label

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use

ADDERALL XR safely and effectively. See full prescribing information

for ADDERALL XR.

ADDERALL XR

(mixed salts of a single-entity amphetamine product)

extended release capsules, for oral use, CII

Initial U.S. Approval: 2001

WARNING: ABUSE AND DEPENDENCE

See full prescribing information for complete boxed warning

• CNS stimulants, including ADDERALL XR, other amphetamine-

containing products, and methylphenidate, have a high potential

for abuse and dependence (5.1, 9.3)

•

Assess the risk of abuse prior to prescribing and monitor for signs

of abuse and dependence while on therapy (9.2, 9.3).

-------------------------INDICATIONS AND USAGE------------------------------

ADDERALL XR, a CNS stimulant, is indicated for the treatment of attention

deficit hyperactivity disorder (ADHD). (1)

• Children (ages 6-12): Efficacy was established in one 3-week outpatient,

controlled trial and one analogue classroom, controlled trial in children

with ADHD. (14)

• Adolescents (ages 13-17): Efficacy was established in one 4-week

controlled trial in adolescents with ADHD. (14)

• Adults: Efficacy was established in one 4-week controlled trial in adults

with ADHD. (14)

---------------------------DOSAGE AND ADMINISTRATION-------------------

• Pediatric patients (ages 6-17): 10 mg once daily in the morning.

Maximum dose for children 6-12 years of age is 30 mg once daily. (2.2,

2.3, 2.4)

• Adults: 20 mg once daily in the morning. (2.5)

• Pediatric patients (ages 6-17) with severe renal impairment: 5 mg once

daily in the morning. Maximum dose for children 6- 12 years of age with

severe renal impairment is 20 mg once daily. (2.6, 8.6)

• Adults with severe renal impairment: 15 mg once daily in the morning.

(2.6, 8.6)

• Patients with ESRD: not recommended. (2.6, 8.6)

-----------------------DOSAGE FORMS AND STRENGTHS--------------------

• Extended release capsules: 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg (3)

------------------------------CONTRAINDICATIONS----------------------------

• Advanced arteriosclerosis (4)

• Symptomatic cardiovascular disease (4)

• Moderate to severe hypertension (4)

• Hyperthyroidism (4)

• Known hypersensitivity or idiosyncrasy to amphetamine (4)

• Glaucoma (4)

• Agitated states (4)

• History of drug abuse (4)

• During or within 14 days following the administration of monoamine

oxidase inhibitors (MAOI) (4, 7.1)

--------------------------WARNINGS AND PRECAUTIONS---------------------

• Serious Cardiovascular Reactions: Sudden death has been reported with

usual doses of CNS stimulants in children and adolescents with structural

cardiac abnormalities or other serious heart problems; sudden death,

stroke, and myocardial infarction have been reported in adults taking CNS

stimulants at usual doses. Stimulant drugs should not be used in patients

with known structural cardiac abnormalities, cardiomyopathy, serious

heart rhythm abnormalities, coronary artery disease, or other serious heart

problems. (5.2)

• Increase in Blood Pressure: Monitor blood pressure and pulse at

appropriate intervals. Use with caution in patients for whom blood

pressure increases may be problematic. (5.2)

• Psychiatric Adverse Events: Stimulants may cause treatment-emergent

psychotic or manic symptoms in patients with no prior history, or

exacerbation of symptoms in patients with pre-existing psychosis.

Evaluate for bipolar disorder prior to stimulant use. Monitor for

aggressive behavior. (5.3)

• Long-Term Suppression of Growth: Monitor height and weight at

appropriate intervals. (5.4)

• Seizures: May lower the convulsive threshold. Discontinue in the

presence of seizures. (5.5)

• Peripheral Vasculopathy, including Raynaud’s phenomenon: Stimulants

used to treat ADHD are associated with peripheral vasculopathy,

including Raynaud’s phenomenon. Careful observation for digital

changes is necessary during treatment with ADHD stimulants. (5.6)

• Serotonin Syndrome: Increased risk when co-administered with

serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during

overdosage situations. If it occurs, discontinue ADDERALL XR and

initiate supportive treatment (4, 5.7, 10).

• Visual Disturbance: Difficulties with accommodation and blurring of

vision have been reported with stimulant treatment. (5.8)

• Tics: May exacerbate tics. Evaluate for tics and Tourette’s syndrome

prior to stimulant administration. (5.9)

--------------------------------ADVERSE REACTIONS-----------------------------

• Children (ages 6 to 12): Most common adverse reactions (≥5% and with a

higher incidence than on placebo) were loss of appetite, insomnia,

abdominal pain, emotional lability, vomiting, nervousness, nausea, and

fever. (6.1)

• Adolescents (ages 13 to 17): Most common adverse reactions (≥5% and

with a higher incidence than on placebo) were loss of appetite, insomnia,

abdominal pain, weight loss, and nervousness. (6.1)

• Adults: Most common adverse reactions ≥5% and with a higher incidence

than on placebo were dry mouth, loss of appetite, insomnia, headache,

weight loss, nausea, anxiety, agitation, dizziness, tachycardia, diarrhea,

asthenia, and urinary tract infections. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Takeda

Pharmaceuticals at 1-800-828-2088 or FDA at 1-800-FDA-1088 or

www.fda.gov/medwatch

--------------------------------DRUG INTERACTIONS-----------------------------

• MAOI antidepressants are contraindicated; MAOIs potentiate the effects

of amphetamine. Do not administer ADDERALL XR during or within 14

days after use of MAOI. (4, 7.1)

• Alkalinizing agents (GI antacids and urinary): These agents increase blood

levels of amphetamine. (7.1)

• Acidifying agents (GI and urinary): These agents reduce blood levels of

amphetamine. (7.1)

• Adrenergic blockers, antihistamines, antihypertensives, phenobarbital,

phenytoin, veratrum alkaloids, and ethosuximide: Effects may be reduced

by amphetamines. (7.1)

• Tricyclic antidepressants, norepinephrine, and meperidine: Effects may be

potentiated by amphetamines. (7.1)

--------------------------USE IN SPECIFIC POPULATIONS---------------------

• Pregnancy: May cause fetal harm. (8.1)

• Lactation: Breastfeeding not recommended. (8.2)

See 17 for PATIENT COUNSELING INFORMATION and Medication

Guide.

Revised: 2/2022

Reference ID: 4943991

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: ABUSE AND DEPENDENCE

1 INDICATIONS AND USAGE

1.1 Attention Deficit Hyperactivity Disorder

2 DOSAGE AND ADMINISTRATION

2.1 Important Information Prior to Initiating Treatment

2.2 Dosing Considerations for All Patients

2.3 Children

2.4 Adolescents

2.5 Adults

2.6 Dosage in Patients with Renal Impairment

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Potential for Abuse and Dependence

5.2 Serious Cardiovascular Reactions

5.3 Psychiatric Adverse Events

5.4 Long-Term Suppression of Growth

5.5 Seizures

5.6 Peripheral Vasculopathy, including Raynaud’s

Phenomenon

5.7 Serotonin Syndrome

5.8 Visual Disturbance

5.9 Tics

5.10 Prescribing and Dispensing

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Adverse Reactions Associated with the Use of

Amphetamine, ADDERALL XR, or ADDERALL

7 DRUG INTERACTIONS

7.1 Clinically Important Interactions with Amphetamines

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

9.2 Abuse

9.3 Dependence

10 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

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

*Sections or subsections omitted from the full prescribing

information are not listed

Reference ID: 4943991

FULL PRESCRIBING INFORMATION

WARNING: ABUSE AND DEPENDENCE

CNS stimulants, including ADDERALL XR, other amphetamine-containing products, and

methylphenidate, have a high potential for abuse and dependence. Assess the risk of abuse prior to

prescribing and monitor for signs of abuse and dependence while on therapy [see Warnings and

Precautions (5.1) and Drug Abuse and Dependence (9.2, 9.3)].

1 INDICATIONS AND USAGE

1.1 Attention Deficit Hyperactivity Disorder

ADDERALL XR

is indicated for the treatment of attention deficit hyperactivity disorder (ADHD).

The efficacy of ADDERALL XR in the treatment of ADHD was established on the basis of two

controlled trials in children aged 6 to 12, one controlled trial in adolescents aged 13 to 17, and one

controlled trial in adults who met DSM-IV

criteria for ADHD [see Clinical Studies (14)].

A diagnosis of ADHD (DSM-IV



) implies the presence of hyperactive-impulsive or inattentive

symptoms that caused impairment and were present before age 7 years. The symptoms must cause

clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in

two or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for

by another mental disorder. For the Inattentive Type, at least six of the following symptoms must have

persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention;

poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained

mental effort; loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least six of

the following symptoms must have persisted for at least 6 months: fidgeting/squirming; leaving seat;

inappropriate running/climbing; difficulty with quiet activities; "on the go;" excessive talking; blurting

answers; can't wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-

impulsive criteria to be met.

