Version October 2024
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Aripiprazole is not approved for the treatment of patients with dementia-related psychosis.
Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients older than 24 years of age; there was a reduction in risk with antidepressant use in patients 65 years of age and older. Closely monitor all antidepressant-treated patients for clinical worsening and for the emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. The safety and efficacy of aripiprazole tablets with sensor have not been established in pediatric patients.
Dosage guidance:
Dosing: All doses are expressed as the equivalent amounts of aripiprazole (base).
Dosage form information: Available formulations include oral tablets and oral solution supplied as aripiprazole (base) and 2 ER formulations available for IM administration: aripiprazole monohydrate (Abilify Maintena and Abilify Asimtufii) and aripiprazole lauroxil (Aristada and Aristada Initio); formulations and product brands vary in dose strength and frequency of administration (see Aripiprazole Lauroxil monograph).
Agitation/Aggression (acute, severe) associated with psychiatric disorders (eg, schizophrenia, bipolar disorder), substance intoxication, or other organic causes (alternative agent) (off-label use) :
Note: Antipsychotics are appropriate when psychosis is suspected to be the primary cause of agitation/aggression. Other agents are used preferentially in some intoxications (eg, stimulants) or alcohol withdrawal. Depending on presentation, may combine with a benzodiazepine (Ref).
Oral: Initial: 10 to 15 mg; may repeat based on response and tolerability every 2 hours up to 30 mg/day (Ref).
Agitation/Aggression and psychosis associated with dementia, severe or refractory (alternative agent) (off-label use):
Note: For short-term adjunctive use while addressing underlying causes of severe symptoms (Ref).
Oral: Initial: 2 to 5 mg once daily; may increase dose based on response and tolerability in 5 mg increments at intervals ≥1 week up to 15 mg once daily. In patients without a clinically significant response after an adequate trial (eg, up to 4 weeks), taper and withdraw therapy. Only continue in patients with a demonstrated benefit and attempt to taper and withdraw at regular intervals; first taper attempt should occur ≤4 months of initiation (Ref).
Note: Patients with dementia with Lewy bodies are at increased risk for severe adverse reactions; caution is required even with low doses (Ref).
Bipolar disorder:
Oral: Acute mania or episodes with mixed features (labeled use), acute hypomania (off-label use), and maintenance treatment (labeled use, formulation specific) as monotherapy or adjunctive therapy: Initial: 10 to 15 mg once daily; may increase dose based on response and tolerability in 5 to 10 mg/day increments at intervals of ≥1 week up to a maximum of 30 mg/day (Ref). Note: Some experts suggest higher initial doses of up to 30 mg/day (Ref). Although the manufacturer's labeling recommends waiting ≥2 weeks before increasing dose due to long half-life of aripiprazole, it may be appropriate to increase dose at 1 week for some patients (Ref). For maintenance treatment, continue dose and combination regimen that was used to achieve control of the acute episode (Ref).
IM, ER injectable suspension (aripiprazole monohydrate) (alternative agent): Note: Establish tolerability with oral aripiprazole prior to initiation of ER injection; due to the prolonged half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
Monthly injection (Abilify Maintena):
Single injection start: IM: 400 mg once monthly (doses should be separated by ≥26 days). Continue (overlap) oral aripiprazole or other oral antipsychotic for 14 days during initiation of the ER injection.
Double injection start: IM: Initial: Administer a single oral aripiprazole 20 mg dose, plus two 400 mg injections in separate injection sites (eg, right deltoid and left gluteal muscle). Maintenance: 400 mg once monthly (doses should be separated by ≥ 26 days) (Canadian product monograph).
Dosage adjustment of monthly ER injection for adverse effects: Consider reducing dose to 300 mg once monthly.
Missed doses of monthly ER injection:
Second or third doses missed:
>4 weeks but <5 weeks since last dose: Administer next dose as soon as possible.
>5 weeks since last dose: Administer oral aripiprazole for 14 days with next injection or administer 1 oral aripiprazole dose of 20 mg plus 2 aripiprazole 400 mg IM injections in separate injection sites (eg, right deltoid and left gluteal muscle) (Canadian product monograph); adjust oral dose as needed based on response and tolerability.
Fourth or subsequent doses missed:
>4 weeks but <6 weeks since last dose: Administer next dose as soon as possible.
>6 weeks since last dose: Administer oral aripiprazole for 14 days with next injection or administer 1 oral aripiprazole dose of 20 mg plus 2 aripiprazole 400 mg IM injections in separate injection sites (eg, right deltoid and left gluteal muscle) (Canadian product monograph); adjust oral dose as needed based on response and tolerability.
Every-2-months injection (Abilify Asimtufii):
IM: 960 mg once every 2 months (56 days); may be given up to 2 weeks before or 2 weeks after the 2-month schedule timepoint. Continue (overlap) oral aripiprazole or other oral antipsychotic for 14 days during initiation of every-2-months ER injection. When converting from monthly injection (Abilify Maintena), administer every-2-months injection in place of the next monthly injection; do not overlap with oral aripiprazole (Ref).
Dosage adjustment of every-2-months ER injection for adverse effects: Consider reducing dose to 720 mg every 2 months.
Missed doses of every-2-months ER injection:
>8 weeks and <14 weeks since last dose: Administer next dose as soon as possible then resume the once every-2-months schedule.
>14 weeks since last dose: Administer oral aripiprazole for 14 days with next injection.
Delusional disorder (off-label use):
Note: Dosing based on expert opinion:
Oral: Initial: 2 to 5 mg once daily; gradually increase to 10 mg/day; if needed, may further increase dose at intervals of ≥1 week based upon response and tolerability up to 30 mg/day (Ref).
Delusional infestation (delusional parasitosis) (alternative agent) (off-label use):
Oral: Initial: 2 to 5 mg once daily; may increase dose gradually based on response and tolerability in 2 mg increments at intervals ≥2 weeks up to 15 mg/day (Ref). Some patients may require doses up to 30 mg/day for optimal response. After achieving adequate response, maintain for ≥1 to 12 months before attempting to taper and discontinue (Ref).
Huntington disease–associated chorea (alternative agent) (off-label use):
Oral: Initial: 2 mg once daily; may increase dose gradually based on response and tolerability up to a usual range of 7.5 to 15 mg/day (Ref).
Major depressive disorder (unipolar), treatment resistant (adjunctive therapy with antidepressant):
Oral: Initial: 2 to 5 mg/day; may increase dose based on response and tolerability in 5 mg increments at intervals ≥1 week up to a manufacturer's maximum of 15 mg/day. A further increase up to 20 mg/day may be necessary in some patients for optimal response (Ref). Although the manufacturer's labeling recommends waiting ≥2 weeks before increasing dose due to long half-life of aripiprazole, it may be appropriate to increase dose at 1 week for some patients (Ref).
Obsessive-compulsive disorder, treatment resistant (adjunctive therapy to antidepressants) (off-label use):
Oral: Initial: 5 mg once daily; may increase dose gradually based on response and tolerability in 5 mg increments at intervals ≥1 week up to 15 mg/day (Ref).
Schizophrenia:
Oral: Initial: 5 to 15 mg once daily; may increase dose based on response and tolerability in 5 mg increments at an interval of ≥4 days with initial low dose (eg, 5 mg) and at intervals ≥1 week thereafter up to a maximum of 30 mg/day (Ref). Although the manufacturer's labeling recommends waiting ≥2 weeks before increasing dose due to long half-life of aripiprazole, it may be appropriate to increase dose at 1 week for some patients (Ref).
IM, ER injectable suspension (aripiprazole monohydrate): Note: Establish tolerability with oral aripiprazole prior to initiation of the ER injection; due to the prolonged half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
Monthly injection (Abilify Maintena):
Single injection start: IM: 400 mg once monthly (doses should be separated by ≥26 days). Continue (overlap) oral aripiprazole or other oral antipsychotic for 14 days during initiation of the ER injection.
Double injection start: IM: Initial: Administer a single oral aripiprazole 20 mg dose, plus two 400 mg injections in separate injection sites (eg, right deltoid and left gluteal muscle). Maintenance: 400 mg once monthly (doses should be separated by ≥26 days) (Canadian product monograph).
Dosage adjustment of monthly ER injection for adverse effects: Consider reducing dose to 300 mg once monthly.
Missed doses of monthly ER injection:
Second or third doses missed:
>4 weeks but <5 weeks since last dose: Administer next dose as soon as possible.
>5 weeks since last dose: Administer oral aripiprazole for 14 days with next injection or administer 1 oral aripiprazole dose of 20 mg plus 2 aripiprazole 400 mg IM injections in separate injection sites (eg, right deltoid and left gluteal muscle) (Canadian product monograph); adjust oral dose as needed based on response and tolerability.
