When the CYP3A4 inducer is discontinued, the dosage should be reduced back to the original dosage over 1-2 weeks.1, 145, 149, 150
The manufacturer recommends avoiding use of potent CYP3A4 inducers for >14 days in patients receiving extended-release aripiprazole injection (Abilify Maintena® or Abilify Asimtufii®).118, 151
In patients receiving extended-release aripiprazole lauroxil injection (Aristada®), if a potent CYP3A4 inducer is used for >2 weeks, dosage of aripiprazole lauroxil should be increased from 441 mg to 662 mg every month; dosage adjustment is not necessary in patients receiving 662-, 882-, or 1064-mg dosages.119 If a potent CYP3A4 inducer is used for <2 weeks, dosage adjustment is not necessary.119
Extended-release aripiprazole lauroxil injection (Aristada Initio®) is only available in a single strength (675 mg); therefore, dosage adjustments in patients receiving potent CYP3A4 inhibitors, potent CYP2D6 inhibitors, or potent CYP3A4 inducers are not possible.147 Use of this extended-release formulation of the drug should be avoided in such patients.147
No dosage adjustment is necessary in patients with mild to severe hepatic impairment (Child-Pugh score 5-15).
No dosage adjustment is necessary in patients with mild to severe renal impairment (glomerular filtration rate [GFR] ≥15 mL/minute).1, 118, 119, 139, 145, 149, 150, 151
No dosage adjustment is necessary in geriatric patients..1, 118, 119, 139, 145, 147, 149, 150
The manufacturer of extended-release IM aripiprazole (Abilify Asimtufii®) states that an insufficient number of patients ≥65 years of age were included in clinical trials to assess differences in response compared to younger adults; however, dosage selection for elderly patients should be undertaken with caution and dosages should be initiated at the lower end of the dosage range.151
The safety and efficacy of Aristada® or Aristada Initio® have not been established in patients >65 years of age.119, 147
Poor CYPD26 Metabolizer Phenotype
Approximately 8% of Caucasian patients and 3-8% of Black/African American patients are known poor metabolizers of CYP2D6, which can result in elevated concentrations of aripiprazole; therefore, dosage adjustment of aripiprazole is needed.1, 118, 119, 139, 145, 147, 149, 150, 151 Patients who are known poor metabolizers of CYP2D6 should receive one-half (50%) of the usual oral aripiprazole dosage.1, 139, 145, 149, 150 Such patients who are also taking a potent CYP3A4 inhibitor should receive 25% of the usual oral aripiprazole dosage.1, 118, 145, 149, 150 Dosage adjustment is not necessary when oral aripiprazole is used as adjunctive treatment of major depressive disorder.1, 139, 145, 149, 150
The manufacturer of aripiprazole extended-release injection (Abilify Maintena®) recommends a dosage of 300 mg every month in patients who are poor CYP2D6 metabolizers.118 In such patients who are also receiving a potent CYP3A4 inhibitor for >14 days, a dosage of 200 mg every month is recommended.118
The manufacturer of aripiprazole extended-release injection (Abilify Asimtufii®) recommends a dosage of 720 mg once every 2 months in patients who are poor CYP2D6 metabolizers.151 The manufacturer recommends avoiding use of Abilify Asimtufii® in such patients who are also receiving a potent CYP3A4 inhibitor for >14 days.151
Dosage of extended-release aripiprazole lauroxil injection (Aristada®) in patients who are poor CYP2D6 metabolizers should be based on the patient's established oral aripiprazole dosage.119 In such patients receiving a concomitant potent CYP3A4 inhibitor for >2 weeks, dosage should be reduced to 441 mg every month; in patients already receiving 441 mg every month, no dosage adjustment is necessary, if tolerated.119 If the potent CYP3A4 inhibitor is used for <2 weeks, this dosage adjustment is not necessary.119 No further dosage adjustment is necessary in patients who are poor CYP2D6 metabolizers receiving a concomitant potent CYP2D6 inhibitor.119
Extended-release aripiprazole lauroxil injection (Aristada Initio®) is only available in a single strength (675 mg) in a single-dose prefilled syrin therefore, dosage adjustments in patients who are poor CYP2D6 metabolizers are not possible.147 Use of this extended-release formulation should therefore be avoided in patients who are poor CYP2D6 metabolizers.147
Increased Mortality in Geriatric Patients with Dementia-related Psychosis
A boxed warning is included in the prescribing information regarding the increased risk of death when antipsychotics are used in geriatric patients for dementia-related psychosis.1, 118, 119, 139, 145, 147, 149, 150, 151 Geriatric patients with dementia-related psychosis treated with antipsychotic medications are at an increased risk of death.1, 118, 119, 150, 151 Analyses of 17 placebo-controlled trials (modal duration of 10 weeks) revealed a 1.6- to 1.7-fold increase in mortality among geriatric patients receiving atypical antipsychotic drugs (i.e., aripiprazole, olanzapine, quetiapine, risperidone) compared with that observed in patients receiving placebo.118, 119, 139, 147, 150, 151 Over the course of a typical 10-week controlled trial, the rate of death in medication-treated patients was about 4.5% compared with a rate of about 2.6% in the placebo group.118, 119, 139, 147, 150, 151 Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.118, 119, 139, 147, 150, 151 ] Observational studies suggest that, similar to atypical antipsychotics, treatment with conventional (first-generation) antipsychotics may increase mortality; the extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic medication as opposed to some characteristic(s) of the patients remains unclear.118, 139, 145, 147, 149, 150, 151
The manufacturers state that aripiprazole is not approved for the treatment of patients with dementia-related psychosis.1, 118, 119, 139, 145, 147, 149, 150, 151 If the clinician elects to treat such patients with aripiprazole, patients should be assessed for the emergence of difficulty swallowing or excessive somnolence, which could predispose to accidental injury or aspiration.1, 145, 149
Increased Risk of Suicidality Thoughts and Behaviors in Children and Young Adults
A boxed warning is included in the prescribing information regarding the possible worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior that may occur in both adult and pediatric patients with major depressive disorder or other psychiatric disorders, whether or not they are taking antidepressants.1, 145, 149 This risk may persist until clinically important remission occurs.1, 145, 149 Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.1, 145, 149 However, there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.1, 145, 149 Pooled analyses of short-term, placebo-controlled studies of antidepressants (i.e., selective serotonin-reuptake inhibitors [SSRIs] and other antidepressants) have shown an increased risk of suicidality in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder and other psychiatric disorders.1, 145, 149 An increased suicidality risk was not demonstrated with antidepressants compared with placebo in adults >24 years of age and a reduced risk was observed in adults ≥65 years of age.1, 145, 149
