See Full Prescribing Information For Complete Boxed Warning

HIGHLIGHTS OF PRESCRIBING INFORMATION These metabolic changes include hyperglycemia, dyslipidemia, and weight
These highlights do not include all the information needed to use gain (5.5)
ABILIFY MAINTENA safely and effectively. See full prescribing  Hyperglycemia and Diabetes Mellitus: Monitor patients for symptoms of
information for ABILIFY MAINTENA. hyperglycemia including polydipsia, polyuria, polyphagia, and weakness.
Monitor glucose regularly in patients with and at risk for diabetes (5.5)
ABILIFY MAINTENA® (aripiprazole) for extended-release injectable  Dyslipidemia: Undesirable alterations have been observed in patients
suspension, for intramuscular use treated with atypical antipsychotics (5.5)
Initial U.S. Approval: 2002  Weight Gain: Gain in body weight has been observed; clinical monitoring
of weight is recommended (5.5)
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS  Orthostatic Hypotension: Use with caution in patients with known
WITH DEMENTIA-RELATED PSYCHOSIS cardiovascular or cerebrovascular disease (5.6)
See full prescribing information for complete boxed warning.  Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood
 Elderly patients with dementia-related psychosis treated with counts in patients with a history of a clinically significant low white blood cell
antipsychotic drugs are at an increased risk of death (5.1) count (WBC)/absolute neutrophil count (ANC). Consider discontinuation if
 ABILIFY MAINTENA is not approved for the treatment of patients clinically significant decline in WBC/ANC in the absence of other causative
with dementia-related psychosis (5.1) factors (5.7)
 Seizures: Use cautiously in patients with a history of seizures or with
conditions that lower the seizure threshold (5.8)
-------------------------- RECENT MAJOR CHANGES --------------------------  Potential for Cognitive and Motor Impairment: Use caution when operating
Dosage and Administration: Pre-filled Dual Chamber Syringe (2.5), machinery (5.9)
Vial (2.6) 07/2015
--------------------------- INDICATIONS AND USAGE -------------------------- ------------------------------ ADVERSE REACTIONS -----------------------------
ABILIFY MAINTENA is an atypical antipsychotic indicated for the treatment Most commonly observed adverse reactions with ABILIFY MAINTENA
of schizophrenia (1) (incidence ≥5% and at least twice that for placebo) were increased weight,
akathisia, injection site pain, and sedation (6.1)
---------------------- DOSAGE AND ADMINISTRATION ----------------------
 Only to be administered by intramuscular injection in the deltoid or gluteal To report SUSPECTED ADVERSE REACTIONS, contact Otsuka
muscle by a healthcare professional (2.1) America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-
 For patients naïve to aripiprazole, establish tolerability with oral 1088 or www.fda.gov/medwatch.
aripiprazole prior to initiating ABILIFY MAINTENA (2.1)
 Recommended starting and maintenance dose is 400 mg administered ------------------------------ DRUG INTERACTIONS-------------------------------
monthly as a single injection. Dose can be reduced to 300 mg in patients Dosage adjustments for patients taking CYP2D6 inhibitors, CYP3A4
with adverse reactions (2.1) inhibitors, or CYP3A4 inducers for greater than 14 days (2.3):
 In conjunction with first dose, take 14 consecutive days of concurrent oral Factors Adjusted
aripiprazole (10 mg to 20 mg) or current oral antipsychotic (2.1) Dose
 Dosage adjustments are required for missed doses (2.2) CYP2D6 Poor Metabolizers
 Known CYP2D6 poor metabolizers: Recommended starting and CYP2D6 Poor Metabolizers taking concomitant CYP3A4 200 mg1
maintenance dose is 300 mg administered monthly as a single injection inhibitors
(2.3) Patients Taking 400 mg of ABILIFY MAINTENA
 ABILIFY MAINTENA comes in two types of kits. See instructions for Strong CYP2D6 or CYP3A4 inhibitors 300 mg
reconstitution/injection/disposal procedures for 1) Pre-filled Dual Chamber CYP2D6 and CYP3A4 inhibitors 200 mg1
Syringe (2.5), and 2) Vials (2.6).
CYP3A4 inducers Avoid use
--------------------- DOSAGE FORMS AND STRENGTHS -------------------- Patients Taking 300 mg of ABILIFY MAINTENA
For extended-release injectable suspension: 300 mg and 400 mg strength Strong CYP2D6 or CYP3A4 inhibitors 200 mg1
lyophilized powder for reconstitution in (3): CYP2D6 and CYP3A4 inhibitors 160 mgError!
Reference source not
 single-dose pre-filled dual chamber syringe
found.
 single-dose vial
1
------------------------------ CONTRAINDICATIONS ----------------------------- 200 mg and 160 mg dose adjustments are obtained only by using the
Known hypersensitivity to aripiprazole (4) 300 mg or 400 mg strength vials.
----------------------- WARNINGS AND PRECAUTIONS ---------------------- ----------------------- USE IN SPECIFIC POPULATIONS ----------------------
 Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-  Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in
Related Psychosis: Increased incidence of cerebrovascular adverse neonates with third trimester exposure (8.1)
reactions (e.g., stroke, transient ischemic attack, including fatalities) (5.2)
 Neuroleptic Malignant Syndrome: Manage with immediate discontinuation See 17 for PATIENT COUNSELING INFORMATION and Medication
and close monitoring (5.3) Guide.
 Tardive Dyskinesia: Discontinue if clinically appropriate (5.4) Revised: 01/2016
 Metabolic Changes: Atypical antipsychotic drugs have been associated with
metabolic changes that may increase cardiovascular/cerebrovascular risk.
Reference ID: 3874224

FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS 7.1 Drugs Having Clinically Important Interactions with ABILIFY
WITH DEMENTIA-RELATED PSYCHOSIS MAINTENA
1 INDICATIONS AND USAGE 7.2 Drugs Having No Clinically Important Interactions with ABILIFY
2 DOSAGE AND ADMINISTRATION MAINTENA
2.1 Dosage Overview for the Treatment of Schizophrenia 8 USE IN SPECIFIC POPULATIONS
2.2 Dosage Adjustments for Missed Doses 8.1 Pregnancy
2.3 Dosage Adjustments for Cytochrome P450 Considerations 8.2 Lactation
2.4 Different Aripiprazole Formulations and Kits 8.4 Pediatric Use
2.5 Pre-filled Dual Chamber Syringe: Preparation and Administration 8.5 Geriatric Use
Instructions 8.6 CYP2D6 Poor Metabolizers
2.6 Vial: Preparation and Administration Instructions 8.7 Hepatic and Renal Impairment
3 DOSAGE FORMS AND STRENGTHS 8.8 Other Specific Populations
4 CONTRAINDICATIONS 10 OVERDOSAGE
5 WARNINGS AND PRECAUTIONS 10.1 Human Experience
5.1 Increased Mortality in Elderly Patients with Dementia- Related 10.2 Management of Overdosage
Psychosis 11 DESCRIPTION
5.2 Cerebrovascular Adverse Reactions, Including Stroke in Elderly 12 CLINICAL PHARMACOLOGY
Patients with Dementia-Related Psychosis 12.1 Mechanism of Action
5.3 Neuroleptic Malignant Syndrome 12.2 Pharmacodynamics
5.4 Tardive Dyskinesia 12.3 Pharmacokinetics
5.5 Metabolic Changes 13 NONCLINICAL TOXICOLOGY
5.6 Orthostatic Hypotension 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
5.7 Leukopenia, Neutropenia, and Agranulocytosis 13.2 Animal Toxicology and/or Pharmacology
5.8 Seizures 14 CLINICAL STUDIES
5.9 Potential for Cognitive and Motor Impairment 16 HOW SUPPLIED/STORAGE AND HANDLING
5.10 Body Temperature Regulation 16.1 How Supplied
5.11 Dysphagia 16.2 Storage
6 ADVERSE REACTIONS 17 PATIENT COUNSELING INFORMATION
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
*Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION
WARNING: 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. ABILIFY MAINTENA is not approved for the
treatment of patients with dementia-related psychosis [see WARNINGS AND
PRECAUTIONS (5.1)].
1 INDICATIONS AND USAGE

ABILIFY MAINTENA (aripiprazole) is indicated for the treatment of schizophrenia
[see CLINICAL STUDIES (14)].
2 DOSAGE AND ADMINISTRATION
2.1 Dosage Overview for the Treatment of Schizophrenia

ABILIFY MAINTENA is only to be administered by intramuscular injection by a
healthcare professional. The recommended starting and maintenance dose of ABILIFY
MAINTENA is 400 mg monthly (no sooner than 26 days after the previous injection).
For patients who have never taken aripiprazole, establish tolerability with oral
aripiprazole prior to initiating treatment with ABILIFY MAINTENA. Due to the half-life
of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
After the first ABILIFY MAINTENA injection, administer oral aripiprazole (10 mg to 20
mg) for 14 consecutive days to achieve therapeutic aripiprazole concentrations during
initiation of therapy. For patients already stable on another oral antipsychotic (and known
to tolerate aripiprazole), after the first ABILIFY MAINTENA injection, continue
treatment with the antipsychotic for 14 consecutive days to maintain therapeutic
antipsychotic concentrations during initiation of therapy.
If there are adverse reactions with the 400 mg dosage, consider reducing the dosage to
300 mg once monthly.
2.2 Dosage Adjustments for Missed Doses

If the second or third doses are missed:
 If more than 4 weeks and less than 5 weeks have elapsed since the last
injection, administer the injection as soon as possible.

 If more than 5 weeks have elapsed since the last injection, restart concomitant
oral aripiprazole for 14 days with the next administered injection.
If the fourth or subsequent doses are missed:
 If more than 4 weeks and less than 6 weeks have elapsed since the last
injection, administer the injection as soon as possible.
 If more than 6 weeks have elapsed since the last injection, restart concomitant
oral aripiprazole for 14 days with the next administered injection.
2.3 Dosage Adjustments for Cytochrome P450 Considerations

Dosage adjustments are recommended in patients who are CYP2D6 poor metabolizers
and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors for greater
than 14 days (see Table 1). Dosage adjustments for 200 mg and 160 mg are obtained only
by using the 300 mg or 400 mg strength vials for intramuscular deltoid or gluteal
injection.
If the CYP3A4 inhibitor or CYP2D6 inhibitor is withdrawn, the ABILIFY MAINTENA

dosage may need to be increased [see DOSAGE AND ADMINISTRATION (2.1)].
Avoid the concomitant use of CYP3A4 inducers with ABILIFY MAINTENA for greater
than 14 days because the blood levels of aripiprazole are decreased and may be below the
effective levels.
Dosage adjustments are not recommended for patients with concomitant use of CYP3A4
inhibitors, CYP2D6 inhibitors or CYP3A4 inducers for less than 14 days.
Table 1: Dose Adjustments of ABILIFY MAINTENA in Patients who are

known CYP2D6 Poor Metabolizers and Patients Taking Concomitant
CYP2D6 Inhibitors, 3A4 Inhibitors, and/or CYP3A4 Inducers for Greater
than 14 days
Factors Adjusted Dose

CYP2D6 Poor Metabolizers
Known CYP2D6 Poor Metabolizers 300 mg
Known CYP2D6 Poor Metabolizers taking concomitant 200 mg1
CYP3A4 inhibitors
Patients Taking 400 mg of ABILIFY MAINTENA
Strong CYP2D6 or CYP3A4 inhibitors 300 mg
CYP2D6 and CYP3A4 inhibitors 200 mg1
Patients Taking 300 mg of ABILIFY MAINTENA
Strong CYP2D6 or CYP3A4 inhibitors 200 mg1
CYP2D6 and CYP3A4 inhibitors 160 mg1

Factors Adjusted Dose
1. 200 mg and 160 mg dosage adjustments are obtained only by using the 300 mg or 400 mg strength
vials.
ABILIFY MAINTENA comes in two types of kits. See instructions for

reconstitution/injection/disposal procedures for 1) Pre-filled Dual Chamber Syringe (2.5),
and 2) Vials (2.6).
2.4 Different Aripiprazole Formulations and Kits

