ABILIFY®
(aripiprazole) Tablets
ABILIFY DISCMELT®
(aripiprazole) Orally Disintegrating Tablets
ABILIFY®
(aripiprazole) Oral Solution
ABILIFY®
(aripiprazole) Injection FOR INTRAMUSCULAR USE ONLY
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WARNINGS
INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDALITY AND ANTIDEPRESSANT DRUGS
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. ABILIFY (aripiprazole) is not approved for the treatment of patients with dementia-related psychosis [see WARNINGS AND PRECAUTIONS].
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of adjunctive ABILIFY or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. ABILIFY is not approved for use in pediatric patients with depression [see WARNINGS AND PRECAUTIONS].
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DRUG DESCRIPTION
Aripiprazole is a psychotropic drug that is available as ABILIFY® (aripiprazole) Tablets, ABILIFY DISCMELT® (aripiprazole) Orally Disintegrating Tablets, ABILIFY® (aripiprazole) Oral Solution, and ABILIFY® (aripiprazole) Injection, a solution for intramuscular injection. Aripiprazole is 7-[4-[4-(2,3-dichlorophenyl)-1piperazinyl]butoxy]-3,4-dihydrocarbostyril. The empirical formula is C23H27Cl2N3O2 and its molecular weight is 448.38. The chemical structure is:
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ABILIFY Tablets are available in 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 30 mg strengths. Inactive ingredients include cornstarch, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. Colorants include ferric oxide (yellow or red) and FD&C Blue No. 2 Aluminum Lake.
ABILIFY DISCMELT Orally Disintegrating Tablets are available in 10 mg and 15 mg strengths. Inactive ingredients include acesulfame potassium, aspartame, calcium silicate, croscarmellose sodium, crospovidone, crème de vanilla (natural and artificial flavors), magnesium stearate, microcrystalline cellulose, silicon dioxide, tartaric acid, and xylitol. Colorants include ferric oxide (yellow or red) and FD&C Blue No. 2 Aluminum Lake.
ABILIFY Oral Solution is a clear, colorless to light yellow solution available in a concentration of 1 mg/mL. The inactive ingredients for this solution include disodium edetate, fructose, glycerin, dl-lactic acid, methylparaben, propylene glycol, propylparaben, sodium hydroxide, sucrose, and purified water. The oral solution is flavored with natural orange cream and other natural flavors.
ABILIFY Injection is available in single-dose vials as a ready-to-use, 9.75 mg/1.3 mL (7.5 mg/mL) clear, colorless, sterile, aqueous solution for intramuscular use only. Inactive ingredients for this solution include 150 mg/mL of sulfobutylether β-cyclodextrin (SBECD), tartaric acid, sodium hydroxide, and water for injection.
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Indications & Dosage
INDICATIONS
Schizophrenia
ABILIFY is indicated for acute and maintenance treatment of Schizophrenia in adults and in adolescents 13 to 17 years of age .
Bipolar Disorder
Monotherapy
ABILIFY is indicated for acute and maintenance treatment of manic and mixed episodes associated with Bipolar I Disorder with or without psychotic features in adults and in pediatric patients 10 to 17 years of age .
Adjunctive Therapy
ABILIFY is indicated as an adjunctive therapy to either lithium or valproate for the acute treatment of manic and mixed episodes associated with Bipolar I Disorder with or without psychotic features in adults and in pediatric patients 10 to 17 years of age .
Adjunctive Treatment of Major Depressive Disorder
ABILIFY is indicated for use as an adjunctive therapy to antidepressants for the acute treatment of Major Depressive Disorder in adults .
Agitation Associated with Schizophrenia or Bipolar Mania
ABILIFY Injection is indicated for the acute treatment of agitation associated with Schizophrenia or Bipolar Disorder, manic or mixed in adults. “Psychomotor agitation” is defined in DSM-IV as “excessive motor activity associated with a feeling of inner tension”. Patients experiencing agitation often manifest behaviors that interfere with their diagnosis and care (eg, threatening behaviors, escalating or urgently distressing behavior, or self-exhausting behavior), leading clinicians to the use of intramuscular antipsychotic medications to achieve immediate control of the agitationDOSAGE AND ADMINISTRATION
Schizophrenia
Usual Dose for Acute Treatment
Adults
The recommended starting and target dose for ABILIFY is 10 mg/day or 15 mg/day administered on a once-a-day schedule without regard to meals. ABILIFY has been systematically evaluated and shown to be effective in a dose range of 10 mg/day to 30 mg/day, when administered as the tablet formulation; however, doses higher than 10 mg/day or 15 mg/day were not more effective than 10 mg/day or 15 mg/day. Dosage increases should not be made before 2 weeks, the time needed to achieve steady-state [see Clinical Studies].