Special Diagnostic Considerations

Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis

requires the use not only of medical but of special psychological, educational, and social resources.

Learning may or may not be impaired. The diagnosis must be based upon a complete history and

evaluation of the patient and not solely on the presence of the required number of DSM-IV



characteristics.

Need for Comprehensive Treatment Program

ADDERALL XR is indicated as an integral part of a total treatment program for ADHD that may include

other measures (psychological, educational, social) for patients with this syndrome. Drug treatment may

not be indicated for all patients with this syndrome. Stimulants are not intended for use in the patient who

exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders,

including psychosis. Appropriate educational placement is essential and psychosocial intervention is often

helpful. When remedial measures alone are insufficient, the decision to prescribe stimulant medication

will depend upon the physician's assessment of the chronicity and severity of the child's symptoms.

Long-Term Use

The effectiveness of ADDERALL XR for long-term use, i.e., for more than 3 weeks in children and 4 weeks

in adolescents and adults, has not been systematically evaluated in controlled trials. Therefore, the physician

who elects to use ADDERALL XR for extended periods should periodically re-evaluate the long-term

usefulness of the drug for the individual patient.

2 DOSAGE AND ADMINISTRATION

Reference ID: 4943991

2.1 Important Information Prior to Initiating Treatment

Prior to initiating treatment with ADDERALL XR, assess for the presence of cardiac disease (e.g.,

perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam)

[see Warnings and Precautions (5.2)].

Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on

therapy. Maintain careful prescription records, educate patients about abuse, monitor for signs for abuse

and overdose, and periodically re-evaluate the need for ADDERALL XR use [see Warnings and

Precautions (5.1), Drug Abuse and Dependence (9)].

2.2 Dosing Considerations for All Patients

Individualize the dosage according to the therapeutic needs and response of the patient. Administer

ADDERALL XR at the lowest effective dosage.

Based on bioequivalence data, patients taking divided doses of immediate-release ADDERALL, (for

example, twice daily), may be switched to ADDERALL XR at the same total daily dose taken once daily.

Titrate at weekly intervals to appropriate efficacy and tolerability as indicated.

ADDERALL XR extended release capsules may be taken whole, or the capsule may be opened and the

entire contents sprinkled on applesauce. If the patient is using the sprinkle administration method, the

sprinkled applesauce should be consumed immediately; it should not be stored. Patients should take the

applesauce with sprinkled beads in its entirety without chewing. The dose of a single capsule should not

be divided. The contents of the entire capsule should be taken, and patients should not take anything less

than one capsule per day.

ADDERALL XR may be taken with or without food.

ADDERALL XR should be given upon awakening. Afternoon doses should be avoided because of the

potential for insomnia.

Where possible, ADDERALL XR therapy should be interrupted occasionally to determine if there is a

recurrence of behavioral symptoms sufficient to require continued therapy.

2.3 Children

In children with ADHD who are 6-12 years of age and are either starting treatment for the first time or

switching from another medication, start with 10 mg once daily in the morning; daily dosage may be

adjusted in increments of 5 mg or 10 mg at weekly intervals. When in the judgment of the clinician a

lower initial dose is appropriate, patients may begin treatment with 5 mg once daily in the morning. The

maximum recommended dose for children 6-12 years of age is 30 mg/day; doses greater than 30 mg/day

have not been studied in children. ADDERALL XR has not been studied in children under 6 years of age.

2.4 Adolescents

The recommended starting dose for adolescents with ADHD who are 13-17 years of age and are either

starting treatment for the first time or switching from another medication is 10 mg/day. The dose may be

increased to 20 mg/day after one week if ADHD symptoms are not adequately controlled.

2.5 Adults

In adults with ADHD who are either starting treatment for the first time or switching from another

medication, the recommended dose is 20 mg/day.

Reference ID: 4943991

2.6 Dosage in Patients with Renal Impairment

In adult patients with severe renal impairment (GFR 15 to < 30 mL/min/1.73m

), the recommended dose

is 15 mg once daily in the morning. In pediatric patients (6 to 17 years of age) with severe renal

impairment, the recommended dose is 5 mg once daily. The maximum dose for children 6 to 12 years of

age with severe renal impairment is 20 mg once daily. ADDERALL XR is not recommended in patients

with end stage renal disease (ESRD) (GFR < 15 mL/min/1.73m

) [see Use in Specific Populations (8.6),

Clinical Pharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHS

ADDERALL XR 5 mg extended release capsules: Clear/blue (imprinted ADDERALL XR 5 mg)

ADDERALL XR 10 mg extended release capsules: Blue/blue (imprinted ADDERALL XR 10 mg)

ADDERALL XR 15 mg extended release capsules: Blue/white (imprinted ADDERALL XR 15 mg)

ADDERALL XR 20 mg extended release capsules: Orange/orange (imprinted ADDERALL XR 20 mg)

ADDERALL XR 25 mg extended release capsules: Orange/white (imprinted ADDERALL XR 25 mg)

ADDERALL XR 30 mg extended release capsules: Natural/orange (imprinted ADDERALL XR 30 mg)

4 CONTRAINDICATIONS

ADDERALL XR administration is contraindicated in patients with the following conditions:

• Advanced arteriosclerosis

• Symptomatic cardiovascular disease

• Moderate to severe hypertension

• Hyperthyroidism

• In patients known to be hypersensitive to amphetamine, or other components of ADDERALL

XR. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been

reported in patients treated with other amphetamine products [see Adverse Reactions (6.2)]

• Glaucoma

• Agitated states

• History of drug abuse

• Patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs

(including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk

of hypertensive crisis [see Warnings and Precautions (5.7) and Drug Interactions (7.1)]

5 WARNINGS AND PRECAUTIONS

5.1 Potential for Abuse and Dependence

CNS stimulants, including ADDERALL XR, other amphetamine-containing products, and

methylphenidate, have a high potential for abuse and dependence. Assess the risk of abuse prior to

prescribing, and monitor for signs of abuse and dependence while on therapy [see Boxed Warning, Drug

Abuse and Dependence (9.2, 9.3)].

5.2 Serious Cardiovascular Reactions

Sudden Death and Pre-existing Structural Cardiac Abnormalities or Other Serious Heart Problems

Reference ID: 4943991

Children and Adolescents

Sudden death has been reported in association with CNS stimulant treatment at usual doses in children

and adolescents with structural cardiac abnormalities or other serious heart problems. Although some

serious heart problems alone carry an increased risk of sudden death, stimulant products generally should

not be used in children or adolescents with known serious structural cardiac abnormalities,

cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place

them at increased vulnerability to the sympathomimetic effects of a stimulant drug [see Contraindications

(4)].

Adults

Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at

usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have

a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy,

serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults

with such abnormalities should also generally not be treated with stimulant drugs [see Contraindications

(4)].

Hypertension and Other Cardiovascular Conditions

Stimulant medications cause a modest increase in average blood pressure (about 2-4 mmHg) and average

heart rate (about 3-6 bpm), and individuals may have larger increases. While the mean changes alone

would not be expected to have short-term consequences, all patients should be monitored for larger

changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying

medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with

pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia [see

Contraindications (4) and Adverse Reactions (6)].

Assessing Cardiovascular Status in Patients being Treated with Stimulant Medications

Children, adolescents, or adults who are being considered for treatment with stimulant medications should

have a careful history (including assessment for a family history of sudden death or ventricular

arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further

cardiac evaluation if findings suggest such disease (e.g. electrocardiogram and echocardiogram). Patients

who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms

suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.

5.3 Psychiatric Adverse Events

Pre-Existing Psychosis

Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in

patients with pre-existing psychotic disorder.

Bipolar Illness

Particular care should be taken in using stimulants to treat ADHD patients with comorbid bipolar disorder

because of concern for possible induction of mixed/manic episode in such patients. Prior to initiating

treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to

determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric

history, including a family history of suicide, bipolar disorder, and depression.

Emergence of New Psychotic or Manic Symptoms

Treatment-emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in

children and adolescents without prior history of psychotic illness or mania can be caused by stimulants at

usual doses. If such symptoms occur, consideration should be given to a possible causal role of the

stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-

term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of

3482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated

patients compared to 0 in placebo-treated patients.

Reference ID: 4943991

Aggression

Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been

reported in clinical trials and the postmarketing experience of some medications indicated for the

treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior

or hostility, patients beginning treatment for ADHD should be monitored for the appearance of or

worsening of aggressive behavior or hostility.

5.4 Long-Term Suppression of Growth

Monitor growth in children during treatment with stimulants. Patients who are not growing or gaining

weight as expected may need to have their treatment interrupted.

Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either

methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups

of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10

to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout

the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height

and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of

development.

In a controlled trial of ADDERALL XR in adolescents, mean weight change from baseline within the

initial 4 weeks of therapy was −1.1 lbs. and −2.8 lbs., respectively, for patients receiving 10 mg and 20

mg ADDERALL XR. Higher doses were associated with greater weight loss within the initial 4 weeks of

treatment. Chronic use of amphetamines can be expected to cause a similar suppression of growth.

5.5 Seizures

There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior

history of seizures, in patients with prior EEG abnormalities in the absence of seizures, and very rarely, in

patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures,

ADDERALL XR should be discontinued.

5.6 Peripheral Vasculopathy, including Raynaud’s Phenomenon

Stimulants, including ADDERALL XR, used to treat ADHD are associated with peripheral vasculopathy,

including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very

rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy,

including Raynaud’s phenomenon, were observed in post-marketing reports at different times and at

therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally

improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is

necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology

referral) may be appropriate for certain patients.

5.7 Serotonin Syndrome

Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in

combination with other drugs that affect the serotonergic neurotransmitter systems such as MAOIs,

selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs),

triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort

[see Drug Interactions (7.1)]. Amphetamines and amphetamine derivatives are known to be metabolized,

to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor inhibition of CYP2D6

metabolism [see Clinical Pharmacology (12.3)]. The potential for a pharmacokinetic interaction exists

with the co-administration of CYP2D6 inhibitors which may increase the risk with increased exposure to

ADDERALL XR. In these situations, consider an alternative non-serotonergic drug or an alternative drug

that does not inhibit CYP2D6 [see Drug Interactions (7.1)]. Serotonin syndrome symptoms may include

mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g.,

Reference ID: 4943991

tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular

symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or

gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Concomitant use of ADDERALL XR with MAOI drugs is contraindicated [see Contraindications (4)].

Discontinue treatment with ADDERALL XR and any concomitant serotonergic agents immediately if

symptoms of serotonin syndrome occur, and initiate supportive symptomatic treatment. Concomitant use

of ADDERALL XR with other serotonergic drugs or CYP2D6 inhibitors should be used only if the

potential benefit justifies the potential risk. If clinically warranted, consider initiating ADDERALL XR

with lower doses, monitoring patients for the emergence of serotonin syndrome during drug initiation or

titration, and informing patients of the increased risk for serotonin syndrome.

5.8 Visual Disturbance

Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

5.9 Tics

Amphetamines have been reported to exacerbate motor and phonic tics and Tourette’s syndrome.

Therefore, clinical evaluation for tics and Tourette’s syndrome in patients and their families should

precede use of stimulant medications.

5.10 Prescribing and Dispensing

The least amount of amphetamine feasible should be prescribed or dispensed at one time in order to

minimize the possibility of overdosage. ADDERALL XR should be used with caution in patients who use

other sympathomimetic drugs.

6 ADVERSE REACTIONS

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.

6.1 Clinical Trials Experience

The premarketing development program for ADDERALL XR included exposures in a total of 1315

participants in clinical trials (635 pediatric patients, 350 adolescent patients, 248 adult patients, and 82

healthy adult subjects). Of these, 635 patients (ages 6 to 12) were evaluated in two controlled clinical

studies, one open-label clinical study, and two single-dose clinical pharmacology studies (N= 40). Safety

data on all patients are included in the discussion that follows. Adverse reactions were assessed by

collecting adverse reactions, results of physical examinations, vital signs, weights, laboratory analyses,

and ECGs.

Adverse reactions during exposure were obtained primarily by general inquiry and recorded by clinical

investigators using terminology of their own choosing. Consequently, it is not possible to provide a

meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping

similar types of reactions into a smaller number of standardized event categories. In the tables and listings

that follow, COSTART terminology has been used to classify reported adverse reactions.

The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at

least once, a treatment-emergent adverse event of the type listed.

Adverse Reactions Leading to Discontinuation of Treatment

Reference ID: 4943991

In two placebo-controlled studies of up to 5 weeks duration among children with ADHD, 2.4% (10/425)

of ADDERALL XR-treated patients discontinued due to adverse reactions (including 3 patients with loss

of appetite, one of whom also reported insomnia) compared to 2.7% (7/259) receiving placebo.

The most frequent adverse reactions leading to discontinuation of ADDERALL XR in controlled and

uncontrolled, multiple-dose clinical trials of children (N=595) were anorexia (loss of appetite) (2.9%),

insomnia (1.5%), weight loss (1.2%), emotional lability (1%), and depression (0.7%). Over half of these

patients were exposed to ADDERALL XR for 12 months or more.

In a separate placebo-controlled 4-week study in adolescents with ADHD, five patients (2.1%)

discontinued treatment due to adverse events among ADDERALL XR-treated patients (N=233) compared

to none

who received placebo (N=54). The most frequent adverse event leading to discontinuation and

considered to be drug-related (i.e. leading to discontinuation in at least 1% of ADDERALL XR-treated

patients and at a rate at least twice that of placebo) was insomnia (1.3%, n=3).

In one placebo-controlled 4-week study among adults with ADHD with doses 20 mg to 60 mg, 23

patients (12.0%) discontinued treatment due to adverse events among ADDERALL XR-treated patients

(N=191) compared to one patient (1.6%) who received placebo (N=64). The most frequent adverse

events leading to discontinuation and considered to be drug-related (i.e. leading to discontinuation in at

least 1% of ADDERALL XR-treated patients and at a rate at least twice that of placebo) were insomnia

(5.2%, n=10), anxiety (2.1%, n=4), nervousness (1.6%, n=3), dry mouth (1.6%, n=3), anorexia (1.6%,

n=3), tachycardia (1.6%, n=3), headache (1.6%, n=3), and asthenia (1.0%, n=2).

Adverse Reactions Occurring in Controlled Trials

Adverse reactions reported in a 3-week clinical trial of children and a 4-week clinical trial in adolescents

and adults, respectively, treated with ADDERALL XR or placebo are presented in the tables below.

Table 1 Adverse Reactions Reported by 2% or More of Children (6-12 Years Old) Receiving

ADDERALL XR with Higher Incidence Than on Placebo in a 584-Patient Clinical

Study

Body System

Preferred Term

ADDERALL

(n=374)

Placebo

(n=210)

General

Abdominal Pain

(stomachache)

Fever

Infection

Accidental Injury

Asthenia (fatigue)

14%

10%

Digestive System

Loss of Appetite

Vomiting

Nausea

Dyspepsia

22%

Nervous System

Insomnia

Emotional Lability

Nervousness

Dizziness

17%

Metabolic/Nutritional

Weight Loss

Table 2 Adverse Reactions Reported by 5% or More of Adolescents (13-17 Years Old) Weighing

≤ 75 kg/165 lbs Receiving ADDERALL XR with Higher Incidence Than Placebo in a

287 Patient Clinical Forced Weekly-Dose Titration Study*

Body System

Preferred Term

ADDERA

Placebo

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LL XR

(n=233)

(n=54)

General

Abdominal Pain

(stomachache)

11%

Digestive System

Loss of Appetite

36%

Nervous System

Insomnia

Nervousness

12%

Metabolic/Nutritional

Weight Loss

*Included doses up to 40 mg

Appears the same due to rounding

Dose-related adverse reactions

Note: The following reactions did not meet the criterion for inclusion in Table 2 but were reported by 2% to 4% of adolescent patients receiving

ADDERALL XR with a higher incidence than patients receiving placebo in this study: accidental injury, asthenia (fatigue), dry mouth,

dyspepsia, emotional lability, nausea, somnolence, and vomiting.

Table 3 Adverse Reactions Reported by 5% or More of Adults Receiving ADDERALL XR with

Higher Incidence Than on Placebo in a 255 Patient Clinical Forced Weekly-Dose

Titration Study*

Body System

Preferred Term

ADDERALL

(n=191)

Placebo

(n=64)

General

Headache

Asthenia

26%

13%

Digestive System

Dry Mouth

Loss of Appetite

Nausea

Diarrhea

35%

33%

Nervous System

Insomnia

Agitation

Anxiety

Dizziness

Nervousness

27%

13%

Cardiovascular System

Tachycardia

Metabolic/Nutritional

Weight Loss

10%

Urogenital System

Urinary Tract Infection

*Included doses up to 60 mg.

Appears the same due to rounding

Note: The following reactions did not meet the criterion for inclusion in Table 3 but were reported by 2% to 4% of adult patients receiving

ADDERALL XR with a higher incidence than patients receiving placebo in this study: infection, photosensitivity reaction, constipation, tooth

disorder (e.g., teeth clenching, tooth infection), emotional lability, libido decreased, somnolence, speech disorder (e.g., stuttering, excessive

speech), palpitation, twitching, dyspnea, sweating, dysmenorrhea, and impotence.