Fourth or subsequent doses missed:
>4 weeks but <6 weeks since last dose: Administer next dose as soon as possible.
>6 weeks since last dose: Administer oral aripiprazole for 14 days with next injection or [Canadian dosing] administer 1 oral aripiprazole dose of 20 mg plus 2 aripiprazole 400 mg IM injections in separate injection sites (eg, right deltoid and left gluteal muscle) (Canadian product monograph); adjust oral dose as needed based on response and tolerability.
Every-2-months injection (Abilify Asimtuifii):
IM: 960 mg once every 2 months (56 days); may be given up to 2 weeks before or 2 weeks after the 2-month schedule timepoint. Continue (overlap) oral aripiprazole or other oral antipsychotic for 14 days during initiation of every-2-months ER injection. When converting from monthly injection (Abilify Maintena), administer every-2-months injection in place of the next monthly injection; do not overlap with oral aripiprazole (Ref).
Dosage adjustment of every-2-months ER injection for adverse effects: Consider reducing dose to 720 mg every 2 months.
Missed doses of every-2-months ER injection:
>8 weeks and <14 weeks since last dose: Administer next dose as soon as possible then resume the once every-2-months schedule.
>14 weeks since last dose: Administer oral aripiprazole for 14 days with next injection.
Tourette syndrome (off-label use): Oral: Initial: 2.5 mg once daily; may increase dose based on response and tolerability in 2.5 mg increments at intervals ≥3 days up to 30 mg/day (Ref).
Dosing conversions:
Orally disintegrating tablets to oral tablet: Orally disintegrating tablets may be substituted for the oral tablet on a mg-per-mg basis.
Oral solution to oral tablet: Oral solution may be substituted for the oral tablet on a mg-per-mg basis, up to 25 mg. Patients receiving 30 mg tablets should be given 25 mg oral solution.
Dosage adjustment based on CYP2D6 metabolizer status:
Oral: Aripiprazole dose should be reduced to 50% of the usual dose in known CYP2D6 poor metabolizers; subsequently adjust dose for favorable response and tolerability.
IM, ER injectable suspension (aripiprazole monohydrate):
Monthly injection (Abilify Maintena):
Single injection start: Reduce aripiprazole dose to 300 mg once monthly in known CYP2D6 poor metabolizers; subsequently adjust dose according to response and tolerability.
Double injection start: Reduce initial 2 aripiprazole doses to 300 mg each and reduce monthly aripiprazole dose to 300 mg once monthly in known CYP2D6 poor metabolizers; subsequently adjust dose according to response and tolerability (Canadian product monograph).
Every-2-months injection (Abilify Asimtufii): Reduce aripiprazole dose to 720 mg every 2 months in known CYP2D6 poor metabolizers.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Discontinuation of therapy:
Oral: In the treatment of chronic psychiatric disease switching therapy rather than discontinuation is generally advised if side effects are intolerable or treatment is not effective. If patient insists on stopping treatment, gradual dose reduction (ie, over several weeks to months) is advised to detect a re-emergence of symptoms and to avoid withdrawal reactions (eg, agitation, alternating feelings of warmth and chill, anxiety, diaphoresis, dyskinesias, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, vertigo) unless discontinuation is due to significant adverse effects. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (Ref).
Long-acting injection: Switching to other treatments is generally advised if side effects are intolerable or treatment is not effective. However, if a patient insists on stopping treatment, gradual dose reduction to avoid withdrawal reactions is generally not needed with long-acting injectable antipsychotics. The risk of withdrawal symptoms from discontinuation of long-acting injectables is low because the rate of drug elimination is slow. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (Ref).
Switching antipsychotics: An optimal universal strategy for switching antipsychotic drugs has not been established. Strategies include: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic) and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). In patients with schizophrenia at high risk of relapse, the current medication may be maintained at full dose as the new medication is increased (ie, overlap); once the new medication is at therapeutic dose, the first medication is gradually decreased and discontinued over 1 to 2 weeks (Ref). Based upon clinical experience, some experts generally prefer cross-titration and overlap approaches rather than abrupt change (Ref).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (highly protein bound; large Vd): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be dialyzed (highly protein bound; large Vd): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
No dosage adjustment necessary.
Note: Avoid for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. If used, consider deprescribing attempts to assess continued need and/or lowest effective dose. Of note, use in certain indications may be appropriate (eg, schizophrenia, bipolar disorder) (Ref).
Refer to adult dosing. Dosages in the lower range of recommended adult dosing are generally sufficient. Titrate dosage slowly and monitor carefully (Ref).
(For additional information see "Aripiprazole (oral and long-acting injectable [Abilify Maintena]): Pediatric drug information")
Dosage guidance:
Dosage form information: Oral solution may be substituted for the oral tablet on a milligram-per-milligram basis, up to 25 mg (eg, patients receiving 30 mg tablets should be given 25 mg oral solution). Orally disintegrating tablets (Abilify Discmelt) are bioequivalent to the IR tablets (Abilify).
Bipolar I disorder; acute mania or episodes with mixed features: Note : Due to decreased risk of extrapyramidal symptoms, second-generation antipsychotics including aripiprazole have replaced first-generation antipsychotics for treatment as monotherapy or in combination with other agents (Ref).
Children ≥10 years and Adolescents <18 years: Oral: Initial: 2 mg once daily for 2 days, followed by 5 mg once daily for 2 days with a further increase to target dose of 10 mg once daily; subsequent dose increases may be made in 5 mg increments, up to a maximum daily dose: 30 mg/day.
Conduct disorder (CD); aggression: Limited data available: Children ≥6 years and Adolescents: Oral: Initial: 1 to 2.5 mg once daily; may titrate at weekly intervals in 2.5 mg/day increments to clinical effectiveness; maximum daily dose: 15 mg/day.
Dosing based on two open-label, prospective studies (Ref) (n=43; age: 6 to 17 years) which evaluated pharmacokinetics and effectiveness in patients with a primary diagnosis of CD (with or without comorbid attention-deficit/hyperactivity disorder); results showed improvement in CD symptom scores with only minor improvements in cognition.
Irritability, associated with autistic disorder: Children ≥6 years and Adolescents <18 years: Oral: Initial: 2 mg once daily for 7 days, followed by 5 mg once daily; subsequent dose increases may be made in 5 mg increments every ≥7 days, up to a maximum daily dose: 15 mg/day.
Schizophrenia: Note : Second-generation antipsychotics (including aripiprazole) are generally the preferred initial treatment in management of pediatric patients with schizophrenia due to decreased risk of extrapyramidal symptoms and tardive dyskinesia (Ref).
Adolescents 13 to <18 years: Oral: Initial: 2 mg once daily for 2 days, followed by 5 mg once daily for 2 days with a further increase to target dose of 10 mg once daily; subsequent dose increases may be made in 5 mg increments up to a maximum daily dose: 30 mg/day. Note: A daily dose of 30 mg/day was not found to be more effective than the 10 mg/day dose.
Tourette syndrome, tic disorder:
Children ≥6 years and Adolescents:
Patient weight <50 kg: Oral: Initial: 2 mg once daily for 2 days, then increase to target dose of 5 mg/day; in patients not achieving optimal control, dose may be further titrated at weekly intervals up to 10 mg/day.
Patient weight ≥50 kg: Oral: Initial: 2 mg once daily for 2 days, then increase to 5 mg/day for 5 days, then increase to target dose of 10 mg/day on day 8 of therapy; in patients not achieving optimal control, dose may be further titrated at weekly intervals in 5 mg/day increments up to 20 mg/day.
Discontinuation of therapy: Children and Adolescents: American Academy of Child and Adolescent Psychiatry (AACAP), American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), National Institute for Health and Care Excellence (NICE), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (Ref); risk for withdrawal symptoms may be highest with highly anticholinergic or dopaminergic antipsychotics (Ref). When stopping antipsychotic therapy in patients with schizophrenia, the CPA guidelines recommend a gradual taper over 6 to 24 months and the APA guidelines recommend reducing the dose by 10% each month (Ref). Continuing antiparkinsonism agents for a brief period after discontinuation may prevent withdrawal symptoms (Ref). When switching antipsychotics, three strategies have been suggested: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic), overlap and taper (maintaining the dose of the first antipsychotic while gradually increasing the new antipsychotic, then tapering the first antipsychotic), and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). Evidence supporting ideal switch strategies and taper rates is limited and results are conflicting (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥6 years and Adolescents: Oral: No dosage adjustment required.
Children ≥6 years and Adolescents: Oral: No dosage adjustment required.
Both activating effects (eg, akathisia, restlessness) and sedating effects (eg, sedated state, drowsiness) may occur with aripiprazole and may lead to nonadherence or discontinuation. Individual patient experience can vary depending on the person's sensitivity toward activation or sedation and the dose used (Ref).