There are two aripiprazole formulations for intramuscular use with different dosages,
dosing frequencies, and indications. ABILIFY MAINTENA is a long-acting aripiprazole
formulation with 4 week dosing intervals indicated for the treatment of schizophrenia. In
contrast, aripiprazole injection (9.75 mg per vial) is a short-acting formulation indicated
for agitation in patients with schizophrenia or mania. Do not substitute these products.
Refer to the prescribing information for aripiprazole injection for more information about
aripiprazole injection.
ABILIFY MAINTENA comes in two types of kits. See instructions for

reconstitution/injection/disposal procedures for 1) Pre-filled Dual Chamber Syringe
available in 300 mg or 400 mg strength syringes [see DOSAGE AND ADMINISTRATION
(2.5)], and 2) Single-use vials available in 300 mg or 400 mg strength vials [see
DOSAGE AND ADMINISTRATION (2.6)].
The 200 mg and 160 mg dosage adjustments are obtained only by using the 300 mg or
400 mg strength vials.
2.5 Pre-filled Dual Chamber Syringe: Preparation and

Administration Instructions
Preparation Prior to Reconstitution
For deep intramuscular deltoid or gluteal injection by healthcare professionals only. Do

not administer by any other route. Inject full syringe contents immediately following
reconstitution. Administer once monthly.
Lay out and confirm that components listed below are provided in the kit:
 One ABILIFY MAINTENA (aripiprazole) pre-filled dual chamber syringe (400

mg or 300 mg as appropriate) for extended release injectable suspension
containing lyophilized powder and Sterile Water for Injection
 One 23 gauge, 1 inch (25 mm) hypodermic safety needle with needle protection
device for deltoid administration in non-obese patients

 One 22 gauge, 1.5 inch (38 mm) hypodermic safety needle with needle protection
device for gluteal administration in non-obese patients or deltoid administration in
obese patients
device for gluteal administration in obese patients
Reconstitution of Lyophilized Powder in Pre-filled Dual Chamber Syringe
Reconstitute at room temperature.
a) Push plunger rod slightly to engage threads. And then, rotate plunger rod until the
rod stops rotating to release diluent. After plunger rod is at complete stop, middle
stopper will be at the indicator line (See Figure 1).
Figure 1
b) Vertically shake the syringe vigorously for 20 seconds until drug is uniformly
milky-white (See Figure 2).
Figure 2
c) Visually inspect the syringe for particulate matter and discoloration prior to
administration. The reconstituted ABILIFY MAINTENA suspension should
6

appear to be a uniform, homogeneous suspension that is opaque and milky-white
in color.
Injection Procedure
Use appropriate aseptic techniques throughout injection procedure. For deep

intramuscular injection only.
a) Twist and pull off Over-cap and Tip-cap (See Figure 3).
Figure 3
b) Select appropriate needle (See Figure 4).
Figure 4
For deltoid administration:
 23 gauge, 1 inch (25 mm) hypodermic safety needle with needle

protection device for non-obese patients
 22 gauge, 1.5 inch (38 mm) hypodermic safety needle with needle
protection device for obese patients

For gluteal administration:
 22 gauge, 1.5 inch (38 mm) hypodermic safety needle with needle protection
device for non-obese patients
 21 gauge, 2 inch (50 mm) hypodermic safety needle with needle protection device
for obese patients
c) While holding the needle cap, ensure the needle is firmly seated on the safety
device with a push. Twist clockwise until SNUGLY fitted (See Figure 5).
Figure 5
d) Then PULL needle-cap straight up (see Figure 6).
Figure 6
e) Hold syringe UPRIGHT and ADVANCE PLUNGER ROD SLOWLY TO

EXPEL THE AIR. Expel air until suspension fills needle base. If it’s not
possible to advance plunger rod to expel the air, check that plunger rod is rotated
to a complete stop (See Figure 7).

Figure 7
f) Inject slowly into the deltoid or gluteal muscle. Do not massage the injection
site.
Disposal Procedure
a) Engage the needle safety device and safely discard all kit components (See Figure
8). ABILIFY MAINTENA pre-filled dual chamber syringe is for single-use
only.
Figure 8
b) Rotate sites of injections between the two deltoid or gluteal muscles.
2.6 Vial: Preparation and Administration Instructions

Preparation Prior to Reconstitution
For deep intramuscular injection by healthcare professionals only. Do not

administer by any other route. Inject immediately after reconstitution. Administer
once monthly.
a) Lay out and confirm that components listed below are provided in the kit:
 Vial of ABILIFY MAINTENA (aripiprazole) for extended-release
injectable suspension lyophilized powder
 5 mL vial of Sterile Water for Injection, USP
 One 3 mL luer lock syringe with pre-attached 21 gauge, 1.5 inch (38 mm)
hypodermic safety needle with needle protection device
 One 3 mL luer lock disposable syringe with luer lock tip

 One vial adapter
 One 23 gauge, 1 inch (25 mm) hypodermic safety needle with needle
protection device for deltoid administration in non-obese patients
 One 22 gauge, 1.5 inch (38 mm) hypodermic safety needle with needle
protection device for gluteal administration in non-obese patients or
deltoid administration in obese patients
 One 21 gauge, 2 inch (50 mm) hypodermic safety needle with needle
protection device for gluteal administration in obese patients
b) ABILIFY MAINTENA should be suspended using the Sterile Water for Injection
as supplied in the kit.
c) The Sterile Water for Injection and ABILIFY MAINTENA vials are for single-
use only.
d) Use appropriate aseptic techniques throughout reconstitution and reconstitute at
room temperature.
e) Select the amount of Sterile Water for Injection needed for reconstitution (see
Table 2).
Table 2: Amount of Sterile Water for Injection Needed for Reconstitution
400 mg Vial 300 mg Vial

Dose Sterile Water for Dose Sterile Water for
Injection Injection
400 mg 1.9 mL 300 mg 1.5 mL
Important: There is more Sterile Water for Injection in the vial than is needed to
reconstitute ABILIFY MAINTENA (aripiprazole) for extended-release injectable
suspension. The vial will have excess Sterile Water for Injection; discard any unused
portion.
Reconstitution of Lyophilized Powder in Vial
a) Remove the cap of the vial of Sterile Water for Injection and remove the cap of
the vial containing ABILIFY MAINTENA lyophilized powder and wipe the tops
with a sterile alcohol swab.
b) Using the syringe with pre-attached hypodermic safety needle, withdraw the pre-
determined Sterile Water for Injection volume from the vial of Sterile Water for
Injection into the syringe (see Figure 9). Residual Sterile Water for Injection will
remain in the vial following withdrawal; discard any unused portion.
10

Figure 9
c) Slowly inject the Sterile Water for Injection into the vial containing the ABILIFY
MAINTENA lyophilized powder (see Figure 10).
Figure 10
d) Withdraw air to equalize the pressure in the vial by pulling back slightly on the
plunger. Subsequently, remove the needle from the vial. Engage the needle safety
device by using the one-handed technique (see Figure 11). Gently press the sheath
against a flat surface until the needle is firmly engaged in the needle protection
sheath. Visually confirm that the needle is fully engaged into the needle
protection sheath, and discard.
Figure 11
e) Shake the vial vigorously for 30 seconds until the reconstituted suspension
appears uniform (see Figure 12).
11

Figure 12
f) Visually inspect the reconstituted suspension for particulate matter and

discoloration prior to administration. The reconstituted ABILIFY MAINTENA is
a uniform, homogeneous suspension that is opaque and milky-white in color.
g) If the injection is not performed immediately after reconstitution keep the vial at
room temperature and shake the vial vigorously for at least 60 seconds to re-
suspend prior to injection.
h) Do not store the reconstituted suspension in a syringe.
Preparation Prior to Injection
a) Use appropriate aseptic techniques throughout injection of the reconstituted

ABILIFY MAINTENA suspension.
b) Remove the cover from the vial adapter package (see Figure 13). Do not remove
the vial adapter from the package.
Figure 13
c) Using the vial adapter package to handle the vial adapter, attach the prepackaged
luer lock syringe to the vial adapter (see Figure 14).
12

Figure 14
d) Use the luer lock syringe to remove the vial adapter from the package and discard
the vial adapter package (see Figure 15). Do not touch the spike tip of the adapter
at any time.
Figure 15
e) Determine the recommended volume for injection (Table 3).
Table 3: ABILIFY MAINTENA Reconstituted Suspension Volume to Inject
400 mg Vial 300 mg Vial

Dose Volume to Inject Dose Volume to Inject
400 mg 2 mL --- ---
300 mg 1.5 mL 300 mg 1.5 mL
200 mg 1 mL 200 mg 1 mL
160 mg 0.8 mL 160 mg 0.8 mL
f) Wipe the top of the vial of the reconstituted ABILIFY MAINTENA suspension
with a sterile alcohol swab.
g) Place and hold the vial of the reconstituted ABILIFY MAINTENA suspension on
a hard surface. Attach the adapter-syringe assembly to the vial by holding the
outside of the adapter and pushing the adapter's spike firmly through the rubber
stopper, until the adapter snaps in place (see Figure 16).
13

Figure 16
h) Slowly withdraw the recommended volume from the vial into the luer lock
syringe to allow for injection (see Figure 17). A small amount of excess product
will remain in the vial.
Figure 17
Injection Procedure
a) Detach the luer lock syringe containing the recommended volume of reconstituted
ABILIFY MAINTENA suspension from the vial.
b) Select the appropriate hypodermic safety needle and attach the needle to the luer
lock syringe containing the suspension for injection. While holding the needle
cap, ensure the needle is firmly seated on the safety device with a push. Twist
clockwise until snugly fitted and then pull the needle cap straight away from the
needle (see Figure 18).
For deltoid administration:
for non-obese patients
device for obese patients
For gluteal administration:
device for non-obese patients
14

for obese patients
Figure 18
(c) Slowly inject the recommended volume as a single intramuscular injection into the
deltoid or gluteal muscle. Do not massage the injection site.
Disposal Procedure
a) Engage the needle safety device as described in Section 2.6, Step (d) of
Reconstitution of Lyophilized Powder in Vial and safely discard all kit
components (see Figure 8). Dispose of the vials, adapter, needles, and syringe
appropriately after injection. The Sterile Water for Injection and ABILIFY
MAINTENA vials are for single-use only.
b) Rotate sites of injections between the two deltoid or gluteal muscles.
3 DOSAGE FORMS AND STRENGTHS

For extended-release injectable suspension: 300 mg and 400 mg of lyophilized powder
for reconstitution in:
 single-dose pre-filled dual chamber syringe
 single-dose vial
The reconstituted extended-release injectable suspension is a uniform, homogeneous

suspension that is opaque and milky-white in color.
4 CONTRAINDICATIONS
ABILIFY MAINTENA is contraindicated in patients with a known hypersensitivity to
aripiprazole. Hypersensitivity reactions ranging from pruritus/urticaria to anaphylaxis
have been reported in patients receiving aripiprazole [see ADVERSE REACTIONS (6.1
and 6.2)].
15

5 WARNINGS AND PRECAUTIONS
5.1 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. Analyses of 17 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 (e.g., heart failure, sudden death) or infectious (e.g., 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 MAINTENA is not approved for the treatment of patients with dementia-
related psychosis.
5.2 Cerebrovascular Adverse Reactions, Including Stroke in

Elderly Patients with Dementia-Related Psychosis
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
reactions (e.g., stroke, transient ischemic attack), including fatalities, in oral aripiprazole-
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
reactions in patients treated with oral aripiprazole. ABILIFY MAINTENA is not
approved for the treatment of patients with dementia-related psychosis.
5.3 Neuroleptic Malignant Syndrome

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant
Syndrome (NMS) may occur with administration of antipsychotic drugs, including
ABILIFY MAINTENA. Rare cases of NMS occurred during aripiprazole 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.
16

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
treatment and medical monitoring; and 3) treatment of any concomitant serious medical
problems for which specific treatments are available. There is no general agreement
about specific pharmacological treatment regimens for uncomplicated NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential
reintroduction of drug therapy should be carefully considered. The patient should be
carefully monitored, since recurrences of NMS have been reported.
5.4 Tardive Dyskinesia