All patients being treated with antidepressants for any indication should be appropriately monitored and closely observed for clinical worsening, suicidality, and unusual changes in behavior, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.1, 139, 145, 149, 150 Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, also should be advised to monitor patients on a daily basis for the emergence of agitation, irritability, or unusual changes in behavior as well as the emergence of suicidality, and to report such symptoms immediately to a healthcare provider.1, 139, 145, 149, 150
Although a causal relationship between the emergence of symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.1, 145, 149 Consequently, consideration should be given to changing the therapeutic regimen or discontinuing therapy in patients whose depression is persistently worse or in patients experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if such manifestations are severe, abrupt in onset, or were not part of the patient's presenting symptoms.1, 145, 149 It is recommended these medications be prescribed in the smallest quantity consistent with good patient management, in order to reduce the risk of overdosage.1, 145, 149
It is generally believed (though not established in controlled trials) that treating a major depressive episode with an antidepressant alone may increase the likelihood of precipitating a mixed or manic episode in patients at risk for bipolar disorder.1, 145, 149 Therefore, patients with depressive symptoms should be adequately screened for bipolar disorder prior to initiating treatment with an antidepressant; such screening should include a detailed psychiatric history (e.g., family history of suicide, bipolar disorder, and depression).1, 145, 149
Aripiprazole is not approved to treat depression in the pediatric population.1, 145, 149
Other Warnings and Precautions
Adverse Cerebrovascular Events, Including Stroke, in Geriatric Patients with Dementia-related Psychosis
An increased incidence of adverse cerebrovascular events (cerebrovascular accidents and transient ischemic attacks [TIAs]), including fatalities, has been observed in geriatric patients with dementia-related psychosis treated with oral aripiprazole in several placebo-controlled studies (2 flexible-dose studies and one fixed-dose study).1, 118, 139, 150, 151 A statistically significant dose-response relationship for adverse cerebrovascular events was observed in patients receiving oral aripiprazole in the fixed-dose study.1, 118, 139, 150, 151 The manufacturers state that aripiprazole is not approved for the treatment of patients with dementia-related psychosis.1, 118, 119, 139, 145, 150, 151
Potential for Dosing and Medication Errors
Medication errors, including substitution and dispensing errors, may occur between the 2 different extended-release IM formulations of aripiprazole lauroxil (e.g., Aristada Initio® and Aristada®).119, 147
Aristada Initio® is for single-dose administration only, while Aristada® is administered either monthly, every 6 weeks, or every 8 weeks.119, 147 Aristada Initio® should not be substituted for Aristada® because of their different pharmacokinetic profiles.119, 147
Neuroleptic Malignant Syndrome
Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the medication and intensive symptomatic treatment, has been reported in patients receiving antipsychotic agents, including rare cases associated with aripiprazole therapy.1, 118, 119, 145, 149 Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia).1, 118, 119, 145, 149 Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.1, 118, 119, 145, 149
Immediately discontinue therapy and initiate supportive and symptomatic treatment if NMS occurs.1, 118, 119, 145, 149 Careful monitoring is recommended if therapy is reinstituted following recovery; the risk that NMS can recur must be considered.1, 118, 149
Because use of antipsychotic agents, including aripiprazole, may be associated with tardive dyskinesia (a syndrome of potentially irreversible, involuntary, dyskinetic movements), aripiprazole should be prescribed in a manner that is most likely to minimize the occurrence of this syndrome.1, 118, 119, 145, 149 Chronic antipsychotic treatment generally should be reserved for patients who suffer from a chronic illness that is known to respond to antipsychotic agents, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate.1, 118, 119, 145, 149 In patients who do require chronic treatment, the lowest dosage and the shortest duration of treatment producing a satisfactory clinical response should be sought, and the need for continued treatment should be reassessed periodically.1, 118, 119, 145, 149
If signs and symptoms of tardive dyskinesia appear in an aripiprazole-treated patient, aripiprazole discontinuance should be considered; however, some patients may require continued treatment with the medication despite the presence of the syndrome.1, 118, 119, 145, 149
Atypical antipsychotic agents have been associated with metabolic changes, including hyperglycemia and diabetes mellitus, dyslipidemia, and body weight gain.1, 118, 119, 139, 145, 149, 150 While all of these drugs produce some metabolic changes, each medication has its own specific risk profile.1, 118, 119, 139, 145, 149, 150
Hyperglycemia and Diabetes Mellitus
Hyperglycemia, sometimes severe and associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients receiving atypical antipsychotic agents.1, 118, 119, 139, 145, 149, 150, 151 Hyperglycemia has been reported in patients treated with aripiprazole.1, 118, 119, 139, 145, 149, 150, 151 In short- and longer-term clinical trials in adult and pediatric patients, clinically important differences between oral aripiprazole and placebo in mean change from baseline to end point in fasting glucose concentrations were not observed.1 While confounding factors such as an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population make it difficult to establish with certainty the relationship between use of agents in this drug class and glucose abnormalities, epidemiologic studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with atypical antipsychotic agents.1, 118, 119, 139, 145, 149, 150, 151
