ARIPIPRAZOLE tablet

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Active ingredient:
ARIPIPRAZOLE (UNII: 82VFR53I78) (ARIPIPRAZOLE - UNII:82VFR53I78)
Available from:
XLCare Pharmaceuticals, Inc.
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Aripiprazole oral tablets are indicated for the treatment of: - Schizophrenia [see Clinical Studies (14.1)] Additional pediatric use information is approved for Otsuka America Pharmaceutical, Inc.’s ABILIFY® (aripiprazole) product. However, due to Otsuka America Pharmaceutical, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. Aripiprazole tablets are contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis [see Adverse Reactions (6.2)]. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including aripiprazole, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neon
Product summary:
Aripiprazole tablets, USP 2 mg are light green to green, modified rectangular, bevel edged biconvex tablets debossed with ‘I’ on one side and ‘94’ on other side. Bottles of 30 Tablets                                                                 NDC 72865-153-30 Bottles of 500 Tablets                                                               NDC 72865-153-05 Aripiprazole tablets, USP 5 mg are light blue to blue, modified rectangular, bevel edged biconvex tablets debossed with ‘I’ on one side and ‘95’ on other side. Bottles of 30 Tablets                                                               NDC 72865-154-30 Bottles of 500 Tablets                                                             NDC 72865-154-05 Aripiprazole tablets, USP 10 mg are light pink to pink, modified rectangular, bevel edged biconvex tablets debossed with ‘I’ on one side and ‘96’ on other side. Bottles of 30 Tablets                                                                 NDC 72865-155-30 Bottles of 500 Tablets                                                               NDC 72865-155-05 Aripiprazole tablets, USP 15 mg are light yellow to yellow, round, bevel edged biconvex tablets debossed with ‘I’ on one side and ‘97’ on other side. Bottles of 30 Tablets                                                                  NDC 72865-156-30 Bottles of 500 Tablets                                                                NDC 72865-156-05 Aripiprazole tablets, 20 mg are white to off-white, round, bevel edged biconvex tablets debossed with ‘I’ on one side and ‘98’ on other side. Bottles of 30 Tablets                                                                   NDC 72865-157-30 Bottles of 500 Tablets                                                                 NDC 72865-157-05 Aripiprazole tablets, USP 30 mg are light pink to pink, round, bevel edged biconvex tablets debossed with ‘I’ on one side and ‘99’ on other side. Bottles of 30 Tablets                                                                   NDC 72865-158-30 Bottles of 500 Tablets                                                                 NDC 72865-158-05 Store at 20º to 25º C (68º to 77ºF) [see USP Controlled Room Temperature].
Authorization status:
Abbreviated New Drug Application
Authorization number:
72865-153-05, 72865-153-30, 72865-154-05, 72865-154-30, 72865-155-05, 72865-155-30, 72865-156-05, 72865-156-30, 72865-157-05, 72865-157-30, 72865-158-05, 72865-158-30

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ARIPIPRAZOLE- aripiprazole tablet

XLCare Pharmaceuticals, Inc.

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MEDICATION GUIDE

Aripiprazole Tablets, USP

(ar'' i pip' ra zole)

What is the most important information I should know about aripiprazole tablets?

(For other side effects, also see “What are the possible side effects of aripiprazole tablets?”)

Serious side effects may happen when you take aripiprazole tablets, including:

Increased risk of death in elderly patients with dementia-related psychosis: Medicines like aripiprazole

tablets can raise the risk of death in elderly people who have lost touch with reality (psychosis) due to

confusion and memory loss (dementia). Aripiprazole tablets are not approved for the treatment of patients

with dementia-related psychosis.

Risk of suicidal thoughts or actions: Antidepressant medicines, depression and other serious mental

illnesses, and suicidal thoughts or actions:

1. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and

young adults within the first few months of treatment.

2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and

actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These

include people who have (or have a family history of) suicidal thoughts or actions.

3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?

Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or

feelings. This is very important when an antidepressant medicine is started or when the dose is

changed.

Call the healthcare provider right away to report new or sudden changes in mood, behavior,

thoughts, or feelings.

Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider

between visits as needed, especially if you have concerns about symptoms.