A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop
in patients treated with antipsychotic drugs. Although the prevalence of the syndrome
appears to be highest among the elderly, especially elderly women, it is impossible to rely
upon prevalence estimates to predict, at the inception of antipsychotic treatment, which
patients are likely to develop the syndrome. Whether antipsychotic drug products differ
in their potential to cause tardive dyskinesia is unknown.
The risk of developing tardive dyskinesia and the likelihood that it will become
irreversible are believed to increase as the duration of treatment and the total cumulative
dose of antipsychotic drugs administered to the patient increase. However, the syndrome
can develop, although much less commonly, after relatively brief treatment periods at low
doses.
There is no known treatment for established tardive dyskinesia, although the syndrome
may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic
treatment, itself, however, may suppress (or partially suppress) the signs and symptoms
of the syndrome and, thereby, may possibly mask the underlying process. The effect of
symptomatic suppression on the long-term course of the syndrome is unknown.
Given these considerations, ABILIFY MAINTENA should be prescribed in a manner

that is most likely to minimize the occurrence of tardive dyskinesia. Chronic
antipsychotic treatment should generally be reserved for patients who suffer from a
chronic illness that 1) is known to respond to antipsychotic drugs and 2) for whom
alternative, equally effective, but potentially less harmful treatments are not available or
17

appropriate. In patients who do require chronic treatment, the smallest dose and the
shortest duration of treatment producing a satisfactory clinical response should be sought.
The need for continued treatment should be reassessed periodically.
If signs and symptoms of tardive dyskinesia appear in a patient treated with ABILIFY
MAINTENA drug discontinuation should be considered. However, some patients may
require treatment with ABILIFY MAINTENA despite the presence of the syndrome.
5.5 Metabolic Changes

Atypical antipsychotic drugs have been associated with metabolic changes that include
hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. While all drugs in the
class have been shown to produce some metabolic changes, each drug has its own
specific risk profile.
Hyperglycemia/Diabetes Mellitus
Hyperglycemia, in some cases extreme and associated with diabetic ketoacidosis,

hyperosmolar coma, or death, has been reported in patients treated with atypical
antipsychotics. There have been reports of hyperglycemia in patients treated with
aripiprazole [see ADVERSE REACTIONS (6.1)]. Assessment of the relationship between
atypical antipsychotic use and glucose abnormalities is complicated by the possibility of
an increased background risk of diabetes mellitus in patients with schizophrenia and the
increasing incidence of diabetes mellitus in the general population. Given these
confounders, the relationship between atypical antipsychotic use and hyperglycemia-
related adverse reactions is not completely understood. However, epidemiological studies
suggest an increased risk of hyperglycemia-related adverse reactions in patients treated
with the atypical antipsychotics.
Patients with an established diagnosis of diabetes mellitus who are started on atypical
antipsychotics should be monitored regularly for worsening of glucose control. Patients
with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes), who are
starting treatment with atypical antipsychotics should undergo fasting blood glucose
testing at the beginning of treatment and periodically during treatment. Any patient
treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia
including polydipsia, polyuria, polyphagia, and weakness. Patients who develop
symptoms of hyperglycemia during treatment with atypical antipsychotics should
undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when
the atypical antipsychotic was discontinued; however, some patients required
continuation of anti-diabetic treatment despite discontinuation of the atypical
antipsychotic drug.
18

In a short-term, placebo-controlled randomized trial in adults with schizophrenia, the
mean change in fasting glucose was +9.8 mg/dL (N=88) in the ABILIFY MAINTENA-
treated patients and +0.7 mg/dL (N=59) in the placebo-treated patients. Table 4 shows the
proportion of ABILIFY MAINTENA-treated patients with normal and borderline fasting
glucose at baseline and their changes in fasting glucose measurements.
Table 4: Proportion of Patients with Potential Clinically Relevant Changes in

Fasting Glucose from a 12-Week Placebo-Controlled
Monotherapy Trial in Adult Patients with Schizophrenia
Category Change (at least
once) from Baseline Treatment Arm n/Na %
Normal to High ABILIFY MAINTENA 7/88 8.0
(<100 mg/dL to ≥126 mg/dL) Placebo 0/75 0.0
Fasting
Glucose Borderline to High ABILIFY MAINTENA 1/33 3.0
(≥100 mg/dL and <126 mg/dL Placebo 3/33 9.1
to ≥126 mg/dL)
a
N = the total number of subjects who had a measurement at baseline and at least one post-baseline result.
n = the number of subjects with a potentially clinically relevant shift.
Dyslipidemia
Undesirable alterations in lipids have been observed in patients treated with atypical
antipsychotics.
Table 5 shows the proportion of adult patients from one short-term, placebo-controlled
randomized trial in adults with schizophrenia taking ABILIFY MAINTENA, with
changes in total cholesterol, fasting triglycerides, fasting LDL cholesterol and HDL
cholesterol.
19

Table 5: Proportion of Patients with Potential Clinically Relevant
Changes in Blood Lipid Parameters From a 12-Week Placebo-
Controlled Monotherapy Trial in Adults with Schizophrenia
Treatment Arm n/Na %
Total Cholesterol ABILIFY MAINTENA 3/83 3.6
Normal to High
Borderline to High ABILIFY MAINTENA 6/27 22.2
(200~<240 mg/dL to ≥240
mg/dL) Placebo 2/19 10.5
Any increase ABILIFY MAINTENA 15/122 12.3

(≥40 mg/dL) Placebo 6/110 5.5
Fasting Triglycerides ABILIFY MAINTENA 7/98 7.1
Normal to High
(150~<200 mg/dL to ≥200

( ≥ 50 mg/dL) Placebo 20/110 18.2
Fasting LDL Cholesterol ABILIFY MAINTENA 1/59 1.7
Normal to High
(100~<160 mg/dL to ≥160

( ≥ 30 mg/dL) Placebo 9/103 8.7
HDL Cholesterol ABILIFY MAINTENA 14/104 13.5
Normal to Low
(≥40 mg/dL to <40 mg/dL) Placebo 11/87 12.6
Any decrease ABILIFY MAINTENA 7/122 5.7

( ≥ 20 mg/dL) Placebo 12/110 10.9
a
n = the number of subjects with a potentially clinically relevant shift.
Weight Gain
Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of
weight is recommended.
20

In one short-term, placebo-controlled trial with ABILIFY MAINTENA, the mean change
in body weight at Week 12 was +3.5 kg (N=99) in the ABILIFY MAINTENA-treated
patients and +0.8 kg (N=66) in the placebo-treated patients.
Table 6 shows the percentage of adult patients with weight gain ≥7% of body weight in a
short-term, placebo-controlled trial with ABILIFY MAINTENA.
Table 6: Percentage of Patients From a 12-Week Placebo-Controlled Trial in

Adult Patients with Schizophrenia with Weight Gain ≥7%
of Body Weight
Treatment Arm Na Patients n (%)
Weight gain ≥7% of ABILIFY MAINTENA 144 31 (21.5)
body weight Placebo 141 12 (8.5)
a
5.6 Orthostatic Hypotension

ABILIFY MAINTENA may cause orthostatic hypotension, perhaps due to its α1-
adrenergic receptor antagonism. In the short-term, placebo-controlled trial in adults with
schizophrenia, the adverse event of presyncope was reported in 1/167 (0.6%) of patients
treated with ABILFY MAINTENA, while syncope and orthostatic hypotension were
each reported in 1/172 (0.6%) of patients treated with placebo. During the stabilization
phase of the randomized-withdrawal (maintenance) study, orthostasis-related adverse
events were reported in 4/576 (0.7%) of patients treated with ABILIFY MAINTENA,
including abnormal orthostatic blood pressure (1/576, 0.2%), postural dizziness (1/576,
0.2%), presyncope (1/576, 0.2%) and orthostatic hypotension (1/576, 0.2%).
In the short-term placebo-controlled trial, there were no patients in either treatment group
with a significant orthostatic change in blood pressure (defined as a decrease in systolic
blood pressure ≥20 mmHg accompanied by an increase in heart rate ≥25 when comparing
standing to supine values). During the stabilization phase of the randomized-withdrawal
(maintenance) study, the incidence of significant orthostatic change in blood pressure was
0.2% (1/575).
5.7 Leukopenia, Neutropenia, and Agranulocytosis

In clinical trials and post-marketing experience, leukopenia and neutropenia have been
reported temporally related to antipsychotic agents, including ABILIFY MAINTENA.
Agranulocytosis has also been reported [see ADVERSE REACTIONS (6.1)].
Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell
count (WBC)/absolute neutrophil count (ANC) and a history of drug-induced
leukopenia/neutropenia. In patients with a history of a clinically significant low
WBC/ANC or drug-induced leukopenia/neutropenia, perform a complete blood count
21

(CBC) frequently during the first few months of therapy. In such patients, consider
discontinuation of ABILIFY MAINTENA at the first sign of a clinically significant
decline in WBC in the absence of other causative factors.
Monitor patients with clinically significant neutropenia for fever or other symptoms or
signs of infection and treat promptly if such symptoms or signs occur. Discontinue
ABILIFY MAINTENA in patients with severe neutropenia (absolute neutrophil count
<1000/mm3) and follow their WBC counts until recovery.
5.8 Seizures
As with other antipsychotic drugs, use ABILIFY MAINTENA cautiously in patients with
a history of seizures or with conditions that lower the seizure threshold. Conditions that
lower the seizure threshold may be more prevalent in a population of 65 years or older.
5.9 Potential for Cognitive and Motor Impairment

ABILIFY MAINTENA, like other antipsychotics, may impair judgment, thinking, or
motor skills. Instruct patients to avoid operating hazardous machinery, including
automobiles, until they are reasonably certain that therapy with ABILIFY MAINTENA
does not affect them adversely.
5.10 Body Temperature Regulation

Disruption of the body's ability to reduce core body temperature has been attributed to
antipsychotic agents. Appropriate care is advised when prescribing ABILIFY
MAINTENA for patients who will be experiencing conditions which may contribute to
an elevation in core body temperature, (e.g., exercising strenuously, exposure to extreme
heat, receiving concomitant medication with anticholinergic activity, or being subject to
dehydration).
5.11 Dysphagia
Esophageal dysmotility and aspiration have been associated with antipsychotic drug use,
including ABILIFY MAINTENA. ABILIFY MAINTENA and other antipsychotic drugs
should be used cautiously in patients at risk for aspiration pneumonia [see WARNINGS
AND PRECAUTIONS (5.1)].
6 ADVERSE REACTIONS
The following adverse reactions are discussed in more detail in other sections of the
labeling:
 Increased Mortality in Elderly Patients with Dementia - Related Psychosis Use

[see BOXED WARNING and WARNINGS AND PRECAUTIONS (5.1)]
22

 Cerebrovascular Adverse Reactions, Including Stroke in Elderly Patients with
Dementia-Related Psychosis [see BOXED WARNING and WARNINGS AND
PRECAUTIONS (5.2)]
 Neuroleptic Malignant Syndrome [see WARNINGS AND PRECAUTIONS (5.3)]
 Tardive Dyskinesia [see WARNINGS AND PRECAUTIONS (5.4)]
 Metabolic Changes [see WARNINGS AND PRECAUTIONS (5.5)]
 Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS (5.6)]
 Leukopenia, Neutropenia, and Agranulocytosis [see WARNINGS AND
PRECAUTIONS (5.7)]
 Seizures [see WARNINGS AND PRECAUTIONS (5.8)]
 Potential for Cognitive and Motor Impairment [see WARNINGS AND
PRECAUTIONS (5.9)]
 Body Temperature Regulation [see WARNINGS AND PRECAUTIONS (5.10)]
 Dysphagia [see WARNINGS AND PRECAUTIONS (5.11)]
6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in the clinical trials of a drug cannot be directly compared to rates in the
clinical trials of another drug and may not reflect the rates observed in practice.
Safety Database of ABILIFY MAINTENA and Oral Aripiprazole
Oral aripiprazole has been evaluated for safety in 16,114 adult patients who participated
in multiple-dose, clinical trials in schizophrenia and other indications, and who had
approximately 8,578 patient-years of exposure to oral aripiprazole. A total of 3,901
patients were treated with oral aripiprazole for at least 180 days, 2,259 patients were
treated with oral aripiprazole for at least 360 days, and 933 patients continuing
aripiprazole treatment for at least 720 days.
ABILIFY MAINTENA has been evaluated for safety in 2,188 adult patients in clinical
trials in schizophrenia, with approximately 2,646 patient-years of exposure to ABILIFY
MAINTENA. A total of 1,230 patients were treated with ABILIFY MAINTENA for at
least 180 days (at least 7 consecutive injections) and 935 patients treated with ABILIFY
MAINTENA had at least 1 year of exposure (at least 13 consecutive injections).
The conditions and duration of treatment with ABILIFY MAINTENA included double-
blind and open-label studies. The safety data presented below are derived from the 12-
week double-blind placebo-controlled study of ABILIFY MAINTENA in adult patients
with schizophrenia.
23

