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Adderall

ADDERALL XR is a once-daily treatment for all types of attention-deficit/hyperactivity disorder (ADHD). ADDERALL XR capsules contain a mixture of different amphetamine salts. ADDERALL XR is thought to act as a dopamine/norepinephrine modulating agent, which means it helps restore a balance of these chemicals (called neurotransmitters) in those areas of the brain that control our ability to focus and pay attention to tasks. Medications like ADDERALL XR have been successfully used to treat ADHD since 1937, making them one of the oldest and most extensively studied continuously prescribed types of medication on the market.

What do neurotransmitters do and how does ADDERALL XR affect them? Dopamine (DA) and norepinephrine (NE) help the brain send signals between nerve cells. Many scientists generally believe that when there are not enough of these chemicals, the signals are not received and acted on properly. It is thought that ADDERALL XR causes more DA and NE to be available to normalize the signal transmission in the brain.

ADDERALL Lawyers have started to take cases for Adderall lawsuits due to injuries or death related to Adderall side effects. If you or someone you love has experienced Adderall side effects you should consult with an Adderall attorney about an Adderall lawsuit. There are many Mass Tort lawyers working on Adderall lawsuits that are qualified to assist you in Adderall litigation. Here are some Adderall lawyers that I have found that are taking Adderall lawsuits:

Adderall Lawsuits - National Mass Tort Lawyers

Parker & Waichman - NY City

Adderall, is used by approximately 700,000 Americans and is one of the most popular drugs for people with the widely-diagnosed condition known as attention deficit hyperactivity disorder. Shire Pharmaceuticals Group PLC sold $759 million of Adderall XR in the U.S. last year and roughly $10 million in Canada.

Canadian regulators issued an Adderall recall due to serious Adderall side effects. Health Canada issued the Adderall recall after reports of 20 sudden deaths.

In a one-page letter to the company, the Canadian regulatory agency, Health Canada, said the "identified risk of sudden death following the recommended doses cannot be managed by label changes." The company said there have been 20 reports of sudden Adderall death's in patients using Adderall extended release and a prior formulation of the medicine since 1994, when Adderall first came on the market.

In a news release, Health Canada said "the incidence of serious adverse reactions leading to death was higher in" the Adderall extended release and earlier formulations of Adderall, when added together, than in other drugs in the same class. Here, the Canadian agency's conclusion appears to differ from that of the FDA. Of the 20 deaths reported in patients taking Adderall, 12 were from strokes, two in children, Health Canada said.

Below is the prescription information provided by SHIRE:

