Usual Adult Dose for Schizophrenia

ORAL FORMULATIONS:
Aripiprazole Immediate-Release (IR):

• Initial dose: 10 or 15 mg orally once a day
• Target dose: 10 to 15 mg per day; effective dose range 10 to 30 mg per day; however, clinical trials have not found doses exceeding 10 or 15 mg per day to be more effective.
• Maximum dose: 30 mg/day

PARENTERAL FORMULATIONS:
Aripiprazole Extended-Release IM Suspension:

• Initial dose: 400 mg IM once; continue aripiprazole IR 10 to 20 mg orally once a day for 14 days
• Maintenance dose: 300 to 400 mg IM once a month; the dose should not be given sooner than 26 days after the previous injection

Aripiprazole Lauroxil Extended-Release IM Suspension:

• Initial dose:
• Patients stable on aripiprazole IR 10 mg/day: 441 mg IM via deltoid or gluteal injection ONCE PLUS aripiprazole lauroxil 675 mg IM ONCE OR aripiprazole IR 10 mg orally once a day for 21 days
• Patients stable on aripiprazole IR 15 mg/day: Initial dose 662 mg IM via gluteal injection ONCE PLUS aripiprazole lauroxil 675 mg IM ONCE OR aripiprazole IR 15 mg orally once a day for 21 days
• Patients stable on aripiprazole IR at least 20 mg/day: 882 mg IM via gluteal injection ONCE PLUS aripiprazole lauroxil 675 mg IM ONCE OR aripiprazole IR once a day for 21 days.
• Maintenance doses: 441 mg, 662 mg, or 882 mg IM monthly, 882 mg IM every 4 to 6 weeks, or 1064 mg IM every 2 months; this drug should not be given sooner than 14 days after the previous injection.

Re-initiation of treatment: 675 mg IM ONCE plus 30 mg of aripiprazole IR orally ONCE

Comments:

• The oral solution and oral tablets can be substituted on a mg-per-mg basis up 25 mg; patients receiving 30 mg tablets should receive 25 mg of the oral solution.
• Oral formulation dose increases, if needed, should be at 2-week intervals to allow time to achieve steady state.
• Prior to initiating therapy with extended-release IM formulations, tolerability should be established with oral formulations; it may take up to 2 weeks to fully assess tolerability due to the half-life of aripiprazole.
• The first dose of the extended-release IM formulation should be given on the same day as the initiation/re-initiation dose; providers should avoid injecting both formulations in the same deltoid or gluteal muscle.
• Providers whose patients who experience adverse reactions with 400 mg/month extended-release IM suspension doses may consider reducing the dose to 300 mg/month.
• Dose regimen adjustments (including addition of oral supplementation) will be needed for missed doses; see dose adjustments section.

Use: Treatment of schizophrenia

Usual Adult Dose for Bipolar Disorder

ORAL FORMULATIONS:
Aripiprazole IR:
Monotherapy:

• Initial dose: 15 mg orally once a day
• Target dose: 15 mg orally once a day; may increase dose based on clinical response. Dose increases, if needed, should be at 2-week intervals to allow time to achieve steady state.
• Maximum dose: 30 mg/day

Adjunctive Therapy with Lithium or Valproate:

• Initial dose: 10 to 15 mg orally once a day
• Target dose: 15 mg orally once a day; may increase dose based on clinical response.
• Maximum dose: 30 mg/day

PARENTERAL FORMULATIONS:
Aripiprazole Extended-Release IM Suspension:

• Initial dose: 400 mg IM once; continue aripiprazole IR 10 to 20 mg orally once a day for 14 days
• Maintenance dose: 300 to 400 mg IM once a month; the dose should not be given sooner than 26 days after the previous injection

Comments:

• The safety of oral doses greater than 30 mg per day has not been studied.
• Dose increases of oral formulations, if needed, should be at 2-week intervals to allow time to achieve steady state.
• Providers whose patients who experience adverse reactions with 400 mg/month extended-release IM suspension doses may consider reducing the dose to 300 mg/month.
• The dose recommended for maintenance treatment is the same dose needed to stabilize patients during acute treatment; healthcare providers should periodically reassess need for maintenance treatment.
• The oral solution and oral tablets can be substituted on a mg-per-mg basis up to 25 mg; patients receiving 30 mg tablets should receive 25 mg of the oral solution.

