ARIPiprazole (Lexi-Drugs)

ALERT: US Boxed Warning
  Increased mortality in elderly patients with dementia-related psychosis:
  Suicidality and antidepressant drugs:
Pronunciation

(ay ri PIP ray zole)

Brand Names: US

Abilify; Abilify Discmelt [DSC]; Abilify Maintena; Abilify MyCite

Brand Names: Canada

Abilify; Abilify Maintena; APO-ARIPiprazole; Auro-ARIPiprazole; PMS-ARIPiprazole; RIVA-ARIPiprazole; SANDOZ ARIPiprazole; TEVA-ARIPiprazole

Dosing: Adult

Note: Abilify immediate-release injection (9.75 mg/1.3 mL) has been discontinued in the US for more than 1 year.

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). Aripiprazole tablets with an ingestible event marker sensor (Abilify Mycite) may be considered in appropriately selected patients. The smartphone app and web portal will detect the ingestion within 30 minutes to 2 hours after ingestion.

Acute agitation (schizophrenia/bipolar mania): IM, immediate release: 9.75 mg as a single dose (range: 5.25 to 15 mg; a lower dose of 5.25 mg IM may be considered when clinical factors warrant); repeated doses may be given at ≥2-hour intervals to a maximum of 30 mg/day. Note: If ongoing therapy with aripiprazole is necessary, transition to oral therapy as soon as possible.

Bipolar I disorder:

Oral: Acute manic or mixed episodes (all oral formulations) and maintenance (tablet with sensor only):

Monotherapy: Initial: 15 mg once daily. May increase to 30 mg once daily if clinically indicated (maximum 30 mg/day); safety of doses >30 mg/day has not been evaluated

Adjunct to lithium or valproic acid: Initial: 10 to 15 mg once daily. Recommended target dose: 15 mg once daily; may increase to 30 mg once daily if clinically indicated (maximum 30 mg/day); safety of doses >30 mg/day has not been evaluated.

IM, extended release: Maintenance: 400 mg once monthly (doses should be separated by ≥26 days); Note: Tolerability should be established using oral aripiprazole prior to initiation of parenteral therapy; due to the half-life of oral aripiprazole it may take up to 2 weeks to fully assess tolerability. Continue oral aripiprazole (or other oral antipsychotic) for 14 days during initiation of parenteral therapy.

Missed doses:

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

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

Dosage adjustment for adverse effects: Consider reducing dose to 300 mg once monthly

Depression (adjunctive with antidepressants): Oral: Initial: 2 to 5 mg/day (range: 2 to 15 mg/day); dose adjustments of up to 5 mg/day may be made in intervals of ≥1 week, up to a maximum of 15 mg/day. Note: Dosing based on patients already receiving antidepressant therapy.

Schizophrenia:

Oral: 10 or 15 mg once daily; may be increased to a maximum of 30 mg once daily (efficacy at dosages above 10 to 15 mg has not been shown to be increased). Dosage titration should not be more frequent than every 2 weeks.

IM, extended release: 400 mg once monthly (doses should be separated by ≥26 days); Note: Tolerability should be established using oral aripiprazole prior to initiation of parenteral therapy; due to the half-life of oral aripiprazole it may take up to 2 weeks to fully assess tolerability. Continue oral aripiprazole (or other oral antipsychotic) for 14 days during initiation of parenteral therapy.

Missed doses:

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

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

Dosage adjustment for adverse effects: Consider reducing dose to 300 mg once monthly

Dosage adjustment with concurrent CYP450 inducer or inhibitor therapy:

Oral and IM, immediate release: Note: Dose reduction does not apply when adjunctive aripiprazole is administered to patients with major depressive disorder; follow usual dosing recommendations.

CYP3A4 inducers (eg, carbamazepine, rifampin): Aripiprazole dose should be doubled over 1 to 2 weeks; dose should be subsequently reduced to the original level over 1 to 2 weeks if concurrent inducer agent is discontinued.

Strong CYP3A4 inhibitors (eg, itraconazole, clarithromycin): Aripiprazole dose should be reduced to 50% of the usual dose, and proportionally increased upon discontinuation of the inhibitor agent.

Strong CYP2D6 inhibitors (eg, quinidine, fluoxetine, paroxetine): Aripiprazole dose should be reduced to 50% of the usual dose, and proportionally increased upon discontinuation of the inhibitor agent.

CYP3A4 and CYP2D6 inhibitors: Aripiprazole dose should be reduced to 25% of the usual dose. In patients receiving inhibitors of differing (eg, moderate 3A4/strong 2D6) or same (eg, moderate 3A4/moderate 2D6) potencies (excluding concurrent strong inhibitors), further dosage adjustments can be made to achieve the desired clinical response. In patients receiving strong CYP3A4 and 2D6 inhibitors, aripiprazole dose is proportionally increased upon discontinuation of one or both inhibitor agents.

IM, extended release: Note: Dosage adjustments are not recommended for concomitant use of CYP3A4 inhibitors, CYP2D6 inhibitors or CYP3A4 inducers for <14 days. In patients who had their aripiprazole dose adjusted for concomitant therapy, the aripiprazole dose may need to be increased if the CYP3A4 and/or CYP2D6 inhibitor is withdrawn.

CYP3A4 inducers: Avoid use; aripiprazole serum concentrations may fall below effective levels.

Strong CYP3A4 or CYP2D6 inhibitors:

Current aripiprazole dose of 300 mg once monthly: Reduce aripiprazole dose to 200 mg once monthly

Current aripiprazole dose of 400 mg once monthly: Reduce aripiprazole dose to 300 mg once monthly

Strong CYP3A4 inhibitors and CYPD2D6 inhibitors:

Current aripiprazole dose of 300 mg once monthly: Reduce aripiprazole dose to 160 mg once monthly

Current aripiprazole dose of 400 mg once monthly: Reduce aripiprazole dose to 200 mg once monthly

Dosage adjustment based on CYP2D6 metabolizer status:

Oral and IM, immediate release: 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 (eg, itraconazole, clarithromycin); subsequently adjust dose for favorable clinical response.

IM, extended release: Reduce aripiprazole dose to 300 mg once monthly in CYP2D6 poor metabolizers; reduce dose to 200 mg once monthly in CYP2D6 poor metabolizers receiving a concurrent CYP3A4 inhibitor for >14 days.

Discontinuation of therapy: American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (APA [Lehman 2004]; Cerovecki 2013; CPA [Addington 2005]; 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 [Addington 2005]). Continuing anti-parkinsonism 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).

Dosing: Geriatric

Refer to adult dosing.

Psychosis/agitation associated with dementia (off-label use):

IM, immediate release: Initial: 2.5 to 10 mg once; a repeat dose of 2.5 to 5 mg may be given at ≥2-hour intervals not to exceed 15 mg/day (Rappaport 2009).

Oral: Initial: 2 to 5 mg once daily; if necessary gradually increase based on response and tolerability not to exceed 15 mg daily. In patients without a clinically significant response after 4 weeks, taper and withdraw therapy. In patients with an adequate response, attempt to taper and withdraw therapy within 4 months, unless symptoms recurred with a previous taper attempt. Assess symptoms at least monthly during taper and for at least 4 months after withdrawal of therapy (APA [Reus 2016]); De Deyn 2005; Mintzer 2007; Streim 2008).

