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ARIPiprazole

Medically reviewed by Drugs.com. Last updated on Jun 3, 2020.

Pronunciation

(ay ri PIP ray zole)

Index Terms

  • BMS 337039
  • OPC-14597

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Prefilled Syringe, Intramuscular:

Abilify Maintena: 300 mg (1 ea); 400 mg (1 ea)

Solution, Oral:

Generic: 1 mg/mL (150 mL)

Suspension Reconstituted ER, Intramuscular:

Abilify Maintena: 300 mg (1 ea); 400 mg (1 ea)

Tablet, Oral:

Abilify: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg [contains corn starch, fd&c blue #2 aluminum lake]

Abilify MyCite: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg [contains corn starch, fd&c blue #2 aluminum lake]

Generic: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg

Tablet Disintegrating, Oral:

Generic: 10 mg, 15 mg

Brand Names: U.S.

  • Abilify
  • Abilify Maintena
  • Abilify MyCite

Pharmacologic Category

  • Second Generation (Atypical) Antipsychotic

Pharmacology

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).

Absorption

IM: Extended-release: Slow, prolonged

Oral: Well absorbed

Distribution

Vd: 4.9 L/kg

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)

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)

Onset of Action

Initial: 1 to 3 weeks

Time to Peak

Plasma:

IM: Extended release (after multiple doses): 4 days (deltoid administration); 5 to 7 days (gluteal administration).

Tablet: 3 to 5 hours; high-fat meals delay time to peak by 3 hours for aripiprazole and 12 hours for dehydro-aripiprazole.

Half-Life Elimination

Aripiprazole: 75 hours; dehydro-aripiprazole: 94 hours; IM, extended release (terminal): ~30 to 47 days (dose-dependent)

CYP2D6 poor metabolizers: Aripiprazole: 146 hours

Protein Binding

≥99%, primarily to albumin

Special Populations: Renal Function Impairment

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.

Special Populations: Hepatic Function Impairment

AUC increased by 31% in mild hepatic impairment and by 8% in moderate impairment, and decreased by 20% in severe impairment.

Special Populations: Elderly

In patients ≥65 years of age who were administered a single oral dose, clearance was 20% lower than that observed in younger patients.

Special Populations: Gender

Cmax and AUC are 30% to 40% higher in women than in men.

Special Populations Note

60% higher exposure to aripiprazole and active metabolites in poor CYP 2D6 metabolizers compared to extensive metabolizers (Sheehan 2010).

Use: Labeled Indications

Oral:

Bipolar disorder: As monotherapy or as an adjunct to lithium or valproate for acute treatment of manic or mixed episodes 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.

Off Label Uses

Agitation/aggression (acute, severe) associated with psychiatric disorders (eg, schizophrenia, bipolar disorder), substance intoxication, or other organic causes

Data from a randomized, double-blind, comparator trial and post hoc pooled analysis support the use of aripiprazole in the treatment of agitation associated with schizophrenia and schizoaffective disorders [Kinon 2008], [Marder 2007].

Based on the World Federation of Societies of Biological Psychiatry (WFSBP) expert consensus for the assessment and management of agitation in psychiatry, oral aripiprazole is effective and recommended in the management of psychomotor agitation associated with psychiatric conditions (eg, schizophrenia, bipolar disorder), substance intoxication, or other organic causes.

Agitation/aggression and psychosis associated with dementia, severe or refractory

Data from randomized, double-blind, placebo-controlled trials support the use of aripiprazole in the treatment psychosis and agitation related to Alzheimer dementia [De Deyn 2005], [Mintzer 2007], [Streim 2008].

Based on the American Psychiatric Association (APA) practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia, antipsychotics, such as aripiprazole, may be considered for the treatment of agitation and psychosis in certain patients; however, evidence for efficacy is modest and use should be limited to patients whose symptoms are dangerous, severe, or cause significant patient distress due to safety risks associated with antipsychotics. Based on the WFSBP guidelines for the treatment of Alzheimer disease and other dementias, drug treatment with aripiprazole for behavioral and psychological aspects (including hyperactivity and psychosis) is recommended, at low doses and for short durations, as a last option after addressing causative factors and using psychosocial interventions.