Patients with preexisting diabetes mellitus in whom therapy with an atypical antipsychotic is initiated should be periodically monitored for worsening of glucose control; those with risk factors for diabetes (e.g., obesity, family history of diabetes) should undergo fasting blood glucose testing upon therapy initiation and periodically throughout treatment.1, 118, 119, 145, 149, 150, 151 Any patient who develops manifestations of hyperglycemia (including polydipsia, polyuria, polyphagia, and weakness) during treatment with an atypical antipsychotic should undergo fasting blood glucose testing.1, 118, 119, 145, 149, 150, 151 In some cases, patients who developed hyperglycemia while receiving an atypical antipsychotic have required continuance of antidiabetic treatment despite discontinuance of the atypical antipsychotic; in other cases, hyperglycemia resolved with discontinuance of the antipsychotic.1, 118, 119, 145, 147, 149, 150, 151
Undesirable changes in lipid parameters have been observed in patients treated with some atypical antipsychotic agents; however, aripiprazole generally does not appear to adversely affect the lipid profile in patients receiving the medication.1, 145, 149, 150 Pooled data from short- and longer-term clinical studies in adult and pediatric patients indicate no clinically important differences from baseline to end point in the proportion of patients with changes in fasting/nonfasting total cholesterol, fasting triglycerides, fasting low-density lipoprotein (LDL)-cholesterol, and fasting/nonfasting high-density lipoprotein (HDL)-cholesterol between aripiprazole-treated patients and those receiving placebo.1
Weight gain has been observed with atypical antipsychotic therapy.1, 118, 119, 145, 149, 150, 151 Clinical monitoring of weight is recommended in patients receiving aripiprazole.1, 118, 119, 145, 149, 150, 151
In an analysis of 13 placebo-controlled monotherapy studies in adults primarily with schizophrenia or bipolar disorder, mean weight gain in aripiprazole-treated patients was 0.3 kg compared with a loss of 0.1 kg in those receiving placebo (with a median exposure of 21-25 days); at 24 weeks, patients receiving aripiprazole or placebo lost an average of 1.5 or 0.2 kg, respectively.1, 145, 149 In 2 placebo-controlled trials in pediatric patients with schizophrenia or bipolar disorder, mean weight gain was 1.6 kg in patients receiving oral aripiprazole and 0.3 kg in those receiving placebo (with a median exposure of 42-43 days); at 24 weeks, mean weight gain was 5.8 and 1.4 kg in aripiprazole- and placebo-treated patients, respectively.1, 145, 149
In pediatric patients receiving aripiprazole for any indication, weight should be monitored and compared to the expected weight gain for normal growth.1, 145, 149
Pathologic Gambling and other Compulsive Behaviors
Intense urges and compulsive behaviors, particularly pathological gambling, have been reported rarely in patients treated with aripiprazole.1, 118, 119, 139 Other compulsive urges reported less frequently than gambling include compulsive or binge eating, compulsive spending or shopping, and compulsive sexual behaviors.1, 118, 119, 139 Impulse-control symptoms may also be associated with the underlying disorder.1, 118, 119, 139 In some, but not all, cases, these uncontrollable urges stopped when the aripiprazole dosage was reduced or the drug was discontinued.1, 118, 119, 139
Aripiprazole-associated compulsive behaviors may result in harm to the patient or others if not recognized.1, 118, 119, 139 Because patients may not recognize such behaviors as abnormal, clinicians should specifically ask patients or caregivers whether any new or intense gambling urges, binge or compulsive eating, compulsive shopping, compulsive sexual urges, or other urges have developed during treatment with the medication.1, 118, 119, 139 If a patient develops new or increased impulsive or compulsive behaviors while receiving aripiprazole, consideration should be given to reducing the dosage or discontinuing the drug.1, 118, 119, 139
Orthostatic hypotension and associated adverse effects (e.g., postural dizziness, syncope, tachycardia) have been reported in patients receiving oral or IM aripiprazole and IM aripiprazole lauroxil, perhaps because of the drug's α1-adrenergic blocking activity.1, 118, 119 The risk of orthostatic hypotension generally appears to be greatest during initiation of therapy and dosage titration.119 The medication should be used with caution in patients with known cardiovascular disease (e.g., heart failure, history of myocardial infarction (MI) or ischemia, conduction abnormalities), cerebrovascular disease, and/or conditions that would predispose patients to hypotension (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy), as well as in patients who are antipsychotic naïve.1, 119 In such patients, the manufacturer of extended-release IM aripiprazole lauroxil states that use of a lower initial dosage of the medication and monitoring of vital signs should be considered.119 The manufacturer of extended-release aripiprazole injection (Abilify Asimtufii®) states that monitoring of vital signs should be considered in patients at increased risk for hypotension.151
Aripiprazole therapy may cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls; as a consequence, fractures or other injuries may occur.1, 118, 119, 139, 145, 147, 149, 150, 151 For patients with diseases or conditions or receiving other medications that could exacerbate these effects, fall risk assessments should be completed when initiating antipsychotic treatment and periodically during long-term therapy.1, 118, 119, 139, 145, 147, 149, 150, 151
Leukopenia, Neutropenia, and Agranulocytosis
In clinical trial and/or postmarketing experience, leukopenia and neutropenia have been temporally related to antipsychotic agents, including aripiprazole.1, 118, 119, 139, 145, 147, 149, 150, 151 Agranulocytosis also has been reported.1, 118, 119, 139, 145, 147, 149, 150, 151
Possible risk factors for leukopenia and neutropenia include preexisting low leukocyte count and a history of drug-induced leukopenia and neutropenia.1, 118, 119, 139, 145, 147, 149, 150, 151 Patients with a preexisting low leukocyte count or a history of drug-induced leukopenia or neutropenia should have their CBC monitored frequently during the first few months of therapy.1, 118, 119, 139, 145, 147, 149, 150, 151 In such patients, aripiprazole should be discontinued at the first sign of a decline in leukocyte count in the absence of other causative factors.1, 118, 119, 139, 145, 147, 149, 150, 151
Patients with clinically significant neutropenia should be carefully monitored for fever or other signs or symptoms of infection and promptly treated if such signs and symptoms occur.1, 118, 119, 139, 145, 147, 149, 150, 151 In patients with severe neutropenia (absolute neutrophil count [ANC] <1000/mm3), aripiprazole should be discontinued and leukocyte count monitored until recovery occurs.1, 118, 119, 139, 145, 147, 149, 150, 151
As with other antipsychotic agents, aripiprazole may cause seizures.1 Seizures have occurred in 0.1% of adult and pediatric patients (6 to 18 years of age) treated with oral aripiprazole.1, 145, 149, 150 Aripiprazole should be used with caution in patients with a history of seizures or other conditions that may lower the seizure threshold; conditions that lower the seizure threshold may be more prevalent in geriatric patients ≥65 years of age.1, 118, 119, 145, 149, 150, 151