Call a healthcare provider right away if you or your family member has any of the following symptoms,

especially if they are new, worse, or worry you:

thoughts about suicide or dying

attempts to commit suicide

new or worse depression

new or worse anxiety

feeling very agitated or restless

panic attacks

trouble sleeping (insomnia)

new or worse irritability

acting aggressive, being angry, or violent

acting on dangerous impulses

an extreme increase in activity and talking (mania)

other unusual changes in behavior or mood

What else do I need to know about antidepressant medicines?

Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an

antidepressant medicine suddenly can cause other symptoms.

Antidepressants are medicines used to treat depression and other illnesses. It is important to

discuss all the risks of treating depression and also the risks of not treating it. Patients and their

families or other caregivers should discuss all treatment choices with the healthcare provider, not

just the use of antidepressants.

Antidepressant medicines have other side effects. Talk to the healthcare provider about the side

effects of the medicine prescribed for you or your family member.

Antidepressant medicines can interact with other medicines. Know all of the medicines that you or

your family member takes. Keep a list of all medicines to show the healthcare provider. Do not

start new medicines without first checking with your healthcare provider.

Not all antidepressant medicines prescribed for children are FDA approved for use in children.

Talk to your child’s healthcare provider for more information.

What are aripiprazole tablets?

Aripiprazole tablets are prescription medicine used to treat:

Schizophrenia

It is not known if aripiprazole tablets are safe or effective in children:

under 13 years of age with schizophrenia

Do not take aripiprazole tablets if you are allergic to aripiprazole or any of the ingredients in aripiprazole

tablets. See the end of this Medication Guide for a complete list of ingredients in aripiprazole tablets.

Before taking aripiprazole tablets, tell your healthcare provider about all your medical conditions,

including if you have or had:

diabetes or high blood sugar in you or your family; your healthcare provider should check your

blood sugar before you start aripiprazole tablets and also during therapy.

seizures (convulsions).

low or high blood pressure.

heart problems or stroke.

pregnancy or plans to become pregnant. It is not known if aripiprazole tablets will harm your

unborn baby.

If you become pregnant while receiving aripiprazole tablets, 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 go to

http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.

breast-feeding or plans to breast-feed. Aripiprazole passes into your breast milk. Talk to your

healthcare provider about the best way to feed your baby if you receive aripiprazole tablets.

low white blood cell count.

Tell your healthcare provider about all the medicines that you take, including prescription and over-the-

counter medicines, vitamins, and herbal supplements.

Aripiprazole tablets and other medicines may affect each other causing possible serious side effects.

Aripiprazole tablets may affect the way other medicines work, and other medicines may affect how

aripiprazole tablets works.

Your healthcare provider can tell you if it is safe to take aripiprazole tablets with your other medicines.

Do not start or stop any medicines while taking aripiprazole tablets without talking to your healthcare

provider first. Know the medicines you take. Keep a list of your medicines to show your healthcare

provider and pharmacist when you get a new medicine.

How should I take aripiprazole tablets?

Take aripiprazole tablets exactly as your healthcare provider tells you to take it. Do not change the

dose or stop taking aripiprazole tablets yourself.

Aripiprazole tablets can be taken with or without food.

Aripiprazole tablets should be swallowed whole.

If you miss a dose of aripiprazole tablets, take the missed dose as soon as you remember. If it is

almost time for the next dose, just skip the missed dose and take your next dose at the regular

time. Do not take two doses of aripiprazole tablets at the same time.

If you take too much aripiprazole tablets, call your healthcare provider or poison control center at

1-800-222-1222 right away, or go to the nearest hospital emergency room.

What should I avoid while taking aripiprazole tablets?

Do not drive, operate heavy machinery, or do other dangerous activities until you know how

aripiprazole tablets affects you. Aripiprazole tablets may make you drowsy.

Avoid getting over-heated or dehydrated.

Do not over-exercise.

In hot weather, stay inside in a cool place if possible.

Stay out of the sun. Do not wear too much or heavy clothing.

Drink plenty of water.

What are the possible side effects of aripiprazole tablets?

Aripiprazole tablets may cause serious side effects, including:

See “What is the most important information I should know about aripiprazole tablets?”