Delusional disorder

Data from a limited number of patients studied in case reports suggest that aripiprazole may be beneficial for the treatment of delusional disorder [Garg 2014], [Iannuzzi 2019], [Miyamoto 2008]. A systematic review suggests antipsychotics as an effective treatment option [Munoz-Negro 2016].

Delusional infestation (delusional parasitosis)

Data from a limited number of patients studied in case reports suggest that aripiprazole may be beneficial for the treatment of delusional infestation [Ladizinski 2010], [Yeh 2014]. Some experts suggest antipsychotics as an effective treatment option [Campbell 2019], [Heller 2013].

Huntington disease-associated chorea

Data from a limited number of patients studied in a noncontrolled trial and case reports suggest that aripiprazole may be beneficial for the treatment of chorea associated with Huntington disease [Brusa 2009], [Lin 2008], [Oulis 2010], [Yavuz 2013].

Obsessive-compulsive disorder, treatment resistant

Data from a limited number of patients studied suggest that aripiprazole augmentation of an antidepressant may be beneficial for the treatment of treatment-resistant obsessive-compulsive disorder (OCD) [Muscatello 2011], [Sayyah 2012].

Based on the APA practice guideline for the treatment of patients with OCD, antipsychotics given as augmentation are recommended in the management of treatment-resistant OCD in patients who have a partial response to initial treatment; however, evidence supporting aripiprazole is limited [Koran 2013].

Contraindications

Hypersensitivity (eg, anaphylaxis, pruritus, urticaria) to aripiprazole or any component of the formulation.

Dosing: Adult

Note: Formulations: Available formulations include oral tablets and oral solution supplied as aripiprazole (base) and 2 ER IM injections: aripiprazole monohydrate and aripiprazole lauroxil (see Aripiprazole Lauroxil monograph). All doses are expressed as the equivalent amounts of aripiprazole (base). Aripiprazole tablets are also available with an embedded device that tracks drug ingestion using a smartphone app (Abilify Mycite).

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 (Moore 2020; WFSBP [Hasan 2012]; Wilson 2012).

Oral: Initial: 10 to 15 mg; may repeat based on response and tolerability every 2 hours up to 30 mg/day (Moore 2020).

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 (APA [Reus 2016]).

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 (APA [Reus 2016]; De Deyn 2005; Mintzer 2007; Streim 2008).

Note: In severe agitation associated with dementia with Lewy bodies, antipsychotics are generally avoided; if use is required, titrating above 2 to 5 mg/day is not recommended (Farlow 2019).

Bipolar disorder:

Oral: Acute manic or mixed episodes (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 (CANMAT [Yatham 2013]; Stovall 2019). Note: Some experts suggest higher initial doses of up to 30 mg/day (Stovall 2019). For maintenance treatment, continue dose and combination regimen that was used to achieve control of the acute episode (CANMAT [Yatham 2013]).

IM, ER injectable suspension (aripiprazole monohydrate) (alternative agent): Maintenance: 400 mg once monthly (doses should be separated by ≥26 days). 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. Continue (overlap) oral aripiprazole or other oral antipsychotic for 14 days during initiation of the ER injection.

Dosage adjustment of ER injection for adverse effects: Consider reducing dose to 300 mg once monthly.

Missed doses of 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; 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; adjust oral dose as needed based on response and tolerability.

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 to 2 weeks based upon response and tolerability up to 30 mg/day (Manschreck 2019; Miyamoto 2008; Stroup 2019).

Delusional infestation (delusional parasitosis) (off-label use):

Note: Dosing based on expert opinion:

Oral: Initial: 2 mg once daily; may increase dose gradually based on response and tolerability in 2 mg increments at intervals ≥2 weeks up to 12 mg/day (Campbell 2019; Heller 2013; Suh 2019). Some patients may require doses up to 30 mg/day for optimal response. After achieving adequate response, maintain for ≥1 to 3 months before attempting to taper and discontinue (Stroup 2019; Suh 2019).

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 (Brusa 2009; Ciammola 2009; Suchowersky 2019).

