MEDICATION GUIDE ADDERALL XR® (ADD-ur-all X-R) CII Read

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

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.

hat 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

mpulsiveness and hyperactivity in patients with ADHD. i

ADDERALL XR

should be used as a part of a total treatment

program for ADHD that may include counseling or other

herapies.

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 street drugs.

ho 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 t

aking or have taken within the past 14 days an anti-

depression medicine called a monoamine oxidase

inhibitor or MAOI

• is sensitive t

o, 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

is not recommended for use in children less

than 3 years old.

ADDERALL XR

may not be right for you or your child.

Before starting ADDERALL XR

tell your or your child’s

doctor about all health conditions (or a family history of)

ncluding:

• heart

problems, heart defects, high blood pressure

• m

ental problems including psychosis, mania, bipolar

illness, or depression

• tics o

r Tourette’s syndrome

• l

iver or kidney problems

• t

hyroid problems

• sei

zures or have had an abnormal brain wave test (EEG)

Tell your doctor if you or your child is pregnant, planning to

ecom

e pregnant, or breastfeeding. b

an 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

DDERALL XR

Your doctor will decide whether ADDERALL XR

can be

taken with other medicines.

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda

Especially tell your doctor if you or your child takes:

• ant

i-depression medicines including MAOIs

• ant

i-psychotic medicines

• lith

ium

• narc

otic pain medicines

• sei

zure medicines

• bl

ood thinner medicines

• b

lood pressure medicines

• stom

ach acid medicines

• co

ld or allergy medicines that contain decongestants

Know the medicines that you or your child takes. Keep a list

your medicines with you to show your doctor and

harmacist.

Do not start any new medicine while taking A

DDERALL

without talking to your doctor first.

ow should ADDERALL XR

be taken?

• Ta

ke ADDERALL XR

exactly as prescribed. Your

doctor may adjust the dose until it is right for you or your

hild.

• Take ADDER

ALL 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

throughout the day.

• Swallo

w ADDERALL XR

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.

• AD

DERALL XR

can be taken with or without food.

• From

time to time, your doctor may stop ADDERALL

treatment for a while to check ADHD symptoms.

• Yo

ur doctor may do regular checks of the blood, 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.

hat are possible side effects of ADDERALL XR

See “Wha

t is the most important information I should

know about ADDERALL XR

?” for information on reported

heart and mental problems.

Other serious side effects

include:

• slo

wing of growth (height and weight) in children

• seizu

res, mainly in patients with a history of seizures

• ey

esight changes or blurred vision

Common side effects include:

• headac

• decreased appetite

• stom

ach ache

• nervousness

• t

rouble 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

re bot

hersome or do not go away. a

This is not a complete list of possible side effects. Ask your

doct

or or pharmacist for more information

ow should I store ADDERALL XR

• Sto

re ADDERALL XR

in a safe place at room

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

• Keep AD

DERALL XR

and all medicines out of the

reach of children.

eneral information about ADDERALL XR

Medicines are sometimes prescribed for purposes other than

those listed in a Medication Guide. Do not use ADDERALL

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

nformation 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 Shire Pharmaceuticals (the

maker of ADDERALL XR

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

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

hat are the ingredients in ADDERALL XR

Active Ingredients: de

xtroamphetamine saccharate,

amphetamine aspartate monohydrate, dextroamphetamine

sulfate, USP, amphetamine sulfate USP

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

Manufactured for Shire US Inc., Wayne, PA 19087.

ADDERALL XR

is registered in the US Patent and

Trademark Office

Rev. 3/07

81 0107 001A XXXXXX

This Medication Guide has been approved by the U.S.

od and Drug Administration.

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda

ADDERALL XR

CAPSULES CII Rx Only

AMPHETAMINES HAVE A HIGH POTENTIAL FOR ABUSE. ADMINISTRATION OF

AMPHETAMINES FOR PROLONGED PERIODS OF TIME MAY LEAD TO DRUG

DEPENDENCE. PARTICULAR ATTENTION SHOULD BE PAID TO THE POSSIBILITY OF

SUBJECTS OBTAINING AMPHETAMINES FOR NON-THERAPEUTIC USE OR DISTRIBUTION

TO OTHERS AND THE DRUGS SHOULD BE PRESCRIBED OR

DISPENSED SPARINGLY.

MISUSE OF AMPHETAMINE MAY CAUSE SUDDEN DEATH AND SERIOUS

CARDIOVASCULAR ADVERSE EVENTS.