Uses:

• Acute treatment of manic and mixed episodes associated with bipolar I disorder
• Acute treatment of manic and mixed episodes of bipolar I disorder as monotherapy and as adjunct to lithium or valproate
• Maintenance treatment of bipolar I disorder as monotherapy and as adjunct to lithium or valproate
• Maintenance monotherapy treatment of bipolar I disorder

Usual Adult Dose for Agitated State

PARENTERAL FORMULATIONS:
Aripiprazole IR Injection:

• Initial dose: 9.75 mg IM once
• Maintenance dose: 5.25 to 15 mg IM once
• Maximum dose: 30 mg/day

Comments:

• If ongoing therapy is clinically indicated, oral therapy should replace injections as soon as possible.
• Doses ranging from 5.25 mg to 15 mg may be considered when clinical factors warrant; no additional benefit has been demonstrated for 15 mg compared to 9.75 mg.
• If additional doses are needed, allow at least 2 hours to elapse between dosing; the efficacy of repeated doses has not been studied.

Use: Treatment of agitation associated with schizophrenia or bipolar mania

Usual Adult Dose for Depression

ORAL FORMULATIONS:
Aripiprazole IR:

• Initial dose: 2 to 5 mg orally once a day
• Doses may be adjusted in increments up to 5 mg per day at intervals of no less than 1 week.
• Maintenance dose: 2 to 15 mg once a day
• Maximum dose: 15 mg/day

Comments:

• Patients should be periodically reassessed to determine need for continued treatment.
• The oral solution and oral tablets can be substituted on a mg-per-mg basis up to 25 mg.

Use: Adjunctive treatment of major depressive disorder

Usual Pediatric Dose for Schizophrenia

ORAL FORMULATIONS:
Aripiprazole IR:
13 to 17 years:

• Initial dose: 2 mg orally once a day; after 2 days, titrate to 5 mg orally once a day, then titrate to 10 mg orally once a day after an additional 2 days
• Maintenance dose: 10 mg orally once a day
• Maximum dose: 30 mg/day

Comments:

• The effective dose range was 10 to 30 mg per day; however, clinical trials have not found doses exceeding 10 mg per day to be more effective.
• After initiation, dose increases, if needed, should be in 5 mg increments at 2-week intervals to allow time to achieve steady state.
• Maintenance treatment in the adolescent population has not been evaluated; extrapolating from adult data, it is recommended that responding patients be continued beyond the acute response, but at the lowest dose needed to maintain remission.
• Healthcare providers should periodically reassess need for maintenance treatment.
• The oral solution and oral tablets can be substituted on a mg-per-mg basis up to 25 mg; patients receiving 30 mg tablets should receive 25 mg of the oral solution.

Use: Treatment of schizophrenia

Usual Pediatric Dose for Bipolar Disorder

ORAL FORMULATIONS:
Aripiprazole IR:
10 to 17 years:
Monotherapy OR Adjunctive Therapy with Lithium or Valproate:

• Initial Dose: 2 mg orally once a day; after 2 days, titrate to 5 mg orally once a day, then titrate to 10 mg orally once a day after an additional 2 days
• Target Dose: 10 mg orally once a day; dose increases, if needed should be in 5 mg increments at 2-week intervals in order to allow time to achieve steady state.
• Maximum Dose: 30 mg/day

Comments:

• The dose for maintenance treatment is the same dose needed to stabilize patients during acute treatment; periodically reassess need for maintenance treatment.
• The oral solution and oral tablets can be substituted on a mg-per-mg basis up to 25 mg; patients receiving 30 mg tablets should receive 25 mg of the oral solution.