Mechanism: Dose-related; sedation is believed to be due to H1 antagonism leading to potential CNS depressant effects; aripiprazole is considered to display modest antagonism at H1 receptors (Ref).
Risk factors:
• Young age (in general, children and adolescents appear to be at higher risk for sedation due to antipsychotics compared to adults (Ref); in studies that included aripiprazole in children and adolescents, younger age has been associated with activating symptoms and higher age has been associated with sedating symptoms) (Ref)
• Specific antipsychotic (aripiprazole is generally considered to be minimally sedating at usual therapeutic doses in comparison with other antipsychotics) (Ref)
Antipsychotics are associated with dyslipidemia in adult and pediatric patients, which is a component of the metabolic syndrome observed with this pharmacologic class. Aripiprazole is associated with a low risk of causing lipid abnormalities; however, hypertriglyceridemia and hypercholesterolemia have been observed (Ref).
Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).
Onset: Varied; metabolic alterations from antipsychotics can develop in as short as 3 months after initiation (Ref).
Risk factors:
• Schizophrenia (regardless of medication use) is associated with a higher rate of morbidity/mortality compared to the general population, primarily due to cardiovascular disease (Ref)
• Specific antipsychotic: Clozapine and olanzapine are associated with a high risk of hyperlipidemia while aripiprazole and ziprasidone are associated with the lowest risk (Ref)
Aripiprazole may cause extrapyramidal symptoms (EPS), also known as drug-induced movement disorders, particularly akathisia in all ages (Ref). Antipsychotics can cause 4 main EPS: Drug-induced parkinsonism, akathisia, acute dystonia, and tardive dyskinesia (Ref). EPS presenting as dysphagia, esophageal motility disorder, or pulmonary aspiration have also been reported with antipsychotics, which may not be recognized as EPS (Ref).
Mechanism: EPS: Dose-related; due to antagonism of dopaminergic D2 receptors in nigrostriatal pathways (as either antagonists or as a partial agonist, such as aripiprazole) (Ref). Akathisia: Mechanism not completely understood, but possibly associated with the low activity of dopaminergic projections from the midbrain to the ventral striatum and imbalance between the dopamine and serotonin neurotransmitter system (Ref). Tardive dyskinesia: Time-related (delayed); results from chronic exposure to dopamine 2 receptor antagonists leading to up-regulation of these receptors over time; aripiprazole has partial agonistic activity at the D2 receptor; however, it has one of the highest D2 receptor affinities among the antipsychotic agents (Ref).
Onset:
Antipsychotics in general:
Acute dystonia: Rapid; in the majority of cases, dystonia usually occurs within the first 5 days after initiating antipsychotic therapy (and even with the first dose, particularly in patients receiving parenteral antipsychotics) or a dosage increase (Ref).
Drug-induced parkinsonism: Varied; onset may be delayed from days to weeks, with 50% to 75% of cases occurring within 1 month and 90% within 3 months of antipsychotic initiation, a dosage increase, or a change in the medication regimen (such as adding another antipsychotic agent or discontinuing an anticholinergic medication) (Ref).
Akathisia: Varied; may begin within several days after antipsychotic initiation but usually increases with treatment duration, occurring within 1 month in up to 50% of cases and within 3 months in 90% of cases (Ref).
Tardive dyskinesia: Delayed; symptoms usually appear after 1 to 2 years of continuous exposure to a dopamine 2 receptor antagonist, and almost never before 3 months, with an insidious onset, evolving into a full syndrome over days and weeks, followed by symptom stabilization and then a chronic waxing and waning of symptoms (Ref).
Esophageal dysfunction (associated with EPS): Varied; ranges from weeks to months following initiation (Ref).
Risk factors:
EPS (in general):
• Prior history of EPS (Ref)
• Higher doses (Ref)
• Younger age (in general, children and adolescents are usually at higher risk for EPS compared to adults) (Ref)
• Specific antipsychotic: Aripiprazole is usually associated with a lower risk of EPS, with the possible exception of akathisia (Ref)
Acute dystonia:
• Males (Ref)
• Young age (Ref)
Drug-induced parkinsonism:
• Females (Ref)
• Older patients (Ref)
Akathisia:
• Higher antipsychotic dosages (Ref)
• Polypharmacy (Ref)
• Mood disorders (Ref)
• Females (Ref)
• Older patients (Ref)
Tardive dyskinesia:
• Age >55 years (Ref)
• Cognitive impairment (Ref)
• Concomitant treatment with anticholinergic medications (Ref)
• Diabetes (Ref)
• Diagnosis of schizophrenia or affective disorders (Ref)
• Female sex (Ref)
• Greater total antipsychotic exposure (especially first-generation antipsychotics) (Ref)
• History of extrapyramidal symptoms (Ref)
• Substance misuse or dependence (Ref)
• Race (White or African descent). Note: Although early literature supported race as a potential risk factor for tardive dyskinesia (Morgenstern 1993), newer studies have challenged this assertion (Ref).
Esophageal dysfunction (associated with EPS):
• Certain comorbidities such as neurologic degenerative disease, dementia, stroke, Parkinson disease, or myasthenia gravis (Ref)
• Older adults >75 years of age (may be risk factor due to age related muscle atrophy, cognitive impairment, reduced esophageal peristalsis) (Ref)
Leukopenia and neutropenia have been reported with aripiprazole (Ref). Agranulocytosis has been reported with other atypical antipsychotics and, per the manufacturer's labeling, has also been reported with aripiprazole.
Mechanism: Non-dose-related; likely idiosyncratic (Ref).
Onset: Varied; in general, drug-induced neutropenia usually manifests after 1 or 2 weeks of exposure and agranulocytosis usually appears 3 to 4 weeks following initiation of therapy; however, the onset may be insidious (Ref).
Risk factors:
• History of drug-induced leukopenia/neutropenia and preexisting low white blood cell count/absolute neutrophil count
• Older adults (Ref)
Antipsychotics are associated with hyperglycemia, to varying degrees, which is a component of the metabolic syndrome observed with this pharmacologic class. Aripiprazole is associated with a low risk of causing metabolic alterations; however, glycemic abnormalities ranging from mild insulin resistance or hyperglycemia to new-onset diabetes mellitus, diabetes mellitus with hyperosmolar coma, and diabetic ketoacidosis, including fatal cases, have been observed very rarely (Ref).
Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).
Onset: Varied; new-onset diabetes has been observed within first 3 months to a median onset of 3.9 years (Ref).
Risk factors:
Antipsychotics in general:
• African American race (Ref)
• Males (Ref)
• Age <35 years (Ref)
• Preexisting obesity, poor exercise habits, or other risk factors for diabetes, including family history of diabetes (Ref)
• Exposure to other agents that also increase the risk of hyperglycemia (Ref)
• Type 2 diabetes mellitus: Extended exposure (mean: 17.2 months) in pediatric patients 10 to 18 years (Ref)
• Specific antipsychotic: Metabolic disturbances appear to be the greatest with clozapine and olanzapine and lowest with aripiprazole (Ref)
Aripiprazole has been associated with an increased risk of developing impulse control disorders, which primarily manifests as pathological gambling, although other reported behaviors include hypersexuality, compulsive buying, compulsive eating, and/or other intense urges (Ref).
Mechanism: Non-dose-related; may be due to aripiprazole’s partial dopamine agonist activity in brain circuits regulating reward pathways such as the mesolimbic circuitry (Ref).
Onset: Varied; case reports and case series of aripiprazole-associated pathological gambling suggest that the onset occurs between a few days and a few months after initiation, with some cases occurring only after an increase in dosage (Ref).
Risk factors:
• History of impulse control disorders and gambling behaviors (Ref)
• The depot formulation (aripiprazole lauroxil) may be associated with an increased risk compared to oral aripiprazole (Ref)
Older adults with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo (Ref). In addition, an increased incidence of cerebrovascular effects (eg, cerebrovascular accident, transient ischemic attacks), including fatalities, have been reported in placebo-controlled aripiprazole trials in older adults with dementia-related psychosis, per the manufacturer's labeling. Of note, aripiprazole is not approved for the treatment of dementia-related psychosis.
Mechanism: Unknown; possible mechanisms include arrhythmia, cardiac arrest, and extrapyramidal effects that may increase the risk of falls, aspirations, and pneumonia (Ref).
Risk factors:
Antipsychotics in general:
• Higher antipsychotic dosage (Ref)
• Dementia-related psychosis (eg, Lewy body dementia, Parkinson disease dementia)
• Older adults
All antipsychotics have been associated with neuroleptic malignant syndrome (NMS), although the incidence is less with second-generation (atypical) antipsychotics compared to first-generation (typical) antipsychotics. There are case reports of NMS with aripiprazole, including monotherapy. Some data suggest that NMS induced by certain second-generation antipsychotics, including aripiprazole, may present with milder or atypical features more frequently compared to NMS induced by other agents; these atypical features include less intense extrapyramidal symptoms or less extreme fever (Ref).