Dosing: Renal Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

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 notinterchangeable.

Attention-deficit/hyperactivity disorder (ADHD): Limited data available: Children ≥8 years and Adolescents: Oral: Initial: 2.5 mg/day; may increase on a weekly basis by 2.5 mg/day increments as tolerated; maximum daily dose: 10 mg/day; dosing based on an open-label, pilot study (n=23, age: 8 to 12 years) which reported significant improvement in ADHD outcome scores without an impact on cognitive measures (positive or negative); mean final dose: 6.7 ± 2.4 mg/day (Findling 2008). Other aripiprazole published reports in pediatric and adolescent patients in which ADHD is a comorbid diagnosis within the study population exist; however, effectiveness in ADHD was not a reported primary outcome measure (Bastiaens 2009; Budman 2008; Findling 2009; Murphy 2009; Valicenti-McDermott 2006).

Autism; treatment of associated irritiability (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/dayNote: 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/dayNote: 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 with concurrent CYP450 inducer or inhibitor therapy:

Oral: Children and Adolescents:

CYP3A4 inducers (eg, carbamazepine, rifampin): Aripiprazole dose should be doubled over 1 to 2 weeks; dose should be subsequently reduced if concurrent inducer agent discontinued.

Strong CYP3A4 inhibitors (eg, ketoconazole): Aripiprazole dose should be reduced to 50% of the usual dose, and proportionally increased upon discontinuation of the inhibitor agent.

CYP2D6 inhibitors (eg, fluoxetine, paroxetine): Aripiprazole dose should be reduced to 50% of the usual dose, and proportionally increased upon discontinuation of the inhibitor agent. Note: When aripiprazole is administered as adjunctive therapy to patients with MDD, the dose should not be adjusted, follow usual dosing recommendations.

CYP3A4 and CYP2D6 inhibitors: Aripiprazole dose should be reduced to 25% of the usual dose. In patients receiving inhibitors of differing (eg, moderate 3A4/strong 2D6) or same (eg, moderate 3A4/moderate 2D6) potencies (excluding concurrent strong inhibitors), further dosage adjustments can be made to achieve the desired clinical response. In patients receiving strong CYP3A4 and 2D6 inhibitors, aripiprazole dose is proportionally increased upon discontinuation of one or both inhibitor agents.

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.

Dosing: Renal Impairment: Pediatric

No dosage adjustment required.

Dosing: Hepatic Impairment: Pediatric

No dosage adjustment required.

Use: Labeled Indications

Oral:

Bipolar I disorder: As monotherapy or as adjunctive therapy to lithium or valproate for acute treatment of manic or mixed episodes and maintenance (tablet with sensor only) associated with bipolar I disorder

Irritability associated with autistic disorder: Treatment of irritability associated with autistic disorder (tablet, orally disintegrating tablet and oral solution only)

Major depressive disorder: Adjunctive treatment of major depressive disorder

Schizophrenia: Treatment of schizophrenia

Tourette disorder: Treatment of Tourette disorder (tablet, orally disintegrating tablet and oral solution only)

Injection:

Agitation associated with schizophrenia or bipolar mania (immediate-release injection only): Treatment of agitation associated with schizophrenia or bipolar mania

Bipolar I disorder (extended-release injection only): Maintenance monotherapy treatment of bipolar I disorder

Schizophrenia (extended-release injection only): Treatment of schizophrenia

Use: Off-Label: Adult

  Psychosis/agitation associated with dementiaLevel of Evidence [B, G]

Data from randomized, double-blind, placebo-controlled trials supports the use of aripiprazole in the treatment psychosis and agitation related to Alzheimer dementia Ref. Additional trials may be necessary to further define the role of aripiprazole in this condition.

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 antipsychotic use. Based on the World Federation of Societies of Biological Psychiatry 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.

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Alzheimer Disease and Other Dementias:

American Psychiatric Association, “Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients with Dementia,” May 2016

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Biological Treatment of Alzheimer’s Disease and Other Dementias,” 2011

Bipolar Disorder:

American Academy of Child and Adolescent Psychiatry. “Practice Parameter for the Assessment and Treatment of Children and Adolescents with Bipolar Disorder,” 2007

American Psychiatric Association. “Practice Guideline for the Treatment of Patients with Bipolar Disorder (Revision),” 2002

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD), “Collaborative Update of CANMAT Guidelines for the Management of Patients with Bipolar Disorder – Update 2013,” February 2013

National Institute for Health and Clinical Excellence (NICE), National Collaborating Centre for Mental Health, “Bipolar Disorder: The Assessment and Management of Bipolar Disorder in Adults, Children and Young People in Primary and Secondary Care,” 2014

“The Texas Implementation of Medication Algorithms: Update to the Algorithms for Treatment of Bipolar I Disorder,” July 2005

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2009 on the Treatment of Acute Mania,” 2009

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2010 on the Treatment of Acute Bipolar Depression,” 2010

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2012 on the Long-term Treatment of Bipolar Disorder,” 2013

Depression:

American Psychiatric Association, Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition, May 2010

National Collaborating Centre for Mental Health (NCCMH), “Depression: The NICE Guideline on the Treatment and Management of Depression in Adults (Updated Edition).” 2010.

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the Acute and Continuation Treatment of Unipolar Depressive Disorders,” 2013

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance Treatment of Major Depressive Disorder and Treatment of Chronic Depressive Disorders and Subthreshold Depressions,” 2002

Schizophrenia:

American Academy of Child and Adolescent Psychiatry, Practice Parameter for the Assessment and Treatment of Children and Adolescents with Schizophrenia

American Psychiatric Association,” Practice Guideline for the Treatment of Patients with Schizophrenia, Second Edition,” 2004

Canadian Psychiatric Association, Clinical Practice Guidelines, “Treatment of Schizophrenia,” November 2005

National Institute for Health and Clinical Excellence (NICE), National Collaborating Center for Mental Health, “Psychosis and Schizophrenia in Adults: Treatment and Management ” March 2014

National Institute for Health and Clinical Excellence (NICE), National Collaborating Center for Mental Health, “Psychosis and Schizophrenia in Children and Young People: Recognition and Management” 2013

“The Texas Algorithm Project Antipsychotic Algorithm for Schizophrenia: 2006 Update,” 2007

WFSBP, “Guidelines for the Biological Treatment of Schizophrenia, Part 1: Update 2012 on the Acute Treatment of Schizophrenia and the Management of Treatment Resistance,” 2012

WFSBP, “Guidelines for the Biological Treatment of Schizophrenia, Part 2: Update 2012 on the Long-Term Treatment of Schizophrenia and Management of Antipsychotic-Induced Side Effects,” 2013

Administration: IM

Injection: For IM use only; do not administer SubQ or IV; Note: Immediate-release and extended-release parenteral products are not interchangeable.

Immediate release: Inject slowly into deep muscle mass

Extended release: Inject slowly into deltoid or gluteal muscle using the appropriate provided needle; for non-obese 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 two deltoid or gluteal muscles. Administer monthly (doses should be separated by ≥26 days).

