ADDERALL (dextroamphetamine)
dextroamphetamine
Medicine that stimulates the brain
Quick Facts
Used For
Adderall is used to treat ADHD (Attention Deficit Hyperactivity Disorder) and Narcolepsy. ADHD makes it...
Common Side Effects
**Heart Problems** Fast or irregular heartbeat, high blood pressure, sudden death, heart...
Prescription
Not Required
Generic Available
No
Indications and Usage
Adderall is used to treat ADHD (Attention Deficit Hyperactivity Disorder) and Narcolepsy.
ADHD makes it hard to focus and sit still. Narcolepsy causes people to fall asleep suddenly during the day.
Adderall®(Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets (Mixed salts of a single entity amphetamine product)) is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and Narcolepsy.
Dosage and Administration
Start with the smallest dose that works for you. Your doctor will adjust your dose based on how well it works and how you feel.
Don’t take this medicine late in the evening because it can keep you awake at night.
Regardless of indication, amphetamines should be administered at the lowest effective dosage, and dosage should be individually adjusted according to the therapeutic needs and response of the patient. Late evening doses should be avoided because of the resulting insomnia.
Contraindications
Do not take Adderall if you are allergic to amphetamine or any part of this medicine. Some people have had serious allergic reactions like swelling or trouble breathing when taking similar medicines.
Do not take Adderall if you are taking MAOI medicines or stopped taking them less than 14 days ago. MAOIs include medicines like linezolid or IV methylene blue. Taking them together can cause dangerously high blood pressure.
In patients known to be hypersensitive to amphetamine, or other components of Adderall®. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products [seeADVERSE REACTIONS].
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 [seeWARNINGSandDRUG INTERACTIONS].
Warnings and Precautions
**WARNINGS**
**Drug Abuse and Addiction**
Adderall can be habit-forming and addictive. People may abuse this medicine or use it in ways that are not safe. This can lead to overdose and death. The risk is higher with larger doses or when people snort or inject the medicine.
Your doctor will check your risk for addiction before giving you this medicine. Keep Adderall in a safe, locked place. Never give your medicine to anyone else. Your doctor will watch for signs of abuse during treatment.
**Heart Problems**
People with serious heart problems who take stimulant medicines like Adderall may die suddenly. Do not use Adderall if you have heart defects, heart muscle disease, irregular heartbeat, or other serious heart problems.
**Higher Blood Pressure and Heart Rate**
Adderall can raise your blood pressure and make your heart beat faster. Your doctor will check your blood pressure and heart rate during treatment.
**Mental Health Problems**
**Worsening of Existing Mental Illness**
Adderall may make symptoms worse in people who already have psychosis or severe mental illness.
**Manic Episodes in People with Bipolar Disorder**
Adderall may trigger manic episodes in people with bipolar disorder. Your doctor will check for signs of bipolar disorder before starting treatment.
**New Mental Health Symptoms**
Adderall can cause hallucinations, delusions, or mania even in people who never had these problems before. This happens in about 1 out of 1000 people who take stimulant medicines. Tell your doctor right away if you have these symptoms.
**Slowed Growth in Children**
Stimulant medicines can cause weight loss and slower growth in children. Your doctor will check your child’s height and weight regularly. Treatment may need to be stopped if your child is not growing normally.
**Seizures**
Adderall may cause seizures in some people, especially those who have had seizures before. Stop taking Adderall if you have a seizure.
**Blood Flow Problems in Fingers and Toes**
Adderall can cause blood flow problems in your fingers and toes. Signs include:
• Numbness, coolness, or pain in fingers or toes
• Color changes from pale to blue to red
• Sores or wounds on fingers or toes
Tell your doctor right away if you notice these symptoms.
**Serotonin Syndrome**
Taking Adderall with certain other medicines can cause a dangerous condition called serotonin syndrome. This can be life-threatening. It can happen when Adderall is taken with:
• Antidepressants (SSRIs, SNRIs, tricyclics)
• Migraine medicines (triptans)
• Pain medicines (fentanyl, tramadol)
• Other medicines like lithium or St. John’s Wort
Signs of serotonin syndrome include:
• Confusion, hallucinations, or coma
• Fast heartbeat or blood pressure changes
• Fever, sweating, or flushing
• Muscle stiffness or twitching
• Nausea, vomiting, or diarrhea
• Seizures
Get emergency help right away if you have these symptoms.
