HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use ABILIFY
`safely and effectively. See full prescribing information for ABILIFY.
`ABILIFY® (aripiprazole) Tablets
`ABILIFY DISCMELT® (aripiprazole) Orally Disintegrating Tablets
`ABILIFY® (aripiprazole) Oral Solution
`ABILIFY® (aripiprazole) Injection FOR INTRAMUSCULAR USE ONLY
`Initial U.S. Approval: 2002
`
`
`
`WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS
`WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL
`THOUGHTS AND BEHAVIORS WITH ANTIDEPRESSANT DRUGS
`See full prescribing information for complete boxed warning.
`Elderly patients with dementia-related psychosis
`treated with
`antipsychotic drugs are at an increased risk of death. ABILIFY is not
`approved for the treatment of patients with dementia-related
`psychosis. (5.1)
`in children,
`Increased risk of suicidal thinking and behavior
`adolescents, and young adults taking antidepressants. Monitor for
`worsening and emergence of suicidal thoughts and behaviors. (5.3)
`
`
`
`
`
`
`
`
` --------------------------- INDICATIONS AND USAGE --------------------------
`ABILIFY is an atypical antipsychotic. The oral formulations are indicated for:
`
`Schizophrenia (14.1)
`
`Acute Treatment of Manic and Mixed Episodes associated with Bipolar I
`(14.2)
`
`Adjunctive Treatment of Major Depressive Disorder (14.3)
`
`Irritability Associated with Autistic Disorder (14.4)
`
`Treatment of Tourette’s disorder (14.5)
`The injection is indicated for:
`
`Agitation associated with schizophrenia or bipolar mania (14.6)
`
` ---------------------- DOSAGE AND ADMINISTRATION ---------------------
`Initial Dose Recommended
`Maximum
`Dose
`Dose
`10-15 mg/day
`30
`mg/day
`30
`mg/day
`30
`mg/day
`30
`mg/day
`30
`mg/day
`
`10-15
`mg/day
`2 mg/day
`
`10 mg/day
`
`15 mg/day
`
`15 mg/day
`
`10-15
`mg/day
`2 mg/day
`
`15 mg/day
`
`10 mg/day
`
`
`
`Schizophrenia – adults (2.1)
`
`Schizophrenia – adolescents
`(2.1)
`Bipolar mania – adults: monotherapy
`(2.2)
`Bipolar mania – adults: adjunct to
`lithium or valproate (2.2)
`Bipolar mania – pediatric patients:
`monotherapy or as an adjunct to
`lithium or valproate (2.2)
`Major Depressive Disorder – Adults
`adjunct to antidepressants (2.3)
`Irritability associated with autistic
`disorder – pediatric patients (2.4)
`Tourette’s
`Patients < 50 kg
`disorder
`(2.5)
`
`–
`
`Patients ≥ 50 kg
`
`2-5 mg/day
`
`5-10 mg/day
`
`2 mg/day
`
`5-10 mg/day
`
`2 mg/day
`
`5 mg/day
`
`2 mg/day
`
`10 mg/day
`
`15
`mg/day
`15
`mg/day
`10
`mg/day
`20
`mg/day
`30
`mg/day
`injected
`IM
`
`with
`associated
`Agitation
`schizophrenia or bipolar mania –
`adults (2.6)
`
`9.75 mg
`/1.3 mL
`injected IM
`
`
`
`
`
`
`
`
`
`
`
`
`
`Oral formulations: Administer once daily without regard to meals (2)
`IM injection: Wait at least 2 hours between doses. Maximum daily dose 30
`mg (2.5)
`Known CYP2D6 poor metabolizers: Half of the usual dose (2.7)
`
` --------------------- DOSAGE FORMS AND STRENGTHS --------------------
`Tablets: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 30 mg (3)
`Orally Disintegrating Tablets: 10 mg and 15 mg (3)
`Oral Solution: 1 mg/mL (3)
`Injection: 9.75 mg/1.3 mL single-dose vial (3)
`
`Reference ID: 3874224
`
`
`
`
`
`
`
`
` ----------------------------- CONTRAINDICATIONS -----------------------------
`Known hypersensitivity to ABILIFY (4)
`
` ---------------------- WARNINGS AND PRECAUTIONS ----------------------
`Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-
`Related Psychosis: Increased incidence of cerebrovascular adverse reactions
`(e.g., stroke, transient ischemic attack, including fatalities) (5.2)