Administration: 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 immediate-release 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.

Administration: Pediatric

Oral (all dosage forms): May be administered with or without 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.

Dietary Considerations

Some products may contain phenylalanine.

Storage/Stability

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).

Injection, solution (immediate release): Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Retain in carton until time of use.

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.

Preparation for Administration: Adult

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.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, agitation, anxiety, headache, nausea, vomiting, weight gain, constipation, insomnia, change in appetite, lack of appetite, rhinitis, pharyngitis, dry mouth, tremors, or drooling. Have patient report immediately to prescriber signs of infection, signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), abnormal movements, twitching, change in balance, difficulty swallowing, vision changes, eye pain, eye irritation, difficulty speaking, severe dizziness, passing out, loss of strength and energy, blurred vision, uncontrollable urges, signs of neuroleptic malignant syndrome (fever, muscle cramps or stiffness, dizziness, severe headache, confusion, change in thinking, tachycardia, abnormal heartbeat, or sweating a lot), or signs of tardive dyskinesia (unable to control body movements; tongue, face, mouth, or jaw sticking out; mouth puckering; or puffing cheeks) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  Geriatric Patients: High-Risk Medication:
  Other safety issues:
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Abilify: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm085804.pdf

Abilify Maintena: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM342207.pdf

Contraindications

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

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 healthcare 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 healthcare 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 (EPS): May cause extrapyramidal symptoms, 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. Complete fall risk assessments at baseline and periodically during treatment in patients with diseases or on medications that may also increase fall risk.

• 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 (FBS) 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 (NMS): Use may be associated with neuroleptic malignant syndrome (NMS); 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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 two formulations available for intramuscular administration: Abilify is an immediate-release short-acting formulation and Abilify Maintena is an extended-release formulation. These products are not interchangeable.

• 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]).

Geriatric Considerations

Aripiprazole has been studied in elderly patients with psychosis associated with Alzheimer’s disease. The package insert does not provide the outcomes of this study other than somnolence was more frequent with aripiprazole (8%) than placebo (1%). Aripiprazole’s delayed onset of action and long half-life may limit its role in treating older persons with psychosis.

Elderly patients have an increased risk of adverse effects to antipsychotics. In light of this risk, and relative to their small beneficial effect in the treatment of dementia-related psychosis and behavioral disorders, patients should be evaluated for possible reversible causes before being started on an antipsychotic. Nonpharmacologic interventions should be tried before initiating an antipsychotic.

Warnings: Additional Pediatric Considerations

Aripiprazole may cause a higher than normal weight gain in children and adolescents; monitor growth (including weight, height, BMI, and waist circumference) in pediatric patients receiving aripiprazole; compare weight gain to standard growth curves. Note: A prospective, nonrandomized cohort study followed 338 antipsychotic naive pediatric patients (age: 4 to 19 years) for a median of 10.8 weeks (range: 10.5 to 11.2 weeks) and reported the following significant mean increases in weight in kg (and % change from baseline): Olanzapine: 8.5 kg (15.2%), quetiapine: 6.1 kg (10.4%), risperidone: 5.3 kg (10.4%), and aripiprazole: 4.4 kg (8.1%) compared to the control cohort: 0.2 kg (0.65%).

Hyperglycemia has been reported with aripiprazole; in analysis of pediatric trials (patients 6 to 18 years, diagnosis including schizophrenia, autistic disorder, bipolar disorder, and Tourette’s disorder), the mean change in fasting glucose was not observed to be significantly different than placebo-treated patients (median exposure range: 43 to 57 days). However, with longer exposure (mean: 17.2 months), an increased risk for the development of type 2 diabetes mellitus (DM) was observed in pediatric patients 10 to 18 years receiving second-generation antipsychotics (SGA); for patients initiated on SGA: 0.4% incidence with mean exposure at time type 2 DM diagnosed: 13.5 months; for SGA noniniators (patients receiving another agent prior to SGA initiation): 0.2% incidence with mean exposure at time of type 2 DM diagnosed: 14.6 months. Amongst specific SGA’s, the risk was highest for aripiprazole (p=0.001) followed by ziprasidone (p=0.06) compared to risperidone as the reference group but not quetiapine or olanzapine (Rubin 2015). Increases in metabolic indices (eg, serum cholesterol, triglycerides) were also reported; however, these changes were not significant in patients receiving aripiprazole (Correll 2009); additionally, in clinical trials, lipid changes observed with aripiprazole monotherapy in pediatric patients were similar to those observed with placebo. Biannual monitoring of cardiometabolic indices after the first 3 months of therapy is suggested (Correll 2009).

Children and adolescents may experience a higher frequency of some adverse effects than adults, including EPS (20% vs 5%), fatigue (17% vs 8%), and somnolence (23% vs 6%).

Pediatric psychiatric disorders are frequently serious mental 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, or irritability associated with autistic 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).

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. 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 needed in a woman planning a pregnancy or 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/).

Breast-Feeding Considerations

Aripiprazole and dehydroaripiprazole 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 (dehydroaripiprazole), 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).

The manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother. The manufacturer of the extended-release injection recommends the development and health benefits of breastfeeding be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from aripiprazole or from the underlying maternal condition. Until additional information is available, use of agents other than aripiprazole in breastfeeding women is preferred (Pacchiarotti 2016; Uguz 2016).

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

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.

IV:

>10%:

Central nervous system: Headache (12%), akathisia (dose-related; 2% to 12%)

Endocrine & metabolic: Weight gain (17% to 22%), increased serum cholesterol (4% to 22%), increased serum triglycerides (7% to 20%), increased LDL cholesterol (10% to 14%), decreased HDL cholesterol (14%)

1% to 10%:

Cardiovascular: Tachycardia (≤2%), anxiety (≥1%)

Central nervous system: Extrapyramidal reaction (10%), drowsiness (9%), sedation (5%), dizziness (4%), dystonia (2%), fatigue (dose-related; 1% to 2%), restlessness (≥1%), insomnia

Endocrine & metabolic: Increased serum glucose (8%), weight loss (4%)

Gastrointestinal: Constipation (10%), xerostomia (4%), diarrhea (3%), vomiting (3%)

Hematologic & oncologic: Neutropenia (6%)

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

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

Respiratory: Upper respiratory tract infection (4%), nasal congestion (2%)

Oral:

>10%:

Central nervous system: Headache (adults: 27%; children and adolescents: 10% to 12%), extrapyramidal reaction (dose-related; children and adolescents: 6% to 27%; adults: 5% to 13%), drowsiness (children and adolescents: 10% to 26%; adults: 5% to 13%), akathisia (dose-related; adults: 2% to 25%; children and adolescents: 6% to 11%), fatigue (dose-related; children and adolescents: 4% to 22%; adults: 6%), sedation (dose-related; children and adolescents: 9% to 21%; adults: 3% to 11%), agitation (19%), insomnia (18%), anxiety (17%)

Endocrine & metabolic: Weight gain (children and adolescents: 3% to 26%; adults 2% to 8%), increased serum glucose (adults: 18%; children and adolescents: 3% to 5%), decreased HDL cholesterol (children and adolescents: 4%)