**Tics and Tourette’s Syndrome**
Adderall can cause new tics (sudden movements or sounds) or make existing tics worse. It can also worsen Tourette’s syndrome. Your doctor will check for tics before starting treatment and watch for them during treatment.
**PRECAUTIONS**
**Information for Patients**
Read the Medication Guide that comes with your prescription.
**Drug Abuse and Addiction**
Learn about the risks of abuse and addiction with Adderall. Store your medicine safely, preferably locked up. Never give Adderall to anyone else. Dispose of unused medicine properly.
**Heart Problems**
Tell your doctor right away if you have chest pain during exercise, fainting, or other signs of heart problems.
**Blood Pressure and Heart Rate**
Know that Adderall can raise your blood pressure and heart rate.
**Mental Health Problems**
Adderall can cause mental health symptoms even in people who never had them before.
**Growth Problems in Children**
Adderall may slow growth and cause weight loss in children.
**Blood Flow Problems in Fingers and Toes**
Watch for numbness, pain, color changes, or wounds on your fingers or toes. Call your doctor right away if you notice unexplained wounds.
**Serotonin Syndrome**
Be careful about taking Adderall with other medicines that affect serotonin. Get emergency help if you have symptoms of serotonin syndrome.
**Tics and Tourette’s Syndrome**
Tell your doctor if you develop new tics or if existing tics get worse.
**Drug Interactions**
**MAO Inhibitors**
Do not take Adderall with MAO inhibitors or within 14 days of stopping an MAO inhibitor. This combination can cause dangerously high blood pressure and may lead to stroke, heart attack, or death.
**Serotonin Medicines**
Taking Adderall with medicines that affect serotonin increases the risk of serotonin syndrome. Your doctor may start with lower doses and watch you closely.
**Other Drug Interactions**
Adderall can interact with many other medicines, including:
• Medicines that change stomach acid levels
• Blood pressure medicines
• Antidepressants
• Seizure medicines
• Pain medicines
Tell your doctor about all medicines you take.
**Pregnancy and Breastfeeding**
**Pregnancy**
Animal studies show that Adderall may harm an unborn baby. There are not enough studies in pregnant women. Use Adderall during pregnancy only if the benefits outweigh the risks.
Babies born to mothers who used amphetamines may be born early, weigh less, or have withdrawal symptoms.
**Breastfeeding**
Adderall passes into breast milk. Do not breastfeed while taking Adderall.
**Use in Children and Older Adults**
**Children**
The long-term effects of Adderall in children are not fully known. Do not give Adderall to children under 3 years old.
**Older Adults**
Adderall has not been studied in people over 65 years old.
=== WARNINGS ===
Abuse, Misuse, and Addiction
Adderall
®
has a high potential for abuse and misuse. The use of Adderall
®
exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Adderall
®
can be diverted for non-medical use into illicit channels or distribution [see
DRUG ABUSE AND DEPENDENCE
: Abuse]. Misuse and abuse of CNS stimulants, including Adderall
®
, can result in overdose and death [see
OVERDOSAGE
], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
Before prescribing Adderall
®
assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks and proper disposal of any unused drug. Advise patients to store amphetamine sulfate in a safe place, preferably locked, and instruct patients to not give Adderall
®
to anyone else. Throughout Adderall
®
treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
Risks to Patients with Serious Cardiac Disease
Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulant treatment at the recommended ADHD dosages.
Avoid Adderall
®
use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.
Increased Blood Pressure and Heart Rate
CNS stimulants cause an increase in blood pressure (mean increase about 2 to 4 mm Hg) and heart rate (mean increase about 3 to 6 bpm). Some patients may have larger increases. Monitor all Adderall
®
-treated patients for potential tachycardia and hypertension.
Psychiatric Adverse Reactions
Exacerbation
of Preexisting Psychosis
CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.
Induction
of a Manic Episode in Patients with Bipolar
Disorder
CNS stimulants may induce a manic or mixed episode in patients. Prior to initiating treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression).
New Psychotic or Manic Symptoms
CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared with 0% of placebo-treated patients. If such symptoms occur, consider discontinuing Adderall
®
.