`Neuroleptic Malignant Syndrome: Manage with immediate discontinuation
`and close monitoring (5.4)
`
`Tardive Dyskinesia: Discontinue if clinically appropriate (5.5)
` Metabolic Changes: Atypical antipsychotic drugs have been associated with
`metabolic changes that include hyperglycemia/diabetes mellitus,
`dyslipidemia, and body weight gain (5.6)
`o Hyperglycemia/Diabetes Mellitus: Monitor glucose regularly in
`patients with and at risk for diabetes (5.6)
`o Dyslipidemia: Undesirable alterations in lipid levels have been
`observed in patients treated with atypical antipsychotics (5.6)
`o Weight Gain: Weight gain has been observed with atypical
`antipsychotic use. Monitor weight (5.6)
`Orthostatic Hypotension: Monitor heart rate and blood pressure and warn
`patients with known cardiovascular or cerebrovascular disease, and risk of
`dehydration or syncope (5.7)
`Leukopenia, Neutropenia, and Agranulocytosis: have been reported with
`antipsychotics including ABILIFY. Patients with a history of a clinically
`significant low white blood cell count (WBC) or a drug-induced
`leukopenia/neutropenia should have their complete blood count (CBC)
`monitored frequently during the first few months of therapy and
`discontinuation of ABILIFY should be considered at the first sign of a
`clinically significant decline in WBC in the absence of other causative
`factors (5.8)
`Seizures/Convulsions: Use cautiously in patients with a history of seizures or
`with conditions that lower the seizure threshold (5.9)
`Potential for Cognitive and Motor Impairment: Use caution when operating
`machinery (5.10)
`Suicide: The possibility of a suicide attempt is inherent in schizophrenia and
`bipolar disorder. Closely supervise high-risk patients (5.12)
`
` ----------------------------- ADVERSE REACTIONS -----------------------------
`Commonly observed adverse reactions (incidence ≥5% and at least twice that
`for placebo) were (6.1):
`
`Adult patients with schizophrenia: akathisia
`
`Pediatric patients (13 to 17 years) with schizophrenia: extrapyramidal
`disorder, somnolence, and tremor
`Adult patients (monotherapy) with bipolar mania: akathisia, sedation,
`restlessness, tremor, and extrapyramidal disorder
`Adult patients (adjunctive therapy with lithium or valproate) with bipolar
`mania: akathisia, insomnia, and extrapyramidal disorder
`Pediatric patients (10 to 17 years) with bipolar mania: somnolence,
`extrapyramidal disorder, fatigue, nausea, akathisia, blurred vision, salivary
`hypersecretion, and dizziness
`Adult patients with major depressive disorder (adjunctive treatment to
`antidepressant therapy): akathisia, restlessness, insomnia, constipation,
`fatigue, and blurred vision
`Pediatric patients (6 to 17 years) with autistic disorder: sedation, fatigue,
`vomiting, somnolence,
`tremor, pyrexia, drooling, decreased appetite,
`salivary hypersecretion, extrapyramidal disorder, and lethargy
`Pediatric patients (6 to 18 years) with Tourette’s disorder: sedation,
`somnolence, nausea, headache, nasopharyngitis, fatigue, increased appetite
`Adult patients with agitation associated with schizophrenia or bipolar mania:
`nausea
`
`To report SUSPECTED ADVERSE REACTIONS, contact Bristol-
`Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or
`www.fda.gov/medwatch.
` ----------------------------- DRUG INTERACTIONS -----------------------------
`Dosage adjustment due to drug interactions (7.1):
`Factors
`Dosage Adjustments for ABILIFY
`Known CYP2D6 Poor Metabolizers
`Administer half of usual dose
`Known CYP2D6 Poor Metabolizers
`Administer a quarter of usual dose
`and strong CYP3A4 inhibitors
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`