Cognitive and Motor Impairment
Like other antipsychotic agents, aripiprazole potentially may impair judgment, thinking, or motor skills.1, 118, 119, 139, 145, 149, 150, 151 In short-term clinical trials, somnolence (including sedation) was reported in 11% of adults treated with oral aripiprazole compared with 6% of those receiving placebo.1, 145, 149, 150 In pediatric patients 6 to 17 years of age, somnolence (including sedation) was reported in 24% of aripiprazole-treated patients compared with 6% of those receiving placebo.1, 145, 149, 150
Caution patients about performing activities that require mental alertness, such as operating hazardous machinery or a motor vehicle, until they are reasonably certain that aripiprazole does not affect then adversely.1, 118, 119, 139, 145, 149, 150, 151
Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents.1, 118, 119, 139, 145, 147, 149, 150, 151 The manufacturers recommend appropriate caution when aripiprazole is used in patients who will be experiencing conditions that may contribute to an elevation in core body temperature (e.g., strenuous exercise, extreme heat, concomitant use of anticholinergic agents, dehydration).1, 118, 119, 139, 145, 147, 149, 150, 151
Attendant risk with psychotic illnesses, bipolar disorder, and major depressive disorder; high-risk patients should be closely supervised.1, 145, 149 Aripiprazole should be prescribed in the smallest quantity consistent with good patient management to reduce the risk of overdosage.1, 145, 149
Esophageal dysmotility and aspiration have been associated with the use of antipsychotic agents, including aripiprazole.1, 118, 119, 139, 145, 147, 149, 150, 151 Aspiration pneumonia is a common cause of morbidity and mortality in geriatric patients, particularly in those with advanced Alzheimer's dementia.1, 145, 149 Aripiprazole should be used with caution in patients at risk for aspiration pneumonia.1, 118, 119, 139, 145, 147, 149, 150, 151
Individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that each aripiprazole 10- or 15-mg orally disintegrating tablet contains aspartame, which is metabolized in the GI tract to provide about 1.12 or 1.68 mg of phenylalanine, respectively, following oral administration.145 Aripiprazole conventional tablets, oral solution, and oral film do not contain aspartame.1, 149, 150
Skin Irritation associated with Abilify MyCite® Wearable Sensor
Symptoms of skin irritation (e.g., rash, pruritus, skin discoloration) may occur at the application site of the wearable sensor (MyCite® patch).139 In clinical studies, 12.4% of the patients receiving aripiprazole tablets with sensor experienced rashes at the site of wearable sensor placement.139 If skin irritation occurs, the manufacturer states that the wearable sensor should be removed.139
Neonates exposed to antipsychotic agents during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery.1, 118, 119, 145, 149, 150, 151 Symptoms reported to date have included agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, and feeding disorder.1, 118, 119, 145, 149, 150, 151 Neonates exhibiting such symptoms should be monitored and managed appropriately.1, 118, 119, 139, 149, 150, 151 The complications have varied in severity; some neonates recovered within hours to days without specific treatment, while others have required prolonged hospitalization.1, 118, 119, 139, 147, 150, 151
There is a pregnancy registry that monitors pregnancy outcomes in females exposed to atypical antipsychotics during pregnancy.1, 118, 119, 145, 147, 150, 151 Clinicians are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 866-961-2388 and [Web].1, 118, 119, 145, 147, 150, 151
Limited data indicate that aripiprazole is present in human milk at a relative infant dose (RID) ranging from 0.7-8.3% of the maternal weight-adjusted dosage.1, 145, 149, 150 Poor weight gain in breast-fed infants exposed to aripiprazole and inadequate milk supply in lactating women have been reported.1, 139, 145, 149, 150 The manufacturers of aripiprazole state that the benefit of aripiprazole therapy to the mother as well as the benefits of breast-feeding to the infant should be weighed against the potential risk to the infant resulting from exposure to the drug or from the underlying maternal condition.1, 118, 119, 139, 145, 149, 150, 151
Safety and efficacy of oral aripiprazole have not been established in pediatric patients with major depressive disorder.1, 145
Safety and efficacy of oral aripiprazole have not been established in pediatric patients with agitation associated with schizophrenia or bipolar mania.1, 145, 149
Safety and efficacy of extended-release IM formulations of aripiprazole and aripiprazole lauroxil have not been evaluated in pediatric patients <18 years of age.118, 119, 151
Safety and efficacy of aripiprazole tablets with sensor have not been established in pediatric patients.139
Safety and efficacy of oral aripiprazole for the acute management of schizophrenia in pediatric patients 13 to 17 years of age have been established in a placebo-controlled study of 6 weeks' duration.1, 145 Although the efficacy of oral aripiprazole for maintenance treatment of schizophrenia in pediatric patients has not been systematically evaluated, the manufacturer states that such efficacy can be extrapolated from adult data in addition to comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients.1, 145
Safety and efficacy of oral aripiprazole monotherapy for the acute management of bipolar mania in pediatric patients 10 to 17 years of age have been established in a placebo-controlled study of 4 weeks' duration.1, 145
The efficacy of oral aripiprazole as an adjunct to lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar disorder in pediatric patients has not been systematically evaluated.1, 145 However, efficacy can be extrapolated from adult data in addition to pharmacokinetic comparisons of aripiprazole between adult and pediatric populations.1, 145
Safety and efficacy of oral aripiprazole for the treatment of irritability associated with autistic disorder have been established in 2 placebo-controlled clinical trials of 8 weeks' duration in pediatric patients 6 to 17 years of age.1, 145 Efficacy of the drug as maintenance therapy for irritability associated with autistic disorder was not established in a longer-term, placebo-controlled relapse prevention trial in pediatric patients 6 to 17 years of age.1, 145
Safety and efficacy of oral aripiprazole for the treatment of Tourette's syndrome have been established in one 8-week, placebo-controlled trial in pediatric patients 7 to 17 years of age and one 10-week, placebo-controlled trial in pediatric patients 6 to 18 years of age.1, 145 Efficacy of the drug as maintenance therapy in pediatric patients with Tourette's syndrome has not been systematically evaluated.1, 145