Adverse Reactions with ABILIFY MAINTENA
Most Commonly Observed Adverse Reactions in Double-Blind, Placebo-Controlled

Clinical Trials in Schizophrenia
Based on the placebo-controlled trial of ABILIFY MAINTENA in schizophrenia, the

most commonly observed adverse reactions associated with the use of ABILIFY
MAINTENA in patients (incidence of 5% or greater and aripiprazole incidence at least
twice that for placebo) were increased weight (16.8% vs 7.0%), akathisia (11.4% vs
3.5%), injection site pain (5.4% vs 0.6%) and sedation (5.4% vs 1.2%).
Commonly Reported Adverse Reactions in Double-Blind, Placebo-Controlled Clinical

Trials in Schizophrenia
The following findings are based on the double-blind, placebo-controlled trial that
compared ABILIFY MAINTENA 400 mg or 300 mg to placebo in patients with
schizophrenia. Table 7 lists the adverse reactions reported in 2% or more of ABILIFY
MAINTENA-treated subjects and at a greater proportion than in the placebo group.
Table 7: Adverse Reactions in ≥ 2% of ABILIFY MAINTENA-Treated

Adult Patients with Schizophrenia in a 12-Week Double-Blind, Placebo-
Controlled Triala
a
Percentage of Patients Reporting Reaction
System Organ Class ABILIFY MAINTENA Placebo
Preferred Term (n=167) (n=172)
Gastrointestinal Disorders
Constipation 10 7
Dry Mouth 4 2
Diarrhea 3 2
Vomiting 3 1
Abdominal Discomfort 2 1
General Disorders and
Administration Site Conditions
Injection Site Pain 5 1
Infections and Infestations
Upper Respiratory Tract
4 2
Infection
Investigations
Increased Weight 17 7
Decreased Weight 4 2
Musculoskeletal And Connective
Tissue Disorders
Arthralgia 4 1
Back Pain 4 2
Myalgia 4 2
24

Musculoskeletal Pain 3 1
Nervous System Disorders
Akathisia 11 4
Sedation 5 1
Dizziness 4 2
Tremor 3 1
Respiratory, Thoracic And
Mediastinal
Nasal Congestion 2 1
a
This table does not include adverse reactions which had an incidence equal to or less than placebo.
Other Adverse Reactions Observed During the Clinical Trial Evaluation of ABILIFY
MAINTENA
The following listing does not include reactions: 1) already listed in previous tables or
elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as
to be uninformative, 4) which were not considered to have significant clinical
implications, or 5) which occurred at a rate equal to or less than placebo.
Reactions are categorized by body system according to the following definitions:
frequent adverse reactions are those occurring in at least 1/100 patients; infrequent
adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those
occurring in fewer than 1/1000 patients:
Blood and Lymphatic System Disorders: rare - thrombocytopenia
Cardiac Disorders: infrequent - tachycardia, rare - bradycardia, sinus tachycardia
Endocrine Disorders: rare - hypoprolactinemia
Eye Disorders: infrequent - vision blurred, oculogyric crisis
Gastrointestinal Disorders: infrequent - abdominal pain upper, dyspepsia, nausea, rare -

swollen tongue
General Disorders and Administration Site Conditions: frequent - fatigue, injection site
reactions (including erythema, induration, pruritus, injection site reaction, swelling, rash,
inflammation, hemorrhage), infrequent - chest discomfort, gait disturbance, rare-
irritability, pyrexia
Hepatobiliary Disorders: rare - drug induced liver injury
Immune System Disorders: rare - drug hypersensitivity
Infections and Infestations: rare - nasopharyngitis
25

Investigations: infrequent - blood creatine phosphokinase increased, blood pressure
decreased, hepatic enzyme increased, liver function test abnormal, electrocardiogram QT-
prolonged, rare - blood triglycerides decreased, blood cholesterol decreased,
electrocardiogram T-wave abnormal
Metabolism and Nutrition Disorders: infrequent - decreased appetite, obesity,

hyperinsulinemia
Musculoskeletal and Connective Tissue Disorders: infrequent - joint stiffness, muscle

twitching, rare - rhabdomyolysis
Nervous System Disorders: infrequent - cogwheel rigidity, extrapyramidal disorder,

hypersomnia, lethargy, rare- bradykinesia, convulsion, dysgeusia, memory impairment,
oromandibular dystonia
Psychiatric Disorders: frequent - anxiety, insomnia restlessness, infrequent- agitation,

bruxism, depression, psychotic disorder, suicidal ideation, rare - aggression,
hypersexuality, panic attack
Renal and Urinary Disorders: rare - glycosuria, pollakiuria, urinary incontinence
Vascular Disorders: infrequent - hypertension
Demographic Differences
An examination of population subgroups was performed across demographic subgroup

categories for adverse reactions experienced by at least 5% of ABILIFY MAINTENA
subjects at least twice rate of the placebo (i.e., increased weight, akathisia, injection site
pain, and sedation) in the double-blind placebo-controlled trial. This analysis did not
reveal evidence of differences in safety differential adverse reaction incidence on the
basis of age, gender, or race alone; however, there were few subjects ≥ 65 years of age.
Injection Site Reactions of ABILIFY MAINTENA
In the data from the short-term, double-blind, placebo-controlled trial with ABILIFY
MAINTENA in patients with schizophrenia, the percent of patients reporting any
injection site-related adverse reaction (all reported as injection site pain) was 5.4% for
patients treated with gluteal administered ABILIFY MAINTENA and 0.6% for placebo.
The mean intensity of injection pain reported by subjects using a visual analog scale
(0=no pain to 100=unbearably painful) approximately one hour after injection was 7.1
(SD 14.5) for the first injection and 4.8 (SD 12.4) at the last visit in the double-blind,
placebo-controlled phase.
26

In an open-label study comparing bioavailability of ABILIFY MAINTENA administered
in the deltoid or gluteal muscle, injection site pain was observed in both groups at
approximately equal rates.
Extrapyramidal Symptoms (EPS)
In the short-term, placebo-controlled trial of ABILIFY MAINTENA in adults with
schizophrenia, the incidence of reported EPS-related events, excluding events related to
akathisia, for ABILIFY MAINTENA-treated patients was 9.6% vs. 5.2% for placebo.
The incidence of akathisia-related events for ABILIFY MAINTENA-treated patients was
11.5% vs. 3.5% for placebo.
Dystonia
Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in

susceptible individuals during the first few days of treatment. Dystonic symptoms
include: spasm of the neck muscles, sometimes progressing to tightness of the throat,
swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these
symptoms can occur at low doses, they occur more frequently and with greater severity
with high potency and at higher doses of first generation antipsychotic drugs. An elevated
risk of acute dystonia is observed in males and younger age groups. In the short-term,
placebo-controlled trial of ABILIFY MAINTENA in adults with schizophrenia, the
incidence of dystonia was 1.8% for ABILIFY MAINTENA vs. 0.6% for placebo.
Neutropenia
In the short-term, placebo-controlled trial of ABILIFY MAINTENA in adults with

schizophrenia, the incidence of neutropenia (absolute neutrophil count ≤1.5 thous/µL) for
ABILIFY MAINTENA-treated patients was 5.7% vs. 2.1% for placebo. An absolute
neutrophil count of <1 thous/µL (i.e. 0.95 thous/µL) was observed in only one patient on
ABILIFY MAINTENA and resolved spontaneously without any associated adverse
events [see WARNINGS AND PRECAUTIONS (5.7)]
Adverse Reactions Reported in Clinical Trials with Oral Aripiprazole
The following is a list of additional adverse reactions that have been reported in clinical
trials with oral aripiprazole and not reported above for ABILIFY MAINTENA:
Cardiac Disorders: palpitations, cardiopulmonary failure, myocardial infarction, cardio-

respiratory arrest, atrioventricular block, extrasystoles, angina pectoris, myocardial
ischemia, atrial flutter, supraventricular tachycardia, ventricular tachycardia
Eye Disorders: photophobia, diplopia, eyelid edema, photopsia
27

Gastrointestinal Disorders: gastroesophageal reflux disease, swollen tongue, esophagitis,
pancreatitis, stomach discomfort, toothache
General Disorders and Administration Site Conditions: asthenia, peripheral edema, chest
pain, face edema, angioedema, hypothermia, pain
Hepatobiliary Disorders: hepatitis, jaundice
Immune System Disorders: hypersensitivity
Injury, Poisoning, and Procedural Complications: heat stroke
Investigations: blood prolactin increased, blood urea increased, blood creatinine

increased, blood bilirubin increased, blood lactate dehydrogenase increased, glycosylated
hemoglobin increased
Metabolism and Nutrition Disorders: anorexia, hyponatremia, hypoglycemia, polydipsia,

diabetic ketoacidosis
Musculoskeletal and Connective Tissue Disorders: muscle rigidity, muscular weakness,

muscle tightness, decreased mobility, rhabdomyolysis, musculoskeletal stiffness, pain in
extremity, muscle spasms
Nervous System Disorders: coordination abnormal, speech disorder, hypokinesia,

hypotonia, myoclonus, akinesia, bradykinesia, choreoathetosis
Psychiatric Disorders: loss of libido, suicide attempt, hostility, libido increased, anger,
anorgasmia, delirium, intentional self injury, completed suicide, tic, homicidal ideation,
catatonia, sleep walking
Renal and Urinary Disorders: urinary retention, polyuria, nocturia
Reproductive System and Breast Disorders: menstruation irregular, erectile dysfunction,

amenorrhea, breast pain, gynecomastia, priapism
Respiratory, Thoracic, and Mediastinal Disorders: nasal congestion, dyspnea,

pharyngolaryngeal pain, cough
Skin and Subcutaneous Tissue Disorders: rash (including erythematous, exfoliative,

generalized, macular, maculopapular, papular rash; acneiform, allergic, contact,
exfoliative, seborrheic dermatitis, neurodermatitis, and drug eruption), hyperhidrosis,
pruritus, photosensitivity reaction, alopecia, urticaria
28

6.2 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of oral
aripiprazole or ABILIFY MAINTENA. Because these reactions are reported voluntarily
from a population of uncertain size, it is not always possible to reliably estimate their
frequency or establish a causal relationship to drug exposure: occurrences of allergic
reaction (anaphylactic reaction, angioedema, laryngospasm, pruritus/urticaria, or
oropharyngeal spasm), pathological gambling, hiccups and blood glucose fluctuation.
7 DRUG INTERACTIONS
7.1 Drugs Having Clinically Important Interactions with ABILIFY

MAINTENA
Table 8: Clinically Important Drug Interactions with ABILIFY MAINTENA:
Concomitant
Drug Name or Clinical Rationale Clinical Recommendation
Drug Class
With concomitant use of

Strong CYP3A4
The concomitant use of oral ABILIFY MAINTENA with a
Inhibitors (e.g.,
aripiprazole with strong CYP 3A4 strong CYP3A4 inhibitor or
ketoconazole) or
or CYP2D6 inhibitors increased CYP2D6 inhibitor for more than
strong CYP2D6
the exposure of aripiprazole 14 days, reduce the ABILIFY
inhibitors (e.g.,
[see CLINICAL MAINTENA dosage
paroxetine,
PHARMACOLOGY (12.3)]. [see DOSAGE AND
fluoxetine)
ADMINISTRATION (2.3)].
Avoid use of ABILIFY

The concomitant use of oral
MAINTENA in combination
Strong CYP3A4 aripiprazole and carbamazepine
with carbamazepine and other
Inducers (e.g., decreased the exposure of
inducers of CYP3A4 for greater
carbamazepine) aripiprazole [see CLINICAL
than 14 days [see DOSAGE
PHARMACOLOGY (12.3)].
AND ADMINISTRATION (2.3)].
Due to its alpha adrenergic Monitor blood pressure and

Antihypertensive antagonism, aripiprazole has the adjust dose accordingly [see
Drugs potential to enhance the effect of WARNINGS AND
certain antihypertensive agents. PRECAUTIONS (5.6)].
Benzodiazepines The intensity of sedation was Monitor sedation and blood

(e.g., lorazepam) greater with the combination of pressure. Adjust dose
29

oral aripiprazole and lorazepam as accordingly.
compared to that observed with
aripiprazole alone. The orthostatic
hypotension observed was greater
with the combination as compared
to that observed with lorazepam
alone [see WARNINGS AND
PRECAUTIONS (5.7)].
7.2 Drugs Having No Clinically Important Interactions with