Hypertension [see Warnings and Precautions (5.2)]

In a controlled 4-week outpatient clinical study of adolescents with ADHD, isolated systolic blood

pressure elevations ≥15 mmHg were observed in 7/64 (11%) placebo-treated patients and 7/100 (7%)

patients receiving ADDERALL XR 10 or 20 mg. Isolated elevations in diastolic blood pressure ≥ 8

mmHg were observed in 16/64 (25%) placebo-treated patients and 22/100 (22%) ADDERALL XR-

treated patients. Similar results were observed at higher doses.

In a single-dose pharmacokinetic study in 23 adolescents with ADHD, isolated increases in systolic blood

pressure (above the upper 95% CI for age, gender, and stature) were observed in 2/17 (12%) and 8/23

(35%), subjects administered 10 mg and 20 mg ADDERALL XR, respectively. Higher single doses were

associated with a greater increase in systolic blood pressure. All increases were transient, appeared

maximal at 2 to 4 hours post dose and not associated with symptoms.

6.2 Adverse Reactions Associated with the Use of Amphetamine, ADDERALL XR, or ADDERALL

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The following adverse reactions have been identified during post-approval use of amphetamine,

ADDERALL XR, or ADDERALL. 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.

Cardiovascular

Palpitations. There have been isolated reports of cardiomyopathy associated with chronic amphetamine

use.

Central Nervous System

Psychotic episodes at recommended doses, overstimulation, restlessness, irritability, euphoria, dyskinesia,

dysphoria, depression, tremor, tics, aggression, anger, logorrhea, dermatillomania, paresthesia (including

formication), and bruxism.

Eye Disorders

Vision blurred, mydriasis.

Gastrointestinal

Unpleasant taste, constipation, intestinal ischemia, and other gastrointestinal disturbances.

Allergic

Urticaria, rash, hypersensitivity reactions including angioedema and anaphylaxis. Serious skin rashes,

including Stevens-Johnson Syndrome and toxic epidermal necrolysis have been reported.

Endocrine

Impotence, changes in libido, frequent or prolonged erections.

Skin

Alopecia.

Vascular Disorders

Raynaud’s phenomenon.

Musculoskeletal and Connective Tissue Disorders

Rhabdomyolysis

7 DRUG INTERACTIONS

7.1 Clinically Important Interactions with Amphetamines

Table 4: Drugs Having Clinically Important Interactions with Amphetamines

Monoamine Oxidase Inhibitors (MAOIs)

Clinical

Impact

Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis.

Potential outcomes include death, stroke, myocardial infarction, aortic dissection,

ophthalmological complications, eclampsia, pulmonary edema, and renal failure.

Intervention

Do not administer ADDERALL XR concomitantly or within 14 days after

discontinuing MAOI [see Contraindications (4)].

Examples

selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue

Serotonergic Drugs

Clinical

Impact

The concomitant use of ADDERALL XR and serotonergic drugs increases the risk

of serotonin syndrome.

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Intervention

Initiate with lower doses and monitor patients for signs and symptoms of serotonin

syndrome, particularly during ADDERALL XR initiation or dosage increase. If

serotonin syndrome occurs, discontinue ADDERALL XR and the concomitant

serotonergic drug(s) [see Warnings and Precautions (5.7)].

Examples

selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake

inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol,

tryptophan, buspirone, St. John’s Wort

CYP2D6 Inhibitors

Clinical

Impact

The concomitant use of ADDERALL XR and CYP2D6 inhibitors may increase the

exposure of ADDERALL XR compared to the use of the drug alone and increase

the risk of serotonin syndrome.

Intervention

Initiate with lower doses and monitor patients for signs and symptoms of serotonin

syndrome particularly during ADDERALL XR initiation and after a dosage

increase. If serotonin syndrome occurs, discontinue ADDERALL XR and the

CYP2D6 inhibitor [see Warnings and Precautions (5.7) and Overdosage (10)].

Examples

paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir

Alkalinizing Agents

Clinical

Impact

Increase blood levels and potentiate the action of amphetamine.

Intervention

Co-administration of ADDERALL XR and gastrointestinal or urinary alkalinizing

agents should be avoided.

Examples

Gastrointestinal alkalinizing agents (e.g., sodium bicarbonate). Urinary alkalinizing

agents (e.g. acetazolamide, some thiazides).

Acidifying Agents

Clinical

Impact

Lower blood levels and efficacy of amphetamines.

Intervention

Increase dose based on clinical response.

Examples

Gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid HCl,

ascorbic acid).

Urinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate,

methenamine salts).

Tricyclic Antidepressants

Clinical

Impact

May enhance the activity of tricyclic or sympathomimetic agents causing striking

and sustained increases in the concentration of d-amphetamine in the brain;

cardiovascular effects can be potentiated.

Intervention

Monitor frequently and adjust or use alternative therapy based on clinical response.

Examples

desipramine, protriptyline

Proton Pump Inhibitors

Clinical

Impact

Time to maximum concentration (T

max

) of amphetamine is decreased compared to

when administered alone.

Intervention

Monitor patients for changes in clinical effect and adjust therapy based on clinical

response.

Examples

Omeprazole

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

ADDERALL XR during pregnancy. Healthcare providers are encouraged to register patients by calling

the National Pregnancy Registry for Psychostimulants at 1-866-961-2388 or visiting online at

https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/othermedications/.

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Risk Summary

Available data from published epidemiologic studies and postmarketing reports on use of prescription

amphetamine in pregnant women have not identified a drug-associated risk of major birth defects and

miscarriage (see Data). Adverse pregnancy outcomes, including premature delivery and low birth weight,

have been seen in infants born to mothers taking amphetamines during pregnancy (see Clinical

Considerations).

No apparent effects on morphological development were observed in embryo-fetal development studies,

with oral administration of amphetamine to rats and rabbits during organogenesis at doses 2 and 12 times,

respectively, the maximum recommended human dose (MRHD) of 20 mg/day given to adolescents, on a

mg/m

basis. However, in a pre- and post-natal development study, amphetamine (d- to l- ratio of 3:1)

administered orally to pregnant rats during gestation and lactation caused a decrease in pup survival and a

decrease in pup body weight that correlated with a delay in developmental landmarks at clinically

relevant doses of amphetamine. In addition, adverse effects on reproductive performance were observed

in pups whose mothers were treated with amphetamine. Long-term neurochemical and behavioral effects

have also been reported in animal developmental studies using clinically relevant doses of amphetamine

(see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is

unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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

Amphetamines, such as ADDERALL XR, cause vasoconstriction and thereby may decrease placental

perfusion. In addition, amphetamines can stimulate uterine contractions, increasing the risk of premature

delivery. Infants born to mothers taking amphetamines during pregnancy have an increased risk of

premature delivery and low birth weight.

Monitor infants born to mothers taking amphetamines for symptoms of withdrawal such as feeding

difficulties, irritability, agitation, and excessive drowsiness.

Data

Animal Data

Amphetamine (d- to l- enantiomer ratio of 3:1) had no apparent effects on embryofetal morphological

development or survival when administered orally to pregnant rats and rabbits throughout the period of

organogenesis at doses of up to 6 and 16 mg/kg/day, respectively. These doses are approximately 2 and

12 times, respectively, the maximum recommended human dose (MRHD) of 20 mg/day given to

adolescents, on a mg/m

basis. Fetal malformations and death have been reported in mice following

parenteral administration of d-amphetamine doses of 50 mg/kg/day (approximately 10 times the MRHD

given to adolescents on a mg/m

basis) or greater to pregnant animals. Administration of these doses was

also associated with severe maternal toxicity.

A study was conducted in which pregnant rats received daily oral doses of amphetamine (d- to l-

enantiomer ratio of 3:1) of 2, 6, and 10 mg/kg from gestation day 6 to lactation day 20. These doses are

approximately 0.8, 2, and 4 times the MRHD of 20 mg/day given to adolescents, on a mg/m

basis. All

doses caused hyperactivity and decreased weight gain in the dams. A decrease in pup survival was seen at

all doses. A decrease in pup body weight was seen at 6 and 10 mg/kg which correlated with delays in

developmental landmarks, such as preputial separation and vaginal opening. Increased pup locomotor

activity was seen at 10 mg/kg on day 22 postpartum but not at 5 weeks postweaning. When pups were

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tested for reproductive performance at maturation, gestational weight gain, number of implantations, and

number of delivered pups were decreased in the group whose mothers had been given 10 mg/kg.

A number of studies from the literature in rodents indicate that prenatal or early postnatal exposure

amphetamine (d- or d, l-) at doses similar to those used clinically can result in long-term neurochemical

and behavioral alterations. Reported behavioral effects include learning and memory deficits, altered

locomotor activity, and changes in sexual function.