Mechanism: Non-dose-related; idiosyncratic. Believed to be due to a reduction in CNS dopaminergic tone, along with the dysregulation of autonomic nervous system activity (Ref).
Onset: Varied; in general, most patients develop NMS within 2 weeks of initiating an antipsychotic, and in some patients, prodromal symptoms emerge within hours of initiation; once the syndrome starts, the full syndrome usually develops in 3 to 5 days (Ref). However, there are many cases of NMS occurring months after stable therapy, including a report of NMS developing 1 year after treatment with aripiprazole (Ref).
Risk factors:
Antipsychotics in general:
• Males (twice as likely to develop NMS compared to females) (Ref)
• Dehydration (Ref)
• High-dose antipsychotic treatment (Ref)
• Concomitant lithium or benzodiazepine (potential risk factors) (Ref)
• Catatonia (Ref)
• Polypharmacy (Ref)
• Pharmacokinetic interactions (Ref)
• Intramuscular administration (Ref)
• Rapid dosage escalation (Ref)
• Psychomotor agitation (Ref)
Antipsychotics have been associated with sexual disorder in both males and females. Antipsychotic treatment has been associated with effects on all phases of sexual activity (libido, arousal, and orgasm); however, many patients with schizophrenia experience more frequent sexual dysfunction, with or without antipsychotic treatment. Conversely, there are also case reports of hypersexuality ,related to impulse control disorders, occurring with use (Ref).
Mechanism: Antipsychotic-induced sexual dysfunction has been attributed to many potential mechanisms, including dopamine receptor antagonism, dopamine D2 receptor antagonism in the hypothalamic infundibular system causing hyperprolactinemia, histamine receptor antagonism, cholinergic receptor antagonism, and alpha-adrenergic receptor antagonism. Of note, in adults, aripiprazole is associated with a minimal risk of causing hyperprolactinemia (Ref).
Risk factors:
• Hyperprolactinemia (although a correlation with sexual dysfunction has been observed, a relationship has not been confirmed) (Ref)
• Schizophrenia (the prevalence of antipsychotic-induced sexual dysfunction in patients with schizophrenia is high [~50% to 60% compared with 31% of males in the general population]) (Ref)
• Specific antipsychotic: Aripiprazole is associated with lower rates of sexual dysfunction relative to other antipsychotics (Ref)
Antipsychotics may impair the body's ability to regulate core body temperature, which may cause a potentially life-threatening heatstroke during predisposing conditions such as a heat wave or strenuous exercise. There are also several case reports of potentially life-threatening hypothermia associated with aripiprazole use (Ref).
Mechanism: Non-dose-related; idiosyncratic. Exact mechanism is unknown; however, body temperature is regulated by the hypothalamus with complex involvement of the dopamine, serotonin, and norepinephrine neurotransmitters. D2 antagonism may cause an increase in body temperature, while 5-HT2A (serotonin) receptor antagonism and 5-HT1 receptor agonism may cause a decrease in body temperature. Aripiprazole is a partial agonist at D2 receptors, an antagonist at 5-HT2A receptor, and a partial agonist at 5-HT1A receptor. In addition, antagonism of peripheral alpha-adrenergic receptors has also been suggested as a factor in the hypothermic effect, by inhibiting peripheral responses to cooling (vasoconstriction and shivering) (Ref).
Onset: Hypothermia: Varied; antipsychotic-induced hypothermia cases indicate a typical onset in the period shortly after initiation of therapy or a dosage increase (first 7 to 10 days) (Ref).
Risk factors:
Heat stroke:
• Psychiatric illness (regardless of medication use) (Ref)
• Dehydration (Ref)
• Strenuous exercise (Ref)
• Heat exposure (Ref)
• Concomitant medications possessing anticholinergic effects (Ref)
Hypothermia:
• In general, predisposing risk factors include: Older adults, cerebrovascular accident, preexisting brain damage, hypothyroidism, malnutrition, shock, sepsis, adrenal insufficiency, diabetes, disability, burns, exfoliative dermatitis, benzodiazepine use, alcohol intoxication, kidney or liver failure (Ref)
• Schizophrenia (regardless of antipsychotic use) (Ref)
Aripiprazole may cause significant weight gain (increase of >7% from baseline), particularly in pediatric patients, which is a component of the metabolic syndrome observed with this pharmacologic class (Ref).
Mechanism: Multiple proposed mechanisms, including actions at serotonin, dopamine, histamine, and muscarinic receptors, with differing effects explained by differing affinity of antipsychotics at these receptors (Ref). Aripiprazole displays a low affinity for histamine H1 receptors, which may account for the relatively low risk of weight gain associated with aripiprazole (Ref).
Onset: Varied; antipsychotic-induced weight gain usually occurs rapidly in the initial period following initiation, then gradually decreases and flattens over several months with patients continuing to gain weight in the long term (Ref).
Risk factors:
• Family history of obesity (Ref)
• Parental BMI (Ref)
• Children and adolescents (Ref)
• Rapid weight gain in the initial period: Younger age, lower baseline BMI, more robust response to antipsychotic, and increase in appetite; rapid weight gain of >5% in the first month has been observed as the best predictor for significant long-term weight gain (Ref)
• Duration of therapy (although weight gain plateaus, patients continue to gain weight over time) (Ref)
• Schizophrenia (regardless of medication) is associated with a higher prevalence of obesity compared to the general population due to components of the illness such as negative symptoms, sedentary lifestyles, and unhealthy diets (Ref)
• Specific antipsychotic: In adults, aripiprazole is considered to have a minimal or low risk for weight gain; clozapine and olanzapine are considered to have high propensity (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults receiving monotherapy unless otherwise indicated.
IM:
>10%:
Endocrine & metabolic: Decreased HDL cholesterol (14%), increased LDL cholesterol (10% to 14%), increased serum cholesterol (4% to 22%), increased serum triglycerides (7% to 27%), weight gain (17% to 22%) (table 1)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
22% |
9% |
Adults |
IM injection |
Schizophrenia |
144 |
141 |
≥7% of body weight |
|
17% |
7% |
Adults |
IM injection |
Schizophrenia |
167 |
172 |
≥7% of body weight |
Nervous system: Akathisia (2% to 12%) (table 2), headache (12%)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
2% |
0% |
Adults |
IM injection |
Agitation associated with schizophrenia or bipolar mania |
501 |
220 |
|
12% |
4% |
Adults |
IM injection |
Schizophrenia |
N/A |
N/A |
|
11% |
4% |
Adults |
IM injection |
Schizophrenia |
167 |
172 |
1% to 10%:
Cardiovascular: Orthostatic hypotension (≤3%), tachycardia (2%)
Endocrine & metabolic: Increased serum glucose (8%), weight loss (4%)
Gastrointestinal: Abdominal distress (2%), constipation (10%), diarrhea (3%), nausea (9%), vomiting (3%), xerostomia (4%)
Hematologic & oncologic: Neutropenia (6%) (table 3)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
|---|---|---|---|---|
|
6% |
2% |
Adults |
IM injection |
Schizophrenia |
Local: Injection-site reaction (≥1%; including bleeding at injection site, bruising at injection site, erythema at injection site, induration at injection site, inflammation at injection site, injection-site pruritus, rash at injection site, swelling at injection), pain at injection site (5%)
Nervous system: Anxiety (≥1%), dizziness (4% to 8%), drowsiness (7%) (table 4), extrapyramidal reaction (10%), fatigue (2%), insomnia (≥1%), sedated state (3% to 5%), restlessness (≥1%), tremor (3%)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
7% |
4% |
Adults |
IM injection |
Agitation associated with schizophrenia or bipolar mania |
501 |
220 |
Neuromuscular & skeletal: Arthralgia (4%), back pain (4%), dystonia (2%), musculoskeletal pain (3%), myalgia (4%)
Respiratory: Nasal congestion (2%), upper respiratory tract infection (4%)
<1%:
Cardiovascular: Abnormal T waves on ECG, bradycardia, chest discomfort, decreased blood pressure, hypertension, orthostatic dizziness, presyncope, prolonged QT interval on ECG, sinus tachycardia, syncope