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

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

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

1% to 10%:

Cardiovascular: Orthostatic hypotension (≤1%)

Central nervous system: Dizziness (3% to 10%), drooling (children and adolescents: 3% to 9%), restlessness (5% to 6%), lethargy (older adults: 5%; children: 3% to 5%), pain (3%), dystonia (2%), irritability (children and adolescents: 2%)

Dermatologic: Skin rash (2%)

Endocrine & metabolic: Increased serum triglycerides (5% to 10%), weight loss (≥1%), increased serum cholesterol (1%)

Gastrointestinal: Dyspepsia (9%), decreased appetite (children and adolescents: 5% to 7%), increased appetite (children and adolescents: 7%), xerostomia (5%), diarrhea (children and adolescents: 4%), toothache (4%), stomach discomfort (3%), upper abdominal pain (children and adolescents: 3%), abdominal distress (2% to 3%), anorexia

Genitourinary: Urinary incontinence (older adults: 5%)

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

Ophthalmic: Blurred vision (3% to 8%)

Respiratory: Nasopharyngitis (children and adolescents: 6% to 9%), cough (3%), pharyngolaryngeal pain (3%), epistaxis (children and adolescents: 2%)

Miscellaneous: Fever (children and adolescents: 4% to 9%)

<1%, postmarketing, and/or case reports: Abdominal distress (injection), abnormal bilirubin levels, abnormal gait, abnormal hepatic function tests, abnormal T waves on ECG, aggressive behavior, agitation (injection), agranulocytosis, akinesia, alopecia, altered serum glucose, amenorrhea, anaphylaxis, angina pectoris, angioedema, anorexia (injection), anorgasmia, aspiration pneumonia, asthenia (injection), ataxia, atrial fibrillation, atrial flutter, atrioventricular block, blurred vision (injection), bradycardia, bradykinesia, bruxism, cardiac arrhythmia, catatonia, cerebrovascular accident, change in libido, chest discomfort, chest pain, choreoathetosis, cogwheel rigidity, decreased appetite (injection), decreased serum cholesterol, decreased serum triglycerides, delayed ejaculation, delirium, depression, diabetes mellitus, diabetic ketoacidosis, diplopia, disruption of body temperature regulation, dysgeusia, dyspepsia (injection), dysphagia, dyspnea, dystonia (oromandibular), edema, elevated glycosylated hemoglobin, erectile dysfunction, esophagitis, extrasystoles, eyelid edema, facial edema, falling, fever (injection), gastroesophageal reflux disease, glycosuria, gynecomastia, heatstroke, hepatic failure, hepatitis, hepatotoxicity, hirsutism, homicidal ideation, hostility, hyperglycemia, hyperhidrosis, hyperinsulinism, hyperlipidemia, hypersensitivity reaction, hypersomnia, hypertension, hypertonia, hypoglycemia, hypokalemia, hypokinesia, hyponatremia, hypotension (oral), hypothermia, hypotonia, impulse control disorder (including pathologic gambling and hypersexuality), increased blood urea nitrogen, increased creatinine clearance, increased creatine phosphokinase, increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased liver enzymes, increased serum bilirubin, increased serum prolactin, inhibition of prolactin secretion, intentional injury, irritability (injection), ischemic heart disease, jaundice, joint stiffness, laryngospasm, lethargy (injection), leukopenia, limb pain (injection), mastalgia, memory impairment, menstrual disease, mobility disorder, muscle rigidity (injection), muscle spasm (injection), muscle twitching, myasthenia, myocardial infarction, myoclonus, nasal congestion (oral), nasopharyngitis (injection), nausea (injection), neuroleptic malignant syndrome, nocturia, obesity, oculogyric crisis, oropharyngeal spasm, pain (oral), palpitations, pancreatitis, panic attack, Parkinson disease, peripheral edema, pharyngolaryngeal pain (injection), photophobia, photopsia, pollakiuria, polydipsia, polyuria, presyncope, priapism, prolonged Q-T interval on ECG, pruritus, psychosis, rhabdomyolysis, seizure (including injection), seizure (tonic clonic), sinus tachycardia, skin photosensitivity, skin rash (injection), sleep apnea (obstructive) (Health Canada, August 16, 2016; Shirani 2011), sleep talking, somnambulism, speech disturbance, stomach discomfort (injection), suicidal ideation, suicidal tendencies, supraventricular tachycardia, swollen tongue, syncope, tardive dyskinesia, thrombocytopenia, tics, tongue spasm, toothache (injection), torsades de pointes, transient ischemic attacks, trismus, uncontrolled diabetes mellitus, upper abdominal pain (injection), urinary incontinence (injection), urinary retention, urticaria, venous thromboembolism, ventricular tachycardia

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Substrate of CYP2D6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions 

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification

Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. 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: Antipsychotic Agents may enhance the adverse/toxic effect of Amisulpride. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk X: Avoid combination

Amphetamines: Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. 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 using an alternative antipsychotic agent when possible in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine or quetiapine, which may convey the lowest interaction risk. Risk D: Consider therapy modification

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

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

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of 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

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

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. 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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.Risk D: Consider therapy modification

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

Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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

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

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

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

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: 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 and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May increase the serum concentration of ARIPiprazole. Management: See full interaction monograph for details. Risk D: Consider therapy modification

CYP2D6 Inhibitors (Weak): 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 and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

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

CYP3A4 Inducers (Strong): May decrease the serum concentration of ARIPiprazole. Management: Double the oral aripiprazole dose and closely monitor. Reduce oral aripiprazole dose to 10-15 mg/day (for adults) if the inducer is discontinued. 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 and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of ARIPiprazole. Management: See full interaction monograph for details. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Weak): 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 and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

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

Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Risk D: Consider therapy modification

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

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

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

DULoxetine: ARIPiprazole may enhance the adverse/toxic effect of DULoxetine. ARIPiprazole may enhance the serotonergic effect of DULoxetine. This could result in serotonin syndrome. DULoxetine may increase the serum concentration of ARIPiprazole. Risk C: Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: 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. Risk D: Consider therapy modification

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

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

FLUoxetine: May enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of neuroleptic malignant syndrome may be increased. ARIPiprazole may enhance the serotonergic effect of FLUoxetine. This could result in serotonin syndrome. FLUoxetine may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose should be reduced by at least half, except when used adjunctively for depression. Consult full interaction monograph or aripiprazole prescribing information for complete details.Risk D: Consider therapy modification

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

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

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

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

Haloperidol: ARIPiprazole may enhance the QTc-prolonging effect of Haloperidol. ARIPiprazole may diminish the therapeutic effect of Haloperidol. Haloperidol may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph. Aripiprazole dose adjustment may not be required when used as adjunctive therapy for major depressive disorder. Risk D: Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone 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

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

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

Imatinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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 anticonvulsants. 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 anticonvulsants. 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 anticonvulsants. Risk D: Consider therapy modification

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

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

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

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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Risk D: Consider therapy modification

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

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: 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. Risk D: Consider therapy modification

Methadone: May enhance the CNS depressant effect of ARIPiprazole. ARIPiprazole may enhance the QTc-prolonging effect of Methadone. Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