Adolescents
The recommended target dose of ABILIFY is 10 mg/day. Aripiprazole was studied in pediatric patients 13 to 17 years of age with Schizophrenia at daily doses of 10 mg and 30 mg. The starting daily dose of the tablet formulation in these patients was 2 mg, which was titrated to 5 mg after 2 days and to the target dose of 10 mg after 2 additional days. Subsequent dose increases should be administered in 5 mg increments. The 30 mg/day dose was not shown to be more efficacious than the 10 mg/day dose. ABILIFY can be administered without regard to meals [see Clinical Studies].
Maintenance Therapy
Adults
While there is no body of evidence available to answer the question of how long a patient treated with aripiprazole should remain on it, systematic evaluation of patients with Schizophrenia who had been symptomatically stable on other antipsychotic medications for periods of 3 months or longer, were discontinued from those medications, and were then administered ABILIFY 15 mg/day and observed for relapse during a period of up to 26 weeks, has demonstrated a benefit of such maintenance treatment [see Clinical Studies]. Patients should be periodically reassessed to determine the need for maintenance treatment.
Adolescents
The efficacy of ABILIFY for the maintenance treatment of Schizophrenia in the pediatric population has not been evaluated. While there is no body of evidence available to answer the question of how long the adolescent patient treated with ABILIFY should be maintained, maintenance efficacy can be extrapolated from adult data along with comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients. Thus, it is generally recommended that responding patients be continued beyond the acute response, but at the lowest dose needed to maintain remission. Patients should be periodically reassessed to determine the need for maintenance treatment.
Switching from Other Antipsychotics
There are no systematically collected data to specifically address switching patients with Schizophrenia from other antipsychotics to ABILIFY or concerning concomitant administration with other antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with Schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized.
Bipolar Disorder
Usual Dose for Acute Treatment
Adults
The recommended starting and target dose is 15 mg as monotherapy or as adjunctive therapy with lithium or valproate given once a day, without regard to meals. The dose can be increased to 30 mg/day based on clinical response. The safety of doses above 30 mg/day has not been evaluated in clinical trials [see Clinical Studies].
Pediatric Patients
The efficacy of aripiprazole has been established in the treatment of pediatric patients 10 to 17 years of age with Bipolar I Disorder at doses of 10 mg/day or 30 mg/day. The recommended target dose of ABILIFY is 10 mg/day, as monotherapy or as adjunctive therapy with lithium or valproate. The starting daily dose of the tablet formulation in these patients was 2 mg/day, which was titrated to 5 mg/day after 2 days and to the target dose of 10 mg/day after 2 additional days. Subsequent dose increases should be administered in 5 mg/day increments. ABILIFY can be administered without regard to meals. [See Clinical Studies.]
Maintenance Therapy
Adults
While there is no body of evidence available to answer the question of how long a patient treated with aripiprazole should remain on it, whether used as monotherapy or as adjunctive therapy, adult patients with Bipolar I Disorder who had been symptomatically stable on ABILIFY Tablets (15 mg/day or 30 mg/day as monotherapy with a starting dose of 30 mg/day) for at least 6 consecutive weeks and then randomized to ABILIFY Tablets (15 mg/day or 30 mg/day) or placebo and monitored for relapse, demonstrated a benefit of such maintenance treatment [see Clinical Studies]. While it is generally agreed that pharmacological treatment beyond an acute response in Mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the use of aripiprazole in such longer-term treatment (beyond 6 weeks). Physicians who elect to use ABILIFY for extended periods, that is, longer than 6 weeks, should periodically re-evaluate the long-term usefulness of the drug for the individual.
Pediatric Patients
The efficacy of ABILIFY for the maintenance treatment of Bipolar I Disorder in the pediatric population has not been evaluated. While there is no body of evidence available to answer the question of how long the pediatric patient treated with ABILIFY should be maintained, maintenance efficacy can be extrapolated from adult data along with comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients. Thus, it is generally recommended that responding patients be continued beyond the acute response, but at the lowest dose needed to maintain remission. Patients should be periodically reassessed to determine the need for maintenance treatment.