`

`
`
`Nursing Mothers: Discontinue drug or nursing, taking into consideration
`importance of drug to the mother (8.3)
`
`See 17 for PATIENT COUNSELING INFORMATION and Medication
`Guide.
`
`Revised: 01/2016
`
`
`
`8
`
`9
`
`7.2
`Drugs Having No Clinically Important Interactions with
`ABILIFY
`USE IN SPECIFIC POPULATIONS
`Pregnancy
`8.1
`Labor and Delivery
`8.2
`Nursing Mothers
`8.3
`Pediatric Use
`8.4
`Geriatric Use
`8.5
`8.6 CYP2D6 Poor Metabolizers
`8.7 Hepatic and Renal Impairment
`8.8 Other Specific Populations
`DRUG ABUSE AND DEPENDENCE
`9.1 Controlled Substance
`9.2
`Abuse
`9.3 Dependence
`10 OVERDOSAGE
`10.1 Human Experience
`10.2 Management of Overdosage
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`13 NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`13.2 Animal Toxicology and/or Pharmacology
`14 CLINICAL STUDIES
`14.1 Schizophrenia
`14.2 Bipolar Disorder
`14.3 Adjunctive Treatment of Major Depressive Disorder
`14.4
`Irritability Associated with Autistic Disorder
`14.5 Tourette’s Disorder
`14.6 Agitation Associated with Schizophrenia or Bipolar Mania
`16 HOW SUPPLIED/STORAGE AND HANDLING
`16.1 How Supplied
`16.2 Storage
`17 PATIENT COUNSELING INFORMATION
`
`
`*Sections or subsections omitted from the full prescribing information are not listed.
`
`Strong CYP2D6 or CYP3A4 inhibitors Administer half of usual dose
`Strong CYP2D6 and CYP3A4
`Administer a quarter of usual dose
`inhibitors
`Strong CYP3A4 inducers
`Double usual dose over 1 to 2 weeks
`
` ---------------------- USE IN SPECIFIC POPULATIONS ----------------------
`Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in
`neonates with third trimester exposure (8.1)
`
`
`
`for
`
`Cytochrome
`
`P450
`
`Important
`
`Interactions with
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS
`WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL
`THOUGHTS AND BEHAVIORS WITH ANTIDEPRESSANT
`DRUGS 
`INDICATIONS AND USAGE
`DOSAGE AND ADMINISTRATION
`2.1
`Schizophrenia
`2.2
`Bipolar I Disorder
`2.3
`Adjunctive Treatment of Major Depressive Disorder
`2.4
`Irritability Associated with Autistic Disorder
`2.5
`Tourette’s Disorder
`2.6
`Agitation Associated with Schizophrenia or Bipolar Mania
`(Intramuscular Injection)
`2.7
`Dosage
`Adjustments
`Considerations
`2.8
`Dosing of Oral Solution
`Dosing of Orally Disintegrating Tablets
`2.9
`DOSAGE FORMS AND STRENGTHS
`3
`CONTRAINDICATIONS
`4
`5 WARNINGS AND PRECAUTIONS
`5.1
`Increased Mortality in Elderly Patients with Dementia-
`Related Psychosis
`5.2
`Cerebrovascular Adverse Events, Including Stroke
`5.3
`Suicidal Thoughts
`and Behaviors
`in Children,
`Adolescents, and Young Adults
`5.4
`Neuroleptic Malignant Syndrome (NMS)
`Tardive Dyskinesia
`5.5
`5.6 Metabolic Changes
`5.7
`Orthostatic Hypotension
`5.8
`Leukopenia, Neutropenia, and Agranulocytosis
`5.9
`Seizures/Convulsions
`5.10 Potential for Cognitive and Motor Impairment
`5.11 Body Temperature Regulation
`5.12 Suicide
`5.13 Dysphagia
`ADVERSE REACTIONS
`6.1
`Clinical Trials Experience
`6.2
`Postmarketing Experience
`DRUG INTERACTIONS
`7.1
`Drugs Having Clinically
`ABILIFY
`
`1
`2
`
`6
`
`7
`
`
`
`Reference ID: 3874224
`
`

`

`FULL PRESCRIBING INFORMATION
` WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS
`WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL
`THOUGHTS AND BEHAVIORS WITH ANTIDEPRESSANT DRUGS
`
`Elderly patients with dementia-related psychosis treated with antipsychotic drugs
`are at an increased risk of death. ABILIFY is not approved for the treatment of
`patients with dementia-related psychosis [see WARNINGS AND PRECAUTIONS
`(5.1)].
`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 [see WARNINGS AND PRECAUTIONS (5.3)].
`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 [see WARNINGS AND PRECAUTIONS (5.3)].
`
`
` INDICATIONS AND USAGE
`
`
`
` 1
`
`ABILIFY Oral Tablets, Orally-Disintegrating Tablets, and Oral Solution are indicated for
`the treatment of:
`
` Schizophrenia [see CLINICAL STUDIES (14.1)]
` Acute Treatment of Manic and Mixed Episodes associated with Bipolar I
`Disorder [see CLINICAL STUDIES (14.2)]
` Adjunctive Treatment of Major Depressive Disorder [see CLINICAL STUDIES
`(14.3)]
`
`Irritability Associated with Autistic Disorder [see CLINICAL STUDIES (14.4)]
` Treatment of Tourette’s Disorder [see CLINICAL STUDIES (14.5)]
`
`ABILIFY Injection is indicated for the treatment of:
`
` Agitation associated with schizophrenia or bipolar mania [see CLINICAL
`STUDIES (14.6)]
`
`Reference ID: 3874224
`
`