Stroke in elderly people (cerebrovascular problems) that can lead to death

Neuroleptic malignant syndrome (NMS): Tell your healthcare provider right away if you have

some or all of the following symptoms: high fever, stiff muscles, confusion, sweating, changes in

pulse, heart rate, and blood pressure. These may be symptoms of a rare and serious condition that

can lead to death. Call your healthcare provider right away if you have any of these symptoms.

Uncontrolled body movements (tardive dyskinesia). Aripiprazole tablets 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 aripiprazole tablets. Tardive dyskinesia may also start after you

stop receiving aripiprazole tablets.

Problems with your metabolism such as:

High blood sugar (hyperglycemia) and diabetes: Increases in blood sugar can happen in some

people who take aripiprazole tablets. 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 aripiprazole

tablets and during your treatment.

Call your healthcare provider if you have any of these symptoms of high blood sugar while receiving

aripiprazole tablets:

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.

Unusual urges. Some people taking aripiprazole tablets have had unusual urges, such as gambling,

binge eating or eating that you cannot control (compulsive), compulsive shopping and sexual

urges.

If you or your family members notice that you are having unusual urges or behaviors, talk to your

healthcare provider.

Orthostatic hypotension (decreased blood pressure): Lightheadedness or fainting may happen

when rising too quickly from a sitting or lying position.

Falls. Aripiprazole tablets may make you sleepy or dizzy, may cause a decrease in your blood

pressure when changing position and can slow your thinking and motor skills which may lead to

falls that can cause fractures or other injuries.

Low white blood cell count

Seizures (convulsions)

Problems with control of your body temperature especially when you exercise a lot or are in an

area that is very hot. It is important for you to drink water to avoid dehydration. See “What should

I avoid while receiving aripiprazole tablets?”

Difficulty swallowing that can cause food or liquid to get into your lungs.

The most common side effects of aripiprazole tablets in adults include:

Nausea

vomiting

constipation

headache

blurred vision

upper respiratory illness

dizziness

anxiety

insomnia

restlessness

inner sense of restlessness/need to move

(akathisia)

The most common side effects of aripiprazole tablets in children include:

feeling sleepy

headache

vomiting

fatigue

increased or decreased appetite

increased saliva or drooling

insomnia

nausea

stuffy nose

weight gain

uncontrolled movement such as restlessness,

tremor

muscle stiffness

These are not all the possible side effects of aripiprazole tablets.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-

FDA-1088.

How should I store aripiprazole tablets?

Store aripiprazole tablets at 68º to 77ºF (20º to 25º C).

Keep aripiprazole tablets and all medicines out of the reach of children.

General information about the safe and effective use of aripiprazole tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use aripiprazole tablets for a condition for which it was not prescribed. Do not give aripiprazole tablets to

other people, even if they have the same symptoms you have. It may harm them. You can ask your

healthcare provider or pharmacist for information about aripiprazole tablets that was written for

healthcare professionals.

For more information, call 1-866-495-1995.

What are the ingredients in aripiprazole tablets?

Active ingredient: aripiprazole USP

Inactive ingredients: corn starch, FD&C Blue #2/Indigo Carmine Al, ferric oxide red, ferric oxide yellow,

hydroxypropyl cellulose, lactose monohydrate, magnesium stearate and microcrystalline cellulose

Additional pediatric use information is approved for Otsuka America Pharmaceutical, Inc.’s ABILIFY®

(aripiprazole) product. However, due to Otsuka America Pharmaceutical, Inc.’s marketing exclusivity

rights, this drug product is not labeled with that information.

Manufactured for:

XLCare Pharmaceuticals, Inc.

242 South Culver Street, Suite 202

Lawrenceville, GA 30046

Manufactured by:

Ascent Pharmaceuticals, Inc.

Central Islip, NY 11722

This Medication Guide has been approved by the U.S. Food and Drug Administration

Revised: 10/20

Revised: 10/2020

Document Id: e72f40d4-73b4-496a-ab11-23efd200778b

34391-3

Set id: b284b294-40a0-4ccd-b7b7-b61267cd4e76

Version: 1

Effective Time: 20201029

XLCare Pharmaceuticals, Inc.

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ARIPIPRAZOLE- aripiprazole tablet

XLCare Pharmaceuticals, Inc.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use ARIPIPRAZOLE TABLETS safely and

effectively. See full prescribing information for ARIPIPRAZOLE TABLETS.