Adjunctive Treatment of Major Depressive Disorder
Usual Dose for Acute Treatment
Adults
The recommended starting dose for ABILIFY as adjunctive treatment for patients already taking an antidepressant is 2 mg/day to 5 mg/day. The efficacy of ABILIFY as an adjunctive therapy for Major Depressive Disorder was established within a dose range of 2 mg/day to 15 mg/day. Dose adjustments of up to 5 mg/day should occur gradually, at intervals of no less than 1 week [see Clinical Studies].
Pediatric Patients
The efficacy of ABILIFY for the adjunctive treatment of Major Depressive Disorder in the pediatric population has not been evaluated.
Maintenance Therapy
The efficacy of ABILIFY for the adjunctive maintenance treatment of Major Depressive Disorder has not been evaluated. While there is no body of evidence available to answer the question of how long the patient treated with ABILIFY should be maintained, patients should be periodically reassessed to determine the need for maintenance treatment.
Agitation Associated with Schizophrenia or Bipolar Mania (Intramuscular Injection)
Usual Dose
Adults
The recommended dose in these patients is 9.75 mg. The effectiveness of aripiprazole injection in controlling agitation in Schizophrenia and Bipolar Mania was demonstrated over a dose range of 5.25 mg to 15 mg. No additional benefit was demonstrated for 15 mg compared to 9.75 mg. A lower dose of 5.25 mg may be considered when clinical factors warrant. If agitation warranting a second dose persists following the initial dose, cumulative doses up to a total of 30 mg/day may be given. However, the efficacy of repeated doses of aripiprazole injection in agitated patients has not been systematically evaluated in controlled clinical trials. The safety of total daily doses greater than 30 mg or injections given more frequently than every 2 hours have not been adequately evaluated in clinical trials [see Clinical Studies].
If ongoing aripiprazole therapy is clinically indicated, oral aripiprazole in a range of 10 mg/day to 30 mg/day should replace aripiprazole injection as soon as possible [see DOSAGE AND ADMINISTRATION].
Administration of ABILIFY Injection
To administer ABILIFY Injection, draw up the required volume of solution into the syringe as shown in Table 1. Discard any unused portion.
Table 1: ABILIFY Injection Dosing Recommendations
| Single-Dose | Required Volume of Solution |
| 5.25 mg | 0.7 mL |
| 9.75 mg | 1.3 mL |
| 15 mg | 2 mL |
ABILIFY Injection is intended for intramuscular use only. Do not administer intravenously or subcutaneously. Inject slowly, deep into the muscle mass.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Pediatric Patients
ABILIFY Intramuscular Injection has not been evaluated in pediatric patients.
Dosage Adjustment
Dosage adjustments in adults are not routinely indicated on the basis of age, gender, race, or renal or hepatic impairment status [see Use In Specific Populations].
Dosage adjustment for patients taking aripiprazole concomitantly with strong CYP3A4 inhibitors: When concomitant administration of aripiprazole with strong CYP3A4 inhibitors such as ketoconazole or clarithromycin is indicated, the aripiprazole dose should be reduced to one-half the usual dose. When the CYP3A4 inhibitor is withdrawn from the combination therapy, the aripiprazole dose should then be increased [see DRUG INTERACTIONS].
Dosage adjustment for patients taking aripiprazole concomitantly with potential CYP2D6 inhibitors: When concomitant administration of potential CYP2D6 inhibitors such as quinidine, fluoxetine, or paroxetine with aripiprazole occurs, aripiprazole dose should be reduced at least to one-half of its normal dose. When the CYP2D6 inhibitor is withdrawn from the combination therapy, the aripiprazole dose should then be increased [see DRUG INTERACTIONS]. When adjunctive ABILIFY is administered to patients with Major Depressive Disorder, ABILIFY should be administered without dosage adjustment as specified in DOSAGE AND ADMINISTRATION.
Dosage adjustment for patients taking potential CYP3A4 inducers: When a potential CYP3A4 inducer such as carbamazepine is added to aripiprazole therapy, the aripiprazole dose should be doubled. Additional dose increases should be based on clinical evaluation. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose should be reduced to 10 mg to 15 mg [see DRUG INTERACTIONS].
Dosing of Oral Solution
The oral solution can be substituted for tablets on a mg-per-mg basis up to the 25 mg dose level. Patients receiving 30 mg tablets should receive 25 mg of the solution [see CLINICAL PHARMACOLOGY].
Dosing of Orally Disintegrating Tablets
The dosing for ABILIFY Orally Disintegrating Tablets is the same as for the oral tablets.