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 (Berman 2009).

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 (Ak 2011; APA 2007; Muscatello 2011; Pessina 2009; Sayyah 2012).

Schizophrenia:

Oral: Initial: 10 or 15 mg once daily; may increase dose based on response and tolerability in 5 mg increments at intervals ≥1 week up to a maximum of 30 mg/day (Kane 2009; Khanna 2014; Stroup 2019).

IM, ER injectable suspension (aripiprazole monohydrate): 400 mg once monthly (doses should be separated by ≥26 days). 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. Continue (overlap) oral aripiprazole or other oral antipsychotic for 14 days during initiation of the ER injection.

Dosage adjustment of ER injection for adverse effects: Consider reducing dose to 300 mg once monthly.

Missed doses of 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; 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; adjust oral dose as needed based on response and tolerability.

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): Reduce aripiprazole dose to 300 mg once monthly in known CYP2D6 poor metabolizers; subsequently adjust dose according to response and tolerability.

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: Gradual dose reduction is advised to avoid withdrawal symptoms (ie, insomnia, headache, GI symptoms) unless discontinuation is due to significant adverse effects. In general, when discontinuing antipsychotic therapy for a chronic psychiatric disorder (eg, bipolar disorder, schizophrenia), decreasing the dose very gradually over weeks to months (eg, reducing the dose by 10% per month) with close monitoring is suggested to allow for detection of prodromal symptoms of disease recurrence (APA [Lehman 2004]; CPA 2005).

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 (Cerovecki 2013; Remington 2005; Takeuchi 2017). Based upon clinical experience, some experts generally prefer cross-titration and overlap approaches rather than abrupt change (Post 2019; Stroup 2019).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: 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. Orally disintegrating tablets (Abilify Discmelt) are bioequivalent to the immediate release tablets (Abilify). Immediate release and extended release parenteral products are not interchangeable.

Autism; treatment of associated irritability (including aggression, deliberate self-injurious behavior, temper tantrums, and quickly changing moods): Children and Adolescents 6 to 17 years: Oral: Initial: 2 mg daily for 7 days, followed by 5 mg daily; subsequent dose increases may be made in 5 mg increments every ≥7 days, up to a maximum daily dose of 15 mg/day.

Bipolar I disorder (acute manic or mixed episodes): Children and Adolescents 10 to 17 years: Oral: Initial: 2 mg daily for 2 days, followed by 5 mg daily for 2 days with a further increase to target dose of 10 mg daily; subsequent dose increases may be made in 5 mg increments, up to a maximum daily dose of 30 mg/day. Note: The safety of doses >30 mg/day has not been evaluated.

Conduct disorder (CD); aggression: Limited data available: Children ≥6 years and Adolescents: Oral: Initial: Patient weight <25 kg: 1 mg/day; 25 to 50 kg: 2 mg/day; 51 to 70 kg: 5 mg/day; >70 kg: 10 mg/day; may titrate after 2 weeks to clinical effectiveness; maximum daily dose: 15 mg/day. Dosing based on an open-label, prospective study (n=23; age: 6 to 17 years) which evaluated pharmacokinetics and effectiveness in patients with a primary diagnosis of CD (with or without comorbid ADHD); results showed improvement in CD symptom scores with only minor improvements in cognition (Findling 2009).

Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) or Asperger Disorder; treatment of associated irritability (aggression, self-injury, tantrums): Limited data available: Children ≥4 years and Adolescents: Oral:

Preschool age: Initial dose: 1.25 mg/day with titration every ≥5 days in 1.25 mg/day increments as tolerated or clinically indicated (Masi 2009).

Prepubertal children: Initial dose: 1.25 to 2.5 mg/day with titration every 3 to 5 days in 1.25 to 2.5 mg/day increments as tolerated or clinically indicated; maximum daily dose: 15 mg/day (Masi 2009; Stigler 2009).

Adolescents: Initial dose: 2.5 to 5 mg/day with titration every 5 days in 2.5 to 5 mg/day increments as tolerated or clinically indicated; doses >5 mg/day were divided twice daily; if sleep disorder was reported, the dose was given in morning and/or at lunchtime (Masi 2009); maximum daily dose: 15 mg/day (Stigler 2009).