ABILIFY MAINTENA
Based on pharmacokinetic studies with oral aripiprazole, no dosage adjustment of
ABILIFY MAINTENA is required when administered concomitantly with famotidine,
valproate, lithium, lorazepam [see CLINICAL PHARMACOLOGY (12.3)].
In addition, no dosage adjustment is necessary for substrates of CYP2D6 (e.g.,
dextromethorphan, fluoxetine, paroxetine, or venlafaxine), CYP2C9 (e.g., warfarin),
CYP2C19 (e.g., omeprazole, warfarin), or CYP3A4 (e.g., dextromethorphan) when co-
administered with ABILIFY MAINTENA. Additionally, no dosage adjustment is
necessary for valproate, lithium, lamotrigine, lorazepam, or sertraline when co-
administered with ABILIFY MAINTENA. [see CLINICAL PHARMACOLOGY (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women
exposed to ABILIFY during pregnancy. For more information contact the National
Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit
http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.
Risk Summary
Neonates exposed to antipsychotic drugs, including ABILIFY MAINTENA, during the
third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms.
There are insufficient data with ABILIFY MAINTENA use in pregnant women to inform
a drug-associated risk. In animal reproduction studies, oral and intravenous aripiprazole
administration during organogenesis in rats and/or rabbits at doses 10 and 11 times,
respectively, the maximum recommended human dose (MRHD) produced fetal death,
decreased fetal weight, undescended testicles, delayed skeletal ossification, skeletal
30

abnormalities, and diaphragmatic hernia. Oral and intravenous aripiprazole
administration during the pre- and post-natal period in rats at doses 10 times the
maximum recommended human dose (MRHD) produced prolonged gestation, stillbirths,
decreased pup weight, and decreased pup survival. Consider the benefits and risks of
ABILIFY MAINTENA and possible risks to the fetus when prescribing ABILIFY
MAINTENA to a pregnant woman. Advise pregnant women of potential fetal risk.
The background risk of major birth defects and miscarriage for the indicated population
are unknown. In the U.S. general population, the estimated background risk of major
birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%,
respectively.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia,

tremor, somnolence, respiratory distress and feeding disorder have been reported in
neonates who were exposed to antipsychotic drugs (including oral aripiprazole) during
the third trimester of pregnancy. These symptoms have varied in severity. Some neonates
recovered within hours or days without specific treatment; others required prolonged
hospitalization. Monitor neonates exhibiting extrapyramidal and/or withdrawal symptoms
and manage symptoms appropriately.
Animal Data
In animal studies, aripiprazole demonstrated developmental toxicity, including possible
teratogenic effects in rats and rabbits.
Pregnant rats were treated with oral doses of 3, 10, and 30 mg/kg/day which are
approximately 1 to 10 times the maximum recommended human dose [MRHD] of 30
mg/day on mg/m2 basis of aripiprazole during the period of organogenesis. Treatment at
the highest dose caused a slight prolongation of gestation and delay in fetal development,
as evidenced by decreased fetal weight and undescended testes. Delayed skeletal
ossification was observed at 3 and 10 times the oral MRHD on mg/m2 basis.
At 3 and 10 times the oral MRHD on mg/m2 basis, delivered offspring had decreased
body weights. Increased incidences of hepatodiaphragmatic nodules and diaphragmatic
hernia were observed in offspring from the highest dose group (the other dose groups
were not examined for these findings). Postnatally, delayed vaginal opening was seen at 3
and 10 times the oral MRHD on mg/m2 basis and impaired reproductive performance
(decreased fertility rate, corpora lutea, implants, live fetuses, and increased post-
implantation loss, likely mediated through effects on female offspring) along with some
31

maternal toxicity were seen at the highest dose; however, there was no evidence to
suggest that these developmental effects were secondary to maternal toxicity.
In pregnant rats treated with aripiprazole intravenously at doses of 3, 9, and

27 mg/kg/day, which are 1 to 9 times the oral MRHD on mg/m2 basis, during the period
of organogenesis, decreased fetal weight and delayed skeletal ossification were seen at
the highest dose which also caused maternal toxicity.
In pregnant rabbits treated with oral doses of 10, 30, and 100 mg/kg/day which are 2 to
11 times human exposure at the oral MRHD based on AUC and 6 to 65 times the oral
MRHD of aripiprazole on mg/m2 basis during the period of organogenesis, decreased
maternal food consumption and increased abortions were seen at the highest dose as well
as increased fetal mortality. Decreased fetal weight and increased incidence of fused
sternebrae were observed at 3 and 11 times the MRHD based on AUC.
In pregnant rabbits receiving aripiprazole injection intravenously at doses of 3 , 10 , and

30 mg/kg/day, which are 2 to 19 times the oral MRHD on mg/m2 basis during the period
of organogenesis, the highest dose caused pronounced maternal toxicity that resulted in
decreased fetal weight, increased fetal abnormalities (primarily skeletal), and decreased
fetal skeletal ossification. The fetal no-effect dose was 5 times the human exposure at the
oral MRHD based on AUC and is 6 times the oral MRHD on mg/m2 basis.
In rats treated with oral doses of 3, 10, and 30 mg/kg/day, which are 1 to 10 times the oral
MRHD of aripiprazole on a mg/m2 basis, peri- and post-natally (from day 17 of gestation
through day 21 postpartum), slight maternal toxicity and slightly prolonged gestation
were seen at the highest dose. An increase in stillbirths and decreases in pup weight
(persisting into adulthood) and survival were also seen at this dose.
In rats treated with aripiprazole intravenously at doses of 3, 8, and 20 mg/kg/day which

are 1 to 6 times the oral MRHD on mg/m2 basis from day 6 of gestation through day 20
postpartum, increased stillbirths were seen at 3 and 6 times the MRHD on mg/m2 basis,
and decreases in early postnatal pup weight and survival were seen at the highest dose;
these doses produced some maternal toxicity. There were no effects on postnatal
behavioral and reproductive development.
8.2 Lactation
Risk Summary
Aripiprazole is present in human breast milk; however, there are insufficient data to
assess the amount in human milk, the effects on the breastfed infant, or the effects on
milk production. The development and health benefits of breastfeeding should be
considered along with the mother’s clinical need for ABILIFY MAINTENA and any
32

potential adverse effects on the breastfed infant from ABILIFY MAINTENA or from the
underlying maternal condition.
8.4 Pediatric Use

ABILIFY MAINTENA has not been studied in children 18 years of age or younger.
However, juvenile animal studies have been conducted in rats and dogs.
Juvenile Animal Studies
Aripiprazole in juvenile rats caused mortality, CNS clinical signs, impaired memory and
learning, and delayed sexual maturation when administered at oral doses of 10, 20,
40mg/kg/day from weaning (21 days old) through maturity (80 days old). At
40mg/kg/day, mortality, decreased activity, splayed hind limbs, hunched posture, ataxia,
tremors and other CNS signs were observed in both genders. In addition, delayed sexual
maturation was observed in males. At all doses and in a dose-dependent manner,
impaired memory and learning, increased motor activity, and histopathology changes in
the pituitary (atrophy), adrenals (adrenocortical hypertrophy), mammary glands
(hyperplasia and increased secretion), and female reproductive organs (vaginal
mucification, endometrial atrophy, decrease in ovarian corpora lutea) were observed. The
changes in female reproductive organs were considered secondary to the increase in
prolactin serum levels. A No Observed Adverse Effect Level (NOAEL) could not be
determined and, at the lowest tested dose of 10mg/kg/day, there is no safety margin
relative to the systemic exposures (AUC0-24) for aripiprazole or its major active
metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. All
drug-related effects were reversible after a 2-month recovery period, and most of the drug
effects in juvenile rats were also observed in adult rats from previously conducted
studies.
Aripiprazole in juvenile dogs (2 months old) caused CNS clinical signs of tremors,
hypoactivity, ataxia, recumbency and limited use of hind limbs when administered orally
for 6 months at 3, 10, 30 mg/kg/day. Mean body weight and weight gain were decreased
up to 18% in females in all drug groups relative to control values. A NOAEL could not
be determined and, at the lowest tested dose of 3mg/kg/day, there is no safety margin
relative to the systemic exposures (AUC0-24) for aripiprazole or its major active
metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. All
drug-related effects were reversible after a 2-month recovery period.
33

8.5 Geriatric Use
Clinical studies of oral aripiprazole did not include sufficient numbers of subjects aged
65 and over to determine whether they respond differently from younger subjects. Other
reported clinical experience and pharmacokinetic data [see CLINICAL
PHARMACOLOGY (12.3)] have not identified differences in responses between the
elderly and younger patients. In general, dose selection for an elderly patient should be
cautious, usually starting at the low end of the dosing range, reflecting the greater
frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or
other drug therapy.
In single-dose and multiple-dose pharmacokinetic studies, there was no detectable age
effect in the population pharmacokinetic analysis of oral aripiprazole in schizophrenia
patients [see CLINICAL PHARMACOLOGY (12.3)]. No dosage adjustments are
recommended based on age alone. ABILIFY MAINTENA is not approved for the
treatment of patients with dementia-related psychosis [see also BOXED WARNING and
WARNINGS AND PRECAUTIONS (5.1)].
8.6 CYP2D6 Poor Metabolizers

Dosage adjustment is recommended in known CYP2D6 poor metabolizers due to high
aripiprazole concentrations. Approximately 8% of Caucasians and 3–8% of
Black/African Americans cannot metabolize CYP2D6 substrates and are classified as
poor metabolizers (PM) [see DOSAGE AND ADMINISTRATION (2.3) and CLINICAL
PHARMACOLOGY (12.3)].
8.7 Hepatic and Renal Impairment

No dosage adjustment for ABILIFY MAINTENA is required on the basis of a patient’s
hepatic function (mild to severe hepatic impairment, Child-Pugh score between 5 and
15), or renal function (mild to severe renal impairment, glomerular filtration rate between
15 and 90 mL/minute) [see CLINICAL PHARMACOLOGY (12.3)].
8.8 Other Specific Populations

No dosage adjustment for ABILIFY MAINTENA is required on the basis of a patient’s
sex, race, or smoking status [see CLINICAL PHARMACOLOGY (12.3)].
34

10 OVERDOSAGE
10.1 Human Experience

The largest known case of acute ingestion with a known outcome involved 1260 mg of
oral aripiprazole (42 times the maximum recommended daily dose) in a patient who fully
recovered.
Common adverse reactions (reported in at least 5% of all overdose cases) reported with
oral aripiprazole overdosage (alone or in combination with other substances) include
vomiting, somnolence, and tremor. Other clinically important signs and symptoms
observed in one or more patients with aripiprazole overdoses (alone or with other
substances) include acidosis, aggression, aspartate aminotransferase increased, atrial
fibrillation, bradycardia, coma, confusional state, convulsion, blood creatine
phosphokinase increased, depressed level of consciousness, hypertension, hypokalemia,
hypotension, lethargy, loss of consciousness, QRS complex prolonged, QT prolonged,
pneumonia aspiration, respiratory arrest, status epilepticus, and tachycardia.
10.2 Management of Overdosage

In case of overdosage, call the Poison Control Center immediately at 1-800-222-1222.
11 DESCRIPTION
Aripiprazole is an atypical antipsychotic which is present in ABILIFY MAINTENA as its
monohydrate polymorphic form. Aripiprazole monohydrate is 7-[4-[4-(2,3-
dichlorophenyl)-1-piperazinyl] butoxy]-3,4 dihydrocarbostyril monohydrate. The
empirical formula is C23H27Cl2N3O2•H2O and its molecular weight is 466.40. The
chemical structure is:
ABILIFY MAINTENA (aripiprazole) is an extended-release injectable suspension

available in 400-mg or 300-mg strength pre-filled dual chamber syringes and 400-mg or
300-mg strength vials. The labeled strengths are calculated based on the anhydrous form
(aripiprazole). Inactive ingredients (per administered dose) for 400 mg and 300 mg
strength products, respectively, include carboxymethyl cellulose sodium (16.64 mg and
12.48 mg), mannitol (83.2 mg and 62.4 mg), sodium phosphate monobasic monohydrate
(1.48 mg and 1.11 mg) and sodium hydroxide (pH adjuster).
35