Endocrine & metabolic: Decreased serum cholesterol, decreased serum triglycerides, hyperinsulinism, hyperprolactinemia, increased libido, obesity
Gastrointestinal: Bruxism, decreased appetite, dysgeusia, dyspepsia, upper abdominal pain
Genitourinary: Delayed ejaculation, glycosuria, pollakiuria, urinary incontinence
Hematologic & oncologic: Thrombocytopenia
Hepatic: Abnormal hepatic function tests, hepatotoxicity
Hypersensitivity: Hypersensitivity reaction, swollen tongue
Nervous system: Abnormal gait, aggressive behavior, agitation, hypersomnia, irritability, lethargy, memory impairment, panic attack, psychotic reaction, seizure, trismus
Neuromuscular & skeletal: Bradykinesia, dystonia (oromandibular), increased creatinine phosphokinase in blood specimen, joint stiffness, muscle twitching, rhabdomyolysis
Ophthalmic: Blurred vision, oculogyric crisis
Respiratory: Nasopharyngitis
Miscellaneous: Fever
Oral:
>10%:
Endocrine & metabolic: Increased serum glucose (children and adolescents: 3% to 5%; adults: 18%), weight gain (children and adolescents: 3% to 26%; adults: 2% to 8%) (table 5)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
26% |
7% |
Children and adolescents |
Oral |
Irritability associated with autistic disorder |
209 |
98 |
≥7% of body weight |
|
5% |
2% |
Children and adolescents |
Oral |
Schizophrenia or bipolar mania |
381 |
187 |
≥7% of body weight |
|
3% |
1% |
Children and adolescents |
Oral |
Schizophrenia, bipolar mania, autistic disorder, or Tourette disorder |
732 |
370 |
N/A |
|
20% |
8% |
Children and adolescents |
Oral |
Tourette disorder |
105 |
66 |
≥7% of body weight |
|
2% |
3% |
Adults |
Oral |
Bipolar mania |
719 |
598 |
≥7% of body weight |
|
8% |
3% |
Adults |
Oral |
Schizophrenia |
852 |
379 |
≥7% of body weight |
Gastrointestinal: Constipation (children and adolescents: 2%; adults: 11%), nausea (children, adolescents, and adults: 8% to 15%), vomiting (children, adolescents, and adults: 8% to 14%)
Local: Application-site rash (MyCite patch: 12%)
Nervous system: Agitation (19%), akathisia (children, adolescents, and adults: 3% to 13%) (table 6), anxiety (17%), drowsiness (children and adolescents: 10% to 26%; adults: 5% to 13%) (table 7), extrapyramidal reaction (children and adolescents: 6% to 27%; adults: 5% to 16%), fatigue (children and adolescents: 4% to 22%; adults: 6%), headache (children and adolescents: 10% to 12%; adults: 27%), insomnia (18%), sedated state (children and adolescents: 9% to 21%; adults: ≤13%), tremor (children, adolescents, and adults: 5% to 12%)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
3% |
9% |
Children and adolescents |
Oral |
Autistic disorder |
N/A |
N/A |
|
10% |
2% |
Children and adolescents |
Oral |
Bipolar mania |
197 |
97 |
|
6% |
4% |
Children and adolescents |
Oral |
Schizophrenia, bipolar mania, autistic disorder, or Tourette disorder |
732 |
370 |
|
4% |
6% |
Children and adolescents |
Oral |
Tourette disorder |
N/A |
N/A |
|
9% |
6% |
Adolescents |
Oral |
Schizophrenia |
N/A |
N/A |
|
13% |
4% |
Adults |
Oral |
Bipolar mania |
917 |
753 |
|
8% |
4% |
Adults |
Oral |
Schizophrenia |
N/A |
N/A |
|
10% |
4% |
Adults |
Oral |
Schizophrenia or bipolar mania |
1,843 |
1,166 |
|
Drug (Aripiprazole) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|---|
|
10% |
4% |
Children and adolescents |
N/A |
Oral |
Autistic disorder |
212 |
101 |
N/A |
|
26% |
3% |
Children and adolescents |
30 mg |
Oral |
Bipolar mania |
N/A |
N/A |
N/A |
|
23% |
3% |
Children and adolescents |
N/A |
Oral |
Bipolar mania |
197 |
97 |
N/A |
|
19% |
3% |
Children and adolescents |
10 mg |
Oral |
Bipolar mania |
N/A |
N/A |
N/A |
|
16% |
4% |
Children and adolescents |
N/A |
Oral |
Schizophrenia, bipolar mania, autistic disorder, or Tourette disorder |
732 |
370 |
N/A |
|
13% |
1% |
Children and adolescents |
N/A |
Oral |
Tourette disorder |
121 |
72 |
N/A |
|
22% |
6% |
Adolescents |
30 mg |
Oral |
Schizophrenia |
N/A |
N/A |
N/A |
|
11% |
6% |
Adolescents |
10 mg |
Oral |
Schizophrenia |
N/A |
N/A |
N/A |
|
13% |
7% |
Adults |
30 mg |
Oral |
Schizophrenia |
N/A |
N/A |
Including sedation |
|
9% |
7% |
Adults |
10 mg |
Oral |
Schizophrenia |
N/A |
N/A |
Including sedation |
|
9% |
7% |
Adults |
15 mg |
Oral |
Schizophrenia |
N/A |
N/A |
Including sedation |
|
8% |
7% |
Adults |
20 mg |
Oral |
Schizophrenia |
N/A |
N/A |
Including sedation |
|
5% |
3% |
Adults |
N/A |
Oral |
Schizophrenia or bipolar mania |
1,843 |
1,166 |
N/A |
1% to 10%:
Cardiovascular: Orthostatic hypotension (children, adolescents, and adults: ≤4%)
Dermatologic: Skin rash (children, adolescents, and adults: ≤2%)
Endocrine & metabolic: Decreased HDL cholesterol (children and adolescents: 4%), increased serum cholesterol (children and adolescents: 1%), increased serum triglycerides (children, adolescents, and adults: 5% to 10%), weight loss (≥1%)
Gastrointestinal: Abdominal distress (children, adolescents, and adults: 2% to 3%), anorexia (≥1%), decreased appetite (children and adolescents: 5% to 7%), diarrhea (children and adolescents: 4%), dyspepsia (9%), increased appetite (children and adolescents: 7%), sialorrhea (children and adolescents: 4% to 8%), stomach discomfort (3%), upper abdominal pain (children and adolescents: 3%), xerostomia (5%)
Genitourinary: Urinary incontinence (≥1%)
Nervous system: Asthenia (children and adolescents: 2%; adults: ≥1%), dizziness (children, adolescents, and adults: 3% to 10%), drooling (children and adolescents: 3% to 9%), irritability (children and adolescents: 2%), lethargy (children and adolescents: 3% to 5%), pain (3%), restlessness (5% to 6%) (table 8)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
6% |
3% |
Adults |
Oral |
Bipolar mania |
917 |
753 |
|
5% |
3% |
Adults |
Oral |
Schizophrenia or bipolar mania |
1,843 |
1,166 |
Neuromuscular & skeletal: Dystonia (children and adolescents: 2%) (table 9), limb pain (4%), muscle rigidity (children and adolescents: 2%), muscle spasm (2%), myalgia (2%), stiffness (children, adolescents, and adults: 2% to 4%)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
2% |
1% |
Children and adolescents |
Oral |
Schizophrenia, bipolar mania, autistic disorder, or Tourette disorder |
732 |
370 |
Ophthalmic: Blurred vision (children, adolescents, and adults: 3% to 8%)
Respiratory: Cough (3%), epistaxis (children and adolescents: 2%), nasopharyngitis (children and adolescents: 6% to 9%), pharyngolaryngeal pain (3%)
Miscellaneous: Fever (children and adolescents: 4% to 9%)
<1%:
Cardiovascular: Acute cardiorespiratory failure, acute myocardial infarction, angina pectoris, atrial fibrillation, atrial flutter, atrioventricular block, bradycardia, chest pain, hypertension, hypotension, ischemic heart disease, orthostatic dizziness, palpitations, peripheral edema, prolonged QT interval on ECG, syncope
Dermatologic: Alopecia, hyperhidrosis, pruritus, skin photosensitivity, urticaria
Endocrine & metabolic: Amenorrhea, change in libido, elevated glycosylated hemoglobin, gynecomastia, hypoglycemia, hypokalemia, hyponatremia, increased lactate dehydrogenase, increased serum prolactin, menstrual disease
Gastrointestinal: Gastroesophageal reflux disease
Genitourinary: Anorgasmia, erectile dysfunction, mastalgia, nocturia, priapism, urinary retention
Hematologic & oncologic: Thrombocytopenia
Hepatic: Hepatitis, increased gamma-glutamyl transferase, increased liver enzymes, increased serum bilirubin, jaundice
Hypersensitivity: Facial edema, hypersensitivity reaction
Nervous system: Aggressive behavior, akinesia, ataxia, catatonia, choreoathetosis, cogwheel rigidity, delirium, homicidal ideation, hypertonia, impaired mobility, memory impairment, myasthenia, myoclonus, parkinsonism, seizure, somnambulism, speech disturbance, tic disorder
Neuromuscular & skeletal: Bradykinesia, hypokinesia, increased creatinine phosphokinase in blood specimen, rhabdomyolysis
Ophthalmic: Diplopia, photophobia
Renal: Increased blood urea nitrogen
Respiratory: Dyspnea, nasal congestion
Frequency not defined (any route or population):
Endocrine & metabolic: Hirsutism
Gastrointestinal: Esophageal motility disorder, tongue spasm
Nervous system: Sleep talking
Respiratory: Pulmonary aspiration
Postmarketing (any route or population):