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

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

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

MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: 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. Risk D: Consider therapy modification

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Risk C: 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. Risk D: Consider therapy modification

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

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

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

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

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

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

PARoxetine: May enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of neuroleptic malignant syndrome may be increased. ARIPiprazole may enhance the serotonergic effect of PARoxetine. This could result in serotonin syndrome. PARoxetine may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose adjustment is recommended, except when used adjunctively for depression. Consult full interaction monograph or aripiprazole prescribing information for complete details. Risk D: Consider therapy modification

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. 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. Risk D: Consider therapy modification

Perhexiline: CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Risk D: Consider therapy modification

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

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

Ritonavir: ARIPiprazole may enhance the adverse/toxic effect of Ritonavir. The risk of metabolic disturbances (e.g. hyperglycemia, weight gain, hyperlipidemia) may be increased. Ritonavir may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph. Aripiprazole dose adjustment may not be required when used as adjunctive therapy for major depressive disorder. 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

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

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Risk C: Monitor therapy

Sertraline: May enhance the adverse/toxic effect of ARIPiprazole. Sertraline may increase the serum concentration of ARIPiprazole. Risk C: Monitor therapy

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

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

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Risk D: Consider therapy modification

St John’s Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

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. Risk D: Consider therapy modification

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

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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

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

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

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

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

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

Trimeprazine: May increase the serum concentration of ARIPiprazole. 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

Food Interactions

Ingestion with a high-fat meal delays time to peak plasma level. Management: Administer without regard to meals.

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).

Advanced Practitioners Physical Assessment/Monitoring

Assess mental status for depression and suicidal ideation. Assess other medicines patient may be taking; alternate therapy or dosage adjustments may be needed. Obtain vital signs (as clinically indicated); blood pressure (baseline; repeat 3 months after antipsychotic initiation, then yearly); ECG (as needed); 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). Obtain CBC, electrolytes, liver function tests, glucose, and fasting lipids. Assess for changes in menstruation, libido, development of galactorrhea, erectile dysfunction, tardive dyskinesia, involuntary movements, or parkinsonian signs. Obtain ophthalmic exam (yearly in patients >40 years; every 2 years in younger patients). Assess for extrapyramidal symptoms prior to and during therapy.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Check vitals, BMI, abdominal girth, and weight as ordered. Monitor for depression or suicidal ideation. Educate patient to report signs of depression, changes in movement, vision changes, changes in menstruation, or changes in sexual function. Monitor for extrapyramidal symptoms prior to and periodically during therapy, particularly akathisia (restlessness).

Product Availability

Abilify immediate-release injection (9.75 mg/1.3 mL) has been discontinued in the US for more than 1 year.

Dosage Forms Considerations

Oral solution contains fructose 200 mg and sucrose 400 mg per mL.

Abilify Mycite is a drug-device combination product comprised of aripiprazole tablets embedded with an Ingestible Event Marker (IEM) sensor intended to track drug ingestion.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Prefilled Syringe, Intramuscular:

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

Solution, Intramuscular:

Abilify: 9.75 mg/1.3 mL (1.3 mL [DSC])

Solution, Oral:

Abilify: 1 mg/mL (150 mL [DSC]) [contains methylparaben, propylene glycol, propylparaben]

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:

Abilify Discmelt: 10 mg [DSC], 15 mg [DSC] [contains aspartame, fd&c blue #2 aluminum lake]

Generic: 10 mg, 15 mg

Dosage Forms: Canada

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

Suspension Reconstituted ER, Intramuscular:

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

Tablet, Oral:

Abilify: 2 mg, 5 mg [contains CORN STARCH, FD&C BLUE #2 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

Anatomic Therapeutic Chemical (ATC) Classification
  • N05AX12
Generic Available (US)

May be product dependent

Pricing: US

Prefilled Syringe (Abilify Maintena Intramuscular)

300 mg (per each): $1,949.77

400 mg (per each): $2,599.69

Solution (ARIPiprazole Oral)

1 mg/mL (per mL): $7.06 – $7.07

Suspension Reconstituted ER (Abilify Maintena Intramuscular)

300 mg (per each): $1,949.77

400 mg (per each): $2,599.69

Tablet, orally-disintegrating (ARIPiprazole Oral)

10 mg (per each): $38.13 – $41.89

15 mg (per each): $38.13 – $41.89

Tablets (Abilify MyCite Oral)

2 mg (per each): $66.00

5 mg (per each): $66.00

10 mg (per each): $66.00

15 mg (per each): $66.00

20 mg (per each): $66.00

30 mg (per each): $66.00

Tablets (Abilify Oral)

2 mg (per each): $35.68

5 mg (per each): $35.68

10 mg (per each): $35.68

15 mg (per each): $35.68

20 mg (per each): $50.45

30 mg (per each): $50.45

Tablets (ARIPiprazole Oral)

2 mg (per each): $30.74 – $32.11

5 mg (per each): $31.83 – $32.11

10 mg (per each): $31.87 – $32.11

15 mg (per each): $30.74 – $32.11

20 mg (per each): $32.00 – $45.41

30 mg (per each): $37.44 – $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.

Mechanism of Action

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).

Pharmacodynamics/Kinetics

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: Initial: 1 to 3 weeks

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: IM: 100%; 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, extended release (terminal): ~30 to 47 days (dose-dependent)

CYP2D6 poor metabolizers: Aripiprazole: 146 hours

Time to peak, plasma:

IM:

Immediate release: 1 to 3 hours

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

Tablet: 3 to 5 hours

With high-fat meal: Aripiprazole: Delayed by 3 hours; dehydro-aripiprazole: Delayed by 12 hours

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)

Pharmacodynamics/Kinetics: Additional Considerations

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.

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

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

Gender: 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).

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health Professional Considerations

Aripiprazole works differently from the classic antipsychotics, such as chlorpromazine, in that it does not appear to block central dopaminergic receptors, but rather seems to be a stabilizer of dopamine-serotonin central systems. The risk of extrapyramidal reactions such as pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia are low and the frequencies reported are similar to placebo. Aripiprazole may be associated with neuroleptic malignant syndrome (NMS).

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Extrapyramidal symptoms (similar to placebo) (see Dental Health Professional Considerations); xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation).

Effects on Bleeding

No information available to require special precautions

Index Terms

BMS 337039; OPC-14597

FDA Approval Date
June 01, 2012
References

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Abilify Mycite (aripiprazole) [prescribing information]. Rockville, MD: Otsuka America Pharmaceutical; November 2017.