`

`2 DOSAGE AND ADMINISTRATION
`2.1 Schizophrenia
`Adults
`The recommended starting and target dose for ABILIFY is 10 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 to 30 mg/day, when
`administered as the tablet formulation; however, doses higher than 10 or 15 mg/day were
`not more effective than 10 or 15 mg/day. Dosage increases should generally not be made
`before 2 weeks, the time needed to achieve steady-state [see CLINICAL STUDIES
`(14.1)].
`
`Maintenance Treatment: Maintenance of efficacy in schizophrenia was demonstrated in a
`trial involving patients with schizophrenia who had been symptomatically stable on other
`antipsychotic medications for periods of 3 months or longer. These patients were
`discontinued from those medications and randomized to either ABILIFY 15 mg/day or
`placebo, and observed for relapse [see CLINICAL STUDIES (14.1)]. Patients should be
`periodically reassessed to determine the continued need for maintenance treatment.
`
`Adolescents
`The recommended target dose of ABILIFY is 10 mg/day. Aripiprazole was studied in
`adolescent 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 (14.1)]. 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.
`
`Reference ID: 3874224
`
`

`

`2.2 Bipolar I Disorder
`Acute Treatment of Manic and Mixed Episodes
`Adults: The recommended starting dose in adults is 15 mg given once daily as
`monotherapy and 10 mg to 15 mg given once daily as adjunctive therapy with lithium or
`valproate. ABILIFY can be given without regard to meals. The recommended target dose
`of ABILIFY is 15 mg/day, as monotherapy or as adjunctive therapy with lithium or
`valproate. The dose may 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.
`
`Pediatrics: The recommended starting dose in pediatric patients (10 to 17 years) as
`monotherapy is 2 mg/day, with titration to 5 mg/day after 2 days, and a target dose of
`10 mg/day after 2 additional days. Recommended dosing as adjunctive therapy to lithium
`or valproate is the same. Subsequent dose increases, if needed, should be administered in
`5 mg/day increments. ABILIFY can be given without regard to meals [see CLINICAL
`STUDIES (14.2)].
`2.3 Adjunctive Treatment of Major Depressive Disorder
`Adults
`The recommended starting dose for ABILIFY as adjunctive treatment for patients already
`taking an antidepressant is 2 to 5 mg/day. The recommended dosage range is 2 to
`15 mg/day. Dosage adjustments of up to 5 mg/day should occur gradually, at intervals of
`no less than 1 week [see CLINICAL STUDIES (14.3)]. Patients should be periodically
`reassessed to determine the continued need for maintenance treatment.
`2.4 Irritability Associated with Autistic Disorder
`Pediatric Patients (6 to 17 years)
`The recommended dosage range for the treatment of pediatric patients with irritability
`associated with autistic disorder is 5 to 15 mg/day.
`
`Dosing should be initiated at 2 mg/day. The dose should be increased to 5 mg/day, with
`subsequent increases to 10 or 15 mg/day if needed. Dose adjustments of up to 5 mg/day
`should occur gradually, at intervals of no less than 1 week [see CLINICAL
`STUDIES (14.4)]. Patients should be periodically reassessed to determine the continued
`need for maintenance treatment.
`2.5 Tourette’s Disorder
`Pediatric Patients (6 to 18 years)
`The recommended dosage range for Tourette’s Disorder is 5 to 20 mg/day.
`
`Reference ID: 3874224
`
`