12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action

The mechanism of action of aripiprazole in the treatment of schizophrenia is unknown.
However, the efficacy of aripiprazole may be mediated through a combination of partial

agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors.
Actions at receptors other than D2, 5-HT1A, and 5-HT2A may explain some of the other
adverse reactions of aripiprazole (e.g., the orthostatic hypotension observed with
aripiprazole may be explained by its antagonist activity at adrenergic alpha1 receptors).
12.2 Pharmacodynamics
Aripiprazole exhibits high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A
receptors (Ki values of 0.34 nM, 0.8 nM, 1.7 nM, and 3.4 nM, respectively), moderate
affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine
H1 receptors (Ki values of 44 nM, 15 nM, 39 nM, 57 nM, and 61 nM, respectively), and
moderate affinity for the serotonin reuptake site (Ki=98 nM). Aripiprazole has no
appreciable affinity for cholinergic muscarinic receptors (IC50>1000 nM). Aripiprazole
functions as a partial agonist at the dopamine D2 and the serotonin 5-HT1A receptors, and
as an antagonist at serotonin 5-HT2A receptor.
Alcohol
There was no significant difference between oral aripiprazole co-administered with

ethanol and placebo co-administered with ethanol on performance of gross motor skills or
stimulus response in healthy subjects. As with most psychoactive medications, patients
should be advised to avoid alcohol while taking ABILIFY MAINTENA.
12.3 Pharmacokinetics
ABILIFY MAINTENA activity is presumably primarily due to the parent drug,
aripiprazole, and to a lesser extent, to its major metabolite, dehydro-aripiprazole, which
has been shown to have affinities for D2 receptors similar to the parent drug and
represents about 29% of the parent drug exposure in plasma.
Aripiprazole absorption into the systemic circulation is slow and prolonged following
intramuscular injection due to low solubility of aripiprazole particles. Following a single
dose administration of ABILIFY MAINTENA in the deltoid and gluteal muscle, the
extent of absorption (AUCt, AUC∞) of aripiprazole was similar for both injection sites,
but the rate of absorption (Cmax) was 31% higher following administration to the deltoid
compared to the gluteal site. However, at steady state, AUC and Cmax were similar for
both sites of injection. Following multiple intramuscular doses, the plasma concentrations
36

of aripiprazole gradually rise to maximum plasma concentrations at a median Tmax of 5 -
7 days for the gluteal muscle and 4 days for the deltoid muscle. After gluteal
administration, the mean apparent aripiprazole terminal elimination half-life was
29.9 days and 46.5 days after multiple injections for every 4-week injection of ABILIFY
MAINTENA 300 mg and 400 mg, respectively. Steady state concentrations for the
typical subject were attained by the fourth dose for both sites of administration.
Approximate dose-proportional increases in aripiprazole and dehydro-aripiprazole
exposure were observed after every four week ABILIFY MAINTENA injections of
300 mg and 400 mg.
Elimination of aripiprazole is mainly through hepatic metabolism involving two P450

isozymes, CYP2D6 and CYP3A4. Aripiprazole is not a substrate of CYP1A1, CYP1A2,
CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2E1 enzymes. Aripiprazole
also does not undergo direct glucuronidation.
Drug Interaction Studies
No specific drug interaction studies have been performed with ABILIFY MAINTENA.
The information below is obtained from studies with oral aripiprazole.
Effects of other drugs on the exposures of aripiprazole and dehydro-aripiprazole are

summarized in Figure 19 and Figure 20, respectively. Based on simulation, a 4.5-fold
increase in mean Cmax and AUC values at steady-state is expected when extensive
metabolizers of CYP2D6 are administered with both strong CYP2D6 and CYP3A4
inhibitors. After oral administration, a 3-fold increase in mean Cmax and AUC values at
steady-state is expected in poor metabolizers of CYP2D6 administered with strong
CYP3A4 inhibitors.
37

Figure 19: The effects of other drugs on aripiprazole pharmacokinetics
Effect of Other Drugs on Abilify

PK Aripiprazole Fold Change and 90% CI
CYP3A4 Inhibitor:
ketoconazole AUC
Cmax
CYP2D6 Inhibitor:
quinidine AUC
Cmax
CYP3A4 Inducer:
carbamazepine AUC
Cmax
Gastric Acid Blockers:

famotidine AUC
Cmax
Other:
valproate AUC
Cmax
lithium AUC
Cmax
lorazepam AUC
Cmax
0.5 1.0 1.5 2.0 2.5 3.0
Change Relative to Reference (without interacting drug)
Figure 20: The effects of other drugs on dehydro-aripiprazole pharmacokinetics
Effect of Other Drugs on Abilify

PK Dehydro-Aripiprazole Fold Change and 90% CI
CYP3A4 Inhibitor:
ketoconazole AUC
Cmax
CYP2D6 Inhibitor:
quinidine AUC
Cmax
CYP3A4 Inducer:
carbamazepine AUC
Cmax
Gastric Acid Blockers:

famotidine AUC
Cmax
Other:
valproate AUC
Cmax
lithium AUC
Cmax
lorazepam AUC
Cmax
0.5 1.0 1.5 2.0 2.5 3.0
The effects of ABILIFY on the exposures of other drugs are summarized in Figure 21. A
population PK analysis in patients with major depressive disorder showed no substantial
change in plasma concentrations of fluoxetine (20 mg/day or 40 mg/day), paroxetine CR
(37.5 mg/day or 50 mg/day), or sertraline (100 mg/day or 150 mg/day) dosed to steady-
state. The steady-state plasma concentrations of fluoxetine and norfluoxetine increased
by about 18% and 36%, respectively, and concentrations of paroxetine decreased by
about 27%. The steady-state plasma concentrations of sertraline and desmethylsertraline
38

were not substantially changed when these antidepressant therapies were coadministered
with aripiprazole.
Figure 21: The effects of oral aripiprazole on pharmacokinetics of other drugs

Effect of Abilify on Other Drugs
PK Fold Change and 90% CI
CYP2D6
dextropmethorphan
DM/DRP
CYP2C9, 2C19
S-warfarin AUC
warfarin Cmax
R-warfarin AUC
Cmax
INR
omeprazole AUC
Cmax
UGT1A4
lamotrigine AUC
Cmax
Other
valproate AUC
Cmax
AUC
lithium Cmax
lorazepam AUC
Cmax
venlafaxine venlafaxine AUC
Cmax
O-desmethylvenlafaxine AUC
Cmax
escitalopram AUC
Cmax
0.5 1.0 1.5 2.0 2.5 3.0
Studies in Specific Populations
No specific pharmacokinetic studies have been performed with ABILIFY MAINTENA

in specific populations. All the information is obtained from studies with oral
aripiprazole.
Exposures of aripiprazole and dehydro-aripiprazole in specific populations are

summarized in Figure 22 and Figure 23, respectively. In addition, in pediatric patients (10
to 17 years of age) administered with oral aripiprazole (20 mg to 30 mg), the body weight
corrected aripiprazole clearance was similar to the adults.
39

Figure 22 Effects of intrinsic factors on aripiprazole pharmacokinetics
Special Populations
PK Aripiprazole Fold Change and 90% CI
CYP2D6
poor vs. extensive metabolizer AUC
Cmax
Gender
female vs. male AUC
Cmax
Age
18-64 vs. >65 years old AUC
Cmax
Hepatic Impairment:
mild vs. normal AUC
Cmax
moderate vs. normal AUC
Cmax
AUC
severe vs. normal Cmax
Renal Impairment:
Severe AUC
Cmax
0.5 1.0 1.5 2.0 2.5 3.0
Change Relative to Reference
Figure 23: Effects of intrinsic factors on dehydro-aripiprazole pharmacokinetics:
PK Dehydro-Aripiprazole Fold Change and 90% CI
CYP2D6
poor vs. extensive metabolizer AUC
Cmax
Gender
female vs. male AUC
Cmax
Age
18-64 vs. >65 years old AUC
Cmax
Hepatic Impairment:
AUC
mild vs. normal Cmax
moderate vs. normal AUC
Cmax
severe vs. normal AUC
Cmax
Renal Impairment:
Severe AUC
Cmax
0.5 1.0 1.5 2.0 2.5 3.0
Change Relative to Reference
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis
Lifetime carcinogenicity studies were conducted in ICR mice, Sprague-Dawley (SD) rats,
and F344 rats. Aripiprazole was administered for 2 years in the diet at doses of 1, 3, 10,
and 30 mg/kg/day to ICR mice and 1, 3, and 10 mg/kg/day to F344 rats (0.2 to 5 times
and 0.3 to 3 times the maximum recommended human dose [MRHD] based on mg/m2,
40

respectively). In addition, SD rats were dosed orally for 2 years at 10, 20, 40, and
60 mg/kg/day (3 to 19 times the MRHD based on mg/m2). Aripiprazole did not induce
tumors in male mice or male rats. In female mice, the incidences of pituitary gland
adenomas and mammary gland adenocarcinomas and adenoacanthomas were increased at
dietary doses of 3 to 30 mg/kg/day (0.1 to 0.9 times human exposure at MRHD based on
AUC and 0.5 to 5 times the MRHD based on mg/m2). In female rats, the incidence of
mammary gland fibroadenomas was increased at a dietary dose of 10 mg/kg/day (0.1
times human exposure at MRHD based on AUC and 3 times the MRHD based
on mg/m2); and the incidences of adrenocortical carcinomas and combined adrenocortical
adenomas/carcinomas were increased at an oral dose of 60 mg/kg/day (14 times human
exposure at MRHD based on AUC and 19 times the MRHD based on mg/m2).
Proliferative changes in the pituitary and mammary gland of rodents have been observed
following chronic administration of other antipsychotic agents and are considered
prolactin-mediated. Serum prolactin was not measured in the aripiprazole carcinogenicity
studies. However, increases in serum prolactin levels were observed in female mice in a
13-week dietary study at the doses associated with mammary gland and pituitary tumors.
Serum prolactin was not increased in female rats in 4-week and 13-week dietary studies
at the dose associated with mammary gland tumors. The relevance for human risk of the
findings of prolactin-mediated endocrine tumors in rodents is unknown.
Mutagenesis
The mutagenic potential of aripiprazole was tested in the in vitro bacterial reverse-
mutation assay, the in vitro bacterial DNA repair assay, the in vitro forward gene
mutation assay in mouse lymphoma cells, the in vitro chromosomal aberration assay in
Chinese hamster lung (CHL) cells, the in vivo micronucleus assay in mice, and the
unscheduled DNA synthesis assay in rats. Aripiprazole and a metabolite (2,3-DCPP)
were clastogenic in the in vitro chromosomal aberration assay in CHL cells with and
without metabolic activation. The metabolite, 2,3-DCPP, produced increases in numerical
aberrations in the in vitro assay in CHL cells in the absence of metabolic activation. A
positive response was obtained in the in vivo micronucleus assay in mice; however, the
response was due to a mechanism not considered relevant to humans.
Impairment of Fertility
Female rats were treated with oral doses of 2, 6, and 20 mg/kg/day (0.6, 2, and 6 times
the maximum recommended human dose [MRHD] on a mg/m2 basis) of aripiprazole
from 2 weeks prior to mating through day 7 of gestation. Estrus cycle irregularities and
increased corpora lutea were seen at all doses, but no impairment of fertility was seen.
Increased pre-implantation loss was seen at 6 and 20 mg/kg/day and decreased fetal
weight was seen at 20 mg/kg/day.
41

Male rats were treated with oral doses of 20, 40, and 60 mg/kg/day (6, 13, and 19 times
the MRHD on a mg/m2 basis) of aripiprazole from 9 weeks prior to mating through
mating. Disturbances in spermatogenesis were seen at 60 mg/kg and prostate atrophy was
seen at 40 and 60 mg/kg, but no impairment of fertility was seen.
13.2 Animal Toxicology and/or Pharmacology

Oral Aripiprazole
Aripiprazole produced retinal degeneration in albino rats in a 26-week chronic toxicity

study at a dose of 60 mg/kg and in a 2-year carcinogenicity study at doses of 40 and
60 mg/kg. The 40 and 60 mg/kg/day doses are 13 and 19 times the maximum
recommended human dose (MRHD) based on mg/m2 and 7 to 14 times human exposure
at MRHD based on AUC. Evaluation of the retinas of albino mice and of monkeys did
not reveal evidence of retinal degeneration. Additional studies to further evaluate the
mechanism have not been performed. The relevance of this finding to human risk is
unknown.
Intramuscular Aripiprazole
The toxicological profile for aripiprazole administered to experimental animals by

intramuscular injection is generally similar to that seen following oral administration at
comparable plasma levels of the drug. With intramuscular injection, however, injection-
site tissue reactions are observed that consist of localized inflammation, swelling,
scabbing and foreign-body reactions to deposited drug. These effects gradually resolved
with discontinuation of dosing.
After 26 weeks of treatment in rats, the no-observed-adverse-effect level (NOAEL) was