The pharmacokinetics of aripiprazole and dehydro-aripiprazole in pediatric patients 10 to 17 years of age are similar to those in adults after correcting for differences in body weight.1
Mean weight gain of 1.6 kg was reported in pediatric patients with schizophrenia or bipolar disorder receiving oral aripiprazole compared with a gain of 0.3 kg in those receiving placebo in 2 short-term studies.1 After 24 weeks of therapy, the mean change from baseline in body weight in the aripiprazole-treated patients was 5.8 kg compared with 1.4 kg in placebo recipients.1 Similar gains in weight were observed in short-term studies in pediatric patients with irritability associated with autistic disorder and Tourette's syndrome.1
A greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and other antidepressants).1 No suicides occurred in these pediatric trials.1 These findings should be carefully considered when assessing potential benefits and risks of aripiprazole in a child or adolescent for any clinical use.1
In clinical studies, approximately 8% of over 13,000 patients treated with oral aripiprazole were ≥65 years of age and approximately 6% were ≥75 years of age.1, 145, 149 Experience from placebo-controlled trials with oral aripiprazole in patients with schizophrenia, bipolar mania, or major depressive disorder who are ≥65 years of age is insufficient to determine whether they respond differently than younger adults.1, 145, 149
The manufacturer of oral and extended-release IM formulations of aripiprazole states that dosage adjustment is not necessary in geriatric patients on the basis of age alone.1, 145, 149 The manufacturer of extended-release IM aripiprazole lauroxil states that the safety and efficacy of the drug have not been evaluated in patients >65 years of age and makes no specific dosage recommendations for geriatric patients.119
The manufacturer of extended-release IM aripiprazole (Abilify Asimtufii®) states that an insufficient number of patients ≥65 years of age were included in clinical trials to assess differences in response compared to younger adults; however, dosage selection for elderly patients should be undertaken with caution and dosages should be initiated at the lower end of the dosage range.151
Geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.1, 118, 119, 139, 145, 147, 149, 150, 151 In addition, an increased incidence of adverse cerebrovascular events (cerebrovascular accidents and TIAs), including fatalities, has been observed in geriatric patients with dementia-related psychosis treated with aripiprazole in placebo-controlled studies.1, 139, 150, 151 Aripiprazole is not approved for the treatment of dementia-related psychosis.1, 139, 150, 151
In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.1, 145, 149
No dosage adjustment of aripiprazole is needed in patients with mild to severe hepatic impairment (Child-Pugh score 5-15).1, 118, 119, 139, 145, 149, 150, 151
No dosage adjustment of aripiprazole is needed in patients with mild to severe renal impairment (glomerular filtration rate [GFR] ≥15 mL/minute).1, 118, 119, 139, 145, 149, 150, 151
In adults with schizophrenia receiving oral aripiprazole in clinical trials, akathisia was the only adverse effect that occurred in ≥5% of patients and at an incidence at least twice that for placebo.1, 139, 145, 149, 151
Adverse effects occurring in ≥5% of adolescents (13 to 17 years of age) with schizophrenia receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include extrapyramidal disorder, somnolence, and tremor.1, 145, 149
Adverse effects occurring in ≥5% of adults with bipolar mania receiving oral aripiprazole as monotherapy in clinical trials and at an incidence at least twice that of placebo include akathisia, sedation, restlessness, tremor, and extrapyramidal disorder.1, 139, 145, 149
Adverse effects occurring in ≥5% of adults with bipolar mania receiving oral aripiprazole as adjunctive therapy with lithium or valproate in clinical trials and at an incidence at least twice that of placebo include akathisia, insomnia, and extrapyramidal disorder.1, 139, 145, 149
Adverse effects occurring in ≥5% of pediatric patients 10 to 17 years of age with bipolar mania receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include somnolence, extrapyramidal disorder, fatigue, nausea, akathisia, blurred vision, salivary hypersecretion, and dizziness.1, 145, 149
Adverse effects occurring in ≥5% of adults with major depressive disorder receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include akathisia, restlessness, insomnia, constipation, fatigue, and blurred vision.1, 139, 145, 149
Adverse effects occurring in ≥5% of pediatric patients 6 to 17 years of age with autistic disorder receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include sedation, fatigue, vomiting, somnolence, tremor, pyrexia, drooling, decreased appetite, salivary hypersecretion, extrapyramidal disorder, and lethargy.1, 145, 149
Adverse effects occurring in ≥5% of pediatric patients 6 to 18 years of age with Tourette's Disorder receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include sedation, somnolence, nausea, headache, nasopharyngitis, fatigue, and increased appetite.1, 145, 149
In clinical trials with aripiprazole tablets with sensor and other components of the digital ingestion tracking system (Abilify MyCite®), skin rash localized at the application site of the wearable sensor (patch) was reported in 12.4% of patients.139
Adverse effects occurring in ≥5% of adults receiving extended-release IM aripiprazole injection in clinical trials and at an incidence at least twice that for placebo include increased weight, akathisia, injection site pain, and sedation.118, 151
In patients receiving extended-release IM aripiprazole lauroxil injection (Aristada®) in clinical trials, akathisia was the only adverse effect that occurred in ≥5% of patients and at an incidence at least twice that for placebo.119
Drugs Affecting Hepatic Microsomal Enzymes
Ketoconazole and Other CYP3A4 Inhibitors
Concurrent oral administration of aripiprazole and ketoconazole, a potent CYP3A4 inhibitor, substantially increased peak serum concentrations and AUC values of aripiprazole and its active metabolite, dehydro-aripiprazole.1 Concomitant use of aripiprazole with other potent CYP3A4 inhibitors (e.g., clarithromycin, itraconazole) would also be expected to result in substantially increased systemic exposure to aripiprazole.1
Except when used in the adjunctive treatment of major depressive disorder, dosage of oral aripiprazole should be reduced by 50% when used concurrently with potent CYP3A4 inhibitors.1, 139, 145, 149, 150 IM dosages of extended-release aripiprazole (Abilify Maintena® or Abilify Asimtufii®) and aripiprazole lauroxil (Aristada®) should be reduced when used concurrently with potent CYP3A4 inhibitors for >14 days.118, 119, 151 When the potent CYP3A4 inhibitor is withdrawn from combined therapy, the aripiprazole dosage should be increased.1 Use of the 675-mg strength of extended-release aripiprazole lauroxil injection (Aristada Initio®) should be avoided in patients receiving potent CYP3A4 inhibitors.147