`

`For patients weighing less than 50 kg, dosing should be initiated at 2 mg/day with
`a target dose of 5 mg/day after 2 days. The dose can be increased to 10 mg/day in
`patients who do not achieve optimal control of tics. Dosage adjustments should
`occur gradually at intervals of no less than 1 week.
`
`For patients weighing 50 kg or more, dosing should be initiated at 2 mg/day for
`2 days, and then increased to 5 mg/day for 5 days, with a target dose of 10 mg/day
`on day 8. The dose can be increased up to 20 mg/day for patients who do not
`achieve optimal control of tics. Dosage adjustments should occur gradually in
`increments of 5 mg/day at intervals of no less than 1 week. [see CLINICAL
`STUDIES (14.5)].
`
`Patients should be periodically reassessed to determine the continued need for
`maintenance treatment.
`2.6 Agitation Associated with Schizophrenia or Bipolar Mania
`(Intramuscular Injection)
`Adults
`The recommended dose in these patients is 9.75 mg. The recommended dosage range is
`5.25 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 ABILIFY
`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 (14. 6)].
`
`If ongoing ABILIFY therapy is clinically indicated, oral ABILIFY in a range of 10 to
`30 mg/day should replace ABILIFY injection as soon as possible [see DOSAGE AND
`ADMINISTRATION (2.1 and 2.2)].
`
`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
`5.25 mg
`9.75 mg
`15 mg
`
`Required Volume of Solution
`0.7 mL
`1.3 mL
`2 mL
`
`Reference ID: 3874224
`
`

`

`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.
`2.7 Dosage Adjustments for Cytochrome P450 Considerations
`
`Dosage adjustments are recommended in patients who are known CYP2D6 poor
`metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6
`inhibitors or strong CYP3A4 inducers (see Table 2). When the coadministered drug is
`withdrawn from the combination therapy, ABILIFY dosage should then be adjusted to its
`original level. When the coadministered CYP3A4 inducer is withdrawn, ABILIFY
`dosage should be reduced to the original level over 1 to 2 weeks. Patients who may be
`receiving a combination of strong, moderate, and weak inhibitors of CYP3A4 and
`CYP2D6 (e.g., a strong CYP3A4 inhibitor and a moderate CYP2D6 inhibitor or a
`moderate CYP3A4 inhibitor with a moderate CYP2D6 inhibitor), the dosing may be
`reduced to one-quarter (25%) of the usual dose initially and then adjusted to achieve a
`favorable clinical response.
`
`Table 2:
`
`Dose Adjustments for ABILIFY in Patients who are known
`CYP2D6 Poor Metabolizers and Patients Taking Concomitant
`CYP2D6 Inhibitors, 3A4 Inhibitors, and/or CYP3A4 Inducers
`Dosage Adjustments for ABILIFY
`Administer half of usual dose
`
`Factors
`Known CYP2D6 Poor Metabolizers
`Known CYP2D6 Poor Metabolizers taking
`concomitant strong CYP3A4 inhibitors (e.g.,
`itraconazole, clarithromycin)
`Strong CYP2D6 (e.g., quinidine, fluoxetine,
`paroxetine) or CYP3A4 inhibitors (e.g.,
`itraconazole, clarithromycin)
`Strong CYP2D6 and CYP3A4 inhibitors
`Strong CYP3A4 inducers (e.g.,
`Double usual dose over 1 to 2 weeks
`carbamazepine, rifampin)
`When adjunctive ABILIFY is administered to patients with major depressive disorder,
`ABILIFY should be administered without dosage adjustment as specified in DOSAGE
`AND ADMINISTRATION (2.3).
`
`Administer a quarter of usual dose
`
`Administer half of usual dose
`
`Administer a quarter of usual dose
`
`Reference ID: 3874224
`
`

`

`2.8 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 (12.3)].
`2.9 Dosing of Orally Disintegrating Tablets
`
`The dosing for ABILIFY Orally Disintegrating Tablets is the same as for the oral tablets
`[see DOSAGE AND ADMINISTRATION (2.1, 2.2, 2.3, and 2.4)].
`
`3 DOSAGE FORMS AND STRENGTHS
`ABILIFY® (aripiprazole) Tablets are available as described in Table 3.
`
`Table 3:
`
`ABILIFY Tablet Presentations
`
`Tablet
`Strength
`2 mg
`
`5 mg
`
`10 mg
`
`15 mg
`
`20 mg
`
`30 mg
`
`Tablet
`Color/Shape
`green
`modified rectangle
`blue
`modified rectangle
`pink
`modified rectangle
`yellow
`round
`white
`round
`pink
`round
`
`Tablet
`Markings
`“A-006”
`and “2”
`“A-007”
`and “5”
`“A-008”
`and “10”
`“A-009”
`and “15”
`“A-010”
`and “20”
`“A-011”
`and “30”
`
`ABILIFY DISCMELT® (aripiprazole) Orally Disintegrating Tablets are available as
`described in Table 4.
`
`Table 4:
`
`ABILIFY DISCMELT Orally Disintegrating Tablet
`Presentations
`
`Tablet
`Strength
`10 mg
`
`15 mg
`
`Tablet
`Color/Shape
`pink (with scattered specks)
`round
`yellow (with scattered specks)
`round
`
`Tablet
`Markings
`“A” and “640”
`“10”
`“A” and “641”
`“15”
`
`Reference ID: 3874224
`
`