ARIPIPRAZOLE tablets, for oral use.

Initial U.S. Approval: 2002

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED

PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS WITH ANTIDEPRESSANT DRUGS

See full prescribing information for complete boxed warning.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased

risk of death. Aripiprazole tablets are not approved for the treatment of patients with dementia-

related psychosis. (5.1)

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking

antidepressants. Monitor for worsening and emergence of suicidal thoughts and behaviors. (5.3)

RECENT MAJOR CHANGES

Warnings and Precautions (5.5) 08/2019

INDICATIONS AND USAGE

Aripiprazole tablets are an atypical antipsychotic. The oral formulations are indicated for: (1)

Schizophrenia (14.1)

DOSAGE AND ADMINISTRATION

Initial Dose (2)

Recommended Dose (2)

Maximum Dose (2)

Schizophrenia – adults (2.1) (2)

10 to 15 mg/day (2)

10 to 15 mg/day (2)

30 mg/day (2)

Schizophrenia – adolescents (2.1) (2)

2 mg/day (2)

10 mg/day (2)

30 mg/day (2)

Oral formulations: Administer once daily without regard to meals (2)

Known CYP2D6 poor metabolizers: Half of the usual dose (2.7)

DOSAGE FORMS AND STRENGTHS

Tablets: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 30 mg (3)

CONTRAINDICATIONS

Known hypersensitivity to aripiprazole tablets (4)

WARNINGS AND PRECAUTIONS

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of

cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack, including fatalities) (5.2)

Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring (5.4)

Tardive Dyskinesia: Discontinue if clinically appropriate (5.5)

Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include

hyperglycemia/diabetes mellitus, dyslipidemia, and body weight gain (5.6)

Hyperglycemia/Diabetes Mellitus: Monitor glucose regularly in patients with and at risk for diabetes (5.6)

Dyslipidemia: Undesirable alterations in lipid levels have been observed in patients treated with atypical antipsychotics

(5.6)

Weight Gain: Weight gain has been observed with atypical antipsychotic use. Monitor weight (5.6)

Pathological Gambling and Other Compulsive Behaviors: Consider dose reduction or discontinuation (5.7)

Orthostatic Hypotension: Monitor heart rate and blood pressure and warn patients with known cardiovascular or

cerebrovascular disease, and risk of dehydration or syncope (5.8)

Leukopenia, Neutropenia, and Agranulocytosis: have been reported with antipsychotics including aripiprazole tablets.

Patients with a history of a clinically significant low white blood cell count (WBC) or a drug-induced

leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few

months of therapy and discontinuation of aripiprazole tablets should be considered at the first sign of a clinically

significant decline in WBC in the absence of other causative factors (5.10)

Seizures/Convulsions: Use cautiously in patients with a history of seizures or with conditions that lower the seizure

threshold (5.11)

Potential for Cognitive and Motor Impairment: Use caution when operating machinery (5.12)

Suicide: The possibility of a suicide attempt is inherent in schizophrenia. Closely supervise high-risk patients (5.14)

ADVERSE REACTIONS

Commonly observed adverse reactions (incidence ≥5% and at least twice that for placebo) were (6.1): (6)

Adult patients with schizophrenia: akathisia

Pediatric patients (13 to 17 years) with schizophrenia: extrapyramidal disorder, somnolence, and tremor

To report SUSPECTED ADVERSE REACTIONS, contact XLCare Pharmaceuticals, Inc. at 1-866-495-1995 or

FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. (6)

DRUG INTERACTIONS

Dosage adjustment due to drug interactions (7.1): (7)

Factors (7)

Dosage Adjustments for Aripiprazole Tablets (7)

Known CYP2D6 Poor Metabolizers (7)

Administer half of usual dose (7)

Known CYP2D6 Poor Metabolizers and strong CYP3A4 inhibitors

Administer a quarter of usual dose (7)

Strong CYP2D6 or CYP3A4 inhibitors (7)

Administer half of usual dose (7)

Strong CYP2D6 and CYP3A4 inhibitors (7)

Administer a quarter of usual dose (7)

Strong CYP3A4 inducers (7)