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Duane DD, “Aripiprazole in Childhood and Adolescence for Tourette Syndrome,”J Child Neurol, 2006, 21(4):358.[PubMed 16900939]

Durkin JP, “Aripiprazole in the Treatment of Bipolar Disorder in Children and Adolescents,”J Child Adolesc Psychopharmacol, 2004, 14(4):505-6.[PubMed 15662141]

Findling RL, Kauffman R, Sallee FR, et al, “An Open-Label Study of Aripiprazole: Pharmacokinetics, Tolerability, and Effectiveness in Children and Adolescents With Conduct Disorder,” J Child Adolesc Psychopharmacol, 2009, 19(4):431-9.[PubMed 19702495]

Gaboriau L, Victorri-Vigneau C, Gérardin M, et al. Aripiprazole: a new risk factor for pathological gambling? A report of 8 case reports. Addict Behav. 2014;39(3):562-565.[PubMed 24315783]

Gill SS, Bronskill SE, Normand SL, et al, “Antipsychotic Drug Use and Mortality in Older Adults With Dementia,” Ann Intern Med, 2007, 146(11):775-86.[PubMed 17548409]

Hasan A, Falkai P, Wobrock T, et al; World Federation of Societies of Biological Psychiatry (WFSBP) Task Force on Treatment Guidelines for Schizophrenia. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012;13(5):318-378. doi: 10.3109/15622975.2012.696143.[PubMed 22834451]

Healthy Canadians Recalls & Alerts. Safety information for antipsychotic drug Abilify and risk of certain impulse-control behaviours. Health Canada website. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/55668a-eng.php. Published November 2, 2015. Accessed November 2, 2015.

Healthy Canadians Recalls & Alerts. Summary safety review – atypical antipsychotics – assessing the potential risk of sleep apnoea. Health Canada website. https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/safety-reviews/summary-safety-review-atypical-antipsychotics-assessing-potential-risk-sleep-apnoea.html. Published August 16, 2016. Accessed August 23, 2016.

Hellerstein DJ, “Aripiprazole as an Adjunctive Treatment for Refractory Major Depression,” Prog Neuropsychopharmacol Biol Psychiatry, 2004, 28(8):1347-8.[PubMed 15588762]

Herzig SJ, LaSalvia MT, Naidus E, et al. Antipsychotics and the risk of aspiration pneumonia in individuals hospitalized for nonpsychiatric conditions: a cohort study. J Am Geriatr Soc. 2017;65(12):2580-2586. doi: 10.1111/jgs.15066.[PubMed 29095482]

Inoue A, Miki S, Seto M, et al, “Aripiprazole, A Novel Antipsychotic Drug, Inhibits Quinpirole-Evoked GTPase Activity But Does Not Up-Regulate Dopamine D2 Receptor Following Repeated Treatment in the Rat Striatal Slices,” Eur J Pharmacol, 1997, 321(1):105-11.[PubMed 9083792]

Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126.[PubMed 10891521]

Jordan S, Koprivica V, Chen R, et al, “The Antipsychotic Aripiprazole Is a Potent, Partial Agonist at the Human 5-HT(1A) Receptor,” Eur J Pharmacol, 2002, 441(3):137-40.[PubMed 12063084]

Kane JM, Carson WH, Saha AR, et al, “Efficacy and Safety of Aripiprazole and Haloperidol Versus Placebo in Patients With Schizophrenia and Schizoaffective Disorder,” J Clin Psychiatry, 2002, 63(9):763-71.[PubMed 12363115]

Ketter TA, Wang PW, Chandler RA, et al, “Adjunctive Aripiprazole in Treatment-Resistant Bipolar Depression,” Ann Clin Psychiatry, 2006, 18(3):169-72.[PubMed 16923655]

Lambert TJ. Switching antipsychotic therapy: what to expect and clinical strategies for improving therapeutic outcomes. J Clin Psychiatry. 2007;68(suppl 6):10-13.[PubMed 17650054]

Larsen ER, Damkier P, Pedersen LH, et al. Use of psychotropic drugs during pregnancy and breast-feeding. Acta Psychiatr Scand Suppl. 2015;(445):1-28.[PubMed 26344706]

Lawler CP, Prioleau C, Lewis MM, et al, “Interactions of the Novel Antipsychotic Aripiprazole (OPC-14597) With Dopamine and Serotonin Receptor Subtypes,” Neuropsychopharmacology, 1999, 20(6):612-27.[PubMed 10327430]

Lutz UC, Hiemke C, Wiatr G, et al, “Aripiprazole in Pregnancy and Lactation: A Case Report,” J Clin Psychopharmacol, 2010. 30(2):204-5.[PubMed 20520299]

Maddalena AS, Fox M, Hofmann M, Hock C. Esophageal dysfunction on psychotropic medication. A case report and literature review. Pharmacopsychiatry. 2004;37(3):134-138. doi: 10.1055/s-2004-818993.[PubMed 15138897]

Marder SR, Essock SM, Miller Al, et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry. 2004;161(8):1334-1349.[PubMed 15285957]

Matsubayashi H, Amano T, and Sasa M, “Inhibition by Aripiprazole of Dopaminergic Inputs to Striatal Neurons From Substantia Nigra,” Psychopharmacology (Berl), 1999, 146(2):139-43.

McGavin JK and Goa KL, “Aripiprazole,” CNS Drugs, 2002, 16(11):779-86.[PubMed 12383035]

Mendhekar DN, Sunder KR, and Andrade C, “Aripiprazole Use in a Pregnant Schizoaffective Woman,” Bipolar Disord, 2006, 8(3):299-300.[PubMed 16696834]

Mervak B, Collins J, and Valenstein M, “Case Report of Aripiprazole Usage During Pregnancy,” Arch Womens Ment Health, 2008, 11(3):249-50.[PubMed 18581041]

Mintzer JE, Tune LE, Breder CD, et al. Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses. Am J Geriatr Psychiatry. 2007;15(11):918-931.[PubMed 17974864]

Moore TA, “Schizophrenia Treatment Guidelines in the United States,” Clin Schizophr Relat Psychoses, 2011, 5(1):40-9.[PubMed 21459738]

Moore TJ, Glenmullen J, Mattison DR. Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs. JAMA Intern Med. 2014;174(12):1930-1933.

Nguyen T, Teoh S, Hackett LP, et al, “Placental Transfer of Aripiprazole,” Aust N Z J Psychiatry, 2011, 45(6):500-1.[PubMed 21413838 ]

Nordeng H, Gjerdalen G, Brede WR, Michelsen LS, Spigset O. Transfer of aripiprazole to breast milk: a case report. J Clin Psychopharmacol. 2014;34(2):272-275[PubMed 24525642]

Pacchiarotti I, León-Caballero J, Murru A, et al. Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder. Eur Neuropsychopharmacol. 2016;26(10):1562-1578.[PubMed 27568278]

Papakostas GI, Petersen TJ, Kinrys G, et al, “Aripiprazole Augmentation of Selective Serotonin Reuptake Inhibitors for Treatment-Resistant Major Depressive Disorder,” J Clin Psychiatry, 2005, 66(10):1326-30.[PubMed 16259548]

Patkar AA, Peindl K, Mago R, et al, “An Open-Label, Rater-Blinded, Augmentation Study of Aripiprazole in Treatment-Resistant Depression,” Prim Care Companion J Clin Psychiatry, 2006, 8(2):82-7.[PubMed 16862232]

Rappaport SA, Marcus RN, Manos G, McQuade RD, Oren DA. A randomized, double-blind, placebo-controlled tolerability study of intramuscular aripiprazole in acutely agitated patients with Alzheimer’s, vascular, or mixed dementia. J Am Med Dir Assoc. 2009;10(1):21-27. doi: 10.1016/j.jamda.2008.06.006.[PubMed 19111849]