Long-Term Suppression of Growth in Pediatric Patients
CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Closely monitor growth (weight and height) in Adderall
®
-treated pediatric patients treated with CNS stimulants.
Pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see
PRECAUTIONS
,
PEDIATRIC USE
].
Seizures
There is some clinical evidence that stimulants 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.
Peripheral Vasculopathy, Including Raynaud’s Phenomenon
Stimulants, including Adderall
®
, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in postmarketing reports and at the therapeutic dosage of CNS stimulants in all age groups throughout the course of treatment. Signs and symptoms generally improved after dosage reduction or discontinuation of the CNS stimulant. Careful observation for digital changes is necessary during Adderall
®
treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for Adderall
®-
treated patients who develop signs or symptoms of peripheral vasculopathy.
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 monoamine oxidase inhibitors (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
]. The coadministration with cytochrome P450 (CYP2D6) inhibitors increase the risk with increased exposure to Adderall
®
. In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 [see
DRUG INTERACTIONS
].
Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., 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
®
with MAOI drugs is contraindicated [see
CONTRAINDICATIONS
].
Discontinue treatment with Adderall
®
and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Adderall
®
with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate Adderall
®
with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome.
Motor and Verbal Tics, and Worsening of
Tourette’s Syndrome
CNS stimulants, including amphetamine sulfate, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette’s syndrome has also been reported. Before initiating Adderall
®
, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome with Adderall
®
, and discontinue treatment if clinically appropriate.
=== PRECAUTIONS ===
Information for Patients
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Abuse, Misuse, and Addiction
Educate patients and their families about the risks of abuse, misuse, and addiction of Adderall
®
, which can lead to overdose and death, and proper disposal of any unused drug [see
WARNINGS
,
DRUG ABUSE AND DEPENDENCE
,
OVERDOSAGE
]. Advise patients to store Adderall
®
in a safe place, preferably locked, and instruct patients to not give Adderall
®
to anyone else.
Risks to Patients with Serious Cardiac Disease
Advise patients that there are potential risks to patients with serious cardiac disease, including sudden death, with Adderall
®
use. Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease [see
WARNINGS
].
Increased Blood Pressure and Heart Rate
Advise patients that Adderall
®
can elevate blood pressure and heart rate [see
WARNINGS
].
Psychiatric Adverse Reactions
Advise patients that Adderall
®
, at recommended doses, can cause psychotic or manic symptoms, even in patients without prior history of psychotic symptoms or mania [see
WARNINGS
].
Long-Term Suppression of Growth in Pediatric Patients
Advise patients that Adderall
®
may cause slowing of growth including weight loss [see
WARNINGS
].
Circulation Problems in Fingers and Toes [Peripheral Vasculopathy, Including Raynaud’s Phenomenon]
Instruct patients beginning treatment with Adderall
®
about the risk of peripheral vasculopathy, including Raynaud’s phenomenon, and 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
®
.
Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.
Serotonin Syndrome
Caution patients about the risk of serotonin syndrome with concomitant use of Adderall
®
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
,
WARNINGS
, and
DRUG INTERACTIONS
]. Advise patients to contact their healthcare provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome.
Motor
and Verbal Tics, and Worsening of Tourette’s Syndrome
Advise patients that motor and verbal tics and worsening of Tourette’s Syndrome may occur during treatment with Adderall
®
. Instruct the patients to notify their healthcare provider if emergence or worsening of tics or Tourette’s syndrome occurs [see
WARNINGS
].
Drug Interactions
MAO Inhibitors
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. Do not administer Adderall
®
concomitantly or within 14 days after discontinuing MAOI [see
CONTRAINDICATIONS
and
WARNINGS
].
Serotonergic Drugs
The concomitant use of Adderall
®
and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during Adderall
®
initiation or dosage increase. If serotonin syndrome occurs, discontinue Adderall
®
and the concomitant serotonergic drug(s) [see
WARNINGS
and
PRECAUTIONS
].
CYP2D6 Inhibitors
The concomitant use of Adderall
®
and CYP2D6 inhibitors may increase the exposure of Adderall
®
compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during Adderall
®
initiation and after a dosage increase. If serotonin syndrome occurs, discontinue Adderall
®
and the CYP2D6 inhibitor [see
WARNINGS
,
OVERDOSAGE
].