Double usual dose over 1 to 2 weeks (7)

USE IN SPECIFIC POPULATIONS

Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure (8.1) (8)

Additional pediatric use information is approved for Otsuka America Pharmaceutical, Inc.’s ABILIFY

(aripiprazole) product. However, due to Otsuka America Pharmaceutical, Inc.’s marketing exclusivity rights,

this drug product is not labeled with that information. (8)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 10/2020

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-

RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS WITH

ANTIDEPRESSANT DRUGS

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Schizophrenia

2.7 Dosage Adjustments for Cytochrome P450 Considerations

2.8 Dosing of Oral Solution

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis

5.2 Cerebrovascular Adverse Events, Including Stroke

5.3 Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults

5.4 Neuroleptic Malignant Syndrome (NMS)

5.5 Tardive Dyskinesia

5.6 Metabolic Changes

®

5.7 Pathological Gambling and Other Compulsive Behaviours

5.8 Orthostatic Hypotension

5.9 Falls

5.10 Leukopenia, Neutropenia, and Agranulocytosis

5.11 Seizures/Convulsions

5.12 Potential for Cognitive and Motor Impairment

5.13 Body Temperature Regulation

5.14 Suicide

5.15 Dysphagia

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Drugs Having Clinically Important Interactions with Aripiprazole

7.2 Drugs Having No Clinically Important Interactions with Aripiprazole

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 CYP2D6 Poor Metabolizers

8.7 Hepatic and Renal Impairment

8.8 Other Specific Populations

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

9.2 Abuse

9.3 Dependence

10 OVERDOSAGE

10.1 Human Experience

10.2 Management of Overdosage

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

14.1 Schizophrenia

14.2 Bipolar Disorder

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

16.2 Storage

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

Sections or subsections omitted from the full prescribing information are not listed.

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH

DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS

WITH ANTIDEPRESSANT DRUGS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an

increased risk of death. Aripiprazole tablets are not approved for the treatment of patients

with dementia-related psychosis [see Warnings and Precautions (5.1)].

Antidepressants increased the risk of suicidal thoughts and behavior in children,

adolescents, and young adults in short-term studies. These studies did not show an

increase in the risk of suicidal thoughts and behavior with antidepressant use in patients

over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and

older [see Warnings and Precautions (5.3)].

In patients of all ages who are started on antidepressant therapy, monitor closely for

worsening, and for emergence of suicidal thoughts and behaviors. Advise families and

caregivers of the need for close observation and communication with the prescriber [see

Warnings and Precautions (5.3)].

1 INDICATIONS AND USAGE

Aripiprazole oral tablets are indicated for the treatment of:

Schizophrenia [see Clinical Studies (14.1)]

Additional pediatric use information is approved for Otsuka America Pharmaceutical, Inc.’s

ABILIFY (aripiprazole) product. However, due to Otsuka America Pharmaceutical, Inc.’s

marketing exclusivity rights, this drug product is not labeled with that information.

2 DOSAGE AND ADMINISTRATION

2.1 Schizophrenia

Adults

The recommended starting and target dose for aripiprazole tablets is 10 or 15 mg/day administered on a

once-a-day schedule without regard to meals. Aripiprazole tablets have been systematically evaluated

and shown to be effective in a dose range of 10 to 30 mg/day, when administered as the tablet

formulation; however, doses higher than 10 or 15 mg/day were not more effective than 10 or 15 mg/day.

Dosage increases should generally not be made before 2 weeks, the time needed to achieve steady-state

[see Clinical Studies (14.1)].

Maintenance Treatment: Maintenance of efficacy in schizophrenia was demonstrated in a trial involving

patients with schizophrenia who had been symptomatically stable on other antipsychotic medications for

periods of 3 months or longer. These patients were discontinued from those medications and

randomized to either aripiprazole tablets 15 mg/day or placebo, and observed for relapse [see Clinical

Studies (14.1)]. Patients should be periodically reassessed to determine the continued need for

maintenance treatment.