Remington G, Chue P, Stip E, Kopala L, Girard T, Christensen B. The crossover approach to switching antipsychotics: what is the evidence? Schizophr Res. 2005;76(2-3):267-272. doi: 10.1016/j.schres.2005.01.009.[PubMed 15949658]

Reus VI, Fochtmann LJ, Eyler AE, et al. The American Psychiatric Association practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia. Am J Psychiatry. 2016;173(5):543-546. http://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.2015.173501. Accessed May 26, 2016. doi: 10.1176/appi.ajp.2015.173501.[PubMed 27133416]

Rugino TA and Janvier YM, “Aripiprazole in Children And Adolescents: Clinical Experience,” J Child Neurol, 2005, 20(7):603-10.[PubMed 16159529]

Schneeweiss S, Setoguchi S, Brookhart A, et al, “Risk of Death Associated With the Use of Conventional Versus Atypical Antipsychotic Drugs Among Elderly Patients,” CMAJ, 2007, 176(5): 627-32.[PubMed 17325327]

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Simon JS and Nemeroff CB, “Aripiprazole Augmentation of Antidepressants for the Treatment of Partially Responding and Nonresponding Patients With Major Depressive Disorder,” J Clin Psychiatry, 2005, 66(10):1216-20.[PubMed 16259533]

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Yoo HK, Lee JS, Paik KW, et al, “Open-label Study Comparing the Efficacy and Tolerability of Aripiprazole and Haloperidol in the Treatment of Pediatric Tic Disorders,” Eur Child Adolesc Psychiatry, 2011, 20(3):127-35.[PubMed 21188439]

Brand Names: International

Abdin (PH); Abilia (EG); Abilify (AE, AT, AU, BB, BE, BG, BH, BR, CH, CL, CN, CO, CY, CZ, DE, DK, EE, EG, ES, FI, FR, GB, GR, HK, HR, HU, ID, IE, IL, IS, IT, JO, JP, KR, LB, LT, LU, MT, MX, MY, NL, NO, PH, PL, PT, PY, RO, RU, SA, SE, SG, SI, SK, TH, TR, TW, VE, VN, ZA); Abilify Discmelt (PH); Abilify Maintena (BE, HK, MY, RO, SG); Abilify OD (JP); Abilify ODT (NZ); Apalife (TH); Apilipex (EG); Arika (TW); Arilex (CL); Arilobe (EG); Arinia (BD, ID); Aripi (ID); Aripipan (LB); Aripizole (KR); Ariple (TW); Ariply (IL); Aripra (KR); Ariprazol (CR, DO, GT, HN, NI, PA, SV); Ariski (ID); Aristab (BR); Arive (IN); Arixind (AR); Arizol (UY); Arizole (LK, TW); Arlemide (AR); Atypral (LB); Azymol (PE, PY); Bisoza (LK, PH); Groven (AR); Ilimit (CR, DO, EC, GT, HN, NI, PA, PE, PY, SV, UY); Irazem (AR); Lemilvo (IE); Mactril (LK); Pipzol (LK, UA); Siblix (AR); Siznil (BD); Sizopra (BD, LK); Viza (CL); Xalipro (LB); Xarip (BD); Zedan (PK); Zipren (ID)

Aripiprazole (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(ay ri PIP ray zole)

Brand Names: US

Abilify; Abilify Discmelt [DSC]; Abilify Maintena; Abilify MyCite

Brand Names: Canada

Abilify; Abilify Maintena

Warning
  • There is a higher chance of death in older adults who take this drug for mental problems caused by dementia. Most of the deaths were linked to heart disease or infection. This drug is not approved to treat mental problems caused by dementia.
  • Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
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.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to aripiprazole or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are breast-feeding or plan to breast-feed.
  • This drug may interact with other drugs or health problems.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert or have clear eyesight until you see how this drug affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Avoid drinking alcohol while taking this drug.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
  • Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
  • Chance of seizures may be higher. Talk with the doctor.
  • Low white blood cell counts have happened with drugs like this one. This may lead to a higher chance of getting an infection. Deadly infections have rarely happened. Tell your doctor if you have ever had a low white blood cell count. Call your doctor right away if you have signs of infection like fever, chills, or sore throat. Talk with your doctor.
  • High blood sugar or diabetes, high cholesterol, and weight gain have happened with drugs like this one. These changes may raise the chance of heart and brain blood vessel disease. Talk with the doctor.
  • Check your blood sugar as you have been told by your doctor.
  • Dizziness, sleepiness, and feeling less stable may happen with this drug. These may lead to falling. Broken bones or other health problems can happen from falling. Talk with the doctor.
  • Older adults with dementia taking drugs like this one have had a higher number of strokes. Sometimes these strokes have been deadly. This drug is not approved to treat mental problems caused by dementia. Talk with your doctor.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Taking this drug in the third trimester of pregnancy may lead to muscle movements that cannot be controlled and withdrawal in the newborn. Talk with the doctor.
  • Oral-disintegrating tablet:
  • If you have phenylketonuria (PKU), talk with your doctor. Some products have phenylalanine.
  • Liquid:
  • If you are not able to break down sucrose or fructose, talk with your doctor. Some products have sucrose or fructose.
  • Tablets with sensor (Abilify MyCite):
  • The patch may have metal. Take off the patch before an MRI.
What are some side effects that I need to call my doctor about right away?
  • 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:
  • All products:
  • 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.
  • Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
  • Trouble controlling body movements, twitching, change in balance, trouble swallowing or speaking.
  • Strong urges that are hard to control (such as eating, gambling, sex, or spending money).
  • Very bad dizziness or passing out.
  • Change in balance.
  • Feeling very tired or weak.
  • Seizures.
  • Blurred eyesight.
  • A very bad and sometimes deadly health problem called neuroleptic malignant syndrome (NMS) may happen. Call your doctor right away if you have any fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, heartbeat that does not feel normal, or are sweating a lot.
  • Some people who take this drug may get a very bad muscle problem called tardive dyskinesia. This muscle problem may not go away even if this drug is stopped. Sometimes, signs may lessen or go away over time after this drug is stopped. The risk of tardive dyskinesia may be greater in people with diabetes and in older adults, especially older women. The risk is also greater the longer you take this drug or with higher doses. Muscle problems may also occur after short-term use with low doses. Call your doctor right away if you have trouble controlling body movements or if you have muscle problems with your tongue, face, mouth, or jaw like tongue sticking out, puffing cheeks, mouth puckering, or chewing.
  • Tablets with sensor (Abilify MyCite):
  • Skin irritation where the patch was placed.
What are some other side effects of this drug?
  • 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:
  • All products:
  • Dizziness.
  • Feeling sleepy.
  • Feeling tired or weak.
  • Restlessness.
  • Anxiety.
  • Headache.
  • Upset stomach or throwing up.
  • Weight gain.
  • Constipation.
  • Trouble sleeping.
  • Feeling more or less hungry.
  • Nose and throat irritation.
  • Dry mouth.
  • Shakiness.
  • Drooling.
  • Stuffy nose.
  • Injection:
  • Pain where the shot was given.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All oral products other than Abilify MyCite:
  • Take with or without food.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • Tablets:
  • Swallow whole. Do not chew, break, or crush.
  • Liquid:
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
  • Oral-disintegrating tablet:
  • Do not push the tablet out of the foil when opening. Use dry hands to take it from the foil. Place on your tongue and let it dissolve. Water is not needed. Do not swallow it whole. Do not chew, break, or crush it.
  • Tablets with sensor (Abilify MyCite):
  • While you are taking this drug, you will also wear a patch with a sensor that tracks when you take one of the tablets. You will also need to use a smartphone app. Be sure you know how to take the tablets, where to put the patch, other details about the patch, and how to use the smartphone app. Follow what your doctor has told you to do. Read the package insert for details. If you have questions, talk with your doctor.
  • Take tablets with or without food. Take with food if it causes an upset stomach.
  • Swallow tablet whole. Do not chew, break, or crush.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • Injection:
  • It is given as a shot into a muscle.
  • All products:
  • Drink lots of noncaffeine liquids every day unless told to drink less liquid by your doctor.
What do I do if I miss a dose?
  • Injection:
  • Call your doctor to find out what to do.
  • All other products:
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Injection:
  • If you need to store this drug at home, talk with your doctor, nurse, or pharmacist about how to store it.
  • All other products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Liquid:
  • After opening, throw away any part not used after 6 months.
  • Oral-disintegrating tablet:
  • Use oral-disintegrating tablet right after opening. Throw away any part of opened pouch that is not used.
  • All products:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Aripiprazole (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(ay ri PIP ray zole)