Acidifying Agents
Lower blood levels and efficacy of amphetamines. Increase dose based on clinical response. Examples of acidifying agents include gastrointestinal acidifying agents and urinary acidifying agents.
Adrenergic Blockers
Adrenergic blockers are inhibited by amphetamines.
Alkalinizing Agents
Increase blood levels and potentiate the action of amphetamine. Co-administration of Adderall
®
and gastrointestinal alkalinizing agents should be avoided. Examples of alkalinizing agents include gastrointestinal alkalinizing agents and urinary alkalinizing agents.
Tricyclic Antidepressants
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. Monitor frequently and adjust or use alternative therapy based on clinical response.
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; coadministration of phenobarbital may produce a synergistic anticonvulsant action.
Phenytoin
Amphetamines may delay intestinal absorption of phenytoin; coadministration of phenytoin may produce a synergistic anticonvulsant action.
Propoxyphene
In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.
Proton Pump Inhibitors
Time to maximum concentration (T
max
) of amphetamine is decreased compared to when administered alone. Monitor patients for changes in clinical effect and adjust therapy based on clinical response. An example of a proton pump inhibitor is omeprazole.
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.
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
2
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
2
body surface area basis).
Pregnancy
Teratogenic Effects
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/m
2
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
2
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
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 with Attention Deficit Hyperactivity Disorder described under
INDICATIONS AND USAGE
.
Geriatric Use
Adderall
®
has not been studied in the geriatric population.
Adverse Reactions
**Heart Problems**
Fast or irregular heartbeat, high blood pressure, sudden death, heart attack. Some people who use amphetamines for a long time may develop heart muscle problems.
**Brain and Nervous System**
Seeing or hearing things that aren’t there, feeling overly excited, restlessness, irritability, feeling very happy, unusual movements, feeling sad, shaking, muscle or speech tics, aggression, anger, talking too much, picking at skin.
**Eye Problems**
Blurred vision, pupils that stay large.
**Stomach and Digestion**
Dry mouth, bad taste, diarrhea, constipation, reduced blood flow to intestines, and other stomach problems. Loss of appetite and weight loss may happen.
**Allergic Reactions**
Hives, rash, allergic reactions including swelling of face or throat and severe allergic reactions. Serious skin rashes that can be life-threatening have been reported.
**Hormone Problems**
Problems getting an erection, changes in sex drive, erections that happen often or last too long.
**Skin**
Hair loss.
**Muscles**
Muscle breakdown that can damage kidneys.
To report side effects, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, motor and verbal tics, aggression, anger, logorrhea, dermatillomania.
Eye Disorders
Vision blurred, mydriasis.
Gastrointestinal
Dryness of the mouth, unpleasant taste, diarrhea, constipation, intestinal ischemia, and other gastrointestinal disturbances. Anorexia and weight loss may 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, frequent or prolonged erections.
Skin
Alopecia.
Musculoskeletal
Rhabdomyolysis.
To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Abuse and Dependence
**Controlled Substance**
Adderall contains amphetamine, which is a controlled drug that the government watches closely.
**Abuse**
Adderall can be habit-forming and addictive. People may abuse this medicine, which can lead to serious drug problems. Some people sell or give away Adderall illegally.
Abuse means using a drug to get high or feel different, even just once. Misuse means taking your medicine in the wrong way or taking someone else’s medicine. Drug addiction happens when someone cannot control their drug use and keeps using it even when it hurts them.
Using Adderall the wrong way can cause:
• Fast heartbeat and breathing
• High blood pressure
• Sweating and big pupils
• Being overly active or restless
• Trouble sleeping
• Not wanting to eat
• Shaking and red skin
• Throwing up and stomach pain
It can also cause anxiety, seeing things that are not there, anger, and thoughts of hurting yourself or others. Taking too much Adderall or using it in dangerous ways like snorting or injecting can cause overdose and death.
**Dependence**
**Physical Dependence**
Your body can become dependent on Adderall. This means your body gets used to the medicine and needs it to feel normal.
If you stop taking Adderall suddenly after using it for a long time, you may have withdrawal symptoms:
• Feeling sad or depressed
• Being very tired
• Bad dreams
• Sleeping too much or too little
• Wanting to eat more
• Moving very slowly or being restless
**Tolerance**
Over time, you may need higher doses of Adderall to get the same effect. This is called tolerance.