Cardiovascular: Pericarditis (Onggo 2023), torsades de pointes (Nelson 2013)
Endocrine & metabolic: Diabetes mellitus (new onset) (van Winkel 2008), diabetes mellitus with hyperosmolar coma (Campanella 2009), diabetic ketoacidosis (Church 2005, Makhzoumi 2008), hypercholesterolemia (Vazquez-Bourgon 2018), hyperglycemia (Church 2005, Stern 2012), hypertriglyceridemia (Vazquez-Bourgon 2018), insulin resistance (Teff 2013)
Gastrointestinal: Dysphagia (Lin 2012), hiccups (Carbone 2021)
Genitourinary: Sexual disorder (La Torre 2013, Serretti 2010)
Hematologic & oncologic: Agranulocytosis, leukopenia (Qureshi 2008), neutropenia (Felin 2018, Majeed 2017), transient neutropenia (pseudoneutropenia) (Pinnaka 2016)
Hypersensitivity: Anaphylaxis, angioedema (Shirk 2021), drug reaction with eosinophilia and systemic symptoms (Taleb 2019)
Nervous system: Cerebrovascular accident, hypothermia (Szota 2019, Zonnenberg 2017), impulse control disorder (including compulsive buying, compulsive eating, hypersexuality, pathological gambling) (Bulbena-Cabré 2016; Dhillon 2017, Peterson 2017), neuroleptic malignant syndrome (Agrawal 2019, Palakurthi 2007), suicidal ideation (Padder 2006, Selvaraj 2010), suicidal tendencies (Meyer 2022), transient ischemic attacks
Neuromuscular & skeletal: Tardive dyskinesia (Aguilar 2019, She 2018)
Respiratory: Hypersensitivity pneumonitis (Gunasekaran 2017), sleep apnea (obstructive) (Health Canada 2016; Kohen 2009; Shirani 2011)
Hypersensitivity (eg, anaphylaxis, pruritus, urticaria) to aripiprazole or any component of the formulation.
Concerns related to adverse reactions:
• Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiac disease, cerebrovascular disease, prior myocardial infarction, ischemic heart disease, or conditions that predispose to hypotension.
• Parkinson disease: Use with caution in patients with Parkinson disease; antipsychotics may aggravate motor disturbances (APA [Keepers 2020]; APA [Reus 2016]).
• Seizures: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.
Dosage form specific issues:
• Lactose: Tablets may contain lactose; avoid use in patients with galactose intolerance or glucose-galactose malabsorption.
• Phenylalanine: Orally disintegrating tablets may contain phenylalanine.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP ["Inactive" 1997]; Zar 2007).
• Product interchangeability: Injection: There are 2 ER aripiprazole formulations available for IM administration: aripiprazole monohydrate (Abilify Maintena and Abilify Asimtufii) and aripiprazole lauroxil (Aristada and Aristada Initio); formulations and product brands vary in dose strength and frequency of administration.
• Tablet with sensor: The ability of aripiprazole tablets with sensor to improve patient compliance or modify aripiprazole dosage has not been established. The use of aripiprazole tablets with sensor to track drug ingestion in “real time” or during an emergency is not recommended because detection may be delayed or not occur.
Other warnings/precautions:
• Discontinuation of therapy: Physical withdrawal symptoms and rebound symptoms (APA [Keepers 2020]; WFSBP [Hasan 2012]). Withdrawal symptoms may include agitation, alternating feelings of warmth and cold, anxiety, diaphoresis, dyskinesia, insomnia, irritability, GI symptoms, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, and vertigo (Lambert 2007; Moncrieff 2020). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anticholinergic or dopaminergic antipsychotics (Cerovecki 2013). Patients with chronic symptoms, repeated relapses, and clear diagnostic features of schizophrenia are at risk for poor outcomes if medications are discontinued (APA [Keepers 2020]).
Pediatric psychiatric disorders are frequently serious disorders which present with variable symptoms that do not always match adult diagnostic criteria. Conduct a thorough diagnostic evaluation and carefully consider risks of psychotropic medication before initiation in pediatric patients with schizophrenia, bipolar disorder, irritability associated with autistic disorder, or Tourette disorder. Medication therapy for pediatric patients with these disorders is indicated as part of a total treatment program that frequently includes educational, psychological, and social interventions. Long-term usefulness of aripiprazole should be periodically re-evaluated in patients receiving the drug for extended periods of time.
Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Shehab 2009).
Oral solution contains fructose 200 mg and sucrose 400 mg per mL.
Aripiprazole tablets are also available with an embedded device that tracks drug ingestion using a smartphone app (Abilify Mycite). Abilify MyCite is a drug-device combination product comprised of aripiprazole tablets embedded with an Ingestible Event Marker (IEM) sensor and packaged with a wearable sensor patch intended to track drug ingestion.
Abilify MyCite Kit is packaged with seven 1-component patches (electronic recording component is contained in each patch).
Abilify MyCite Starter Kit is packaged with 1 sensor pod and 7 adhesive patches (electronic recording component is contained in the pod).
Abilify MyCite Maintenance Kit is packaged with 7 adhesive patches (for use with the sensor pod supplied separately).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Prefilled Syringe, Intramuscular:
Abilify Maintena: 300 mg (extended release) (1 ea); 400 mg (extended release) (1 ea)
Prefilled Syringe, Intramuscular [preservative free]:
Abilify Asimtufii: 720 mg/2.4 mL (extended release) (2.4 mL); 960 mg/3.2 mL (extended release) (3.2 mL) [contains polyethylene glycol (macrogol)]
Solution, Oral:
Generic: 1 mg/mL (150 mL)
Suspension Reconstituted ER, Intramuscular:
Abilify Maintena: 300 mg (extended release) (1 ea); 400 mg (extended release) (1 ea)
Tablet, Oral:
Abilify: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake]
Abilify MyCite: 2 mg [DSC], 5 mg [DSC], 10 mg [DSC], 15 mg [DSC], 20 mg [DSC], 30 mg [DSC] [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake]
Generic: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg
Tablet Disintegrating, Oral:
Generic: 10 mg, 15 mg
Tablet Therapy Pack, Oral:
Abilify MyCite Maintenance Kit: 2 mg (30 ea); 5 mg (30 ea); 10 mg (30 ea); 15 mg (30 ea); 20 mg (30 ea); 30 mg (30 ea) [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake]
Abilify MyCite Starter Kit: 2 mg (30 ea); 5 mg (30 ea); 10 mg (30 ea); 15 mg (30 ea); 20 mg (30 ea); 30 mg (30 ea) [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake]
May be product dependent
Prefilled Syringe (Abilify Asimtufii Intramuscular)
720MG/2.4ML (per mL): $2,114.88
960MG/3.2ML (per mL): $2,114.88
Prefilled Syringe (Abilify Maintena Intramuscular)
300 mg (per each): $2,537.86
400 mg (per each): $3,383.81
Solution (ARIPiprazole Oral)
1 mg/mL (per mL): $2.08 - $7.07
Suspension Reconstituted ER (Abilify Maintena Intramuscular)
300 mg (per each): $2,537.86
400 mg (per each): $3,383.81
Tablet Therapy Pack (Abilify MyCite Maintenance Kit Oral)
2 mg (per each): $67.98
5 mg (per each): $67.98
10 mg (per each): $67.98
15 mg (per each): $67.98
20 mg (per each): $67.98
30 mg (per each): $67.98
Tablet Therapy Pack (Abilify MyCite Starter Kit Oral)
2 mg (per each): $67.98
5 mg (per each): $67.98
10 mg (per each): $67.98
15 mg (per each): $67.98
20 mg (per each): $67.98
30 mg (per each): $67.98
Tablet, orally-disintegrating (ARIPiprazole Oral)
10 mg (per each): $41.87 - $41.89
15 mg (per each): $41.87 - $41.89
Tablets (Abilify Oral)
2 mg (per each): $23.35
5 mg (per each): $23.35
10 mg (per each): $23.35
15 mg (per each): $23.35
20 mg (per each): $33.02
30 mg (per each): $33.02
Tablets (ARIPiprazole Oral)
2 mg (per each): $0.09 - $32.11
5 mg (per each): $0.11 - $32.11
10 mg (per each): $0.14 - $32.11
15 mg (per each): $0.18 - $32.11
20 mg (per each): $0.25 - $45.41
30 mg (per each): $0.26 - $45.41
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension Reconstituted ER, Intramuscular:
Abilify Maintena: 300 mg (extended release) (1 ea); 400 mg (extended release) (1 ea)
Tablet, Oral:
Abilify: 2 mg, 5 mg [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake]
Abilify: 10 mg, 15 mg, 20 mg, 30 mg [contains corn starch]
Generic: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg
IM: Extended release: For IM use only; do not administer SUBQ or IV.