Quinidine and Other CYP2D6 Inhibitors
Concurrent oral administration of aripiprazole and quinidine, a potent CYP2D6 inhibitor, substantially increased the AUC of aripiprazole but decreased the AUC of its active metabolite, dehydro-aripiprazole.1 Concomitant use of aripiprazole with other potent CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) would also be expected to result in substantially increased systemic exposure to aripiprazole.1
Except when used in the adjunctive treatment of major depressive disorder, dosage of oral aripiprazole should be reduced by 50% when used concurrently with potent CYP2D6 inhibitors.1 IM dosages of extended-release aripiprazole (Abilify Maintena® or Abilify Asimtufii®) and aripiprazole lauroxil (Aristada®) should be reduced when used concurrently with potent CYP2D6 inhibitors for >14 days.118, 119, 151 When the potent CYP2D6 inhibitor is withdrawn from combined therapy, the aripiprazole dosage should be increased.1 Use of the 675-mg strength of extended-release aripiprazole lauroxil injection (Aristada Initio®) should be avoided in patients receiving potent CYP2D6 inhibitors.147
Carbamazepine and Other CYP3A4 Inducers
Concurrent administration of aripiprazole and carbamazepine, a potent CYP3A4 inducer, substantially decreased peak plasma concentrations and AUC of aripiprazole and its active metabolite, dehydro-aripiprazole.1, 118, 119 Concomitant use of aripiprazole with other potent CYP3A4 inducers (e.g., rifampin) may result in substantially decreased systemic exposure to aripiprazole.1
Oral aripiprazole dosage should be doubled over 1-2 weeks of concurrent use with potent CYP3A4 inducers.1, 145, 149, 150 Concurrent use of CYP3A4 inducers and extended-release aripiprazole injection (Abilify Maintena® or Abilify Asimtufii®) for >14 days should be avoided since aripiprazole concentrations may fall below therapeutic concentrations.118, 151 The 441-mg dose of extended-release aripiprazole lauroxil (Aristada®) should be increased to 662 mg when used concurrently with potent CYP3A4 inducers for >2 weeks; dosage adjustment is not required in patients receiving 662-, 882-, or 1064-mg doses of the drug.119 When the potent CYP3A4 inducer is withdrawn from combined therapy, the aripiprazole dosage should be reduced to the original dosage over 1-2 weeks.1, 145, 149, 150 Use of the 675-mg strength of extended-release aripiprazole lauroxil injection (Aristada Initio®) should be avoided in patients receiving potent CYP3A4 inducers.147
Drugs Metabolized by Hepatic Microsomal Enzymes
Substrates of CYP isoenzymes 2C9, 2C19, 2D6, and 3A4: Clinically important pharmacokinetic interaction is unlikely; dosage adjustment is not necessary.1, 118, 119
Potential pharmacologic interaction (possible disruption of body temperature regulation); aripiprazole should be used with caution in patients concurrently receiving drugs with anticholinergic activity.1, 118, 119
Potential pharmacologic interaction (additive hypotensive effects due to α1-adrenergic antagonism); aripiprazole should be used with caution in patients receiving hypotensive agents.1, 118, 119, 139 During concomitant use, blood pressure should be monitored and antihypertensive dosage(s) adjusted accordingly.1, 118, 119, 139
Lorazepam and Other Benzodiazepines
Clinically important pharmacokinetic changes have not been reported during concurrent administration of lorazepam and aripiprazole.1, 118, 119 The manufacturers state that routine dosage adjustment of aripiprazole or lorazepam is not necessary when the drugs are concurrently administered.1, 118 However, increased sedative and orthostatic hypotensive effects have been reported in patients receiving these drugs in combination.1, 118, 119 If aripiprazole therapy in conjunction with a benzodiazepine is considered necessary, the patient should be carefully monitored for excessive sedation and orthostatic hypotension and dosage of the drug(s) adjusted, if necessary.1, 118, 119
Concomitant administration of ethanol and oral aripiprazole in healthy individuals did not have clinically important effects on gross motor skills or stimulus response compared with administration of ethanol with placebo.118 The manufacturers of the extended-release IM formulations of aripiprazole (Abilify Maintena® and Abilify Asimtufii®) states that alcohol should be avoided during therapy.118, 151 The manufacturers of other commercially available formulations of aripiprazole and aripiprazole lauroxil do not provide specific recommendations concerning alcohol use in the prescribing information for the drugs.1, 119, 139, 145, 149, 150
Clinically important pharmacokinetic interaction is unlikely.1, 118, 119 Dosage adjustment of aripiprazole or dextromethorphan (a CYP3A4 and CYP2D6 substrate) is not necessary during concurrent administration.1, 118, 119, 139
Dosage adjustment of aripiprazole or escitalopram, a CYP219 substrate, is not necessary during concurrent administration.1
Concomitant use of aripiprazole and famotidine may result in decreased peak plasma concentrations and systemic exposure of aripiprazole and its active metabolite, dehydro-aripiprazole; however, a clinically important pharmacokinetic interaction between the drugs appears unlikely.1, 139 No dosage adjustment of aripiprazole or famotidine is necessary during concurrent administration.1, 139
Fluoxetine, Paroxetine, and Sertraline
A population pharmacokinetic analysis in patients with major depressive disorder did not demonstrate substantial changes in the pharmacokinetics of fluoxetine, paroxetine, or sertraline (dosed to steady state) following the addition of aripiprazole therapy.1, 118, 119 Therefore, dosage adjustment of fluoxetine, paroxetine, and sertraline is not necessary in patients concomitantly receiving aripiprazole therapy.1, 118, 119
However, fluoxetine and paroxetine are potent CYP2D6 inhibitors and the manufacturer recommends oral aripiprazole dosage be reduced to 50% the usual dosage in patients receiving concomitant therapy with potent CYP2D6 inhibitors, including fluoxetine and paroxetine.1 When fluoxetine or paroxetine is withdrawn from combined therapy with aripiprazole, the aripiprazole dosage should be increased back to the original dosage.1 When adjunctive aripiprazole is concurrently administered to patients with major depressive disorder receiving fluoxetine or paroxetine, dose adjustment is not necessary.1
Pharmacokinetic interaction is unlikely; no dosage adjustment of aripiprazole or lamotrigine is necessary during concurrent administration.1