Use: Acute treatment of manic and mixed episodes associated with bipolar I disorder

Usual Pediatric Dose for Autism

ORAL FORMULATIONS:
Aripiprazole IR:
6 to 17 years:

• Initial dose: 2 mg orally once a day
• Dose titration: Increase dose to 5 mg orally once a day, with subsequent increases to 10 mg or 15 mg orally once a day if needed. If needed, dose adjustments in increments of up to 5 mg per day should occur at intervals of no less than 1 week.
• Maintenance dose: 5 to 15 mg orally once a day
• Maximum dose: 15 mg orally/day

Comments:

• Doses should be individualized according to tolerability and response.
• The efficacy of maintenance treatment of irritability associated with autistic disorder has not been evaluated.
• Patients should be periodically reassessed to determine need for continued treatment.
• The oral solution and oral tablets can be substituted on a mg-per-mg basis up to 25 mg.

Use: Treatment of irritability associated with autistic disorder (including aggression, deliberate self-injurious behavior, temper tantrums, and quickly changing moods)

Usual Pediatric Dose for Tourette's Syndrome

ORAL FORMULATIONS:
Aripiprazole IR:
6 to 18 years:
Less than 50 kg:

• Initial dose: 2 mg orally once a day; after 2 days, titrate to 5 mg orally once a day. Healthcare providers may increase the dose to 10 mg once a day in patients who do not achieve optimal control of tics.
• Dose adjustments should occur gradually at intervals of no less than 1 week.
• Maximum dose: 10 mg/day

50 kg or more:

• Initial dose: 2 mg orally once a day; after 2 days, titrate to 5 mg orally once a day, then titrate to 10 mg orally once a day on day 8. Healthcare providers may increase the dose to 20 mg once a day in patients who do not achieve optimal control of tics.
• Dose adjustments should occur gradually in increments of 5 mg per day at intervals of no less than 1 week.
• Maximum dose: 20 mg/day

Comments:

• Patients should be periodically assessed to determine the continued need for maintenance treatment.
• The oral solution and oral tablets can be substituted on a mg-per-mg basis up to 25 mg.

Use: Treatment of Tourette's disorder

Renal Dose Adjustments

Mild to severe renal dysfunction (glomerular filtration rate [GFR] 15 to 90 mL/min): No adjustment recommended.

Liver Dose Adjustments

Mild to severe liver dysfunction (Child-Pugh score 5 to 15): No adjustment recommended.

Dose Adjustments

ORAL FORMULATIONS:
Aripiprazole IR Formulation Substitutions:

• Dosing for oral tablets is the same as dosing for the oral disintegrating tablets.
• Oral solution can be substituted for tablets on a mg-per-mg basis up to 25 mg; patients receiving 30 mg tablets should receive 25 mg of the oral solution.

CYP450 Dose Adjustments:

• Known CYP450 2D6 poor metabolizers (PM): Administer one-half usual dose.
• Known CYP450 2D6 PM receiving concomitant strong CYP450 3A4 inhibitors: Administer one-quarter usual dose.
• Concomitantly receiving strong CYP450 2D6 OR 3A4 inhibitors: Administer one-half usual dose.
• Concomitantly receiving strong CYP450 2D6 AND 3A4 inhibitors: Administer one-quarter usual dose.
• Concomitantly receiving CYP450 3A4 inducer: Double the usual dose over 1 to 2 weeks.

IMPORTANT NOTES:

• When coadministered drug is withdrawn, aripiprazole dose should be adjusted to the original level over 1 to 2 weeks.
• Patients receiving a combination of strong, moderate, and weak inhibitors of CYP450 3A4 and CYP450 2D6 may need an initial dose reduction to one-quarter of the usual dose with adjustments to achieve a clinical response.
• When this drug is administered to patients with major depressive disorder, dose adjustments are not recommended.

PARENTERAL FORMULATIONS:

• Consider the pharmacokinetics and prolonged-characteristics of this formulation when adjusting dose and dosing interval.
• Doses of aripiprazole lauroxil 441 mg, 662 mg, 882 mg, and 1064 mg correspond to aripiprazole 300 mg, 450 mg, 600 mg, and 724 mg, respectively.

Aripiprazole Extended-Release IM Suspension:

• IM extended-release: If there are adverse reactions with 400 mg, consider reducing to 300 mg once a month.

MISSED DOSES:
Second or Third dose:

• If more than 4 weeks and less than 5 weeks have elapsed: Administer as soon as possible.
• If more than 5 weeks since the last injection: Restart concomitant aripiprazole IR for 14 days with the next administered injection.

Fourth or Subsequent Doses:

• If more than 4 weeks and less than 6 weeks have elapsed: Administer as soon as possible.
• If more than 6 weeks since the last injection: Restart concomitant aripiprazole IR for 14 days with the next administered injection.

CYP450 DOSE ADJUSTMENTS:

• Known CYP450 2D6 poor metabolizers (PM): Adjust dose to 300 mg IM monthly.
• Known CYP450 2D6 PM receiving concomitant CYP450 3A4 inhibitors for greater than 14 days: Adjust dose to 200 mg IM monthly.

For patients receiving 400 mg IM once monthly:

• Concomitant strong CYP450 2D6 or CYP450 3A4 inhibitor for greater than 14 days: Adjust dose to 300 mg IM monthly.
• Concomitant CYP450 2D6 AND CYP450 3A4 inhibitors for greater than 14 days: Adjust dose to 200 IM mg monthly.
• Avoid adding CYP450 3A4 inducers.

For patients receiving 300 mg IM once monthly:

• Concomitant strong CYP450 2D6 or CYP450 3A4 inhibitors for greater than 14 days: Adjust dose to 200 mg IM monthly.
• Concomitant strong CYP450 2D6 AND CYP450 3A4 inhibitors for greater than 14 days: Adjust dose to 160 mg IM monthly.
• Avoid adding CYP450 3A4 inducers.

IMPORTANT NOTES:

• Dose adjustments are not needed for patients with concomitant use of CYP450 3A4 inhibitors, CYP450 2D6 inhibitors or CYP450 3A4 inducers for less than 14 days.
• If the CYP450 3A4 or CYP450 2D6 inhibitor is withdrawn, the aripiprazole dose may need to be increased.
• Avoid concomitant use of CYP450 3A4 inducers for greater than 14 days as aripiprazole concentrations may decrease below effective levels.

Aripiprazole Lauroxil Extended-Release IM Suspension:
EARLY DOSING: This drug should not be given earlier than 14 days after the previous injection.
Dosing interval:

• Aripiprazole lauroxil 441 and 662 mg: 1 month
• Aripiprazole lauroxil 882 mg: 4 to 6 weeks
• Aripiprazole lauroxil 1064 mg: 2 months

MISSED DOSES:
Monthly 441 mg dose:

• If 6 weeks or less have elapsed: Administer as soon as possible.
• If more than 6 weeks but less than 7 weeks have elapsed: Supplement with aripiprazole lauroxil 675 mg IM ONCE OR supplement with 7 days of oral aripiprazole
• If more than 7 weeks have elapsed: Re-initiate with aripiprazole lauroxil 675 mg IM ONCE plus 30 mg oral aripiprazole ONCE OR supplement with 21 days of oral aripiprazole

Monthly 662 mg dose:

• If 8 weeks or less have elapsed: Administer as soon as possible.
• If more than 8 weeks but less than 12 weeks have elapsed: Supplement with aripiprazole lauroxil 675 mg IM ONCE OR supplement with 7 days of oral aripiprazole
• If more than 12 weeks have elapsed: Re-initiate with aripiprazole lauroxil 675 mg IM ONCE plus 30 mg oral aripiprazole ONCE OR supplement with 21 days of oral aripiprazole

Monthly OR every 6 weeks 882 mg dose:

• If 8 weeks or less have elapsed: Administer as soon as possible.
• If more than 8 weeks but less than 12 weeks have elapsed: Supplement with aripiprazole lauroxil 675 mg IM ONCE OR supplement with 7 days of aripiprazole IR
• If more than 12 weeks have elapsed: Re-initiate with aripiprazole lauroxil 675 mg IM ONCE plus 30 mg aripiprazole IR ONCE OR supplement with 21 days of aripiprazole IR

Every 2 months 1064 mg dose:

• If 10 weeks or less have elapsed: Administer as soon as possible.
• If more than 10 weeks but less than 12 weeks have elapsed: Supplement with aripiprazole lauroxil 675 mg IM ONCE OR supplement with 7 days of aripiprazole IR
• If more than 12 weeks have elapsed: Re-initiate with aripiprazole lauroxil 675 mg IM ONCE plus 30 mg aripiprazole IR ONCE OR supplement with 21 days of aripiprazole IR

CYP450 DOSE ADJUSTMENTS:

• Known CYP450 2D6 PM, or taking strong CYP450 3A4 inhibitors, strong 2D6 inhibitors, or strong 3A4 inducers: Use of formulations with one strength in a single-dose prefilled syringe should be avoided.
• Known CYP450 2D6 PM receiving concomitant strong CYP450 2D6 inhibitor: No dose adjustment required.
• Known CYP450 2D6 PM receiving concomitant CYP450 3A4 inhibitors for greater than 14 days: 441 mg dose requires no dose adjustment, if tolerated; 662 mg, 882 mg, and 1064 mg doses should be decreased to 441 mg.
• Concomitant CYP450 3A4 inhibitors: 441 mg monthly requires no dose adjustment, if tolerated; 662 mg, 882 mg, and 1064 mg doses should be reduced to the next lower strength.
• Concomitant strong CYP450 2D6 for greater than 14 days: 441 mg monthly requires no dose adjustment, if tolerated; 662 mg, 882 mg, and 1064 mg doses should be reduced to the next lower strength.
• Concomitant strong CYP450 2D6 and strong CYP450 3A4 inhibitors for greater than 14 days: Avoid use of 662 mg, 882 mg, or 1064 mg dose; no dose adjustment for 441 mg dose, if tolerated.
• Concomitant CYP450 3A4 inducers: Increase the 441 mg monthly to 662 mg monthly; no dose adjustments for 662 mg, 882 mg, or 1064 mg doses.

IMPORTANT NOTES:

• Aripiprazole IR supplementation: Patients should be given the same dose of aripiprazole IR as when they started aripiprazole lauroxil.
• Dose adjustments are not needed for patients with concomitant use of CYP450 modulators for less than 14 days.

Switching from Other Antipsychotics:

• There are no specific recommendations for switching antipsychotics or concomitant administration with other antipsychotics, so while immediate discontinuation of the previous antipsychotic may be acceptable for some patients, more gradual discontinuation may be most appropriate for others.
• In all cases, it is best to minimize the overlap period.

Precautions

US BOXED WARNINGS:
INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS:

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

SUICIDAL THOUGHTS AND BEHAVIORS WITH ANTIDEPRESSANT DRUGS:

• Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies.
• These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older.

Recommendations:

• In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors.
• Advise families and caregivers of the need for close observation and communication with the prescriber.

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients

Safety and efficacy of aripiprazole IR have not been established:

• In patients younger than 18 years with major depressive disorder or agitation associated with schizophrenia or bipolar mania.
• In patients younger than 13 years with schizophrenia.
• In patients younger than 10 years with bipolar I disorder.
• In patients younger than 6 years with irritability associated with autistic disorder or Tourette's disorder.

Safety and efficacy of extended-release IM aripiprazole have not been established in patients younger than 18 years.

Safety and efficacy of aripiprazole IR tablets with sensors have not been established in children.

Safety and efficacy of extended-release aripiprazole lauroxil have not been established in patients younger than 18 years and older than 65 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
Oral Formulations:

• Take orally with or without food; swallow tablet whole without chewing, crushing, or dividing.
• Patients receiving aripiprazole IR tablets with sensor systems (tablets embedded with ingestible event marker [IEM] sensors, wearable sensors [patches], and the associated smartphone application) should consult with the manufacturer product information.
• Oral solution 1 mg/mL: Use calibrated dosing cup.
• Oral disintegrating tablet (ODT): Remove tablet from blister by peeling back the foil just prior to administration; do not push tablet through foil as this could damage tablet. With dry hands, place tablet on tongue and allow to disintegrate; liquid is not required but may be taken if needed.
• Missed doses: Take the missed dose as soon as remembered. If it is almost time for the next dose, skip the missed dose and take the next dose at the regular time; do not take 2 doses at the same time.

Immediate-Release IM formulation:

• Inject IM slowly, deep into muscle mass; do not give IV or subcutaneously.

Extended-Release IM Injectable Suspensions: To be administered by a health care professional using the appropriate enclosed safety needles.

Aripiprazole Extended-Release Injectable Suspension:

• Administer by deep IM gluteal injection once a month; do not administer IV or subcutaneously.

Aripiprazole lauroxil Extended-Release IM Suspension:

• Administer by deep IM gluteal (441 mg, 662 mg, or 882 mg) or deltoid (441 mg only) injection once a month or every 6 weeks as prescribed; do not administer IV or subcutaneously.
• Administer by IM gluteal or deltoid (675 mg only) injection ONCE with oral aripiprazole; do not administer IV or subcutaneously.

Storage requirements:

• Oral solution: Opened bottles can be used for up to 6 months after opening; do not use beyond the expiration date on the bottle.
• Immediate-release injection: Protect from light by storing in original packaging until ready for use.
• Aripiprazole Extended-Release IM Suspension:
• Store pre-filled dual chamber syringes below 30C (86F); do not freeze; protect from light by storing in original packaging until ready to use.
• Store vials at 25C (77F); do not freeze.

Aripiprazole lauroxil Extended-Release IM Suspension: Store pre-filled syringes at 20C to 25C (68F to 77F), with excursions permitted between 15C and 30C (59F and 86F).

Reconstitution/preparation techniques: The manufacturer product information should be consulted.

General:

• Patients should be periodically reassessed to determine continued need for treatment.
• There are 4 IM formulations; the immediate-release and 3 extended-release formulations; these are not interchangeable.
• An aripiprazole IR tablets with sensors are embedded with IEM sensors, which transmit ingestion information to a wearable sensor (patch) and mobile patient application upon contact with gastric fluid.
• Limitations of use: The ability of aripiprazole IR tablet with sensors to improve compliance/modify dosage has not been established, and the use of this formulation to track drug ingestion in "real-time" or during an emergency is not recommended as detection may be delayed or may not occur.

Monitoring:

• HEMATOLOGIC: CBC frequently during the first few months in patients with preexisting low WBC and/or a prior history of drug-induced leukopenia or neutropenia.
• METABOLIC: Monitor for increases in blood sugar, weight, and lipids.
• PSYCHIATRIC: Monitor for clinical worsening and suicidality; close supervision of high-risk patients should accompany drug therapy.
• Monitor for pathological gambling and decreased impulse control, especially in those with a history of these behaviors.

Patient advice:

• Patients, families, and caregivers should report worsening of depression, suicidal ideation, or any unusual changes in behavior, especially during early antidepressant treatment and when doses are adjusted up or down. Decreased impulse control has been reported, and any patient experiencing signs/symptoms of poor impulse control should report the side effect.
• This drug may impair judgment, thinking, or motor skills; have patients avoid driving or operating machinery until adverse effects are determined.
• Advise patients to speak to their healthcare provider if they are pregnant, intend to become pregnant, or are breastfeeding.
• Advise patients that this drug may cause metabolic changes such as increases in blood sugar, body weight and lipids.
• Patients should avoid overheating and dehydration.
• Patients should speak with their healthcare provider if they are taking, or plan to take any new prescription or over the counter medications because there is a potential for drug interactions; patients should be advised to avoid alcohol as it may make some side effects worse.

Frequently asked questions

• Why should you take aripiprazole in the morning?
• Does Abilify cause weight gain?
• Vraylar vs Abilify - How do they compare?
• What is the difference between Abilify and Abilify Maintena?
• How does Abilify MyCite work?