Monthly injection (Abilify Maintena): Inject slowly into deltoid or gluteal muscle using the appropriate provided needle; for nonobese patients, use the 1-inch (25 mm) needle with deltoid administration or the 1.5-inch (38 mm) needle with gluteal administration; for obese patients, use the 1.5-inch (38 mm) needle with deltoid administration or the 2-inch (51 mm) needle with gluteal administration. Do not massage muscle after administration. Rotate injection sites between the 2 deltoid or gluteal muscles. Administer monthly (doses should be separated by ≥26 days).
Every-2-months injection (Abilify Asimtufii): Inject slowly into gluteal muscle using the appropriate provided needle; for nonobese patients, use the 22-gauge, 1.5-inch (38 mm) needle; for obese patients, use the 21-gauge, 2-inch (51 mm) needle. Do not massage muscle after administration. Administer every 2 months (doses should be separated by 56 days); may be given up to 2 weeks before or 2 weeks after the 2-month schedule timepoint.
Oral: Administer with or without food.
Orally disintegrating tablet: Remove from foil blister by peeling back (do not push tablet through the foil). Place tablet in mouth immediately upon removal. Tablet dissolves rapidly in saliva and may be swallowed without liquid. If needed, can be taken with liquid. Do not split tablet.
Tablet with sensor: Swallow tablets whole; do not divide, crush, or chew. Each tablet is embedded with an ingestible event marker (IEM). The patch that accompanies the tablets is a wearable sensor that detects a signal from the IEM sensor after the tablet is ingested and transmits data to a smartphone within 30 minutes to 2 hours of ingestion. If the detection system fails (ie, tablet is not detected after ingestion), do not repeat the dose. Before use, ensure that the patient is capable and willing to use smartphones and apps, that the app is compatible with the patient's specific smartphone, and that the smartphone is paired with the patch prior to use. There are 2 types of patches; refer to corresponding instructions for use within the app. Apply the 1-component patch only when instructed by the app to the left side of the body just above the lower edge of the rib cage. Apply the 2-component patch only when instructed by the app to the left or right side of the body just above the lower edge of the rib cage. Do not place the patch in areas where the skin is scraped, cracked, inflamed, or irritated, or in a location that overlaps the area of the most recently removed patch. Instruct patients to keep the patch on when showering, swimming, or exercising. The patch should be changed weekly or sooner as needed. The app will prompt patient to change the patch and will direct patient to apply and remove the patch correctly. Patients undergoing an MRI need to remove their patch and replace with a new one as soon as possible. If there is skin irritation, instruct patients to remove the patch. Refer to the information provided in the product packaging and electronic instructions for use with the Mycite app.
Oral: May administer all dosage forms without regard to food.
Orally disintegrating tablet: Do not remove tablet from blister pack until ready to administer; do not push tablet through foil (tablet may become damaged); peel back foil to expose tablet; use dry hands to remove tablet and place immediately on tongue. Tablet dissolves rapidly in saliva and may be swallowed without liquid; if needed, tablet can be taken with liquid. Do not split tablet.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Abilify Maintena: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/202971s013lbl.pdf#page=52
Abilify MyCite: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021436s048lbl.pdf#page=47
Oral:
Bipolar disorder: As monotherapy or as an adjunct to lithium or valproate for acute treatment of mania or episodes with mixed features associated with bipolar disorder and maintenance treatment (tablet with sensor only) of bipolar disorder.
Irritability associated with autistic disorder: Treatment of irritability associated with autistic disorder (tablet, orally disintegrating tablet, and oral solution only) in children and adolescents.
Major depressive disorder (unipolar), treatment resistant: Adjunctive treatment of unipolar major depressive disorder in patients with an inadequate response to prior antidepressant therapy.
Schizophrenia: Treatment of schizophrenia.
Tourette disorder: Treatment of Tourette disorder (tablet, orally disintegrating tablet, and oral solution only) in children and adolescents.
Injection: Extended release:
Bipolar disorder: Maintenance monotherapy treatment of bipolar disorder.
Schizophrenia: Treatment of schizophrenia.
Agitation/aggression (acute, severe) associated with psychiatric disorders (eg, schizophrenia, bipolar disorder), substance intoxication, or other organic causes; Agitation/aggression and psychosis associated with dementia, severe or refractory; Delusional disorder; Delusional infestation (delusional parasitosis); Huntington disease-associated chorea; Obsessive-compulsive disorder, treatment resistant; Tourette syndrome
Abilify may be confused with Ambien
ARIPiprazole may be confused with proton pump inhibitors (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, RABEprazole)
Beers Criteria: Antipsychotics are identified in the Beers Criteria as potentially inappropriate medications to be avoided in patients 65 years and older due to an increased risk of stroke and a greater rate of cognitive decline and mortality in patients with dementia. Evidence also suggests there may be an increased risk of mortality with use independent of dementia. Avoid antipsychotics for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. In addition, antipsychotics should be used with caution in older adults due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults. Use of antipsychotics may be appropriate for labeled indications, including schizophrenia, bipolar disorder, Parkinson disease psychosis, adjunctive therapy for major depressive disorder, or for short-term use as an antiemetic (Beers Criteria [AGS 2023]).
Antipsychotics are identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) due to an increased risk of falls. Initiation is not recommended for treatment of sleep disorder. Some disease states of concern include dementia, Parkinson disease, sleep disorder, dysphagia, and coronary, cerebral, or peripheral vascular disease (O’Mahony 2023).
There are two ER formulations available for IM administration: Aripiprazole monohydrate (Abilify Maintena) and aripiprazole lauroxil (Aristada and Aristada Initio).
Substrate of CYP2D6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents With Seizure Threshold Lowering Potential: May enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Amisulpride (Oral): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome or increased QTc interval may be increased. Risk C: Monitor therapy
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Armodafinil: May decrease the serum concentration of ARIPiprazole. Risk C: Monitor therapy
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Asenapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Benperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cabergoline: May diminish the therapeutic effect of Antipsychotic Agents. Risk X: Avoid combination
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Cariprazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Clothiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
CloZAPine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions or avoidance are required for indications other than major depressive disorder. Dose adjustments vary based on formulation, initial starting dose, and the additional use of CYP3A4 inhibitors. See interact monograph for details Risk D: Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of ARIPiprazole. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of ARIPiprazole. Management: For indications other than major depressive disorder: double the oral aripiprazole dose over 1 to 2 weeks and closely monitor. Avoid use of strong CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions are required for indications other than major depressive disorder. Dose reductions vary based on formulation, initial starting dose, CYP2D6 genotype, and use of CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider therapy modification
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Deutetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Donepezil: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Flupentixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider therapy modification
Galantamine: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Risk C: Monitor therapy
Haloperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Huperzine A: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Iloperidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Loxapine: CNS Depressants may enhance the CNS depressant effect of Loxapine. Risk D: Consider therapy modification
Lumateperone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Lurasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mavorixafor: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Mequitazine: Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination
MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for extrapyramidal symptoms and excessive sedation may be increased. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Molindone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
OLANZapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paliperidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Periciazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Perphenazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Pimozide: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Pipamperone [INT]: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pipamperone [INT]. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Piribedil: Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Risk X: Avoid combination
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Promazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
QUEtiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Risk C: Monitor therapy
RisperiDONE: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Rivastigmine: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Serotonergic Agents (High Risk): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Sertindole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor therapy
Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Risk X: Avoid combination
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for NMS and extrapyramidal symptoms may be increased. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thioridazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Thiothixene: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of ARIPiprazole. Trimeprazine may increase the serum concentration of ARIPiprazole. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ziprasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Ingestion of oral formulations with a high-fat meal delays time to peak plasma level. Management: Administer without regard to meals.
If treatment is needed in a woman planning a pregnancy, use of an agent other than aripiprazole is preferred (Larsen 2015).
Aripiprazole crosses the placenta; aripiprazole and dehydro-aripiprazole can be detected in the cord blood at delivery (Nguyen 2011; Watanabe 2011).
Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms [EPS]) and/or withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization.
Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (Yonkers 2009). The ACOG recommends that therapy during pregnancy be individualized; treatment with psychiatric medications during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. Safety data related to atypical antipsychotics during pregnancy is limited, as such, routine use is not recommended. However, if a woman is inadvertently exposed to an atypical antipsychotic while pregnant, continuing therapy may be preferable to switching to an agent that the fetus has not yet been exposed to; consider risk:benefit (ACOG 2008). If treatment is initiated during pregnancy, use of an agent other than aripiprazole is preferred (Larsen 2015).
Health care providers are encouraged to enroll women exposed to aripiprazole during pregnancy in the National Pregnancy Registry for Atypical Antipsychotics (866-961-2388 or http://www.womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/).
Aripiprazole and dehydro-aripiprazole are present in breast milk. (Nordeng 2014)
The relative infant dose (RID) of aripiprazole is 8.3% when calculated using the highest mean breast milk concentration located and compared to a weight-adjusted maternal dose of 10 mg/day.
In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000). However, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015).
The RID of aripiprazole was calculated using a mean milk concentration of 56 ng/mL (aripiprazole) and 8.8 ng/mL (dehydro-aripiprazole), providing an estimated daily infant dose via breast milk of 47 mcg/day. This milk concentration was obtained following maternal administration of aripiprazole 10 mg/day during pregnancy and while breastfeeding. Milk samples were obtained at 8 and 10 weeks' postpartum. The RID was calculated by the authors of the study using the actual maternal weight. Peak milk concentrations appeared ~3 hours after the dose, but remained relatively constant throughout the dosing interval (Nordeng 2014).
Although reports of aripiprazole use in breastfeeding women are limited, lactation failure has been observed in some cases (Lutz 2010; Mendhekar 2006; Nordeng 2014). In general, infants exposed to second generation antipsychotics via breast milk should be monitored weekly for the first month of exposure for symptoms, such as appetite changes, insomnia, irritability, or lethargy (Uguz 2016).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Until additional information is available, use of agents other than aripiprazole in breastfeeding women is preferred (Pacchiarotti 2016; Uguz 2016).
Some products may contain phenylalanine.
|
Frequency of Antipsychotic Monitoring for Aripiprazolea,b | ||
|---|---|---|
|
Monitoring parameter |
Frequency of monitoring |
Comments |
|
Adherence |
Every visit |
|
|
Blood chemistries (electrolytes, renal function, liver function, TSH) |
Annually |
|
|
CBC |
As clinically indicated |
Check frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia |
|
Extrapyramidal symptoms |
Every visit; 4 weeks after initiation and dose change; annually. Use a formalized rating scale at least annually or every 6 months if high riskc |
|
|
Fall risk |
Every visit |
|
|
Fasting plasma glucose/HbA1c |
4 months after initiation; annually |
Check more frequently than annually if abnormal. Follow diabetes guidelines. |
|
Lipid panel |
4 months after initiation; annually |
Check more frequently than annually if abnormal. Follow lipid guidelines. |
|
Mental status and alertness |
Every visit |
|
|
Metabolic syndrome history |
Annually |
Evaluate for personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease |
|
Prolactin |
Ask about symptoms at every visit until dose is stable. Check prolactin level if symptoms are reported. |
Hyperprolactinemia symptoms: Changes in menstruation, libido, gynecomastia, development of galactorrhea, and erectile and ejaculatory function |
|
Tardive dyskinesia |
Every visit; annually. Use a formalized rating scale at least annually or every 6 months if high riskd |
|
|
Vital signs (BP, orthostatics, temperature, pulse, signs of infection) |
Every visit (at least weekly during first 3 to 4 weeks of treatment); 4 weeks after dose change. |
|
|
Weight/Height/BMI |
8 and 12 weeks after initiation and dose change; quarterly |
Consider monitoring waist circumference at baseline and annually, especially in patients with or at risk for metabolic syndrome. Consider changing antipsychotic if BMI increases by ≥1 unit. Some experts recommend checking weight and height at every visit. |
|
a For all monitoring parameters, it is appropriate for check at baseline and when clinically relevant (based on symptoms or suspected adverse reactions) in addition to the timeline. b ADA 2004; APA [Keepers 2020]; de Hert 2011; Gugger 2011; manufacturer’s labeling. c Risk factors for extrapyramidal symptoms (EPS) include prior history of EPS, high doses of antipsychotics, young age (children and adolescents at higher risk than adults), and dopaminergic affinity of individual antipsychotic. d Risk factors for tardive dyskinesia include age >55 years; females; White or African ethnicity; presence of a mood disorder, intellectual disability, or CNS injury; and past or current EPS. | ||
Timing of serum samples: Draw trough just before next dose (Hiemke 2018).
Therapeutic reference range: 100 to 350 ng/mL (SI: 223 to 780.5 nmol/L) (Hiemke 2018). Note: Dosing should be based on therapeutic response as opposed to serum concentrations, however therapeutic drug monitoring can be used to confirm adherence (APA [Keepers 2020]).
Laboratory alert level: 1,000 ng/mL (SI: 2,230 nmol/L) (Hiemke 2018).
Aripiprazole is a quinolinone antipsychotic which exhibits high affinity for D2, D3, 5-HT1A, and 5-HT2A receptors; moderate affinity for D4, 5-HT2C, 5-HT7, alpha1 adrenergic, and H1 receptors. It also possesses moderate affinity for the serotonin reuptake transporter; has no affinity for muscarinic (cholinergic) receptors. Aripiprazole functions as a partial agonist at the D2 and 5-HT1A receptors, and as an antagonist at the 5-HT2A receptor (de Bartolomeis 2015).
Note: In pediatric patients 10 to 17 years of age, the pharmacokinetic parameters of aripiprazole and dehydro-aripiprazole have been shown to be similar to adult values when adjusted for weight.
Onset of action: Oral:
Bipolar disorder, acute mania: Initial effects may be observed within days of treatment with continued improvements over 1 to 2 weeks (Goikolea 2013; Tohen 2000; Welten 2016).
Major depressive disorder, unipolar: Initial effects may be observed within 1 week with continued improvements over 6 to 12 weeks (Wen 2014).
Schizophrenia: Initial effects may be observed within 1 to 2 weeks of treatment with continued improvements through 4 to 6 weeks (Agid 2003; Levine 2010).
Absorption:
IM: Extended-release: Slow, prolonged.
Oral: Well absorbed.
Distribution: Vd: 4.9 L/kg.
Protein binding: ≥99%, primarily to albumin.
Metabolism: Hepatic dehydrogenation, hydroxylation and N-dealkylation via CYP2D6, CYP3A4 (dehydro-aripiprazole metabolite has affinity for D2 receptors similar to the parent drug and represents 40% of the parent drug exposure in plasma) (Sheehan 2010).
Bioavailability: Tablet: 87%; Note: Orally disintegrating tablets are bioequivalent to tablets; oral solution to tablet ratio of geometric mean for peak concentration is 122% and for AUC is 114%.
Half-life elimination: Aripiprazole: 75 hours; dehydro-aripiprazole: 94 hours; IM, monthly injection extended release (terminal): ~30 to 47 days (dose-dependent).
CYP2D6 poor metabolizers: Aripiprazole: 146 hours.
Time to peak, plasma:
IM, extended release:
Monthly injection (Abilify Maintena): After multiple doses, 4 days with deltoid administration and 5 to 7 days with gluteal administration.
Every-2-months injection (Abilify Asimtufii): After multiple doses, a flat plasma concentration profile is maintained from days 1 through 49.
Tablet: 3 to 5 hours; high-fat meals delay time to peak by 3 hours for aripiprazole and 12 hours for dehydro-aripiprazole.
Excretion: Feces (55%, ~18% of the total dose as unchanged drug; 37% of the total dose as changed drug); urine (25%, <1% of the total dose as unchanged drug; 25% of the total dose as changed drug) (Sheehan 2010)
Altered kidney function: In severe renal impairment (CrCl <30 mL/minute), Cmax increased by 36% (aripiprazole) and 53% (dehydro-aripiprazole), but AUC was 15% lower for aripiprazole and 7% higher for dehydro-aripiprazole.
Hepatic function impairment: AUC increased by 31% in mild hepatic impairment and by 8% in moderate impairment, and decreased by 20% in severe impairment.
Older adult: In patients ≥65 years of age who were administered a single oral dose, clearance was 20% lower than that observed in younger patients.
Sex: Cmax and AUC are 30% to 40% higher in women than in men.
CYP 2D6 metabolizers: 60% higher exposure to aripiprazole and active metabolites in poor CYP 2D6 metabolizers compared to extensive metabolizers (Sheehan 2010).
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