50 mg/kg in male rats and 100 mg/kg in female rats, which are approximately 1 and 2
times, respectively, the maximum recommended human 400 mg dose of aripiprazole
extended-release injectable suspension on a mg/m2 body surface area. At the NOAEL in
rats, the AUC7d values were 14.4 µg·h/mL in males and 104.1 µg·h/mL in females. In
dogs at 52 weeks of treatment at the NOAEL of 40 mg/kg, which is approximately 3
times the MRHD (400 mg) on a mg/m2 body surface area, the AUC7d values were
approximately 59 µg·h/mL in males and 44 µg·h/mL in females. In patients at the MRHD
of 400 mg, the AUCτ (0-28 days) was 163 µg·h/mL. For comparison to this human AUC,
extrapolating the animal AUC7d values to an AUC28d results in AUC28d values of
approximately 58 and 416 µg·h/mL for male and female rats, respectively, and 236 and
175 µg·h/mL for male and female dogs, respectively.
42

14 CLINICAL STUDIES
The efficacy of ABILIFY MAINTENA for treatment of schizophrenia was established
in:
 One short-term (12-week), randomized, double-blind, placebo-controlled trial in

acutely relapsed adults, Protocol 31-12-291 (Study 1)
 One longer-term, double-blind, placebo-controlled, randomized-withdrawal

(maintenance) trial in adults, Protocol 31-07-246 (Study 2).
Short-Term Efficacy
In the short-term (12-week), randomized, double-blind, placebo-controlled trial in acutely
relapsed adults (Study 1), the primary measure used for assessing psychiatric signs and
symptoms was the Positive and Negative Syndrome Scale (PANSS). The PANSS is a 30
item scale that measures positive symptoms of schizophrenia (7 items), negative
symptoms of schizophrenia (7 items), and general psychopathology (16 items), each rated
on a scale of 1 (absent) to 7 (extreme); total PANSS scores range from 30 to 210. The
primary endpoint was the change from baseline in PANSS total score to week 10.
The inclusion criteria for this short-term trial included adult inpatients who met DSM-IV-
TR criteria for schizophrenia. In addition, all patients entering the trial must have
experienced an acute psychotic episode as defined by both PANSS Total Score ≥ 80 and
a PANSS score of > 4 on each of four specific psychotic symptoms (conceptual
disorganization, hallucinatory behavior, suspiciousness/persecution, unusual thought
content) at screening and baseline. The key secondary endpoint was the change from
baseline in Clinical Global Impression-Severity (CGI-S) assessment scale to week 10.
The CGI-S rates the severity of mental illness on a scale of 1 (normal) to 7 (among the
most extremely ill) based on the total clinical experience of the rater in treating patients
with schizophrenia. Patients had a mean PANSS total score of 103 (range 82 to 144) and
a CGI-S score of 5.2 (markedly ill) at entry.
In this 12-week study (n=339) comparing ABILIFY MAINTENA (n=167) to placebo

(n=172), patients were administered 400 mg ABILIFY MAINTENA or placebo on days
0, 28, and 56. The dose could be adjusted down and up within the range of 400 to 300
mg on a one time basis. ABILIFY MAINTENA was superior to placebo in improving
the PANSS total score at the end of week 10 (see Table 9).
43

Table 9: Schizophrenia Short-term Study
Study Treatment Group Primary Efficacy Measure: PANSS Total Score
Number Mean Baseline LS Mean Change Placebo-subtracted
Score (SD) from Baseline (SE) Differencea (95% CI)
Study 1 ABILIFY MAINTENA 102.4 (11.4) -26.8 (1.6) -15.1 (-19.4, -10.8)
(400 to 300 mg)
Placebo 103.4 (11.1) -11.7 (1.6) --
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence
interval.
a
Difference (drug minus placebo) in least-squares mean change from baseline.
The change in PANSS total score by week is shown in Figure 24. ABILIFY MAINTENA
also showed improvement in symptoms represented by CGI-S score mean change from
baseline to week 10. The results of exploratory subgroup analyses by gender, race, age,
ethnicity, and BMI were similar to the results of the overall population.
Figure 24: Weekly PANSS Total Score-Change in the 12-Week, Placebo-

Controlled Study with ABILIFY MAINTENA
n = the number of patients remaining in the respective study arm at each time point
44

Longer-Term Efficacy
The efficacy of ABILIFY MAINTENA in maintaining symptomatic control in

schizophrenia was established in a double-blind, placebo-controlled, randomized-
withdrawal trial in adult patients (Study 2) who met DSM-IV-TR criteria for
schizophrenia and who were being treated with at least one antipsychotic medication.
Patients had at least a 3-year history of illness and a history of relapse or symptom
exacerbation when not receiving antipsychotic treatment.
In addition to the PANSS and CGI-S, clinical ratings during this trial included the:
 Clinical Global Impression-Improvement (CGI-I) scale, a scale of 1 (very much

improved) to 7 (very much worse) based on the change from baseline in clinical
condition and
 Clinical Global Impression-Severity of Suicide (CGI-SS) scale, which is

comprised of 2 parts: Part 1 rates the severity of suicidal thoughts and behavior on
a scale of 1 (not at all suicidal) to 5 (attempted suicide) based on the most severe
level in the last 7 days from all information available to the rater and Part 2 rates
the change from baseline in suicidal thoughts and behavior on a scale of 1 (very
much improved) to 7 (very much worse).
This trial included:
 A 4 to 6 week open-label, oral conversion phase for patients on antipsychotic

medications other than aripiprazole. A total of 633 patients entered this phase.
 An open-label, oral aripiprazole stabilization phase (target dose of 10 mg to
30 mg once daily). A total of 710 patients entered this phase. Patients were 18 to
60 years old (mean 40 years) and 60% were male. The mean PANSS total score
was 66 (range 33 to 124). The mean CGI-S score was 3.5 (mildly to moderately
ill). Prior to the next phase, stabilization was required. Stabilization was defined
as having all of the following for four consecutive weeks: an outpatient status,
PANSS total score ≤80, CGI-S ≤4 (moderately ill), and CGI-SS score ≤2 (mildly
suicidal) on Part 1 and ≤5 (minimally worsened) on Part 2; and a score of ≤4 on
each of the following PANSS items: conceptual disorganization, suspiciousness,
hallucinatory behavior, and unusual thought content.
 A minimum 12-week uncontrolled, single-blind ABILIFY MAINTENA
stabilization phase (treatment with 400 mg of ABILIFY MAINTENA given every
4 weeks in conjunction with oral aripiprazole [10 mg to 20 mg/day] for the first
2 weeks). The dose of ABILIFY MAINTENA may have been decreased to
300 mg due to adverse reactions. A total of 576 patients entered this phase. The
mean PANSS total score was 59 (range 30 to 80) and the mean CGI-S score was
45

3.2 (mildly ill). Prior to the next phase, stabilization was required (see above for
the definition of stabilization) for 12 consecutive weeks.
 A double-blind, placebo-controlled randomized-withdrawal phase to observe for
relapse (defined below). A total of 403 patients were randomized 2:1 to the same
dose of ABILIFY MAINTENA they were receiving at the end of the stabilization
phase, (400 mg or 300 mg administered once every 4 weeks) or placebo. Patients
had a mean PANSS total score of 55 (range 31 to 80) and a CGI-S score of 2.9
(mildly ill) at entry. The dose could be adjusted up and down or down and up
within the range of 300 to 400 mg on a one time basis.
The primary efficacy endpoint was time from randomization to relapse. Relapse was
defined as the first occurrence of one or more of the following criteria:
 CGI-I of ≥5 (minimally worse) and

1. an increase on any of the following individual PANSS items (conceptual
disorganization, hallucinatory behavior, suspiciousness, unusual thought
content) to a score >4 with an absolute increase of ≥2 on that specific item
since randomization or
2. an increase on any of the following individual PANSS items (conceptual
disorganization, hallucinatory behavior, suspiciousness, unusual thought
content) to a score >4 and an absolute increase ≥4 on the combined four
PANSS items (conceptual disorganization, hallucinatory behavior,
suspiciousness, unusual thought content) since randomization
 Hospitalization due to worsening of psychotic symptoms (including partial
hospitalization), but excluding hospitalization for psychosocial reasons
 CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much
worse) or 7 (very much worse) on Part 2, or
 Violent behavior resulting in clinically significant self-injury, injury to another
person, or property damage.
A pre-planned interim analysis demonstrated a statistically significantly longer time to

relapse in patients randomized to the ABILIFY MAINTENA group compared to placebo-
treated patients and the trial was subsequently terminated early because maintenance of
efficacy was demonstrated. The final analysis demonstrated a statistically significantly
longer time to relapse in patients randomized to the ABILIFY MAINTENA group than
compared to placebo-treated patients. The Kaplan-Meier curves of the cumulative
proportion of patients with relapse during the double-blind treatment phase for ABILIFY
MAINTENA and placebo groups are shown in Figure 25.
46

Figure 25: Kaplan-Meier Estimation of Cumulative Proportion of Patients with
Relapse1
1
This figure is based on a total of 80 relapse events
The key secondary efficacy endpoint, percentage of subjects meeting the relapse criteria,
was statistically significantly lower in patients randomized to the ABILIFY MAINTENA
group (10%) than in the placebo group (40%).
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied

Pre-filled Dual Chamber Syringe:
ABILIFY MAINTENA (aripiprazole) pre-filled dual chamber syringe for extended-

release injectable suspension in single-use syringes is available in 300 mg or 400 mg
strength syringes. The pre-filled dual chamber syringe consists of a front chamber that
contains the lyophilized powder of aripiprazole monohydrate and a rear chamber that
contains sterile water for injection.
47

The 300 mg kit includes (NDC 59148-045-80):
 300 mg single-dose pre-filled dual chamber syringe containing ABILIFY

MAINTENA (aripiprazole) for extended-release injectable suspension lyophilized
powder and Sterile Water for Injection
obese patients
 400 mg single-dose pre-filled dual chamber syringe containing ABILIFY

MAINTENA (aripiprazole) for extended-release injectable suspension lyophilized
powder and Sterile Water for Injection
obese patients
Single-Use Vial:
ABILIFY MAINTENA (aripiprazole) extended-release injectable suspension in single-

use vials is available in 300 mg or 400 mg strength vials.
 300 mg single-use vial of ABILIFY MAINTENA (aripiprazole) extended-release

 5 mL single-use vial of Sterile Water for Injection, USP
 One 3 mL luer lock syringe with pre-attached 21 gauge, 1.5 inch hypodermic
safety needle with needle protection device
48

obese patients
 400 mg single-use vial of ABILIFY MAINTENA (aripiprazole) extended-release

 5 mL single-use vial of Sterile Water for Injection, USP
 One 3 mL luer lock syringe with pre-attached 21 gauge, 1.5 inch hypodermic
safety needle with needle protection device
obese patients
16.2 Storage
Pre-filled dual chamber syringe:
Store below 30°C [86°F]. Do not freeze. Protect the syringe from light by storing in the
original package until time of use.
Vial:
Store at 25°C (77°F), excursions permitted between 15°C and 30°C (59°F to 86°F) [see
USP Controlled Room Temperature].
17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (MEDICATION GUIDE)
Neuroleptic Malignant Syndrome
Counsel patients about a potentially fatal adverse reaction referred to as NMS that has
been reported in association with administration of antipsychotic drugs. Advise patients,
family members, or caregivers to contact a health care provider or report to the
49

emergency room if they experience signs and symptoms of NMS [see WARNINGS AND
PRECAUTIONS (5.3)].
Tardive Dyskinesia
Advise patients that abnormal involuntary movements have been associated with the
administration of antipsychotic drugs. Counsel patients to notify their health care
provider if they notice any movements which they cannot control in their face, tongue, or
other body part [see WARNINGS AND PRECAUTIONS (5.4)].
Metabolic Changes (Hyperglycemia and Diabetes Mellitus, Dyslipidemia, and