DESCRIPTION

ADDERALL XR

is a once daily extended-release, single-entity amphetamine product. ADDERALL XR

combines the neutral sulfate salts of dextroamphetamine and amphetamine, with the dextro isomer of

amphetamine saccharate and d,l-amphetamine aspartate monohydrate. The ADDERALL XR

capsule contains

two types of drug-containing beads designed to give a double-pulsed delivery of amphetamines, which prolongs

the release of amphetamine from ADDERALL XR

compared to the conventional ADDERALL

(immediate-

release) tablet formulation.

EACH CAPSULE CONTAINS: 5 mg 10 mg 15 mg 20 mg 25 mg 30 mg

Dextroamphetamine Saccharate 1.25 mg 2.5 mg 3.75 mg 5.0 mg 6.25 mg 7.5 mg

Amphetamine Aspartate Monohydrate 1.25 mg 2.5 mg 3.75 mg 5.0 mg 6.25 mg 7.5 mg

Dextroamphetamine Sulfate USP 1.25 mg 2.5 mg 3.75 mg 5.0 mg 6.25 mg 7.5 mg

Amphetamine Sulfate USP 1.25 mg 2.5 mg 3.75 mg 5.0 mg 6.25 mg 7.5 mg

Total amphetamine base equivalence 3.1 mg 6.3 mg 9.4 mg 12.5 mg 15.6 mg 18.8 mg

Inactive Ingredients and Colors: The inactive ingredients in ADDERALL XR

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.

CLINICAL PHARMACOLOGY

Pharmacodynamics

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

therapeutic action in Attention Deficit Hy

peractivity Disorder (ADHD) is not known. Amphetamines are thought

to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of

these monoamines into the extraneuronal space.

Pharmacokinetics

Pharmacokinetic studies of

ADDERALL XR

have been conducted in healthy adult and pediatric (6-12 yrs)

subjects, and adolescent (13-17 yrs) and pediatric patients with ADHD. Both

ADDERALL

(immediate-

release) tablets and

ADDERALL XR

capsules contain d-amphetamine and 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.

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda

12 16 20 24

DDERALL XR

20 mg qd

DDERALL

10 mg bid

DDERALL XR

20 mg qd

DDERALL

10 mg bid

DEXTROAMPHETAMINE

LEVOAMPHETAMINE

TIME (HOURS)

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

Figure 1 Mean d-amphetamine and l-amphetamine plasma concentrations following administration

ADDERALL XR

20 mg (8am) and ADDERALL

(immediate-release) 10 mg bid (8am and 12 noon) in

the fed state.

A single dose of

ADDERALL XR

20 mg capsules provided comparable plasma concentration profiles of both

d-amphetamine and l-amphetamine to ADDERALL

(immediate-release) 10 mg bid administered 4 hours apart.

The mean elimination half-life for d-am

phetamine 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).

ADDERALL XR



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

adolescents weighing greater than 75 kg/165lbs, 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-am

phetamine and l-amphetamine, but prolongs T

max

by 2.5

hours (from 5.2 hrs at fasted state to 7.7 hrs after a high-fat meal) for d-amphetamine and 2.1 hours (from 5.6 hrs

at fasted state to 7.7 hrs after a high fat meal) for l-amphetamine after administration of ADDERALL XR

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 o

f the benzene ring to form 4-hydroxyamphetamine, or

on the side chain α or β carbons to form alpha-hydroxy-amphetamine or norephedrine, respectively.

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda

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, where

as 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 PRECAUTIONS).

Special Populations

Comparison of the pharmacokinetics of d- and l-amphetam

ine after oral administration of ADDERALL XR

pediatric (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 (t

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

Systemic exposure to amphetamine was 20-30% higher in wom

en (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, am

phetamine pharmacokinetics

appeared to be comparable among Caucasians (N=33), Blacks (N=8) and Hispanics (N=10).

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda

Clinical Trials

Children

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-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

demonstrated statistically significant improvements in teacher-rated behavior and performance measures,

compared to patients treated with placebo.

Adolescents

A double-blind, randomized, multi-center, parallel-group, plac

ebo-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 ADHD-RS-IV total scores for the primary

cohort. 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.

Adults

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.

INDICATIONS

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 PHARMACOLOGY), along with extrapolation from the

known efficacy of ADDERALL

, the immediate-release formulation of this substance.