An open-labeled, pilot study (n=25; mean age: 8.6 years; range: 5 to 17 years) reported an 88% response with a mean final dose of 7.8 mg/day (range: 2.5 to 15 mg/day) (Stigler 2009). A retrospective, noncontrolled, open-label study of 34 PDD patients (mean age: 10.2 years; range: 4 to 15 years) included 10 patients with autistic disorder and 24 patients with PDD-NOS reported a mean final dose: 8.1 ± 4.9 mg/day and an overall response rate of 32.4% (29.2% in patients with PDD-NOS) (Masi 2009). In a retrospective chart review of children and adolescents with developmental disability and a wide range of psychiatric disorders (n=32; age: 5 to 19 years), a mean starting dose of aripiprazole of 7.1 ± 0.32 mg/day and a mean maintenance dose of 10.55 ± 6.9 mg/day was used; a response rate of 56% was reported for the overall population. However, a study population subset analysis in patients with mental retardation (n=18) showed a lower response rate in patients with mental retardation with PDD-NOS (38%) than in patients with mental retardation without PDD-NOS (100%) (Valicenti-McDermott 2006).

Schizophrenia: Adolescents 13 to 17 years: Oral: Initial: 2 mg daily for 2 days, followed by 5 mg daily for 2 days with a further increase to target dose of 10 mg daily; subsequent dose increases may be made in 5 mg increments up to a maximum daily dose of 30 mg/day. Note: 30 mg/day was not found to be more effective than the 10 mg/day dose.

Tourette syndrome, tic disorders: Children ≥6 years and Adolescents: Oral:

Patient weight <50 kg: Initial: 2 mg 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: Initial: 2 mg 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 (AACAP [McClellan 2007]; APA [Lehman 2004]; Cerovecki 2013; CPA 2005; NICE 2013; WFSBP [Hasan 2012]); risk for withdrawal symptoms may be highest with highly anticholinergic or dopaminergic antipsychotics (Cerovecki 2013). 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 (APA [Lehman 2004]; CPA 2005). Continuing antiparkinsonism agents for a brief period after discontinuation may prevent withdrawal symptoms (Cerovecki 2013). 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 (Cerovecki 2013; Remington 2005).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosage adjustment based on CYP2D6 metabolizer status:

Oral: Children and Adolescents: Aripiprazole dose should be reduced to 50% of the usual dose in CYP2D6 poor metabolizers and to 25% of the usual dose in poor metabolizers receiving a concurrent strong CYP3A4 inhibitor; subsequently adjust dose for favorable clinical response.

Reconstitution

Injection, powder (extended release):

Prefilled syringe: Reconstitute at room temperature. Rotate the syringe plunger rod to release diluent. Shake vigorously for 20 seconds or until the suspension is uniform; the resulting suspension will be milky white and opaque. (Refer to manufacturer’s labeling for full preparation technique.) Inject full syringe contents immediately following reconstitution.

Vial for reconstitution: Reconstitute using 1.5 mL sterile water for injection (SWFI) (provided) for the 300 mg vial or 1.9 mL SWFI (provided) for the 400 mg vial to a final concentration of 200 mg/mL; residual SWFI should be discarded after reconstitution. Shake vigorously for 30 seconds or until the suspension is uniform; the resulting suspension will be milky white and opaque. If the suspension is not administered immediately after reconstitution, shake vigorously for 60 seconds prior to administration.

Administration

IM: Extended release: For IM use only; do not administer SubQ or IV. 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).

Oral: Administer with or without food. Tablet and oral solution may be interchanged on a mg-per-mg basis, up to 25 mg. Doses using 30 mg tablets should be exchanged for 25 mg oral solution. Orally-disintegrating tablets (Abilify Discmelt) are bioequivalent to the IR tablets (Abilify).

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, and that the app is compatible with the patient's specific smartphone. Apply patch only when instructed by the app to the left 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.

Dietary Considerations

Some products may contain phenylalanine.

Storage

Injection, powder (extended release):

Prefilled syringe: Store below 30°C (86°F). Do not freeze. Protect from light and store in original package.