ADDERALL XR® CAPSULES CII Rx Only
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 Hyperactivity 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 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 (Tmax) 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.
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 bid (8 am 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-lives for d-amphetamine and l-amphetamine in adults are 10 hours and 13 hours,
respectively. In children aged 6 to 12 years, the mean elimination half-life is 1 hour shorter for d-amphetamine
(9 hours) and 2 hours shorter for l-amphetamine (11 hours). Children had higher systemic exposure to
amphetamine (Cmax 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.
ADDERALL XR® demonstrates linear pharmacokinetics over the dose range of 20 to 60 mg in adults 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 Tmax 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®
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.
Special Populations
Pediatric Patients
Children eliminated amphetamine faster than adults. The elimination half-life (t1/2) 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 (Cmax 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 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 (Cmax and AUC)
were normalized by dose (mg/kg), these differences diminished.
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).
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 XR®
demonstrated statistically significant improvements in teacher-rated behavior and performance measures,
compared to patients treated with placebo.
Adults
A double-blind, randomized, placebo-controlled, parallel-group study was conducted in adults (N=255) who met
DSM-IV-TR 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, 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 hyperactiveimpulsive
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 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 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, moderate 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 monoamine oxidase inhibitors (hypertensive crises may
result).
WARNINGS
Psychosis: Clinical experience suggests that, in psychotic patients, administration of amphetamine may
exacerbate symptoms of behavior disturbance and thought disorder.
Long-Term Suppression of Growth: Data are inadequate to determine whether chronic use of stimulants in
children, including amphetamine, may be causally associated with suppression of growth. Therefore, growth
should be monitored during treatment, and patients who are not growing or gaining weight as expected should
have their treatment interrupted.
Sudden Death and Pre-existing Structural Cardiac Abnormalities: Sudden death has been reported in
association with amphetamine treatment at usual doses in children with structural cardiac abnormalities.
Adderall XR® generally should not be used in children or adults with structural cardiac abnormalities.
PRECAUTIONS
General: The least amount of amphetamine feasible should be prescribed or dispensed at one time in order to
minimize the possibility of overdosage.
Hypertension: Caution is to be exercised in prescribing amphetamines for patients with even mild hypertension
(see CONTRAINDICATIONS). Blood pressure and pulse should be monitored at appropriate intervals in patients
taking ADDERALL XR®, especially patients with hypertension.
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 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 machinery or vehicles; the patient should therefore be cautioned accordingly.
Drug Interactions: Acidifying agents—Gastrointestinal acidifying agents (guanethidine, reserpine, glutamic acid
HCI, 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
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—Amphetamines 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 antidepressants, 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—Amphetamines may counteract the sedative effect of antihistamines.
Antihypertensives—Amphetamines may antagonize the hypotensive effects of antihypertensives.
Chlorpromazine—Chlorpromazine blocks dopamine and norepinephrine receptors, thus inhibiting the central
stimulant effects of amphetamines, and can be used to treat amphetamine poisoning.
Ethosuximide—Amphetamines may delay intestinal absorption of ethosuximide.
Haloperidol—Haloperidol blocks dopamine receptors, thus inhibiting the central stimulant effects of
amphetamines.
Lithium carbonate—The anorectic and stimulatory effects of amphetamines may be inhibited by lithium
carbonate.
Meperidine—Amphetamines 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—Amphetamines enhance the adrenergic effect of norepinephrine.
Phenobarbital—Amphetamines may delay intestinal absorption of phenobarbital; co-administration of
phenobarbital may produce a synergistic anticonvulsant action.
Phenytoin—Amphetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may
produce a synergistic anticonvulsant action.
Propoxyphene—In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal
convulsions can occur.
Veratrum alkaloids—Amphetamines inhibit the hypotensive effect of veratrum alkaloids.
Drug/Laboratory Test Interactions: Amphetamines can cause a significant elevation in plasma corticosteroid
levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.
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.
0
0 4 8 12 16 24 20
5
10
15
20
25
30
TIME (HOURS)
MEAN PLASMA CONCENTRATIONS OF DEXTRO AND LEVOAMPHETAMINE (ng/mL)
DEXTROAMPHETAMINE
LEVOAMPHETAMINE
ADDERALL XR® 20 mg qd
ADDERALL® 10 mg bid
ADDERALL® 10 mg bid
ADDERALL XR® 20 mg qd
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/m2 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 vitrosister 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/m2 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
dose of 30 mg/day [child] on a mg/m2 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/m2 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 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.
There are no adequate and well-controlled studies in pregnant women. 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
The premarketing development program for ADDERALL XR® included exposures in a total of 965 participants in
clinical trials (635 pediatric patients, 248 adult patients, 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 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
treatment-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 among 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 one placebo-controlled 4-week study among adults with ADHD, patients who discontinued treatment 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 adults treated with ADDERALL XR® or 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 XR® with
Higher Incidence Than on Placebo in a 584 Patient Clinical Study
Body System Preferred Term ADDERALL XR® (n=374) Placebo (n=210)
General Abdominal Pain (stomachache) 14% 10%
Accidental Injury 3% 2%
Asthenia (fatigue) 2% 0%
Fever 5% 2%
Infection 4% 2%
Viral Infection 2% 0%
Digestive Loss of Appetite 22% 2%
System Diarrhea 2% 1%
Dyspepsia 2% 1%
Nausea 5% 3%
Vomiting 7% 4%
Nervous System Dizziness 2% 0%
Emotional Lability 9% 2%
Insomnia 17% 2%
Nervousness 6% 2%
Metabolic/Nutritional Weight Loss 4% 0%
Table 2 Adverse Events 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 XR® (n=191) Placebo (n=64)
General Asthenia 6% 5%
Headache 26% 13%
Digestive System Loss of Appetite 33% 3%
Diarrhea 6% 0%
Dry Mouth 35% 5%
Nausea 8% 3%
Nervous System Agitation 8% 5%
Anxiety 8% 5%
Dizziness 7% 0%
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 2 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.
*included doses up to 60 mg.
The following adverse reactions have been associated with amphetamine use:
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 recommended 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 may occur as undesirable effects.
Allergic: Urticaria.
Endocrine: Impotence, changes in libido.
DRUG ABUSE AND DEPENDENCE
ADDERALL XR® is a Schedule II controlled substance.
Amphetamines have been extensively abused. Tolerance, extreme psychological dependence, and severe social
disability have occurred. There are reports of patients who have increased the dosage to many times that
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 amphetamines 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. Management 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
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 years 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.
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.
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.
Store at 25° C (77° F). Excursions permitted to 15-30° C (59-86° 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 damage, 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
ADDERALL® and ADDERALL XR® are registered in the US Patent and Trademark Office
Copyright ©2004 Shire US Inc.
001268
381 0107 005 Rev. 11/04
A-PI