8.2 Lactation

Risk Summary

Based on limited case reports in published literature, amphetamine (d- or d, l-) is present in human milk,

at relative infant doses of 2% to 13.8% of the maternal weight-adjusted dosage and a milk/plasma ratio

ranging between 1.9 and 7.5. There are no reports of adverse effects on the breastfed infant. Long-term

neurodevelopmental effects on infants from amphetamine exposure are unknown. It is possible that large

dosages of amphetamine might interfere with milk production, especially in women whose lactation is not

well established. Because of the potential for serious adverse reactions in nursing infants, advise patients

that breastfeeding is not recommended during treatment with ADDERALL XR.

8.4 Pediatric Use

ADDERALL XR is indicated for use in children 6 years of age and older.

The safety and efficacy of ADDERALL XR in children under 6 years of age have not been studied. Long-

term effects of amphetamines in children have not been well established.

Long-Term Growth Suppression

Growth should be monitored during treatment with stimulants, including ADDERALL XR, and pediatric

patients aged 6 to 17 years who are not growing or gaining weight as expected may need to have their

treatment interrupted [see Warnings and Precautions (5.4)].

Juvenile Animal Toxicity Data

Juvenile rats treated with mixed amphetamine salts early in the postnatal period through sexual

maturation demonstrated transient changes in motor activity. Learning and memory was impaired at

approximately 6 times the maximum recommended human dose (MRHD) given to children on a mg/m

basis. No recovery was seen following a drug free period. A delay in sexual maturation was observed at a

dose approximately 6 times the MRHD given to children on a mg/m

basis, although there was no effect

on fertility.

In a juvenile developmental study, rats received daily oral doses of amphetamine (d to l enantiomer ratio

of 3:1) of 2, 6, or 20 mg/kg on days 7-13 of age; from day 14 to approximately day 60 of age these doses

were given b.i.d. for total daily doses of 4, 12, or 40 mg/kg. The latter doses are approximately 0.6, 2, and

6 times the MRHD of 30 mg/day, given to children on a mg/m

basis. Post dosing hyperactivity was seen

at all doses; motor activity measured prior to the daily dose was decreased during the dosing period but

the decreased motor activity was largely absent after an 18 day drug-free recovery period. Performance in

the Morris water maze test for learning and memory was impaired at the 40 mg/kg dose, and sporadically

at the lower doses, when measured prior to the daily dose during the treatment period; no recovery was

seen after a 19 day drug-free period. A delay in the developmental milestones of vaginal opening and

preputial separation was seen at 40 mg/kg but there was no effect on fertility.

8.5 Geriatric Use

ADDERALL XR has not been studied in the geriatric population.

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8.6 Renal Impairment

Due to reduced clearance of amphetamines in patients with severe renal impairment (GFR 15 to <30

mL/min/1.73m

), the recommended dose should be reduced. ADDERALL XR is not recommended in

patients with ESRD (GFR < 15 ml/min/1.73m

) [see Dosage and Administration (2.6), Clinical

Pharmacology (12.3)].

d-Amphetamine is not dialyzable.

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

ADDERALL XR contains amphetamine, a Schedule II controlled substance.

9.2 Abuse

ADDERALL XR is a CNS stimulant that contains amphetamine, which has a high potential for abuse.

Abuse is characterized by impaired control of drug use, compulsive use despite harm, and craving.

Signs and symptoms of amphetamine abuse may include increased heart rate, respiratory rate, blood

pressure, and/or sweating, dilated pupils, hyperactivity, restlessness, insomnia, decreased appetite, loss of

coordination, tremors, flushed skin, vomiting, and/or abdominal pain. Anxiety, psychosis, hostility,

aggression, suicidal or homicidal ideation have also been observed. Abusers of amphetamines may use

other unapproved routes of administration which can result in overdose and death [see Overdosage (10)].

To reduce the abuse of CNS stimulants, including ADDERALL XR, assess the risk of abuse prior to

prescribing. After prescribing, keep careful prescription records, educate patients and their families about

abuse and proper storage and disposal of CNS stimulants. Monitor for signs of abuse while on therapy and

re-evaluate the need for ADDERALL XR use.

9.3 Dependence

Tolerance (a state of adaptation in which exposure to a specific dose of a drug results in a reduction of the

drug’s desired and/or undesired effects over time, in such a way that a higher dose of the drug is required

to produce the same effect that was once obtained at a lower dose) may occur during chronic therapy of

CNS stimulants including ADDERALL XR.

Physical Dependence (which is manifested by a withdrawal syndrome produced by abrupt cessation, rapid

dose reduction, or administration of an antagonist) may occur in patients treated with CNS stimulants

including ADDERALL XR. Withdrawal symptoms after abrupt cessation of CNS stimulants include

dysphoric mood; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and

psychomotor retardation or agitation.

10 OVERDOSAGE

Manifestations of amphetamine overdose include restlessness, tremor, hyperreflexia, rapid respiration,

confusion, assaultiveness, hallucinations, panic states, hyperpyrexia and rhabdomyolysis. Fatigue and

depression usually follow the central nervous system stimulation. Serotonin syndrome has been reported

with amphetamine use, including ADDERALL XR. Cardiovascular effects include arrhythmias,

hypertension or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea,

vomiting, diarrhea and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma.

Treatment

Consult with a Certified Poison Control Center for up to date guidance and advice.

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The prolonged release of mixed amphetamine salts from ADDERALL XR should be considered when

treating patients with overdose.

d-Amphetamine is not dialyzable.

11 DESCRIPTION

ADDERALL XR extended-release capsules contain mixed salts of a single-entity amphetamine, a CNS

stimulant. ADDERALL XR contains equal amounts (by weight) of four salts: dextroamphetamine sulfate,

amphetamine sulfate, dextroamphetamine saccharate and amphetamine (D,L)-aspartate monohydrate.

This results in a 3.1:1 mixture of dextro- to levo- amphetamine base equivalent.

The 5 mg, 10 mg, 15 mg, 20 mg, 25 mg and 30 mg strength extended release capsules are for oral

administration. Adderall XR contains two types of drug-containing beads (immediate-release and delayed

release) which prolong the release of amphetamine compared to the ADDERALL (immediate-release)

tablet formulation.

Each capsule contains:

Capsule Strength

Dextroamphetamine Saccharate

Amphetamine (D,L)-Aspartate Monohydrate 1.25 mg 2.5 mg

Dextroamphetamine Sulfate

Amphetamine Sulfate

5 mg 10 mg

1.25 mg 2.5 mg

15 mg

3.75 mg

20 mg

5.0 mg

25 mg

6.25 mg

30 mg

7.5 mg

Total amphetamine base equivalence

d-amphetamine base equivalence

l-amphetamine base equivalence

3.1 mg 6.3 mg

2.4 mg 4.7 mg

0.75 mg 1.5 mg

9.4 mg

7.1 mg

2.3 mg

12.5 mg

9.5 mg

3.0 mg

15.6 mg

11.9 mg

3.8 mg

18.8

14.2

4.5 mg

Inactive Ingredients and Colors

The inactive ingredients in ADDERALL XR extended release capsules include: gelatin capsules,

hydroxypropyl methylcellulose, methacrylic acid copolymer, opadry beige, sugar spheres, talc, and

triethyl citrate. Gelatin capsules contain edible inks, kosher gelatin, and titanium dioxide. The 5 mg, 10

mg, and 15 mg capsules also contain FD&C Blue #2. The 20 mg, 25 mg, and 30 mg capsules also

contain red iron oxide and yellow iron oxide.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode

of therapeutic action in ADHD is not known.

12.2 Pharmacodynamics

Amphetamines block the reuptake of norepinephrine and dopamine into the presynaptic neuron and

increase the release of these monoamines into the extraneuronal space.

12.3 Pharmacokinetics

Pharmacokinetic studies of ADDERALL XR have been conducted in healthy adult and pediatric (children

aged 6-12 yrs) subjects, and adolescent (13-17 yrs) and children with ADHD. Both ADDERALL

(immediate-release) tablets and ADDERALL XR extended release capsules contain d-amphetamine and

Reference ID: 4943991

l-amphetamine salts in the ratio of 3:1. Following administration of ADDERALL (immediate-release), the

peak plasma concentrations occurred in about 3 hours for both d-amphetamine and l-amphetamine.

The time to reach maximum plasma concentration (T

max

) for ADDERALL XR is about 7 hours, which is

about 4 hours longer compared to ADDERALL (immediate-release). This is consistent with the

extended-release nature of the product.