Vial for reconstitution: Store unused vials at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). If the suspension is not administered immediately after reconstitution, store at room temperature in the vial (do not store in a syringe).

Oral solution and tablets: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Use oral solution within 6 months after opening. Do not store in conditions where tablets are exposed to humid conditions.

Mycite Patch: Store at 15°C to 30°C (59°F to 86°F); 15% to 93% relative humidity.

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Monitor therapy

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Monitor therapy

Amisulpride (Oral): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome may be increased. Avoid combination

Amphetamines: Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. 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). Consider therapy modification

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Armodafinil: May decrease the serum concentration of ARIPiprazole. Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Avoid combination

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. Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the adverse/toxic effect of Antipsychotic Agents. Avoid combination

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Cabergoline: May diminish the therapeutic effect of Antipsychotic Agents. Avoid combination

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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. Monitor therapy

CYP2D6 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, and the additional use of CYP3A4 inhibitors. See full interaction monograph for details. Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of ARIPiprazole. 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. 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. 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, CYP2D6 genotype, and use of CYP2D6 inhibitors. See full interaction monograph for details. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to concomitant therapy when possible. If concomitant therapy cannot be avoided, monitor for reduced clinical effects of the CYP3A4 substrate. Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deutetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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 anticonvulsants. 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 anticonvulsants. 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 anticonvulsants. Consider therapy modification

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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. 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. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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. 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. Consider therapy modification

Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Avoid combination

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. 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 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. Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. 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). Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

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. Avoid combination

Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. 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. Consider therapy modification

Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Trimeprazine: May increase the serum concentration of ARIPiprazole. 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. Consider therapy modification

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Unless otherwise noted, frequency of adverse reactions is shown as reported for adult patients receiving aripiprazole monotherapy. Spectrum and incidence of adverse effects similar in children; exceptions noted when incidence is much higher in children.

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% [placebo: 7% to 9%])

Nervous system: Akathisia (dose-related; 2% to 12% [placebo: 0% to 4%]), headache (12%)

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% [placebo: 2%])

Local: Injection site reaction (≤1%; including erythema, induration, inflammation, hemorrhage, pruritus, rash, swelling), pain at injection site (5%)

Nervous system: Anxiety (≥1%), dizziness (4% to 8%), drowsiness (7% [placebo: 4%]), dystonia (2%), extrapyramidal reaction (10%), fatigue (dose-related; 1% to 2%), insomnia (≥1%), sedated state (3% to 5%), restlessness (≥1%)

Neuromuscular & skeletal: Arthralgia (4%), back pain (4%), musculoskeletal pain (3%), myalgia (4%), tremor (dose-related; 3%)

Respiratory: Nasal congestion (2%), upper respiratory tract infection (4%)

<1%:

Cardiovascular: Abnormal T waves on ECG, bradycardia, chest discomfort, hypertension, increased blood pressure, presyncope, prolonged QT interval on ECG, sinus tachycardia

Endocrine & metabolic: Decreased serum cholesterol, decreased serum triglycerides, glycosuria, hyperprolactinemia, increased libido, obesity

Gastrointestinal: Bruxism, decreased appetite, dysgeusia, dyspepsia, hyperinsulinism, swollen tongue, upper abdominal pain

Genitourinary: Pollakiuria, urinary incontinence

Hematologic & oncologic: Thrombocytopenia

Hepatic: Abnormal hepatic function tests, hepatotoxicity

Hypersensitivity: Hypersensitivity reaction

Nervous system: Abnormal gait, aggressive behavior, agitation, delayed ejaculation, dystonia (oromandibular), hypersomnia, irritability, lethargy, memory impairment, panic attack, psychotic reaction, seizure, suicidal ideation, syncope, trismus

Neuromuscular & skeletal: Bradykinesia, 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 (adults: 18%; children and adolescents: 3% to 5%), weight gain (children and adolescents: 3% to 26% [placebo: 1% to 8%]; adults: 2% to 8% [placebo: 0.6% to 3%])

Gastrointestinal: Constipation (adults: 11%; children and adolescents: 2%), nausea (8% to 15%), vomiting (8% to 14%)