A diagnosis of Attention Deficit Hyperactivity Disorder (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

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda

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 child 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 children with this syndrome. Stimulants are not

intended for use in the child 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.

CONTRAINDICATIONS

Advanced arteriosclerosis, symptomatic cardiovascular disease, m

oderate to severe hypertension,

hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines, glaucoma.

Agitated states.

Patients with a history of drug abuse.

During or within 14 days following the administration of m

onoamine oxidase inhibitors (hypertensive crises may

result).

WARNINGS

Serious Cardiovascular Events

Sudden Death and Pre-existing Structural Cardiac Abnorm

alities or Other Serious Heart Problems

Children and Adolescents

Sudden death has been reported in association with CNS stim

ulant 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).

Adults

Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stim

ulant 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).

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda

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) [see ADVERSE EVENTS], 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).

Assessing Cardiovascular Status in Patients being Treated with Stimulant Medications

Children, adolescents, or adults who are being considered for treatm

ent 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.

Psychiatric Adverse Events

Pre-Existing Psychosis

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

with pre-existing psy

chotic 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 m

ania 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.

Aggression

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

n 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.

Long-Term Suppression of Growth

Careful follow-up of weight and height in children ages

7 to 10 years who were randomized to either

This label may not be the latest approved by FDA.

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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. Published data are

inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth,

however, it is anticipated that they will likely have this effect as well. Therefore, growth should be monitored

during treatment with stimulants, and patients who are not growing or gaining weight as expected may need to

have their treatment interrupted.

Seizures

There is some clinical evidence that stim

ulants may lower the convulsive threshold in patients with prior history

of seizure, in patients with prior EEG abnormalities in 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, the drug should be

discontinued.

Visual Disturbance

Difficulties with accommodation and blurring of vision have been reported with stim

ulant treatment.

PRECAUTIONS

General:

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.

Tics: Amphetamines have been reported to exacerbate m

otor and phonic tics and Tourette’s syndrome.

Therefore, clinical evaluation for tics and Tourette’s Syndrome in children and their families should precede use

of stimulant medications.

Information for Patients: Amphetamines may impair the ability of the patient to engage in potentially

hazardous activities such as operating m

achinery or vehicles; the patient should therefore be cautioned

accordingly.

Prescribers or other health professionals should inform patients,

their families, and their caregivers about the

benefits and risks associated with treatment with amphetamine and should counsel them in its appropriate use. A

patient Medication Guide is available for ADDERALL XR



. The prescriber or health professional should

instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in

understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication

Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is

reprinted at the end of this document.

Drug Interactions: Acidifying agents -Gastrointestinal acidify

ing agents (guanethidine, reserpine, glutamic acid

HCl, ascorbic acid, etc.) lower absorption of amphetamines.

Urinary acidifying agents

-These agents (ammonium chloride, sodium acid phosphate, etc.) increase the

concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion. Both

groups of agents lower blood levels and efficacy of amphetamines.

Adrenergic blockers -Adrenergic blockers are inhibited by

amphetamines.

Alkalinizing agents -Gastrointestinal alkalinizing agents (sodium

bicarbonate, etc.) increase absorption of

amphetamines. Co-administration of ADDERALL XR

and gastrointestinal alkalinizing agents, such as antacids,

should be avoided. Urinary alkalinizing agents (acetazolamide, some thiazides) increase the concentration of the

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non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion. Both groups of agents

increase blood levels and therefore potentiate the actions of amphetamines.

Antidepressants, tricyclic -Am

phetamines may enhance the activity of tricyclic antidepressants or

sympathomimetic agents; d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause

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

cardiovascular effects can be potentiated.

MAO inhibitors -MAOI an

tidepressants, as well as a metabolite of furazolidone, slow amphetamine metabolism.

This slowing potentiates amphetamines, increasing their effect on the release of norepinephrine and other

monoamines from adrenergic nerve endings; this can cause headaches and other signs of hypertensive crisis. A

variety of toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results.

Antihistamines -Am

phetamines may counteract the sedative effect of antihistamines.

Antihypertensives -Am

phetamines may antagonize the hypotensive effects of antihypertensives.

Chlorpromazine -Chlorprom

azine blocks dopamine and norepinephrine receptors, thus inhibiting the central

stimulant effects of amphetamines, and can be used to treat amphetamine poisoning.

Ethosuximide -Am

phetamines may delay intestinal absorption of ethosuximide.