Adolescents

The recommended target dose of aripiprazole tablets is 10 mg/day. Aripiprazole was studied in

adolescent patients 13 to 17 years of age with schizophrenia at daily doses of 10 mg and 30 mg. The

starting daily dose of the tablet formulation in these patients was 2 mg, which was titrated to 5 mg after 2

days and to the target dose of 10 mg after 2 additional days. Subsequent dose increases should be

administered in 5 mg increments. The 30 mg/day dose was not shown to be more efficacious than the 10

mg/day dose. Aripiprazole tablets can be administered without regard to meals [see Clinical Studies

®

(14.1)]. Patients should be periodically reassessed to determine the need for maintenance treatment.

Switching from Other Antipsychotics

There are no systematically collected data to specifically address switching patients with schizophrenia

from other antipsychotics to aripiprazole tablets or concerning concomitant administration with other

antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be

acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate

for others. In all cases, the period of overlapping antipsychotic administration should be minimized.

Additional pediatric use information is approved for Otsuka America Pharmaceutical, Inc.’s

ABILIFY (aripiprazole) product. However, due to Otsuka America Pharmaceutical, Inc.’s

marketing exclusivity rights, this drug product is not labeled with that information.

2.7 Dosage Adjustments for Cytochrome P450 Considerations

Dosage adjustments are recommended in patients who are known CYP2D6 poor metabolizers and in

patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers (see

Table 2). When the coadministered drug is withdrawn from the combination therapy, aripiprazole tablets

dosage should then be adjusted to its original level. When the coadministered CYP3A4 inducer is

withdrawn, aripiprazole tablets dosage should be reduced to the original level over 1 to 2 weeks.

Patients who may be receiving a combination of strong, moderate, and weak inhibitors of CYP3A4 and

CYP2D6 (e.g., a strong CYP3A4 inhibitor and a moderate CYP2D6 inhibitor or a moderate CYP3A4

inhibitor with a moderate CYP2D6 inhibitor), the dosing may be reduced to one-quarter (25%) of the

usual dose initially and then adjusted to achieve a favorable clinical response.

Table 2: Dose Adjustments for Aripiprazole Tablets in Patients who are known CYP2D6 Poor

Metabolizers and Patients Taking Concomitant CYP2D6 Inhibitors, 3A4 Inhibitors, and/or

CYP3A4 Inducers

Factors

Dosage Adjustments for Aripiprazole

Tablets

Known CYP2D6 Poor Metabolizers

Administer half of usual dose

Known CYP2D6 Poor Metabolizers taking

concomitant strong CYP3A4 inhibitors (e.g.,

itraconazole, clarithromycin)

Administer a quarter of usual dose

Strong CYP2D6 (e.g., quinidine, fluoxetine,

paroxetine) or CYP3A4 inhibitors (e.g., itraconazole,

clarithromycin)

Administer half of usual dose

Strong CYP2D6 and CYP3A4 inhibitors

Administer a quarter of usual dose

Strong CYP3A4 inducers (e.g., carbamazepine,

rifampin)

Double usual dose over 1 to 2 weeks

2.8 Dosing of Oral Solution

The oral solution can be substituted for tablets on a mg-per-mg basis up to the 25 mg dose level.

Patients receiving 30 mg tablets should receive 25 mg of the solution [see Clinical Pharmacology

(12.3)].

3 DOSAGE FORMS AND STRENGTHS

Aripiprazole Tablets, USP are available as described in Table 3.

Table 3: Aripiprazole Tablets Presentations

®

Tablet Strength

Tablet

Color/Shape

Tablet

Markings

2 mg

Lightgreen to green

modified rectangle

“I” and “94”

5 mg

Lightblue to blue

modified rectangle

“I” and “95”

10 mg

Lightpink to pink

modified rectangle

“I” and “96”

15 mg

Lightyellow to yellow

round

“I” and “97”

20 mg

white to off-white round

“I” and “98”

30 mg

Lightpink to pink

round

“I ” and “99”

4 CONTRAINDICATIONS

Aripiprazole tablets are contraindicated in patients with a history of a hypersensitivity reaction to

aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis [see Adverse Reactions (6.2)].

5 WARNINGS AND PRECAUTIONS

5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Increased Mortality

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an

increased risk of death. Aripiprazole is not approved for the treatment of patients with dementia-

related psychosis [see Boxed Warning].