TIME (HOURS)

Figure 1 Mean d-amphetamine and l-amphetamine Plasma Concentrations Following

Administration of ADDERALL XR 20 mg (8 am) and ADDERALL (immediate-release) 10 mg Twice

Daily (8 am and 12 noon) in the Fed State.

A single dose of ADDERALL XR 20 mg extended release capsules provided comparable plasma

concentration profiles of both d-amphetamine and l-amphetamine to ADDERALL (immediate-release) 10

mg twice daily administered 4 hours apart.

The mean elimination half-life for d-amphetamine is 10 hours in adults; 11 hours in adolescents aged 13-

17 years and weighing less than or equal to 75 kg/165 lbs; and 9 hours in children aged 6 to 12 years. For

the l-amphetamine, the mean elimination half-life in adults is 13 hours; 13 to 14 hours in adolescents; and

11 hours in children aged 6 to 12 years. On a mg/kg body weight basis, children have a higher clearance

than adolescents or adults (see Special Populations below).

ADDERALL XR demonstrates linear pharmacokinetics over the dose range of 20 to 60 mg in adults and

adolescents weighing greater than 75 kg/165 lbs, over the dose range of 10 to 40 mg in adolescents

weighing less than or equal to 75 kg/165 lbs, and 5 to 30 mg in children aged 6 to 12 years. There is no

unexpected accumulation at steady state in children.

Food does not affect the extent of absorption of d-amphetamine and l-amphetamine, but prolongs T

max

2.5 hours (from 5.2 hrs at fasted state to 7.7 hrs after a high-fat meal) for d-amphetamine and 2.7 hours

(from 5.6 hrs at fasted state to 8.3 hrs after a high fat meal) for l-amphetamine after administration of

MEAN PLASMA CONCENTRATIONS OF DEXTRO AND LEVOAMPHETAMINE (ng/mL)

ADDERALL XR

20 mg qd

ADDERALL

10 mg bid

ADDERALL XR

20 mg qd

ADDERALL

10 mg bid

DEXTROAMPHETAMINE

LEVOAMPHETAMINE

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ADDERALL XR 30 mg. Opening the capsule and sprinkling the contents on applesauce results in

comparable absorption to the intact capsule taken in the fasted state. Equal doses of ADDERALL XR

strengths are bioequivalent.

Metabolism and Excretion

Amphetamine is reported to be oxidized at the 4 position of the benzene ring to form 4-

hydroxyamphetamine, or on the side chain α or β carbons to form alpha-hydroxy-amphetamine or

norephedrine, respectively. Norephedrine and 4-hydroxy-amphetamine are both active and each is

subsequently oxidized to form 4-hydroxy-norephedrine. Alpha-hydroxy-amphetamine undergoes

deamination to form phenylacetone, which ultimately forms benzoic acid and its glucuronide and the

glycine conjugate hippuric acid. Although the enzymes involved in amphetamine metabolism have not

been clearly defined, CYP2D6 is known to be involved with formation of 4-hydroxy-amphetamine. Since

CYP2D6 is genetically polymorphic, population variations in amphetamine metabolism are a possibility.

Amphetamine is known to inhibit monoamine oxidase, whereas the ability of amphetamine and its

metabolites to inhibit various P450 isozymes and other enzymes has not been adequately elucidated. In

vitro experiments with human microsomes indicate minor inhibition of CYP2D6 by amphetamine and

minor inhibition of CYP1A2, 2D6, and 3A4 by one or more metabolites. However, due to the probability

of auto-inhibition and the lack of information on the concentration of these metabolites relative to in vivo

concentrations, no predications regarding the potential for amphetamine or its metabolites to inhibit the

metabolism of other drugs by CYP isozymes in vivo can be made.

With normal urine pHs, approximately half of an administered dose of amphetamine is recoverable in

urine as derivatives of alpha-hydroxy-amphetamine and approximately another 30-40% of the dose is

recoverable in urine as amphetamine itself. Since amphetamine has a pKa of 9.9, urinary recovery of

amphetamine is highly dependent on pH and urine flow rates. Alkaline urine pHs result in less ionization

and reduced renal elimination, and acidic pHs and high flow rates result in increased renal elimination

with clearances greater than glomerular filtration rates, indicating the involvement of active secretion.

Urinary recovery of amphetamine has been reported to range from 1% to 75%, depending on urinary pH,

with the remaining fraction of the dose hepatically metabolized. Consequently, both hepatic and renal

dysfunction have the potential to inhibit the elimination of amphetamine and result in prolonged

exposures. In addition, drugs that effect urinary pH are known to alter the elimination of amphetamine,

and any decrease in amphetamine’s metabolism that might occur due to drug interactions or genetic

polymorphisms is more likely to be clinically significant when renal elimination is decreased [see Drug

Interactions (7)].

Special Populations

Comparison of the pharmacokinetics of d- and l-amphetamine after oral administration of ADDERALL

XR in children (6-12 years) and adolescent (13-17 years) ADHD patients and healthy adult volunteers

indicates that body weight is the primary determinant of apparent differences in the pharmacokinetics of

d- and l-amphetamine across the age range. Systemic exposure measured by area under the curve to

infinity (AUC

∞

) and maximum plasma concentration (C

max

) decreased with increases in body weight,

while oral volume of distribution (V

/F), oral clearance (CL/F), and elimination half-life (t

1/2

) increased

with increases in body weight.

Pediatric Patients

On a mg/kg weight basis, children eliminated amphetamine faster than adults. The elimination half-life

1/2

) is approximately 1 hour shorter for d-amphetamine and 2 hours shorter for l-amphetamine in

children than in adults. However, children had higher systemic exposure to amphetamine (C

max

and AUC)

than adults for a given dose of ADDERALL XR, which was attributed to the higher dose administered to

children on a mg/kg body weight basis compared to adults. Upon dose normalization on a mg/kg basis,

children showed 30% less systemic exposure compared to adults.

Gender

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Systemic exposure to amphetamine was 20-30% higher in women (N=20) than in men (N=20) due to the

higher dose administered to women on a mg/kg body weight basis. When the exposure parameters (C

max

and AUC) were normalized by dose (mg/kg), these differences diminished. Age and gender had no direct

effect on the pharmacokinetics of d- and l-amphetamine.

Race

Formal pharmacokinetic studies for race have not been conducted. However, amphetamine

pharmacokinetics appeared to be comparable among Caucasians (N=33), Blacks (N=8) and Hispanics

(N=10).

Patients with Renal Impairment

The effect of renal impairment on d- and l-amphetamine after administration of ADDERALL XR has not

been studied. The impact of renal impairment on the disposition of amphetamine is expected to be similar

between oral administration of lisdexamfetamine and Adderall XR.

In a pharmacokinetic study of lisdexamfetamine in adult subjects with normal and impaired renal

function, mean d-amphetamine clearance was reduced from 0.7 L/hr/kg in normal subjects to 0.4 L/hr/kg

in subjects with severe renal impairment (GFR 15 to <30mL/min/1.73m

). Dialysis did not significantly

affect the clearance of d-amphetamine [see Use in Specific Populations (8.6)].

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

No evidence of carcinogenicity was found in studies in which d,l-amphetamine (enantiomer ratio of 1:1)

was administered to mice and rats in the diet for 2 years at doses of up to 30 mg/kg/day in male mice, 19

mg/kg/day in female mice, and 5 mg/kg/day in male and female rats. These doses are approximately 2.4,

1.5, and 0.8 times, respectively, the maximum recommended human dose of 30 mg/day given to children,

on a mg/m

basis.

Mutagenesis

Amphetamine, in the enantiomer ratio d- to l- ratio of 3:1, was not clastogenic in the mouse bone marrow

micronucleus test in vivo and was negative when tested in the E. coli component of the Ames test in vitro.

d,l-Amphetamine (1:1 enantiomer ratio) has been reported to produce a positive response in the mouse

bone marrow micronucleus test, an equivocal response in the Ames test, and negative responses in the in

vitro sister chromatid exchange and chromosomal aberration assays.

Impairment of Fertility

Amphetamine, in the enantiomer ratio d- to l- ratio of 3:1, did not adversely affect fertility or early

embryonic development in the rat at doses of up to 20 mg/kg/day (approximately 8 times the maximum

recommended human dose of 20 mg/day given to adolescents, on a mg/m

basis).

13.2 Animal Toxicology and/or Pharmacology

Acute administration of high doses of amphetamine (d- or d,l-) has been shown to produce long-lasting

neurotoxic effects, including irreversible nerve fiber damage, in rodents. The significance of these

findings to humans is unknown.