HOW SUPPLIED
Dosage Forms And Strengths
ABILIFY® (aripiprazole) Tablets are available as described in Table 2.
Table 2: ABILIFY Tablet Presentations
| Tablet Strength | Tablet Color/Shape | Tablet Markings |
| 2 mg | green modified rectangle | A-006 and “2” |
| 5 mg | blue modified rectangle | A-007 and “5” |
| 10 mg | pink modified rectangle | A-008 and “10” |
| 15 mg | yellow round | A-009 and “15” |
| 20 mg | white round | A-010 and “20” |
| 30 mg | pink round | A-011 and “30” |
ABILIFY DISCMELT® (aripiprazole) Orally Disintegrating Tablets are available as described in Table 3.
Table 3: ABILIFY DISCMELT Orally Disintegrating Tablet Presentations
| Tablet Strength | Tablet Color/Shape | Tablet Markings |
| 10 mg | pink (with scattered specks) round | A and “640” 10 |
| 15 mg | yellow (with scattered specks) round | A and “641” 15 |
ABILIFY® (aripiprazole) Oral Solution (1 mg/mL) is a clear, colorless to light yellow solution, supplied in child-resistant bottles along with a calibrated oral dosing cup.
ABILIFY® (aripiprazole) Injection for Intramuscular Use is a clear, colorless solution available as a ready-to-use, 9.75 mg/1.3 mL (7.5 mg/mL) solution in clear, Type 1 glass vials.
ABILIFY® (aripiprazole) Tablets have markings on one side and are available in the strengths and packages listed in Table 14.
Table 14: ABILIFY Tablet Presentations
| Tablet Strength | Tablet Color/Shape | Tablet Markings | Pack Size | NDC Code |
| 2 mg | green modified rectangle | A-006 and “2” | Bottle of 30 | 59148-006-13 |
| 5 mg | blue modified rectangle | A-007 and “5” | Bottle of 30 | 59148-007-13 |
| Blister of 100 | 59148-007-35 | |||
| 10 mg | pink modified rectangle | A-008 and “10” | Bottle of 30 | 59148-008-13 |
| Blister of 100 | 59148-008-35 | |||
| 15 mg | yellow round | A-009 and “15” | Bottle of 30 | 59148-009-13 |
| 20 mg | white round | A-010 and “20” | Blister of 100 | 59148-009-35 |
| Bottle of 30 | 59148-010-13 | |||
| Blister of 100 | 59148-010-35 | |||
| 30 mg | pink round | A-011 and “30” | Bottle of 30 | 59148-011-13 |
| Blister of 100 | 59148-011-35 |
ABILIFY DISCMELT® (aripiprazole) Orally Disintegrating Tablets are round tablets with markings on either side. ABILIFY DISCMELT is available in the strengths and packages listed in Table 15.
Table 15: ABILIFY DISCMELT Orally Disintegrating Tablet Presentations
| Tablet Strength | Tablet Color | Tablet Markings | Pack Size | NDC Code |
| 10 mg | pink (with scattered specks) | A and “640” 10 | Blister of 30 | 59148-640-23 |
| 15 mg | yellow (with scattered specks) | A and “641” 15 | Blister of 30 | 59148-641-23 |
ABILIFY® (aripiprazole) Oral Solution (1 mg/mL) is supplied in child-resistant bottles along with a calibrated oral dosing cup. ABILIFY Oral Solution is available as follows:
150 mL bottle NDC 59148-013-15
ABILIFY® (aripiprazole) Injection for intramuscular use is available as a ready-to-use, 9.75 mg/1.3 mL (7.5 mg/mL) solution in clear, Type 1 glass vials as follows:
9.75 mg/1.3 mL single-dose vial NDC 59148-016-65
Storage
Tablets
Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
Oral Solution
Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Opened bottles of ABILIFY Oral Solution can be used for up to 6 months after opening, but not beyond the expiration date on the bottle. The bottle and its contents should be discarded after the expiration date.
Injection
Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from light by storing in the original container. Retain in carton until time of use.
Tablets manufactured by Otsuka Pharmaceutical Co, Ltd, Tokyo, 101-8535 Japan or Bristol-Myers Squibb Company, Princeton, NJ 08543 USA
Orally Disintegrating Tablets, Oral Solution, and Injection manufactured by Bristol-Myers Squibb Company, Princeton, NJ 08543 USA
Distributed and marketed by Otsuka America Pharmaceutical, Inc, Rockville, MD 20850 USA. Marketed by Bristol-Myers Squibb Company, Princeton, NJ 08543 USA.
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