`

`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.
`
`4 CONTRAINDICATIONS
`
`ABILIFY is contraindicated in patients with a history of a hypersensitivity reaction to
`aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis [see ADVERSE
`REACTIONS (6.2)].
`
`5 WARNINGS AND PRECAUTIONS
`5.1 Increased Mortality
`in Elderly Patients with Dementia-
`Related Psychosis
`Increased Mortality
`Elderly patients with dementia-related psychosis treated with antipsychotic drugs
`are at an increased risk of death. ABILIFY (aripiprazole) is not approved for the
`treatment of patients with dementia-related psychosis [see BOXED WARNING].
`
`Safety Experience in Elderly Patients with Psychosis Associated with
`Alzheimer’s Disease
`In three, 10-week, placebo-controlled studies of ABILIFY in elderly patients with
`psychosis associated with Alzheimer’s disease (n=938; mean age: 82.4 years; range: 56-
`99 years), the adverse reactions that were reported at an incidence of ≥3% and ABILIFY
`incidence at least twice that for placebo were lethargy [placebo 2%, ABILIFY 5%],
`somnolence (including sedation) [placebo 3%, ABILIFY 8%], and incontinence
`(primarily, urinary incontinence) [placebo 1%, ABILIFY 5%], excessive salivation
`[placebo 0%, ABILIFY 4%], and lightheadedness [placebo 1%, ABILIFY 4%].
`
`The safety and efficacy of ABILIFY in the treatment of patients with psychosis
`associated with dementia have not been established. If the prescriber elects to treat such
`patients with ABILIFY, assess for the emergence of difficulty swallowing or excessive
`somnolence, which could predispose to accidental injury or aspiration [see BOXED
`WARNING].
`5.2 Cerebrovascular Adverse Events, Including Stroke
`
`In placebo-controlled clinical studies (two flexible dose and one fixed dose study) of
`dementia-related psychosis, there was an increased incidence of cerebrovascular adverse
`
`Reference ID: 3874224
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`

`

`events (e.g., stroke, transient ischemic attack), including fatalities, in ABILIFY-treated
`patients (mean age: 84 years; range: 78-88 years). In the fixed-dose study, there was a
`statistically significant dose response relationship for cerebrovascular adverse events in
`patients treated with ABILIFY. ABILIFY is not approved for the treatment of patients
`with dementia-related psychosis [see BOXED WARNING].
`5.3 Suicidal Thoughts and Behaviors in Children, Adolescents,
`and Young Adults
`
`Patients with major depressive disorder (MDD), both adult and pediatric, may experience
`worsening of their depression and/or the emergence of suicidal ideation and behavior
`(suicidality) or unusual changes in behavior, whether or not they are taking
`antidepressant medications, and this risk may persist until significant remission occurs.
`Suicide is a known risk of depression and certain other psychiatric disorders, and these
`disorders themselves are the strongest predictors of suicide. There has been a long-
`standing concern, however, that antidepressants may have a role in inducing worsening of
`depression and the emergence of suicidality in certain patients during the early phases of
`treatment. Pooled analyses of short-term, placebo-controlled trials of antidepressant drugs
`(SSRIs and others) showed that these drugs increase the risk of suicidal thinking and
`behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with MDD
`and other psychiatric disorders. 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 with antidepressants compared to placebo in adults aged 65 and older.
`
`The pooled analyses of placebo-controlled trials in children and adolescents with MDD,
`Obsessive Compulsive Disorder (OCD), or other psychiatric disorders included a total of
`24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses
`of placebo-controlled trials in adults with MDD or other psychiatric disorders included a
`total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in
`over 77,000 patients. There was considerable variation in risk of suicidality among drugs,
`but a tendency toward an increase in the younger patients for almost all drugs studied.
`There were differences in absolute risk of suicidality across the different indications, with
`the highest incidence in MDD. The risk differences (drug vs. placebo), however, were
`relatively stable within age strata and across indications. These risk differences (drug-
`placebo difference in the number of cases of suicidality per 1000 patients treated) are
`provided in Table 5.
`
`Reference ID: 3874224
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`