14 CLINICAL STUDIES

Pediatric Patients

A double-blind, randomized, placebo-controlled, parallel-group study was conducted in children aged 6-

12 (N=584) who met DSM-IV

criteria for ADHD (either the combined type or the hyperactive-

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impulsive type). Patients were randomized to fixed-dose treatment groups receiving final doses of 10, 20,

or 30 mg of ADDERALL XR or placebo once daily in the morning for three weeks. Significant

improvements in patient behavior, based upon teacher ratings of attention and hyperactivity, were

observed for all ADDERALL XR doses compared to patients who received placebo, for all three weeks,

including the first week of treatment, when all ADDERALL XR subjects were receiving a dose of 10

mg/day. Patients who received ADDERALL XR showed behavioral improvements in both morning and

afternoon assessments compared to patients on placebo.

In a classroom analogue study, patients (N=51) receiving fixed doses of 10 mg, 20 mg or 30 mg

ADDERALL XR demonstrated statistically significant improvements in teacher-rated behavior and

performance measures, compared to patients treated with placebo.

A double-blind, randomized, multi-center, parallel-group, placebo-controlled study was conducted in

adolescents aged 13-17 (N=327) who met DSM-IV

criteria for ADHD. The primary cohort of patients

(n=287, weighing ≤ 75kg/165lbs) was randomized to fixed-dose treatment groups and received four

weeks of treatment. Patients were randomized to receive final doses of 10 mg, 20 mg, 30 mg, and 40 mg

ADDERALL XR or placebo once daily in the morning. Patients randomized to doses greater than 10 mg

were titrated to their final doses by 10 mg each week. The secondary cohort consisted of 40 subjects

weighing >75kg/165lbs who were randomized to fixed-dose treatment groups receiving final doses of 50

mg and 60 mg ADDERALL XR or placebo once daily in the morning for 4 weeks. The primary efficacy

variable was the Attention Deficit Hyperactivity Disorder-Rating Scale IV

(ADHD-RS-IV) total score for

the primary cohort. The ADHD-RS-IV is an 18-item scale that measures the core symptoms of ADHD.

Improvements in the primary cohort were statistically significantly greater in all four primary cohort

active treatment groups (ADDERALL XR 10 mg, 20 mg, 30 mg, and 40 mg) compared with the placebo

group. There was not adequate evidence that doses greater than 20 mg/day conferred additional benefit.

Adult Patients

A double-blind, randomized, placebo-controlled, parallel-group study was conducted in adults (N=255)

who met DSM-IV

criteria for ADHD. Patients were randomized to fixed-dose treatment groups

receiving final doses of 20, 40, or 60 mg of ADDERALL XR or placebo once daily in the morning for

four weeks. Significant improvements, measured with the Attention Deficit Hyperactivity Disorder-

Rating Scale (ADHD-RS), an 18- item scale that measures the core symptoms of ADHD, were observed

at endpoint for all ADDERALL XR doses compared to patients who received placebo for all four weeks.

There was not adequate evidence that doses greater than 20 mg/day conferred additional benefit.

16 HOW SUPPLIED/STORAGE AND HANDLING

ADDERALL XR 5 mg extended release capsules: Clear/blue (imprinted ADDERALL XR 5 mg), bottles

of 100, NDC 54092-381-01

ADDERALL XR 10 mg extended release capsules: Blue/blue (imprinted ADDERALL XR 10 mg),

bottles of 100, NDC 54092-383-01

ADDERALL XR 15 mg extended release capsules: Blue/white (imprinted ADDERALL XR 15 mg),

bottles of 100, NDC 54092-385-01

ADDERALL XR 20 mg extended release capsules: Orange/orange (imprinted ADDERALL XR 20 mg),

bottles of 100, NDC 54092-387-01

ADDERALL XR 25 mg extended release capsules: Orange/white (imprinted ADDERALL XR 25 mg),

bottles of 100, NDC 54092-389-01

ADDERALL XR 30 mg extended release capsules: Natural/orange (imprinted ADDERALL XR 30 mg),

bottles of 100, NDC 54092-391-01

Dispense in a tight, light-resistant container as defined in the USP.

Store at room temperature, 20º C to 25º C (68º F to 77º F). Excursions permitted to 15-30º C (59-86ºF)

[see USP CONTROLLED ROOM TEMPERATURE].

Disposal

Reference ID: 4943991

Comply with local laws and regulations on drug disposal of CNS stimulants. Dispose of remaining,

unused, or expired ADDERALL XR at authorized collection sites such as retail pharmacies, hospital or

clinic pharmacies, and law enforcement locations. If no take-back program or authorized collector is

available, mix ADDERALL XR with an undesirable, nontoxic substance to make it less appealing to

children and pets. Place the mixture in a container such as a sealed plastic bag and discard ADDERALL

XR in the household trash.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Controlled Substance Status/Potential for Abuse, Misuse, and Dependence

Advise patients that ADDERALL XR is a federally controlled substance because it can be abused or lead

to dependence. Additionally, emphasize that ADDERALL XR should be stored in a safe place to prevent

misuse and/or abuse. Evaluate patient history (including family history) of abuse or dependence on

alcohol, prescription medicines, or illicit drugs [see Warnings and Precautions (5.1), Drug Abuse and

Dependence (9)].

Serious Cardiovascular Risks

Advise patients of serious cardiovascular risk (including sudden death, myocardial infarction, stroke, and

hypertension) with ADDERALL XR. Patients who develop symptoms such as exertional chest pain,

unexplained syncope, or other symptoms suggestive of cardiac disease during treatment should undergo a

prompt cardiac evaluation [see Warnings and Precautions (5.2)].

Psychiatric Risks

Prior to initiating treatment with ADDERALL XR, adequately screen patients with comorbid depressive

symptoms to determine if they are at risk for bipolar disorder. Such screening should include a detailed

psychiatric history, including a family history of suicide, bipolar disorder, and/or depression.

Additionally, ADDERALL XR therapy at usual doses may cause treatment-emergent psychotic or manic

symptoms in patients without prior history of psychotic symptoms or mania [see Warnings and

Precautions (5.3)].

Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud’s

phenomenon]

Instruct patients beginning treatment with ADDERALL XR about the risk of peripheral vasculopathy,

including Raynaud’s Phenomenon, and in associated signs and symptoms: fingers or toes may feel numb,

cool, painful, and/or may change color from pale, to blue, to red. Instruct patients to report to their

physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.

Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on

fingers or toes while taking ADDERALL XR. Further clinical evaluation (e.g., rheumatology referral)

may be appropriate for certain patients [see Warnings and Precautions (5.6)].

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome with concomitant use of ADDERALL XR and

other serotonergic drugs including SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium,

tramadol, tryptophan, buspirone, St. John’s Wort, and with drugs that impair metabolism of serotonin (in

particular MAOIs, both those intended to treat psychiatric disorders and also others such as linezolid [see

Contraindications (4), Warnings and Precautions (5.7) and Drug Interactions (7.1)]. Advise patients to

contact their healthcare provider or report to the emergency room if they experience signs or symptoms of

serotonin syndrome.

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Concomitant Medications

Advise patients to notify their physicians if they are taking, or plan to take, any prescription or over-the-

counter drugs because there is a potential for interactions [see Drug Interactions (7.1)].

Growth

Monitor growth in children during treatment with ADDERALL XR, and patients who are not growing or

gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions

(5.4)].

Pregnancy Registry

Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women

exposed to ADDERALL XR during pregnancy [see Use in Specific Populations (8.1)].

Pregnancy

Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant

during treatment with ADDERALL XR. Advise patients of the potential fetal effects from the use of

ADDERALL XR during pregnancy [see Use in Specific Populations (8.1)].

Lactation

Advise women not to breastfeed if they are taking ADDERALL XR [see Use in Specific Populations

(8.2)].

Impairment in Ability to Operate Machinery or Vehicles

ADDERALL XR may impair the ability of the patient to engage in potentially hazardous activities such

as operating machinery or vehicles; the patient should therefore be cautioned accordingly.

Distributed by Takeda Pharmaceuticals America, Inc., Lexington, MA 02421, Made in USA.

For more information call 1-800-828-2088

ADDERALL XR

is a registered trademark of Takeda Pharmaceuticals U.S.A., Inc.

ADDERALL

is a registered trademark of Takeda Pharmaceuticals U.S.A., Inc. under license to

Duramed Pharmaceuticals, Inc.

Reference ID: 4943991

MEDICATION GUIDE

ADDERALL XR

(ADD-ur-all X-R) CII

Read the Medication Guide that comes with ADDERALL XR before you or your child starts taking it and

each time you get a refill. There may be new information. This Medication Guide does not take the place

of talking to your doctor about you or your child’s treatment with ADDERALL XR.

What is the most important information I

should know about ADDERALL XR?

ADDERALL XR is a stimulant medicine.

The following have been reported with use of

stimulant medicines.

1. Heart-related problems:

• sudden death in patients who have heart

problems or heart defects

• stroke and heart attack in adults

• increased blood pressure and heart rate

Tell your doctor if you or your child have any

heart problems, heart defects, high blood

pressure, or a family history of these problems.