Clinically important pharmacokinetic interaction is unlikely; no dosage adjustment of aripiprazole or lithium is necessary during concurrent administration.1
Clinically important pharmacokinetic interaction is unlikely; no dosage adjustment of aripiprazole or omeprazole is necessary during concurrent administration.1
Clinically important pharmacokinetic interaction is unlikely; no dosage adjustment of aripiprazole or valproate is necessary during concurrent administration.1
Dosage adjustment of aripiprazole or venlafaxine is not necessary during concurrent administration.1
Concurrent administration of aripiprazole did not substantially affect warfarin pharmacokinetics, suggesting a lack of a clinically important effect of aripiprazole on CYP2C9 and CYP2C19 metabolism.1 Dosage adjustment of aripiprazole or warfarin is not necessary during concurrent administration.1
Aripiprazole is a quinolinone derivative2, 5 antipsychotic agent that differs chemically from other currently available antipsychotic agents (e.g., butyrophenones, phenothiazines)2, 3, 4, 5, 6, 7 and has been referred to as an atypical or second-generation antipsychotic agent.1, 2, 7, 28, 69 The exact mechanism of action of aripiprazole in schizophrenia, bipolar disorder, major depressive disorder, irritability associated with autistic disorder, Tourette's syndrome, and agitation associated with schizophrenia or bipolar mania has not been fully elucidated but, like that of other drugs with efficacy in these conditions (e.g., olanzapine, risperidone, ziprasidone), may involve the drug's activity at dopamine D2 and serotonin type 1 (5-HT1A) and type 2 (5-HT2A) receptors.1, 2, 3, 4, 5, 6, 7 However, aripiprazole appears to differ from other atypical antipsychotic agents because the drug demonstrates partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors.1, 2, 3, 5, 5, 6, 7, 69 Antagonism at other receptors (e.g., α1-adrenergic receptors, histamine H1 receptors) may contribute to other therapeutic and adverse effects (e.g., orthostatic hypotension, somnolence) observed with aripiprazole.1, 69
Aripiprazole is well absorbed following oral administration; peak plasma concentrations following oral administration of conventional tablets occur within 3-5 hours.1 Following administration of aripiprazole oral film, peak plasma concentrations are attained in a median of 1.5 hours.150 Administration with a high-fat meal does not affect peak plasma concentration or systemic exposure of aripiprazole or dehydro-aripiprazole.1 Absolute oral bioavailability of conventional tablets is 87%.1 Following administration of the oral solution, plasma aripiprazole concentrations are higher than those after administration of equivalent dosages of the conventional tablets.147 Steady-state plasma concentrations of both aripiprazole and dehydro-aripiprazole are achieved within 14 days with oral administration.1 Aripiprazole is extensively metabolized in the liver principally via dehydrogenation, hydroxylation, and N -dealkylation by the cytochrome P-450 (CYP) 3A4 and 2D6 isoenzymes.1 The major active metabolite of aripiprazole, dehydro-aripiprazole, exhibits affinity for D2 receptors similar to that of the parent compound and represents approximately 40% of aripiprazole area under the concentration-time curve (AUC) in plasma.1 Poor CYP2D6 metabolizers have substantially increased aripiprazole and dehydro-aripiprazole exposures compared with extensive metabolizers.1 Approximately 18% of an orally administered dose of aripiprazole is excreted unchanged in feces and less than 1% is excreted unchanged in urine.1 The mean elimination half-life of aripiprazole and dehydro-aripiprazole is approximately 75 and 94 hours, respectively.1, 150 In poor metabolizers of CYP2D6, the mean elimination half-life is approximately 146 hours.1, 150
Following IM administration of extended-release aripiprazole (Abilify Maintena®), the low solubility of aripiprazole particles results in prolonged aripiprazole absorption.118 Following multiple IM doses, peak plasma aripiprazole concentrations occur after a median of 4 or 5-7 days when administered into the deltoid or gluteal muscle, respectively.118 Single IM injections into the deltoid result in 31% higher peak plasma concentrations compared with the gluteal site; however, aripiprazole systemic exposures and peak plasma concentrations at steady state were similar for both injection sites.118 Dose-proportional increases in aripiprazole and dehydro-aripiprazole systemic exposures were observed following extended-release aripiprazole IM doses of 300 or 400 mg given every 4 weeks.118 Steady-state plasma concentrations of aripiprazole are achieved by the fourth dose of extended-release aripiprazole for both sites of administration.118 Following gluteal administration of multiple 300- or 400-mg doses of extended-release aripiprazole every 4 weeks, the mean terminal half-life of aripiprazole is 29.9 or 46.5 days, respectively.118
Following gluteal injection of extended-release aripiprazole (Abilify Asimtufii®), the low solubility of aripiprazole particles results in prolonged aripiprazole absorption.151 The release profile of aripiprazole results in prolonged plasma concentrations over a 2-month period.151 Over the approved dosage range, extended-release aripiprazole exhibits linear pharmacokinetics.151 It demonstrates a flat plasma concentration profile, with the time to maximum plasma concentrations occurring after 1-49 days.151 Steady-state plasma concentrations of aripiprazole are achieved by the fourth dose of extended-release aripiprazole.151 Steady state plasma concentrations are similar for Abilify Maintena® 400 mg once monthly and Abilify Asimtufii® 960 mg every 2 months.151
Aripiprazole lauroxil is a prodrug of aripiprazole.119 Following IM injection, aripiprazole lauroxil is probably converted by enzyme-mediated hydrolysis to N -hydroxymethyl aripiprazole, which is then hydrolyzed to aripiprazole.119 Following IM administration of extended-release aripiprazole lauroxil (Aristada®), aripiprazole begins to appear in the systemic circulation in 5-6 days and is continually released for an additional 36 days.119 Plasma concentrations of aripiprazole increase with consecutive doses and reach steady-state concentrations following the fourth monthly injection.119 With the addition of a single IM injection of extended-release aripiprazole lauroxil (Aristada Initio®) and 30 mg of oral aripiprazole at the time of the first Aristada® injection, aripiprazole concentrations reach therapeutic plasma levels within 4 days.119 A similar effect is achieved when oral aripiprazole is administered for 21 days following the first Aristada injection.119 IM injection of extended-release aripiprazole lauroxil (441 mg) into the deltoid and gluteal areas results in similar systemic exposure; therefore, these injection sites are considered interchangeable.119 In addition, IM administration of aripiprazole lauroxil 882 mg every 6 weeks or 1064 mg every 2 months results in plasma aripiprazole concentrations that are within the established therapeutic range for dosages of 441 and 882 mg once monthly.119 The mean elimination half-life of aripiprazole ranges from about 54-57 days following monthly, every 6 week, or every 2 month injections of extended-release aripiprazole lauroxil (Aristada Initio®) .119