Safety Experience in Elderly Patients with Psychosis Associated with Alzheimer’s Disease

In three, 10-week, placebo-controlled studies of aripiprazole tablets in elderly patients with psychosis

associated with Alzheimer’s disease (n=938; mean age: 82.4 years; range: 56 to 99 years), the adverse

reactions that were reported at an incidence of ≥3% and aripiprazole tablets incidence at least twice that

for placebo were lethargy [placebo 2%, aripiprazole tablets 5%], somnolence (including sedation)

[placebo 3%, aripiprazole tablets 8%], and incontinence (primarily, urinary incontinence) [placebo 1%,

aripiprazole tablets 5%], excessive salivation [placebo 0%, aripiprazole tablets 4%], and

lightheadedness [placebo 1%, aripiprazole tablets 4%].

The safety and efficacy of aripiprazole in the treatment of patients with psychosis associated with

dementia have not been established. If the prescriber elects to treat such patients with aripiprazole,

assess for the emergence of difficulty swallowing or excessive somnolence, which could predispose

to accidental injury or aspiration [see Boxed Warning].

5.2 Cerebrovascular Adverse Events, Including Stroke

In placebo-controlled clinical studies (two flexible dose and one fixed dose study) of dementia-related

psychosis, there was an increased incidence of cerebrovascular adverse events (e.g., stroke, transient

ischemic attack), including fatalities, in aripiprazole-treated patients (mean age: 84 years; range: 78 to

88 years). In the fixed-dose study, there was a statistically significant dose response relationship for

cerebrovascular adverse events in patients treated with aripiprazole. Aripiprazole is not approved for

the treatment of patients with dementia-related psychosis [see Boxed Warning].

5.3 Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of

their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes

in behavior, whether or not they are taking antidepressant medications, and this risk may persist until

significant remission occurs. Suicide is a known risk of depression and certain other psychiatric

disorders, and these disorders themselves are the strongest predictors of suicide. There has been a

long-standing concern, however, that antidepressants may have a role in inducing worsening of

depression and the emergence of suicidality in certain patients during the early phases of treatment.

Pooled analyses of short-term, placebo-controlled trials of antidepressant drugs (SSRIs and others)

showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children,

adolescents, and young adults (ages 18 to 24) with MDD and other psychiatric disorders. Short-term

studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in

adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65

and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, Obsessive

Compulsive Disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9

antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults

with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2

months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of

suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs

studied. There were differences in absolute risk of suicidality across the different indications, with the

highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable

within age strata and across indications. These risk differences (drug-placebo difference in the number

of cases of suicidality per 1000 patients treated) are provided in Table 5.

Table 5:

Age Range

Drug-Placebo Difference in Number of Cases of Suicidality

per 1000 Patients Treated

Increases Compared to Placebo

<18

14 additional cases

18 to 24

5 additional cases

Decreases Compared to Placebo

25 to 64

1 fewer case

≥65

6 fewer cases

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the

number was not sufficient to reach any conclusion about drug effect on suicide.

It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months.

However, there is substantial evidence from placebo-controlled maintenance trials in adults with

depression that the use of antidepressants can delay the recurrence of depression.

All patients being treated with antidepressants for any indication should be monitored

appropriately and observed closely for clinical worsening, suicidality, and unusual changes in

behavior, especially during the initial few months of a course of drug therapy, or at times of dose

changes, either increases or decreases.

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility,

aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been

reported in adult and pediatric patients being treated with antidepressants for MDD as well as for other

indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such

symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not

been established, there is concern that such symptoms may represent precursors to emerging suicidality.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing

the medication, in patients whose depression is persistently worse, or who are experiencing emergent

suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if

these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.

Families and caregivers of patients being treated with antidepressants for major depressive

disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the

need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior,

and the other symptoms described above, as well as the emergence of suicidality, and to report

such symptoms immediately to healthcare providers. Such monitoring should include daily

observation by families and caregivers. Prescriptions for aripiprazole should be written for the

smallest quantity of tablets consistent with good patient management, in order to reduce the risk

of overdose.

It should be noted that aripiprazole is not approved for use in treating depression in the pediatric

population.

5.4 Neuroleptic Malignant Syndrome (NMS)

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS)

may occur with administration of antipsychotic drugs, including aripiprazole. 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.

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.

5.5 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.