Haloperidol -Haloperidol blocks dopam

ine receptors, thus inhibiting the central stimulant effects of

amphetamines.

Lithium carbonate -The anorectic and stim

ulatory effects of amphetamines may be inhibited by lithium

carbonate.

Meperidine -Am

phetamines potentiate the analgesic effect of meperidine.

Methenamine therapy -Urinary

excretion of amphetamines is increased, and efficacy is reduced, by acidifying

agents used in methenamine therapy.

Norepinephrine -Am

phetamines enhance the adrenergic effect of norepinephrine.

Phenobarbital -Am

phetamines may delay intestinal absorption of phenobarbital; co-administration of

phenobarbital may produce a synergistic anticonvulsant action.

Phenytoin -Am

phetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may

produce a synergistic anticonvulsant action.

Propoxyphene -In cases of propoxy

phene overdosage, amphetamine CNS stimulation is potentiated and fatal

convulsions can occur.

Veratrum alkaloids -Am

phetamines inhibit the hypotensive effect of veratrum alkaloids.

Drug/Laboratory Test Interactions: Am

phetamines can cause a significant elevation in plasma corticosteroid

levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.

Carcinogenesis/Mutagenesis and Impairment of Fertility:

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 [child] on a mg/m

body surface area basis.

Amphetamine, in the enantiomer ratio present in ADDERALL

(immediate-release)(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.

Amphetamine, in the enantiomer ratio present in ADDERALL

(immediate-release)(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 5 times the maximum recommended human dose of 30 mg/day on a mg/m

body surface area

basis).

Pregnancy:

Pregnancy Category C. Amphetamine, in the enantiomer ratio present in ADDERALL

(d- to l- ratio

of 3:1), had no apparent effects on embryofetal morphological development or survival when orally administered

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 1.5 and 8 times, respectively, the maximum recommended human

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dose of 30 mg/day [child] on a mg/m

body surface area basis. Fetal malformations and death have been reported

in mice following parenteral administration of d-amphetamine doses of 50 mg/kg/day (approximately 6 times that

of a human dose of 30 mg/day [child] on a mg/m

basis) or greater to pregnant animals. Administration of these

doses was also associated with severe maternal toxicity.

A number of studies in rodents indicate that prenatal or early postnatal exposure to amphetamine (d- or d,l-), at

doses sim

ilar 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.

There are no adequate and well-controlled studies in pregnant wom

en. There has been one report of severe

congenital bony deformity, tracheo-esophageal fistula, and anal atresia (vater association) in a baby born to a

woman who took dextroamphetamine sulfate with lovastatin during the first trimester of pregnancy.

Amphetamines should be used during pregnancy only if the potential benefit justifies the potential risk to the

fetus.

Nonteratogenic Effects: Infants

born to mothers dependent on amphetamines have an increased risk of

premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as

demonstrated by dysphoria, including agitation, and significant lassitude.

Usage in Nursing Mothers: Amphetamines are excreted in human milk. Mothers taking amphetamines should

be advised to refrain from nursing.

Pediatric Use: ADDERALL XR

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

Use in Children Under Six Years of Age: Effects of ADDERALL XR

in 3-5 year olds have not been studied.

Long-term effects of amphetamines in children have not been well established. Amphetamines are not

recommended for use in children under 3 years of age.

Geriatric Use: ADDERALL XR

has not been studied in the geriatric population.

ADVERSE EVENTS

Hypertension: [See WARNINGS section] In a controlled 4-week outpatient clinical study of adolescents with

ADHD, isolated sy

stolic 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



-treated patients. Similar results were observed at higher doses.

In a single-dose pharmacokinetic study in 23 adolescents, isolated increases in sy

stolic 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.

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 events, results of physical

examinations, vital signs, weights, laboratory analyses, and ECGs.

Adverse events during exposure were obtained primarily by

general inquiry and recorded by clinical

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

estimate of the proportion of individuals experiencing adverse events without first grouping similar types of

events into a smaller number of standardized event categories. In the tables and listings that follow, COSTART

terminology has been used to classify reported adverse events.

The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a

treatm

ent-emergent adverse event of the type listed.

Adverse events associated with discontinuation of treatment: In two placebo-controlled studies of up to 5

weeks duration am

ong children with ADHD, 2.4% (10/425) of ADDERALL XR

treated patients discontinued

due to adverse events (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 events associated with discontinuation of

ADDERALL XR

in controlled and uncontrolled, multiple-dose clinical trials of pediatric patients (N=595) are

presented below. Over half of these patients were exposed to ADDERALL XR

for 12 months or more.