Local: Application site rash (Mycite patch: 12%)

Nervous system: Agitation (19%), akathisia (dose-related; 2% to 13% [placebo: 0% to 4%]), anxiety (17%), drowsiness (dose-related; children and adolescents: 10% to 26% [placebo: 1% to 6%]; adults: 5% to 13% [placebo: 3% to 7%]), extrapyramidal reaction (dose-related; children and adolescents: 6% to 27%; adults: 5% to 16%), fatigue (dose-related; children and adolescents: 4% to 22%; adults: 6%), headache (adults: 27%; children and adolescents: 10% to 12%), sedated state (dose-related; children and adolescents: 9% to 21%; adults: 3% to 11%), insomnia (18%)

Neuromuscular & skeletal: Tremor (dose-related; 5% to 12%)

1% to 10%:

Cardiovascular: Orthostatic hypotension (≤4%)

Dermatologic: Skin rash (children and adolescents: ≤2%)

Endocrine & metabolic: Decreased HDL cholesterol (children and adolescents: 4%), increased serum cholesterol (children and adolescents: 1%), increased serum triglycerides (5% to 10%), weight loss (≥1%)

Gastrointestinal: Abdominal distress (2% to 3%), anorexia, decreased appetite (children and adolescents: 5% to 7%), diarrhea (children and adolescents: 4%), dyspepsia (9%), increased appetite (children and adolescents: 7%), sialorrhea (dose-related; children and adolescents; 4% to 8%), stomach discomfort (3%), upper abdominal pain (children and adolescents: 3%), xerostomia (5%)

Genitourinary: Urinary incontinence (≥1%)

Nervous system: Dizziness (3% to 10%), drooling (children and adolescents: 3% to 9%), dystonia (children and adolescents: 2% [placebo: 1%]), irritability (children and adolescents: 2%), lethargy (3% to 5%), pain (3%), restlessness (5% to 6% [placebo: 3%])

Neuromuscular & skeletal: Asthenia (≥1%), limb pain (4%), muscle rigidity (children and adolescents: 2%), muscle spasm (2%), myalgia (2%), stiffness (2% to 4%)

Ophthalmic: Blurred vision (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 myocardial infarction, angina pectoris, atrial fibrillation, atrial flutter, atrioventricular block, bradycardia, chest pain, choreoathetosis, facial edema, hypertension, hypotension, ischemic heart disease, palpitations, peripheral edema, prolonged QT interval on ECG

Dermatologic: Alopecia, hyperhidrosis, pruritus, skin photosensitivity, urticaria

Endocrine & metabolic: Amenorrhea, change in libido, gynecomastia, hirsutism (children and adolescents), hypoglycemia, hypokalemia, hyponatremia, increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased serum prolactin, menstrual disease

Gastrointestinal: Gastroesophageal reflux disease, tongue spasm (children and adolescents)

Genitourinary: Erectile dysfunction, mastalgia, nocturia, priapism, urinary retention

Hematologic & oncologic: Elevated glycosylated hemoglobin, thrombocytopenia

Hepatic: Hepatitis, increased liver enzymes, increased serum bilirubin, jaundice

Hypersensitivity: Hypersensitivity reaction

Nervous system: Aggressive behavior, anorgasmia, ataxia, catatonia, cogwheel rigidity, delirium, hypertonia, impaired mobility, memory impairment, myasthenia, myoclonus, parkinsonism, seizure, sleep talking (children and adolescents), somnambulism, speech disturbance, tic disorder

Neuromuscular & skeletal: Akinesia, bradykinesia, hypokinesia, rhabdomyolysis

Ophthalmic: Diplopia, oculogyric crisis, photophobia

Renal: Increased blood urea nitrogen

Respiratory: Dyspnea, nasal congestion

Postmarketing (any indication):

Cardiovascular: Cerebrovascular accident, syncope, transient ischemic attacks

Endocrine & metabolic: Diabetic ketoacidosis (rare: <1%) (Church 2005, Makhzoumi 2008), diabetes mellitus (new onset) (rare: <1%) (van Winkel 2008), hyperglycemia (rare: <1%) (Church 2005, Stern 2012), hypertriglyceridemia (Vazquez-Bourgon 2018), hypercholesterolemia (Vazquez-Bourgon 2018), insulin resistance (rare: <1%) (Teff 2013)