Tardive dyskinesia 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 that symptomatic

suppression has upon the long-term course of the syndrome is unknown.

Given these considerations, aripiprazole 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

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 tarvdive dyskinesia appear in a patient on aripiprazole, drug discontinuation

should be considered. However, some patients may require treatment with aripiprazole despite the

presence of the syndrome.

5.6 Metabolic Changes

Atypical antipsychotic drugs have been associated with metabolic changes that include

hyperglycemia/diabetes mellitus, dyslipidemia, and body 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 ketoacidosis or 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, 6.2)]. 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 events is not

completely understood. However, epidemiological studies suggest an increased risk of hyperglycemia-

related adverse reactions in patients treated with the atypical antipsychotics. Because aripiprazole was

not marketed at the time these studies were performed, it is not known if aripiprazole is associated with

this increased risk. Precise risk estimates for hyperglycemia-related adverse reactions in patients

treated with atypical antipsychotics are not available.

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 suspect drug.

Adults

In an analysis of 13 placebo-controlled monotherapy trials in adults, primarily with schizophrenia or

another indication, the mean change in fasting glucose in aripiprazole-treated patients (+4.4 mg/dL;

median exposure 25 days; N=1057) was not significantly different than in placebo-treated patients (+2.5

mg/dL; median exposure 22 days; N=799). Table 6 shows the proportion of aripiprazole-treated patients

with normal and borderline fasting glucose at baseline (median exposure 25 days) that had treatment-

emergent high fasting glucose measurements compared to placebo-treated patients (median exposure 22

days).

Table 6: Changes in Fasting Glucose From Placebo-Controlled Monotherapy Trials in Adult

Patients

Category Change (at

least once) from

Bas eline

Treatment Arm

n/N

%

Fasting Glucose

Normal to High

(<100 mg/dL to ≥126

mg/dL)

Aripiprazole Tablets

31/822

Placebo

22/605

Borderline to High

(≥100 mg/dL and <126

mg/dL to ≥126 mg/dL)

Aripiprazole Tablets

31/176

17.6

Placebo

13/142

At 24 weeks, the mean change in fasting glucose in aripiprazole-treated patients was not significantly

different than in placebo-treated patients [+2.2 mg/dL (n=42) and +9.6 mg/dL (n=28), respectively].

Pediatric Patients and Adolescents

In an analysis of two placebo-controlled trials in adolescents with schizophrenia (13 to 17 years) and

pediatric patients with another indication (10 to 17 years), the mean change in fasting glucose in

aripiprazole-treated patients (+4.8 mg/dL; with a median exposure of 43 days; N=259) was not

significantly different than in placebo-treated patients (+1.7 mg/dL; with a median exposure of 42 days;

N=123).

Table 8 shows the proportion of patients with changes in fasting glucose levels from the pooled

adolescent schizophrenia and another indication (median exposure of 42 to 43 days).

Table 8: Changes in Fasting Glucose From Placebo-Controlled Trials in Pediatric and

Adolescent Patients

Category Change (at

least once) from

Bas eline

Indication

Treatment Arm

n/N

%

Fasting Glucose

Normal to High

(<100 mg/dL to ≥126

mg/dL)

Pooled Schizophrenia and

another indication

Aripiprazole Tablets

2/236

Placebo

2/110

Fasting Glucose

Borderline to High

(≥100 mg/dL and <126

mg/dL to ≥126 mg/dL)

Pooled Schizophrenia and

another indication

Aripiprazole Tablets

1/22

Placebo

0/12

At 12 weeks in the pooled adolescent schizophrenia and another indication trials, the mean change in

fasting glucose in aripiprazole-treated patients was not significantly different than in placebo-treated

patients [+2.4 mg/dL (n=81) and +0.1 mg/dL (n=15), respectively].

Dyslipidemia

Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.

There were no significant differences between aripiprazole- and placebo-treated patients in the

proportion with changes from normal to clinically significant levels for fasting/nonfasting total

cholesterol, fasting triglycerides, fasting LDLs, and fasting/nonfasting HDLs. Analyses of patients with

at least 12 or 24 weeks of exposure were limited by small numbers of patients.

Adults

Table 9 shows the proportion of adult patients, primarily from pooled schizophrenia and another

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