Adverse event

% of pediatric patients discontinuing (n=595)

Anorexia (loss of appetite) 2.9

Insomnia 1.5

Weight loss 1.2

Emotional lability 1.0

Depression 0.7

In a separate placebo-controlled 4-week study in adolescents with ADHD, eight patients (3.4%) discontinued

treatm

ent due to adverse events among ADDERALL XR

-treated patients (N=233). Three patients discontinued

due to insomnia and one patient each for depression, motor tics, headaches, light-headedness, and anxiety.

In one placebo-controlled 4-week study among adults with ADHD, patients who discontinued treatm

ent due to

adverse events among ADDERALL XR

-treated patients (N=191) were 3.1% (n=6) for nervousness including

anxiety and irritability, 2.6% (n=5) for insomnia, 1% (n=2) each for headache, palpitation, and somnolence; and,

0.5% (n=1) each for ALT increase, agitation, chest pain, cocaine craving, elevated blood pressure, and weight

loss.

Adverse events occurring in a controlled trial: Adverse events reported in a 3-week clinical trial of pediatric

patients and a 4-week clinical trial in adolescents and adults, respectively

, treated with ADDERALL XR

placebo are presented in the tables below.

The prescriber should be aware that these figures cannot be used to predict the incidence of

adverse events in the

course of usual medical practice where patient characteristics and other factors differ from those which prevailed

in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical

investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the

prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the

adverse event incidence rate in the population studied.

Table 1 Adverse Events Reported by More Than 1% of Pediatric Patients Receiving ADDERALL

with Higher Incidence Than on Placebo in a 584 Patient Clinical Study

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Body System Preferred Term ADDERALL XR

(n=374)

Placebo

(n=210)

General

Abdominal Pain (stomachache)

Accidental Injury

Asthenia (fatigue)

Fever

Infection

Viral Infection

14%

10%

Digestive System

Loss of Appetite

Diarrhea

Dyspepsia

Nausea

Vomiting

22%

Nervous System

Dizziness

Emotional Lability

Insomnia

Nervousness

17%

Metabolic/Nutritional

Weight Loss 4% 0%

Table 2 Adverse Events Reported by 5% or more of Adolescents Weighing  75 kg/165 lbs

Receiving ADDERALL X

with Higher Incidence Than Placebo in a 287 Patient Clinical

Forced Weekly-Dose Titration Study*

Body System Preferred Term ADDERALL

XR®

(n=233)

Placebo

(n=54)

General

Abdominal Pain (stomachache)

11%

Digestive System

Loss of Appetite

36%

Nervous System

Insomnia

Nervousness

12%

Metabolic/Nutritional

Weight Loss

9% 0%

Appears the same due to rounding

Dose-related adverse events

Note: The following events 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 (f

atigue), dry mouth,

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

*Included doses up to 40 mg

Table 3 Adverse Events Reported by 5% or More of Adults Receiving ADDERALL X

with Higher

Incidence Than on Placebo in a 255 Patient Clinical Forced Weekly-Dose Titration Study*

Body System Preferred Term ADDERALL XR

(n=191)

Placebo

(n=64)

General

Asthenia

Headache

26%

13%

Digestive System

Loss of Appetite

Diarrhea

Dry Mouth

Nausea

33%

35%

Nervous System

Agitation

Anxiety

Dizziness

Insomnia

27%

13%

Cardiovascular System

Tachycardia 6% 3%

Metabolic/Nutritional

Weight Loss 11% 0%

Urogenital System

Urinary Tract Infection 5% 0%

Note: The following events 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, emotional lability, libido decreased, somnolence,

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

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*Included doses up to 60 mg.

The following adverse reactions have been associated with the use of amphetamine, ADDERALL XR

, or

ADDERALL

Cardiovascular: Palpitations, tachycardia, elevation of

blood pressure, sudden death, myocardial infarction.

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

Central Nervous System: Psychotic episodes at recom

mended doses, overstimulation, restlessness, dizziness,

insomnia, euphoria, dyskinesia, dysphoria, depression, tremor, headache, exacerbation of motor and phonic tics

and Tourette's syndrome, seizures, stroke.

Gastrointestinal: Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal

disturbances. Anorexia and weight loss m

ay occur as undesirable effects.