Brand Names: US

Abilify; Abilify Discmelt [DSC]; Abilify Maintena; Abilify MyCite

Brand Names: Canada

Abilify; Abilify Maintena

Warning
  • Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • There is a higher chance of death in older adults who take this drug for mental problems caused by dementia. Most of the deaths were linked to heart disease or infection. This drug is not approved to treat mental problems caused by dementia.
What is this drug used for?
  • It is used to treat schizophrenia.
  • It is used to treat low mood (depression).
  • It is used to treat bipolar problems.
  • 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 your child for other reasons. Talk with the doctor.
  • Tablets with sensor (Abilify MyCite):
  • If your child has been given this form of this drug, talk with the doctor for information about the benefits and risks. Talk with the doctor if you have questions or concerns about giving this drug to your child.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child is breast-feeding a baby:
  • Talk with the doctor if your child is breast-feeding a baby or plans to breast-feed a baby.
  • This drug may interact with other drugs or health problems.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • All products:
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • To lower the chance of feeling dizzy or passing out, have your child rise slowly if your child has been sitting or lying down. Have your child be careful going up and down stairs.
  • Have your child’s blood work checked often. Talk with your child’s doctor.
  • If your child drinks grapefruit juice or eats grapefruit often, talk with your child’s doctor.
  • Have your child avoid tasks or actions that call for alertness or clear eyesight until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • Have your child be careful in hot weather or while your child is being active. Have your child drink lots of fluids to stop fluid loss.
  • Chance of seizures may be higher. Talk with the doctor.
  • Low white blood cell counts have happened with drugs like this one. This may lead to a higher chance of getting an infection. Deadly infections have rarely happened. Tell your doctor if you have ever had a low white blood cell count. Call your doctor right away if you have signs of infection like fever, chills, or sore throat. Talk with your doctor.
  • High blood sugar or diabetes, high cholesterol, and weight gain have happened with drugs like this one. These changes may raise the chance of heart and brain blood vessel disease. Talk with the doctor.
  • Have your child’s blood sugar checked as you have been told by your child’s doctor.
  • Dizziness, sleepiness, and feeling less stable may happen with this drug. These may lead to falling. Broken bones or other health problems can happen from falling. Talk with the doctor.
  • If your child is pregnant:
  • Tell the doctor if your child is pregnant or becomes pregnant. You will need to talk about the benefits and risks of your child using this drug while pregnant.
  • Taking this drug in the third trimester of pregnancy may lead to muscle movements that cannot be controlled and withdrawal in the newborn. Talk with the doctor.
  • Oral-disintegrating tablet:
  • If your child has phenylketonuria (PKU), talk with your child’s doctor. Some products have phenylalanine.
  • Liquid:
  • If your child is not able to break down sucrose or fructose, talk with your child’s doctor. Some products have sucrose or fructose.
What are some side effects that I need to call my child’s doctor about right away?
  • 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 child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • 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.
  • Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
  • Trouble controlling body movements, twitching, change in balance, trouble swallowing or speaking.
  • Strong urges that are hard to control (such as eating, gambling, sex, or spending money).
  • Very bad dizziness or passing out.
  • Change in balance.
  • Feeling very tired or weak.
  • Seizures.
  • Blurred eyesight.
  • A very bad and sometimes deadly health problem called neuroleptic malignant syndrome (NMS) may happen. Call your child’s doctor right away if your child has any fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, heartbeat that does not feel normal, or is sweating a lot.
  • Some people who take this drug may get a very bad muscle problem called tardive dyskinesia. This muscle problem may not go away even if this drug is stopped. Sometimes, signs may lessen or go away over time after this drug is stopped. The risk of tardive dyskinesia may be greater in people with diabetes and in older adults, especially older women. The risk is also greater the longer your child takes this drug or with higher doses. Muscle problems may also occur after short-term use with low doses. Call your child’s doctor right away if your child has trouble controlling body movements or if your child has muscle problems with his/her tongue, face, mouth, or jaw like tongue sticking out, puffing cheeks, mouth puckering, or chewing.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • All products:
  • Dizziness.
  • Feeling sleepy.
  • Feeling tired or weak.
  • Anxiety.
  • Headache.
  • Upset stomach or throwing up.
  • Weight gain.
  • Restlessness.
  • Constipation.
  • Trouble sleeping.
  • Feeling more or less hungry.
  • Nose and throat irritation.
  • Dry mouth.
  • Shakiness.
  • Drooling.
  • Stuffy nose.
  • Injection:
  • Pain where the shot was given.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All oral products:
  • Give this drug with or without food.
  • To gain the most benefit, do not miss giving your child doses.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • Tablets:
  • Have your child swallow whole. Do not let your child chew, break, or crush.
  • Liquid:
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
  • Oral-disintegrating tablet:
  • Do not push the tablet out of the foil when opening. Use dry hands to take it from the foil. Place on your child’s tongue and let it dissolve. Water is not needed. Do not let your child swallow it whole. Do not let your child chew, break, or crush it.
  • Injection:
  • It is given as a shot into a muscle.
  • All products:
  • Have your child drink lots of noncaffeine liquids every day unless told to drink less liquid by your child’s doctor.
What do I do if my child misses a dose?
  • All oral products:
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not take 2 doses at the same time or extra doses.
  • Injection:
  • Call your child’s doctor to find out what to do.
How do I store and/or throw out this drug?
  • All oral products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Liquid:
  • After opening, throw away any part not used after 6 months.
  • Oral-disintegrating tablet:
  • Give oral-disintegrating tablet right after opening. Throw away any part of opened pouch that is not used.
  • Injection:
  • If you need to store this drug at home, talk with your child’s doctor, nurse, or pharmacist about how to store it.
  • All products:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.