Gastrointestinal: Dysphagia (rare: <1%) (Lin 2012)

Genitourinary: Sexual disorder (La Torre 2013, Serretti 2010)

Hematologic & oncologic: Agranulocytosis, leukopenia (rare: <1%) (Qureshi 2008), neutropenia (Felin 2018, Majeed 2017), transient neutropenia (pseudoneutropenia) (Pinnaka 2016)

Hypersensitivity: Anaphylaxis, angioedema

Immunologic: Drug reaction with eosinophilia and systemic symptoms (Taleb 2019)

Nervous system: Diabetes mellitus with hyperosmolar coma (rare: <1%) (Campanella 2009), hypothermia (rare: <1%) (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), sleep apnea (obstructive) (Health Canada, 2016; Kohen 2009; Shirani 2011), suicidal ideation (Padder 2006, Selvaraj 2010), suicidal tendencies, tardive dyskinesia (rare: <1%) (Aguilar 2019, She 2018)

Respiratory: Hypersensitivity pneumonitis (Gunasekaran 2017)

ALERT: U.S. Boxed Warning

Increased mortality in elderly patients with dementia-related psychosis:

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Aripiprazole is not approved for the treatment of patients with dementia-related psychosis.

Suicidality and antidepressant drugs:

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.

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with health care provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Aripiprazole is not FDA approved for adjunctive treatment of depression in children.

- The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy. Patients should be screened for bipolar disorder prior to initiation of treatment of major depression.

- Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their health care provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse reactions:

• Altered cardiac conduction: May alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics.

• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, preexisting low WBC/ANC or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil count <1,000/mm3.

• Cerebrovascular effects: An increased incidence of cerebrovascular effects (eg, transient ischemic attack, stroke), including fatalities, has been reported in placebo-controlled trials of aripiprazole for the unapproved use in elderly patients with dementia-related psychosis.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Dyslipidemia: Has been reported with atypical antipsychotics; risk profile may differ between agents. In clinical trials, lipid changes observed with aripiprazole monotherapy were similar to those observed with placebo.

• Esophageal dysmotility/aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; risk increases with age. Use with caution in patients at risk for aspiration pneumonia (eg, Alzheimer dementia), particularly in patients >75 years (Herzig 2017; Maddalena 2004).

• Extrapyramidal symptoms: May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is generally much lower relative to typical/conventional antipsychotics; frequencies reported are similar to placebo). Risk of dystonia (and probably other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Lehman 2004]; Soares-Weiser 2007). Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.

• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability.

• Hyperglycemia: Atypical antipsychotics have been associated with development of hyperglycemia; in some cases, may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. Use with caution in patients with diabetes or other disorders of glucose regulation; monitor for worsening of glucose control. Patients with risk factors for diabetes (eg, obesity or family history) should have a baseline fasting blood sugar and periodic assessment of glucose regulation. Reports of hyperglycemia with aripiprazole therapy have been few and specific risk associated with this agent is not known.

• Impulse control disorders: Has been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, uncontrolled sexual urges, uncontrolled spending, binge or compulsive eating, and/or other intense urges. Patients with prior history of impulse control issues may be at increased risk. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in most, but not all, cases (Gaboriau 2014; Moore 2014; Smith 2011).

• Neuroleptic malignant syndrome: Use may be associated with neuroleptic malignant syndrome; monitor for mental status changes, fever, muscle rigidity and/or autonomic instability.

• 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).

• Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.

• Weight gain: Significant weight gain (>7% of baseline weight) has been observed with antipsychotic therapy; incidence varies with product. Monitor waist circumference and BMI.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiac disease, cerebrovascular disease, prior myocardial infarction, ischemic heart disease, or conditions which predispose to hypotension.

• Dementia: [US Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in patients with Lewy body dementia or Parkinson disease dementia due to greater risk of adverse effects, increased sensitivity to extrapyramidal effects, and association with irreversible cognitive decompensation or death (APA [Reus 2016]). Aripiprazole is not approved for the treatment of dementia-related psychosis.