Your doctor should check you or your child

carefully for heart problems before starting

ADDERALL XR.

Your doctor should check you or your child’s

blood pressure and heart rate regularly during

treatment with ADDERALL XR.

Call your doctor right away if you or your

child has any signs of heart problems such as

chest pain, shortness of breath, or fainting

while taking ADDERALL XR.

2. Mental (Psychiatric) problems:

All Patients

• new or worse behavior and thought

problems

• new or worse bipolar illness

• new or worse aggressive behavior or

hostility

Children and Teenagers

• new psychotic symptoms (such as hearing

voices, believing things that are not true,

are suspicious) or new manic symptoms

Tell your doctor about any mental problems you

or your child have, or about a family history of

suicide, bipolar illness, or depression.

Call your doctor right away if you or your

child have any new or worsening mental

symptoms or problems while taking

ADDERALL XR, especially seeing or hearing

things that are not real, believing things that

are not real, or are suspicious.

3. Circulation problems in fingers and toes

[Peripheral vasculopathy, including

Raynaud’s phenomenon]:

• Fingers or toes may feel numb, cool,

painful

• Fingers or toes may change from pale, to

blue, to red

Tell your doctor if you have or your child has

numbness, pain, skin color change, or sensitivity

to temperature in your fingers or toes.

Call your doctor right away if you have or

your child has any unexplained wounds

appearing on fingers or toes while taking

ADDERALL XR.

What Is ADDERALL XR?

ADDERALL XR is a once daily central nervous

system stimulant prescription medicine. It is

used for the treatment of Attention Deficit

Hyperactivity Disorder (ADHD).

ADDERALL XR may help increase attention

and decrease impulsiveness and hyperactivity in

patients with ADHD.

ADDERALL XR should be used as a part of a

total treatment program for ADHD that may

include counseling or other therapies.

ADDERALL XR is a federally controlled

substance (CII) because it can be abused or

lead to dependence. Keep ADDERALL XR

in a safe place to prevent misuse and abuse.

Selling or giving away ADDERALL XR may

harm others, and is against the law.

Tell your doctor if you or your child have (or

have a family history of) ever abused or been

dependent on alcohol, prescription medicines or

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street drugs.

Who should not take ADDERALL XR?

ADDERALL XR should not be taken if you

or your child:

• have heart disease or hardening of the arteries

• have moderate to severe high blood pressure

• have hyperthyroidism

• have an eye problem called glaucoma

• are very anxious, tense, or agitated

• have a history of drug abuse

• are taking or have taken within the past 14

days an anti-depression medicine called a

monoamine oxidase inhibitor or MAOI.

• is sensitive to, allergic to, or had a reaction to

other stimulant medicines

ADDERALL XR has not been studied in

children less than 6 years old.

ADDERALL XR may not be right for you or

your child. Before starting ADDERALL XR

tell you or your child’s doctor about all health

conditions (or a family history of) including if

you or your child:

• have heart problems, heart defects, or high

blood pressure

• have mental problems including psychosis,

mania, bipolar illness, or depression

• have tics or Tourette’s syndrome

• have liver problems

• have kidney problems

• have end stage renal disease (ESRD)

• have thyroid problems

• have seizures or have had an abnormal brain

wave test (EEG)

• have circulation problems in fingers and toes

• are pregnant or plan to become pregnant. It is

not known if ADDERALL XR will harm

your unborn baby.

o There is a pregnancy registry for

females who are exposed to

ADDERALL XR during pregnancy. The

purpose of the registry is to collect

information about the health of females

exposed to ADDERALL XR and their

baby. If you or your child becomes

pregnant during treatment with

ADDERALL XR, talk to your

healthcare provider about registering

with the National Pregnancy Registry of

Psychostimulants at 1-866-961-2388 or

visit online at

https://womensmentalhealth.org/clinical

-and -research-

programs/pregnancyregistry/othermedic

ations/.

o are breastfeeding or plan to breastfeed.

ADDERALL XR passes into breast

milk. You or your child should not

breastfeed during treatment with

ADDERALL XR.

Can ADDERALL XR be taken with other

medicines?

Tell your doctor about all of the medicines

that you or your child takes including

prescription and non-prescription medicines,

vitamins, and herbal supplements.

ADDERALL XR and some medicines may

interact with each other and cause serious side

effects. Sometimes the doses of other medicines

will need to be adjusted while taking

ADDERALL XR.

Your doctor will decide whether ADDERALL

XR can be taken with other medicines.

Especially tell your doctor if you or your

child takes:

• anti-depression medicines including MAOIs

• anti-psychotic medicines

• lithium

• narcotic pain medicines

• seizure medicines

• blood thinner medicines

• blood pressure medicines

• stomach acid medicines

• cold or allergy medicines that contain

decongestants

Know the medicines that you or your child

takes. Keep a list of your medicines with you to

show your doctor and pharmacist.

Do not start any new medicine while taking

ADDERALL XR without talking to your

doctor first.

How should ADDERALL XR be taken?

• Take ADDERALL XR exactly as

prescribed. Your doctor may adjust the dose

until it is right for you or your child.

• Take ADDERALL XR once a day in the

morning when you first wake up.

ADDERALL XR is an extended release

capsule. It releases medicine into your body

Reference ID: 4943991

throughout the day.

• Swallow ADDERALL XR extended release

capsules whole with water or other liquids.

If you or your child cannot swallow the

capsule, open it and sprinkle the medicine

over a spoonful of applesauce. Swallow all

of the applesauce and medicine mixture

without chewing immediately. Follow with a

drink of water or other liquid. Never chew

or crush the capsule or the medicine inside

the capsule.

• ADDERALL XR can be taken with or

without food.

• From time to time, your doctor may stop

ADDERALL XR treatment for a while to

check ADHD symptoms.

• Your doctor may do regular checks of the

heart and blood pressure while taking

ADDERALL XR. Children should have

their height and weight checked often while

taking ADDERALL XR. ADDERALL XR

treatment may be stopped if a problem is

found during these check-ups.

• If you or your child takes too much

ADDERALL XR or overdoses, call your

doctor or poison control center right away,

or get emergency treatment.

What are possible side effects of ADDERALL

XR?

See “What is the most important information

I should know about ADDERALL XR?” for

information on reported heart and mental

problems.

Other serious side effects include:

• slowing of growth (height and weight) in

children

• seizures, mainly in patients with a history of

seizures

• eyesight changes or blurred vision

Common side effects include:

• headache

● decreased appetite

• stomach ache

● nervousness

• trouble sleeping

● mood swings

• weight loss

● dizziness

• dry mouth

● fast heart beat

ADDERALL XR may affect you or your child’s

ability to drive or do other dangerous activities.

Talk to your doctor if you or your child has side

effects that are bothersome or do not go away.

This is not a complete list of possible side

effects. Ask your doctor or pharmacist for more

information.

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 ADDERALL XR?

• Store ADDERALL XR in a safe place at

room temperature, 59 to 86° F (15 to 30° C).

• Keep ADDERALL XR and all medicines

out of the reach of children.

General information about ADDERALL XR

Medicines are sometimes prescribed for

purposes other than those listed in a Medication

Guide. Do not use ADDERALL XR for a

condition for which it was not prescribed. Do

not give ADDERALL XR to other people, even

if they have the same condition. It may harm

them and it is against the law.

This Medication Guide summarizes the most

important information about ADDERALL XR.

If you would like more information, talk with

your doctor. You can ask your doctor or

pharmacist for information about ADDERALL

XR that was written for healthcare professionals.

For more information, you may also contact

Takeda Pharmaceuticals (the maker of

ADDERALL XR) at 1-800-828-2088 or visit the

website at http://www.adderallxr.com.

What are the ingredients in ADDERALL

XR?

Active Ingredients: dextroamphetamine

saccharate, amphetamine aspartate monohydrate,

dextroamphetamine sulfate, amphetamine

sulfate

Inactive Ingredients: gelatin capsules,

hydroxypropyl methylcellulose, methacrylic

acid copolymer, opadry beige, sugar spheres,

talc, and triethyl citrate. Gelatin capsules contain

edible inks, kosher gelatin, and titanium dioxide.

The 5 mg, 10 mg, and 15 mg capsules also

contain FD&C Blue #2. The 20 mg, 25 mg, and

30 mg capsules also contain red iron oxide and

yellow iron oxide

Reference ID: 4943991

Distributed by:

Takeda Pharmaceuticals America, Inc.

Lexington, MA 02421

ADDERALL XR

is a registered trademark of

Takeda Pharmaceuticals U.S.A., Inc.

rights reserved.

Rev. 2/2022

This Medication Guide has been approved by

the U.S. Food and Drug Administration.

Reference ID: 4943991