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.

DRUG ABUSE AND DEPENDENCE

ADDERALL XR

is a Schedule II controlled substance.

Amphetamines have been extensively abused. Tolerance, extrem

e psychological dependence, and severe social

disability have occurred. There are reports of patients who have increased the dosage to levels many times higher

than recommended. Abrupt cessation following prolonged high dosage administration results in extreme fatigue

and mental depression; changes are also noted on the sleep EEG. Manifestations of chronic intoxication with

amphetamines may include severe dermatoses, marked insomnia, irritability, hyperactivity, and personality

changes. The most severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable

from schizophrenia.

OVERDOSAGE

Individual patient response to amphetamines varies widely. Toxic symptoms may occur idiosyncratically at low

doses.

Symptoms: Manifestations of acute overdosage with amphetam

ines include restlessness, tremor, hyperreflexia,

rapid respiration, confusion, assaultiveness, hallucinations, panic states,

hyperpyrexia and rhabdomyolysis. Fatigue and depression usually

follow the central nervous system stimulation.

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. Managem

ent of

acute amphetamine intoxication is largely symptomatic and includes gastric lavage, administration of activated

charcoal, administration of a cathartic and sedation. Experience with hemodialysis or peritoneal dialysis is

inadequate to permit recommendation in this regard. Acidification of the urine increases amphetamine excretion,

but is believed to increase risk of acute renal failure if myoglobinuria is present. If acute severe hypertension

complicates amphetamine overdosage, administration of intravenous phentolamine has been suggested.

However, a gradual drop in blood pressure will usually result when sufficient sedation has been achieved.

Chlorpromazine antagonizes the central stimulant effects of amphetamines and can be used to treat amphetamine

intoxication.

The prolonged release of mixed amphetamine salts from ADDERALL XR

should be considered when treating

patients with overdose.

DOSAGE AND ADMINISTRATION

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Dosage should be individualized according to the therapeutic needs and response of the patient.

ADDERALL XR

should be administered at the lowest effective dosage.

Children

In children with ADHD who are 6 y

ears of age and older 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 is 30 mg/day; doses greater than 30 mg/day of ADDERALL XR

have not been studied in

children. Amphetamines are not recommended for children under 3 years of age. ADDERALL XR

has not been

studied in children under 6 years of age.

Adolescents

The recommended starting dose for adolescents who are 13-1

7 years of age with ADHD is 10 mg/day. The dose

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

Adults

In adults with ADHD who are either starting treatm

ent for the first time or switching from another

medication, the recommended dose is 20 mg/day.

Patients Currently Using ADDERALL

- Based on bioequivalence data, patients taking divided doses of

immediate-release ADDERALL

for example twice a day, 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

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, drug administration should be interrupted occasionally

to determine if there is a recurrence of

behavioral symptoms sufficient to require continued therapy.

HOW SUPPLIED:

ADDERALL XR

5 mg Capsules: Clear/blue (imprinted ADDERALL XR 5 mg), bottles of 100, NDC

54092-381-01

ADDERALL XR

10 mg Capsules: Blue/blue (imprinted ADDERALL XR 10 mg), bottles of 100, NDC

54092-383-01

ADDERALL XR

15 mg Capsules: Blue/white (imprinted ADDERALL XR 15 mg), bottles of 100, NDC

54092-385-01

ADDERALL XR

20 mg Capsules: Orange/orange (imprinted ADDERALL XR 20 mg), bottles of 100,

NDC 54092-387-01

ADDERALL XR

25 mg Capsules: Orange/white (imprinted ADDERALL XR 25 mg), bottles of 100, NDC

54092-389-01

ADDERALL XR

30 mg 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.

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Store at 25º C (77º F). Excursions permitted to 15-30º C (59-86º F) [see USP Controlled Room Temperature]

ANIMAL TOXICOLOGY

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

neurotoxic effects, including irreversible nerve fiber da

mage, in rodents. The significance of these findings to

humans is unknown.

Manufactured for Shire US Inc., Wayne, PA 19087. Made in USA.

For more information call 1-800-828-2088 or visit www.adderallxr.com

Pharmacist: Medication Guide to be dispensed to patients

ADDERALL XR

is registered in the US Patent and Trademark Office

ADDERALL



is a registered trademark of Shire LLC, under license to Duramed Pharmaceuticals, Inc.

XXXXXX

381 0107 0011 Rev. 3/07

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