Weight Gain)
Educate patients about the risk of metabolic changes, how to recognize symptoms of
hyperglycemia and diabetes mellitus, and the need for specific monitoring, including
blood glucose, lipids, and weight [see WARNINGS AND PRECAUTIONS (5.5)].
Orthostatic Hypotension
Educate patients about the risk of orthostatic hypotension and syncope especially early in
treatment, and also at times of re-initiating treatment or increases in dosage
[see WARNINGS AND PRECAUTIONS (5.6)].
Leukopenia/Neutropenia
Advise patients with a pre-existing low WBC count or a history of drug-induced

leucopenia/neutropenia that they should have their CBC monitored while receiving
ABILIFY MAINTENA [see WARNINGS AND PRECAUTIONS (5.7)].
Interference with Cognitive and Motor Performance
Because ABILIFY MAINTENA may have the potential to impair judgment, thinking, or
motor skills, instruct patients to be cautious about operating hazardous machinery,
including automobiles, until they are reasonably certain that ABILIFY MAINTENA
therapy does not affect them adversely [see WARNINGS AND PRECAUTIONS (5.9)].
Heat Exposure and Dehydration
Advise patients regarding appropriate care in avoiding overheating and dehydration [see
WARNINGS AND PRECAUTIONS (5.10)].
Concomitant Medication
Advise patients to inform their health care providers of any changes to their current
prescription or over-the-counter medications since there is a potential for clinically
significant interactions [see DRUG INTERACTIONS (7)].
50

Pregnancy
Advise patients that ABILIFY MAINTENA may cause extrapyramidal and/or

withdrawal symptoms in a neonate and to notify their healthcare provider with a known
or suspected pregnancy. Advise patients that there is a pregnancy exposure registry that
monitors pregnancy outcomes in women exposed to ABILIFY MAINTENA during
pregnancy [see USE IN SPECIFIC POPULATIONS (8.1)].
Distributed and marketed by Otsuka America Pharmaceutical, Inc., Rockville, MD 20850

USA
Marketed by Lundbeck, Deerfield, IL 60015 USA
ABILIFY MAINTENA is a trademark of Otsuka Pharmaceutical Company.
01/2016
©2016, Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan
51

MEDICATION GUIDE
ABILIFY MAINTENA® (a-BIL-i-fy main-TEN-a)
(aripiprazole)
for extended-release injectable suspension, for intramuscular use
What is the most important information I should know about ABILIFY

MAINTENA?
Each injection of ABILIFY MAINTENA must be administered by a healthcare

professional only.
ABILIFY MAINTENA may cause serious side effects, including:
 Increased risk of death in elderly people with dementia-related psychosis.

ABILIFY MAINTENA is not for the treatment of people who have lost touch
with reality (psychosis) due to confusion and memory loss (dementia).
 Neuroleptic malignant syndrome (NMS) a serious condition that can lead to
death. Tell your healthcare provider right away if you have some or all of the
following symptoms of NMS:
o high fever o stiff muscles

o confusion o sweating
o changes in pulse, heart rate, and
blood pressure
Call your healthcare provider or go to the nearest emergency room right away if you
have any of these symptoms.
What is ABILIFY MAINTENA?
ABILIFY MAINTENA is a prescription medicine given by injection by a healthcare

professional and used to treat schizophrenia.
It is not known if ABILIFY MAINTENA is safe and effective in children under 18 years
of age.
Who should not receive ABILIFY MAINTENA?
Do not receive ABILIFY MAINTENA if you are allergic to aripiprazole or any of the
ingredients in ABILIFY MAINTENA. See the end of this leaflet for a complete list of
ingredients in ABILIFY MAINTENA.
52

What should I tell my healthcare provider before receiving ABILIFY MAINTENA?
Before you receive ABILIFY MAINTENA, tell your healthcare provider if you:
 have never taken ABILIFY (aripiprazole) before

 have diabetes or high blood sugar or a family history of diabetes or high blood
sugar. Your healthcare provider should check your blood sugar before you start
receiving ABILIFY MAINTENA and during your treatment.
 have or had seizures (convulsions)
 have or had low or high blood pressure
 have or had heart problems or a stroke
 have or had a low white blood cell count
 have any other medical problems including problems that may affect you
receiving an injection in your arm or buttocks
 are pregnant or plan to become pregnant. It is not known if ABILIFY
MAINTENA will harm your unborn baby.
o If you become pregnant while taking ABILIFY MAINTENA, talk to your
healthcare provider about registering with the National Pregnancy Registry for
Atypical Antipsychotics. You can register by calling 1-866-961-2388 or visit
http://womensmentalhealth.org/clinical-and-research-
programs/pregnancyregistry/
 are breastfeeding or plan to breastfeed. ABILIFY MAINTENA can pass into your
milk and may harm your baby. Talk to your healthcare provider about the best
way to feed your baby if you receive ABILIFY MAINTENA.
Tell your healthcare provider about all the medicines you take, including prescription
medicines, over-the-counter medicines, vitamins, and herbal supplements.
ABILIFY MAINTENA and other medicines may affect each other causing possible
serious side effects. ABILIFY MAINTENA may affect the way other medicines work,
and other medicines may affect how ABILIFY MAINTENA works.
Your healthcare provider can tell you if it is safe to take ABILIFY MAINTENA with
your other medicines. Do not start or stop any medicines while taking ABILIFY
MAINTENA without talking to your healthcare provider first.
Know the medicines you take. Keep a list of them to show your healthcare provider and
pharmacist when you get a new medicine.
How should I receive ABILIFY MAINTENA?
 Follow your ABILIFY MAINTENA treatment schedule exactly as your healthcare provider
tells you to.
53

 ABILIFY MAINTENA is an injection given in your arm or buttock by your
healthcare provider 1 time every month. You may feel a little pain in your arm or
buttock during your injection.
 After your first injection of ABILIFY MAINTENA you should continue your
current antipsychotic medicine for 2 weeks.
 You should not miss a dose of ABILIFY MAINTENA. If you miss a dose for
some reason, call your healthcare provider right away to discuss what you should
do next.
What should I avoid while receiving ABILIFY MAINTENA?
 Do not drive, operate machinery, or do other dangerous activities until you know
how ABILIFY MAINTENA affects you. ABILIFY MAINTENA may make you
feel drowsy.
 Do not drink alcohol while you receive ABILIFY MAINTENA.
 Do not become too hot or dehydrated while you receive ABILIFY MAINTENA.
 Do not exercise too much.
 In hot weather, stay inside in a cool place if possible.
 Stay out of the sun.
 Do not wear too much clothing or heavy clothing.
 Drink plenty of water.
What are the possible side effects of ABILIFY MAINTENA?
ABILIFY MAINTENA may cause serious side effects, including:
 See "What is the most important information I should know about ABILIFY
MAINTENA?"
 Uncontrolled body movements (tardive dyskinesia). ABILIFY MAINTENA
may cause movements that you cannot control in your face, tongue, or other body
parts. Tardive dyskinesia may not go away, even if you stop receiving ABILIFY
MAINTENA. Tardive dyskinesia may also start after you stop receiving
ABILIFY MAINTENA.
 Problems with your metabolism such as:
 High blood sugar (hyperglycemia): Increases in blood sugar can happen
in some people who take ABILIFY MAINTENA. Extremely high blood
sugar can lead to coma or death. If you have diabetes or risk factors for
diabetes (such as being overweight or a family history of diabetes), your
healthcare provider should check your blood sugar before you start
receiving ABILIFY MAINTENA and during your treatment.
54

Call your healthcare provider if you have any of these symptoms of high blood
sugar while receiving ABILIFY MAINTENA:
 feel very thirsty

 need to urinate more than usual
 feel very hungry
 feel weak or tired
 feel sick to your stomach
 feel confused, or your breath smells fruity
 Increased fat levels (cholesterol and triglycerides) in your blood.
 Weight gain. You and your healthcare provider should check your weight
regularly.
 Decreased blood pressure (orthostatic hypotension). You may feel lightheaded
or faint when you rise too quickly from a sitting or lying position.
 Low white blood cell count
 Seizures (convulsions)
 Problems controlling your body temperature so that you feel too warm. See
"What should I avoid while receiving ABILIFY MAINTENA?"
 Difficulty swallowing
The most common side effect of ABILIFY MAINTENA includes feeling like you need
to move to stop unpleasant feelings in your legs (restless leg syndrome or akathisia),
injection site pain, or sleepiness (sedation).
Tell your healthcare provider if you have any side effect that bothers you or does not go
away.
These are not all the possible side effects of ABILIFY MAINTENA. For more
information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to
FDA at 1-800-FDA-1088.
General information about the safe and effective use of ABILIFY MAINTENA
This Medication Guide summarizes the most important information about ABILIFY
MAINTENA. If you would like more information, talk with your healthcare provider.
You can ask your healthcare provider or pharmacist for information about ABILIFY
MAINTENA. If you would like more information, talk with your healthcare provider.
You can ask your pharmacist or healthcare provider for information about ABILIFY
MAINTENA that is written for healthcare professionals.
55

For more information about ABILIFY MAINTENA, go to
www.ABILIFYMAINTENA.com or call 1-800-441-6763.
What are the ingredients in ABILIFY MAINTENA?
Active ingredient: aripiprazole monohydrate
Inactive ingredients: carboxymethyl cellulose sodium, mannitol, sodium phosphate

monobasic monohydrate and sodium hydroxide
This Medication Guide has been approved by the U.S. Food and Drug Administration.
ABILIFY MAINTENA is a trademark of Otsuka Pharmaceutical Company.
01/2016
© 2016, Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan
56

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HIGHLIGHTS OF PRESCRIBING INFORMATION These metabolic changes include hyperglycemia, dyslipidemia, and weight

Reference ID: 3874224

Reference ID: 3874224

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Dosage Overview for the Treatment of Schizophrenia

2.2 Dosage Adjustments for Missed Doses

Reference ID: 3874224

If the fourth or subsequent doses are missed:

2.3 Dosage Adjustments for Cytochrome P450 Considerations

If the CYP3A4 inhibitor or CYP2D6 inhibitor is withdrawn, the ABILIFY MAINTENA

Table 1: Dose Adjustments of ABILIFY MAINTENA in Patients who are

Factors Adjusted Dose

Reference ID: 3874224

ABILIFY MAINTENA comes in two types of kits. See instructions for

2.4 Different Aripiprazole Formulations and Kits

ABILIFY MAINTENA comes in two types of kits. See instructions for

2.5 Pre-filled Dual Chamber Syringe: Preparation and

For deep intramuscular deltoid or gluteal injection by healthcare professionals only. Do

 One ABILIFY MAINTENA (aripiprazole) pre-filled dual chamber syringe (400

Reference ID: 3874224

Reconstitution of Lyophilized Powder in Pre-filled Dual Chamber Syringe

Reconstitute at room temperature.

Reference ID: 3874224

Use appropriate aseptic techniques throughout injection procedure. For deep

b) Select appropriate needle (See Figure 4).

For deltoid administration:

 23 gauge, 1 inch (25 mm) hypodermic safety needle with needle

Reference ID: 3874224

d) Then PULL needle-cap straight up (see Figure 6).

e) Hold syringe UPRIGHT and ADVANCE PLUNGER ROD SLOWLY TO

Reference ID: 3874224

b) Rotate sites of injections between the two deltoid or gluteal muscles.

2.6 Vial: Preparation and Administration Instructions

For deep intramuscular injection by healthcare professionals only. Do not

Reference ID: 3874224

Table 2: Amount of Sterile Water for Injection Needed for Reconstitution

400 mg Vial 300 mg Vial

Reconstitution of Lyophilized Powder in Vial

Reference ID: 3874224

Reference ID: 3874224

f) Visually inspect the reconstituted suspension for particulate matter and

Preparation Prior to Injection

a) Use appropriate aseptic techniques throughout injection of the reconstituted

Reference ID: 3874224

e) Determine the recommended volume for injection (Table 3).

Table 3: ABILIFY MAINTENA Reconstituted Suspension Volume to Inject

400 mg Vial 300 mg Vial

Reference ID: 3874224

For deltoid administration:

For gluteal administration:

Reference ID: 3874224

3 DOSAGE FORMS AND STRENGTHS

The reconstituted extended-release injectable suspension is a uniform, homogeneous

Reference ID: 3874224

5.1 Increased Mortality in Elderly Patients with Dementia-

5.2 Cerebrovascular Adverse Reactions, Including Stroke in

5.3 Neuroleptic Malignant Syndrome