`

`Table 5:
`Age Range
`
`Drug-Placebo Difference in Number of Cases of
`Suicidality per 1000 Patients Treated
`Increases Compared to Placebo
`
`14 additional cases
`<18
`5 additional cases
`18-24
`Decreases Compared to Placebo
`
`1 fewer case
`25-64
`6 fewer cases
`≥65
`No suicides occurred in any of the pediatric trials. There were suicides in the adult trials,
`but the number was not sufficient to reach any conclusion about drug effect on suicide.
`
`It is unknown whether the suicidality risk extends to longer-term use, ie, beyond several
`months. However, there is substantial evidence from placebo-controlled maintenance
`trials in adults with depression that the use of antidepressants can delay the recurrence of
`depression.
`
`All patients being treated with antidepressants for any indication should be
`monitored appropriately and observed closely for clinical worsening, suicidality,
`and unusual changes in behavior, especially during the initial few months of a
`course of drug therapy, or at times of dose changes, either increases or decreases.
`
`The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility,
`aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania,
`have been reported in adult and pediatric patients being treated with antidepressants for
`MDD as well as for other indications, both psychiatric and nonpsychiatric. Although a
`causal link between the emergence of such symptoms and either the worsening of
`depression and/or the emergence of suicidal impulses has not been established, there is
`concern that such symptoms may represent precursors to emerging suicidality.
`
`Consideration should be given to changing the therapeutic regimen, including possibly
`discontinuing the medication, in patients whose depression is persistently worse, or who
`are experiencing emergent suicidality or symptoms that might be precursors to worsening
`depression or suicidality, especially if these symptoms are severe, abrupt in onset, or
`were not part of the patient’s presenting symptoms.
`
`Families and caregivers of patients being treated with antidepressants for major
`depressive disorder or other indications, both psychiatric and nonpsychiatric,
`should be alerted about the need to monitor patients for the emergence of agitation,
`irritability, unusual changes in behavior, and the other symptoms described above,
`as well as the emergence of suicidality, and to report such symptoms immediately to
`healthcare providers. Such monitoring should include daily observation by families
`and caregivers. Prescriptions for ABILIFY should be written for the smallest
`
`Reference ID: 3874224
`
`

`

`quantity of tablets consistent with good patient management, in order to reduce the
`risk of overdose.
`
`Screening Patients for Bipolar Disorder: A major depressive episode may be the initial
`presentation of bipolar disorder. It is generally believed (though not established in
`controlled trials) that treating such an episode with an antidepressant alone may increase
`the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar
`disorder. Whether any of the symptoms described above represent such a conversion is
`unknown. However, prior to initiating treatment with an antidepressant, patients with
`depressive symptoms should be adequately screened to determine if they are at risk for
`bipolar disorder; such screening should include a detailed psychiatric history, including a
`family history of suicide, bipolar disorder, and depression.
`
`It should be noted that ABILIFY is not approved for use in treating depression in the
`pediatric population.
`5.4 Neuroleptic Malignant Syndrome (NMS)
`
`A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant
`Syndrome (NMS) may occur with administration of antipsychotic drugs, including
`ABILIFY. Rare cases of NMS occurred during ABILIFY treatment in the worldwide
`clinical database. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity,
`altered mental status, and evidence of autonomic instability (irregular pulse or blood
`pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may
`include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute
`renal failure.
`
`The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a
`diagnosis, it is important to exclude cases where the clinical presentation includes both
`serious medical
`illness (e.g., pneumonia, systemic
`infection) and untreated or
`inadequately treated extrapyramidal signs and symptoms (EPS). Other important
`considerations in the differential diagnosis include central anticholinergic toxicity, heat
`stroke, drug fever, and primary central nervous system pathology.
`
`The management of NMS should include: 1) immediate discontinuation of antipsychotic
`drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic
`treatme