Aripiprazole Tablets with Sensor
Aripiprazole is available as part of a digital ingestion tracking system comprised of the following components: aripiprazole tablets embedded with an ingestible event marker sensor (IEM; Abilify MyCite®); a wearable sensor (MyCite® patch), which detects the signal from the IEM sensor after ingestion and transmits data to a compatible mobile device (i.e., a smart phone); a software application (app) for compatible mobile devices (e.g., smart phones; MyCite® App), which displays information for the patient; and a web-based portal for healthcare professionals and caregivers.139
Following oral administration of aripiprazole tablets with sensor, magnesium and cuprous chloride within the sensor react with gastric fluid to activate and power the sensor.139 Once activated, the ingestible sensor communicates with the wearable sensor within a 9-foot proximity using Bluetooth® technology.139 The wearable sensor records the date and time of ingestions and transmits the data to the mobile software application.139, 142 The mobile software application records and displays ingestion data for patients to review;139 subjective data such as activity level, mood, and quality of rest also may be reported to the software application.142 Healthcare professionals, caregivers, and/or family members may access ingestion data shared by the patient through a web-based portal or dashboard.139, 142 The manufacturer states that this access is granted by the patient and may be withdrawn by the patient at any time.142
Most ingestions of aripiprazole tablets with sensor are detected within 30 minutes of oral administration; however, it may take up to 2 hours for the mobile device and web portal to detect ingestion of the sensor and, in some cases, the ingestion may not be detected at all.139 In a study to assess accuracy and latency of post-ingestion detection of the ingestible sensor in 29 healthy individuals, a wearable sensor was placed and paired with a mobile device provided and monitored by investigators.143 Placebo tablets with embedded ingestible sensors were then administered under observation every 2 hours for 4 doses without regard to food.143 The overall ingestion detection rate was 96.6%; approximately 90% of ingestions were detected by the mobile software application within 30 minutes of ingestion.143 Mean time from ingestion to detection by the wearable sensor was 1.1-1.3 minutes and from detection by the wearable sensor to detection on the cloud-based server was 6.2-10.3 minutes.143
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Solution | 5 mg/5 mL* | Aripiprazole Oral Solution | |
Tablets | 2 mg* | Abilify® | Otsuka | |
Aripiprazole Tablets | ||||
5 mg* | Abilify® | Otsuka | ||
Aripiprazole Tablets | ||||
10 mg* | Abilify® | Otsuka | ||
Aripiprazole Tablets | ||||
15 mg* | Abilify® | Otsuka | ||
Aripiprazole Tablets | ||||
20 mg* | Abilify® | Otsuka | ||
Aripiprazole Tablets | ||||
30 mg* | Abilify® | Otsuka | ||
Aripiprazole Tablets | ||||
Tablets with sensor | 2 mg | Abilify MyCite® (available as 30-day starter kit containing 30 tablets embedded with sensor, 1 MyCite® pod and 7 wearable sensor strips; also available as maintenance kit containing 30 tablets embedded with sensor and 7 wearable sensor strips) | Otsuka | |
5 mg | Abilify MyCite® (available as 30-day starter kit containing 30 tablets embedded with sensor, 1 MyCite® pod and 7 wearable sensor strips; also available as maintenance kit containing 30 tablets embedded with sensor and 7 wearable sensor strips) | Otsuka | ||
10 mg | Abilify MyCite® (available as 30-day starter kit containing 30 tablets embedded with sensor, 1 MyCite® pod and 7 wearable sensor strips; also available as maintenance kit containing 30 tablets embedded with sensor and 7 wearable sensor strips) | Otsuka | ||
15 mg | Abilify MyCite® (available as 30-day starter kit containing 30 tablets embedded with sensor, 1 MyCite® pod and 7 wearable sensor strips; also available as maintenance kit containing 30 tablets embedded with sensor and 7 wearable sensor strips) | Otsuka | ||
20 mg | Abilify MyCite® (available as 30-day starter kit containing 30 tablets embedded with sensor, 1 MyCite® pod and 7 wearable sensor strips; also available as maintenance kit containing 30 tablets embedded with sensor and 7 wearable sensor strips) | Otsuka | ||
30 mg | Abilify MyCite® (available as 30-day starter kit containing 30 tablets embedded with sensor, 1 MyCite® pod and 7 wearable sensor strips; also available as maintenance kit containing 30 tablets embedded with sensor and 7 wearable sensor strips) | Otsuka | ||
Tablets, orally disintegrating | 10 mg* | Aripiprazole Orally Disintegrating Tablets | ||
15 mg* | Aripiprazole Orally Disintegrating Tablets | |||
Parenteral | For injectable suspension, extended-release, for IM use | 300 mg | Abilify Maintena® (available as kit containing either a single-dose vial, sterile water for injection, needles, and syringe or a prefilled dual-chamber syringe, sterile water for injection, and needles) | Otsuka (also promoted by Lundbeck) |
400 mg | Abilify Maintena® (available as kit containing either a single-dose vial, sterile water for injection, needles, and syringe or a prefilled dual-chamber syringe, sterile water for injection, and needles) | Otsuka (also promoted by Lundbeck) | ||
Injectable suspension, extended-release, for IM use | 720 mg/2.4 mL | Abilify Asimtufii® (available as a kit containing 1 prefilled syringe and 2 safety needles) | Otsuka (also promoted by Lundbeck) | |
960 mg/3.2 mL | Abilify Asimtufii® (available as kit containing either a single-dose vial, sterile water for injection, needles, and syringe or a prefilled dual-chamber syringe, sterile water for injection, and needles) | Otsuka (also promoted by Lundbeck) |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injectable suspension, extended-release, for IM use | 441 mg/1.6 mL | Aristada® (available as kit containing prefilled syringe and needles) | Alkermes |
662 mg/2.4 mL | Aristada® (available as kit containing prefilled syringe and needles) | Alkermes | ||
675 mg/2.4 mL | Aristada Initio® (available as kit containing prefilled syringe and needles) | Alkermes | ||
882 mg/3.2 mL | Aristada® (available as kit containing prefilled syringe and needles) | Alkermes | ||
1064 mg/3.9 mL | Aristada® (available as kit containing prefilled syringe and needles) | Alkermes |
Only references cited for selected revisions after 1984 are available electronically.
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