• Parkinson disease: Use with caution in patients with Parkinson disease; antipsychotics may aggravate motor disturbances (APA [Lehman 2004; 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.

• Product interchangeability: Injection There are 2 ER formulations available for IM administration: Aripiprazole monohydrate (Abilify Maintena) and aripiprazole lauroxil (Aristada and Aristada Initio).

• 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: When discontinuing antipsychotic therapy, the American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid physical withdrawal symptoms, including anorexia, anxiety, diaphoresis, diarrhea, dizziness, dyskinesia, headache, myalgia, nausea, paresthesia, restlessness, tremulousness and vomiting (APA [Lehman 2004]; CPA [Addington 2005]; Lambert 2007; WFSBP [Hasan 2012]). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anticholinergic or dopaminergic antipsychotics (Cerovecki 2013). Additional factors such as duration of antipsychotic exposure, the indication for use, medication half-life and risk for relapse should be considered. In schizophrenia, there is no reliable indicator to differentiate the minority who will not from the majority who will relapse with drug discontinuation. However, studies in which the medication of well-stabilized patients were discontinued indicate that 75% of patients relapse within 6 to 24 months. Indefinite maintenance antipsychotic medication is generally recommended, and especially for patients who have had multiple prior episodes or two episodes within 5 years (APA [Lehman 2004]).

Monitoring Parameters

Mental status; vital signs (as clinically indicated); blood pressure (baseline; repeat 3 months after antipsychotic initiation, then yearly); weight, height, BMI, waist circumference (baseline; repeat at 4, 8, and 12 weeks after initiating or changing therapy, then quarterly; consider switching to a different antipsychotic for a weight gain ≥5% of initial weight); CBC (as clinically indicated; monitor frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia); electrolytes and liver function (annually and as clinically indicated); personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease (baseline; repeat annually); fasting plasma glucose level/HbA1c (baseline; repeat 3 months after starting antipsychotic, then yearly); fasting lipid panel (baseline; repeat 3 months after initiation of antipsychotic; if LDL level is normal repeat at 2- to 5-year intervals or more frequently if clinical indicated); changes in menstruation, libido, development of galactorrhea, erectile and ejaculatory function (yearly); abnormal involuntary movements or parkinsonian signs (baseline; repeat weekly until dose stabilized for at least 2 weeks after introduction and for 2 weeks after any significant dose increase); tardive dyskinesia (every 12 months; high-risk patients every 6 months); ocular examination (yearly in patients >40 years; every 2 years in younger patients) (ADA 2004; Lehman 2004; Marder 2004); fall risk (baseline and periodically during treatment in patients with diseases or on medications that may also increase fall risk).

Reproductive Considerations

If treatment is needed in a woman planning a pregnancy, use of an agent other than aripiprazole is preferred (Larsen 2015).

Pregnancy Considerations

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/).

Patient Education

What is this drug used for?

• It is used to treat schizophrenia.

• It is used to treat bipolar problems.

• It is used to treat low mood (depression).

• It is used to treat certain behavior problems in patients with autism.

• It is used to treat Tourette's syndrome.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Fatigue

• Agitation

• Anxiety

• Headache

• Nausea

• Vomiting

• Weight gain

• Constipation

• Trouble sleeping

• Change in appetite

• Lack of appetite

• Stuffy nose

• Sore throat

• Dry mouth

• Tremors

• Drooling

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Depression like thoughts of suicide, anxiety, emotional instability, or confusion.

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit.

• Abnormal movements

• Twitching

• Change in balance

• Trouble swallowing

• Vision changes

• Eye pain

• Eye irritation

• Trouble speaking

• Severe dizziness

• Passing out

• Loss of strength and energy

• Blurred vision

• Uncontrollable urges

• Neuroleptic malignant syndrome like fever, muscle cramps or stiffness, dizziness, severe headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot.

• Tardive dyskinesia like unable to control body movements; tongue, face, mouth, or jaw sticking out; mouth puckering; or puffing cheeks.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions