Brand names: Abilify, Aristada
Drug class: Atypical Antipsychotics
- Dopamine Receptor Partial Agonists
ATC class: N05AX12
VA class: CN709
Chemical name: 3,4-Dihydro-7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-2(1H)-quinolinone
Molecular formula: C23H27Cl2N3O2 C36H51Cl2N3O4
CAS number: 129722-12-9

Introduction

Quinolinone derivative; atypical or second-generation antipsychotic agent.

Uses for Aripiprazole

Schizophrenia

Used orally (as aripiprazole) and IM (as extended-release aripiprazole or aripiprazole lauroxil injection) for treatment of schizophrenia.

American Psychiatric Association (APA) considers most atypical antipsychotic agents first-line drugs for the management of the acute phase of schizophrenia (including first psychotic episodes).

Patients who do not respond to or tolerate one drug may be successfully treated with an agent from a different class or with a different adverse effect profile.

Immediate-release aripiprazole injection (no longer commercially available in the US) has been used IM for acute management of agitation in patients with schizophrenia.

Bipolar Disorder

Used orally alone or in conjunction with lithium or valproate for acute treatment of manic and mixed episodes associated with bipolar I disorder with or without psychotic features. Also used orally as monotherapy or as adjunctive therapy with lithium or valproate for maintenance treatment of bipolar I disorder.

Used IM (as extended-release aripiprazole injection [Abilify Maintena]) as monotherapy for maintenance treatment of bipolar I disorder.

Immediate-release aripiprazole injection (no longer commercially available in the US) has been used IM for acute management of agitation in patients with bipolar I disorder.

Adjunctive Therapy of Major Depressive Disorder

Used orally as adjunctive therapy to antidepressants for treatment of major depressive disorder.

Irritability Associated with Autistic Disorder

Used orally for acute treatment of irritability associated with autistic disorder.

Tourette's Syndrome

Used orally for treatment of Tourette's syndrome (Gilles de la Tourette’s syndrome).

Aripiprazole Dosage and Administration

General

• Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments. (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

• When switching from other antipsychotic agents to aripiprazole, abrupt discontinuance of previous agent may be acceptable for some patients with schizophrenia, but gradual discontinuance may be most appropriate for others. In all cases, minimize period of overlapping antipsychotic administration.

• Aripiprazole tablets with sensor (Abilify MyCite) are part of a digital ingestion tracking system intended to provide objective data on drug ingestion. (See Aripiprazole Tablets with Sensor under Actions.) The ability of aripiprazole tablets with sensor to improve patient compliance or usefulness in modifying aripiprazole dosage has not been established. 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 may not occur. (See Precautions Related to Aripiprazole Tablets with Sensor under Cautions.)

Administration

Administer aripiprazole orally or by IM injection. Administer aripiprazole lauroxil only by IM injection.

Establish tolerability with oral aripiprazole prior to initiating IM therapy with extended-release aripiprazole or aripiprazole lauroxil.

Oral Administration

Administer orally as conventional tablets, tablets with sensor, orally disintegrating tablets, or oral solution once daily without regard to meals. (See Food under Pharmacokinetics.)

Orally Disintegrating Tablets

Just prior to administration, peel open blister package; with dry hands, remove orally disintegrating tablet. Do not push tablet through foil.

Place tablet on tongue to dissolve; manufacturer recommends taking without liquid, but may take with liquid, if necessary.

Do not divide orally disintegrating tablet.

Tablets with Sensor (Abilify MyCite)

Aripiprazole is available as part of a digital ingestion tracking system comprised of the following components: aripiprazole tablets embedded with an ingestible event marker sensor (IEM; Abilify MyCite); a wearable sensor (MyCite patch), which detects the signal from the ingested sensor and transmits data to a compatible mobile device (i.e., a smart phone); a software application (app) for compatible mobile devices (e.g., smart phones; MyCite App), which displays information for the patient; and a web-based portal for healthcare professionals and caregivers.

Prior to initial patient use, facilitate use of the Abilify MyCite system. Ensure that patients are capable and willing to use a mobile device and the software application. Before using any component of the system, instruct patients to download the application and follow all the instructions for use and ensure that the software is compatible with their specific mobile device.

Administer tablets with sensor once daily without regard to meals. Swallow tablets whole; do not divide, crush, or chew.

Prior to use of the software application, the patient's mobile device should be powered on and Bluetooth enabled. Patients should apply the accompanying wearable sensor when prompted by the mobile software application; the application will instruct patients to apply and remove the sensor correctly. Patients should confirm that their mobile device is paired with the wearable sensor prior to use; the mobile software application will display a status icon on the mobile device to indicate that the patch is properly adhered and functioning. For further information, refer to the information provided in the product packaging as well as the instructions for use within the mobile software application.

Most ingestions of aripiprazole tablets with sensor will be detected within 30 minutes following ingestion; however, it may take up to 2 hours for the smart phone application and web portal to detect the ingestion. In some cases, ingestion of the tablet sensor may not be detected. If the tablet with sensor is not detected following ingestion, do not repeat the dose.

Apply the wearable sensor topically to the left side of the body just above the lower edge of the rib cage. Avoid application to areas where the skin is scraped, cracked, inflamed, or irritated or areas overlapping the area of the most recently removed sensor.

Change the wearable sensor weekly or sooner as needed; the mobile software application will remind patients when to change the sensor. Instruct patients to keep the wearable sensor in place while showering, swimming, or exercising. Remove the wearable sensor before undergoing magnetic resonance imaging (MRI) and replace with a new sensor as soon as possible.

If skin irritation occurs, remove the wearable sensor. (See Skin Irritation associated with Abilify MyCite Wearable Sensor under Cautions.)

IM Administration of Extended-release Aripiprazole (Abilify Maintena)

Extended-release IM aripiprazole is available in 300- and 400-mg vials and prefilled syringes; do not confuse this formulation with extended-release aripiprazole lauroxil (Aristada and Aristada Initio, which are available in 441-, 662-, 675-, 882-, and 1064-mg prefilled syringes) or the immediate-release IM aripiprazole formulation (Abilify; 9.75 mg/vial), which is no longer commercially available in the US.

Must be administered by a healthcare professional.

Administer extended-release aripiprazole injection only by deep IM injection slowly into the deltoid or gluteal muscle. Do not massage injection site following IM administration. Rotate injection sites.

Administer monthly; allow at least 26 days to elapse between doses.

Reconstitution

Abilify Maintena is commercially available in 2 types of kits that contain aripiprazole lyophilized powder in either single-use vials or prefilled dual-chamber syringes with all the components required for reconstitution and administration (e.g., sterile water for injection diluent, needles, syringes); consult manufacturer's instructions for use for specific information on preparation, reconstitution, and administration.

Because entire contents of prefilled dual-chamber syringes should be administered after reconstitution, use single-use vials for dosages <300 mg.

Following reconstitution, shake prefilled syringe or vials vigorously for 20 or 30 seconds, respectively, to ensure a uniform and homogeneous suspension, which appears opaque and milky-white. If using vials, withdraw the appropriate dose of aripiprazole using the syringe supplied by the manufacturer. If a vial of reconstituted suspension is not administered immediately, shake the vial vigorously for at least 60 seconds to resuspend the drug; do not store in syringe after reconstitution. If using prefilled syringes, inject entire contents immediately following reconstitution (i.e., within 30 minutes).

IM Administration of Extended-release Aripiprazole Lauroxil (Aristada, Aristada Initio)

Extended-release aripiprazole lauroxil (Aristada) is available in 441-, 662-, 882-, and 1064-mg prefilled syringes for the treatment of schizophrenia; do not confuse this formulation with extended-release aripiprazole (Abilify Maintena; available in 300- and 400-mg vials and prefilled syringes) or the immediate-release aripiprazole formulation (no longer commercially available in the US).

Extended-release aripiprazole lauroxil injection also is available in 675-mg prefilled syringes (Aristada Initio). Use only as a single IM dose to initiate treatment or as a single dose to re-initiate treatment following a missed dose of extended-release aripiprazole lauroxil (Aristada). Aristada Initio is for single-dose administration only; do not use for repeated dosing. Aristada Initio is not interchangeable with Aristada because of their different pharmacokinetic profiles.

Must be administered by a healthcare professional.

Available as kits containing extended-release aripiprazole lauroxil injectable suspension in prefilled syringes and safety needles for IM injection. Prior to use, tap the prefilled syringe ≥10 times to dislodge any material that may have settled, then shake vigorously for ≥30 seconds to ensure a uniform suspension. If not administered within 15 minutes, shake the syringe again for 30 seconds.

Administer only by IM injection rapidly and continuously into the deltoid (for 441- and 675-mg doses only) or gluteal muscle (for 441-, 662-, 675-, 882-, and 1064-mg doses). Select needle based on injection site; use longer needles in patients with a larger amount of subcutaneous tissue overlaying the injection site muscle. Avoid concurrent administration of the 2 different aripiprazole lauroxil injection formulations (Aristada Initio and Aristada) in the same muscle.

Administer 441- and 662-mg doses of extended-release aripiprazole lauroxil (Aristada) monthly; may administer the 882-mg dose monthly or every 6 weeks. Administer 1064-mg doses every 2 months. Allow at least 14 days to elapse between doses.

Dosage

Aripiprazole oral solution may be given at same dose on mg-per-mg basis as the tablet strengths of the drug up to a dose of 25 mg. However, if oral solution is used in patients receiving 30-mg tablets, use a dose of 25 mg of the oral solution.

Dosing of aripiprazole orally disintegrating tablets is the same as for conventional tablets of the drug.

Dosage of aripiprazole lauroxil expressed in terms of aripiprazole lauroxil.

Extended-release aripiprazole lauroxil (Aristada) doses of 441, 662, 882, and 1064 mg correspond to aripiprazole doses of 300, 450, 600, and 724 mg, respectively.

If used with CYP3A4 inhibitors, CYP2D6 inhibitors, and/or CYP3A4 inducers, dosage adjustment may be required. (See Interactions.)

Pediatric Patients

Schizophrenia

Oral

Adolescents ≥13 years of age: Recommended target dosage for treatment is 10 mg once daily. Therapy has been initiated at 2 mg once daily, with subsequent titration to 5 mg once daily after 2 days and to 10 mg once daily after 2 additional days.

Subsequent dosage increases should be made in 5-mg, once-daily increments.

Dosages of 10 and 30 mg once daily evaluated in clinical trials; the 30-mg daily dosage was not more effective than the 10-mg daily dosage in adolescents.

Although efficacy as maintenance treatment not systematically evaluated in adolescents with schizophrenia, the manufacturer states that such efficacy can be extrapolated from adult data in addition to comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients. Periodically reassess need for continued therapy. (See Pediatric Use under Cautions.)

Bipolar Disorder

Manic or Mixed Episodes: Monotherapy or Combination Therapy

Oral

Children and adolescents ≥10 years of age: Target dosage for acute treatment is 10 mg once daily. Recommended initial dosage when given as monotherapy is 2 mg once daily, with subsequent titration to 5 mg once daily after 2 days and to the target dosage of 10 mg once daily after 2 additional days.

Recommended dosage when aripiprazole is given as adjunctive therapy with lithium or valproate is the same as that for monotherapy.

Daily dosage may be increased, if necessary, in 5-mg increments. In pediatric clinical studies, dosages of 10 and 30 mg daily were effective.

Irritability Associated with Autistic Disorder

Oral

Children and adolescents 6–17 years of age: Initially, 2 mg once daily, then increase dosage to 5 mg daily, with subsequent increases to 10 or 15 mg daily, if necessary. Increase dosage gradually, at intervals of ≥1 week. Efficacy established within a dosage range of 5–15 mg daily in clinical studies.

Periodically reassess need for continued therapy.

Tourette's Syndrome

Oral

Children and adolescents 6–18 years of age weighing <50 kg: Initially, 2 mg once daily for 2 days, then increase dosage to 5 mg once daily. If optimal control of tics not achieved, may increase dosage to 10 mg once daily. Adjust dosage gradually at intervals of ≥1 week.

Children and adolescents 6–18 years of age weighing ≥50 kg: Initially, 2 mg once daily for 2 days, then increase to 5 mg once daily for 5 days, with a recommended target dosage of 10 mg once daily on day 8. If optimal control of tics not achieved, may increase dosage up to 20 mg once daily. Adjust dosage gradually in increments of 5 mg daily at intervals of ≥1 week.

Periodically reassess need for continued maintenance therapy.

Adults

Schizophrenia

Oral

Initial and target dosage for treatment is 10 or 15 mg once daily.