Controlled Substance
Adderall
®
contains amphetamine, a Schedule II controlled substance.
Abuse
Adderall
®
has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction [see
WARNINGS
and
PRECAUTIONS
]. Adderall
®
can be diverted for non-medical use into illicit channels or distribution.
Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.
Misuse and abuse of amphetamines may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with CNS stimulants abuse and/or misuse. Misuse and abuse of CNS stimulants, including Adderall
®
, can result in overdose and death [see
OVERDOSAGE
], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
Dependence
Physical Dependence
Adderall
®
may produce physical dependence. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.
Withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of CNS stimulants including Adderall
®
include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.
Tolerance
Adderall
®
may produce tolerance. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
Description
Adderall contains a mix of four different amphetamine salts that work together as the active medicine.
Other ingredients that don’t affect how the medicine works: silicon dioxide, sugar, corn starch, magnesium stearate, cellulose, and saccharin sodium.
Colors:
• 5 mg Adderall is white with no added colors
• 7.5 mg and 10 mg contain blue coloring
• 12.5 mg, 15 mg, 20 mg and 30 mg contain yellow coloring
+——————————————+————+————-+———–+————-+————+———–+———–+
| EACH TABLET CONTAINS | 5 mg | 7.5 mg | 10 mg | 12.5 mg | 15 mg | 20 mg | 30 mg |
+——————————————+————+————-+———–+————-+————+———–+———–+
| DextroamphetamineSaccharate | 1.25 mg | 1.875 mg | 2.5 mg | 3.125 mg | 3.75 mg | 5 mg | 7.5 mg |
| Amphetamine Aspartate Monohydrate Equ… | 1.25 mg1 | 1.875 mg2 | 2.5 mg3 | 3.125 mg4 | 3.75 mg5 | 5 mg6 | 7.5 mg7 |
| DextroamphetamineSulfate, USP | 1.25 mg | 1.875 mg | 2.5 mg | 3.125 mg | 3.75 mg | 5 mg | 7.5 mg |
| AmphetamineSulfate, USP | 1.25 mg | 1.875 mg | 2.5 mg | 3.125 mg | 3.75 mg | 5 mg | 7.5 mg |
| Total Amphetamine Base Equivalence | 3.13 mg | 4.7 mg | 6.3 mg | 7.8 mg | 9.4 mg | 12.6 mg | 18.8 mg |
+——————————————+————+————-+———–+————-+————+———–+———–+
A single-entity amphetamine product combining the neutral sulfate salts of dextroamphetamine and amphetamine, with the dextro isomer of amphetamine saccharate and d, l-amphetamine aspartate.
Inactive Ingredients:colloidal silicon dioxide, compressible sugar (sucrose and maltodextrin), corn starch, magnesium stearate, microcrystalline cellulose and saccharin sodium.
Colors:Adderall®5 mg is a white to off-white tablet, which contains no color additives.
Adderall®7.5 mg and 10 mg contain FD&C Blue #1 Aluminum Lake as a color additive.
Adderall®12.5 mg, 15 mg, 20 mg and 30 mg contain FD&C Yellow #6 Aluminum Lake as a color additive.
================================================================================
TABLE: Table
================================================================================
+——————————————+————+————-+———–+————-+————+———–+———–+
| EACH TABLET CONTAINS | 5 mg | 7.5 mg | 10 mg | 12.5 mg | 15 mg | 20 mg | 30 mg |
+——————————————+————+————-+———–+————-+————+———–+———–+
| DextroamphetamineSaccharate | 1.25 mg | 1.875 mg | 2.5 mg | 3.125 mg | 3.75 mg | 5 mg | 7.5 mg |
| Amphetamine Aspartate Monohydrate Equ… | 1.25 mg1 | 1.875 mg2 | 2.5 mg3 | 3.125 mg4 | 3.75 mg5 | 5 mg6 | 7.5 mg7 |
| DextroamphetamineSulfate, USP | 1.25 mg | 1.875 mg | 2.5 mg | 3.125 mg | 3.75 mg | 5 mg | 7.5 mg |
| AmphetamineSulfate, USP | 1.25 mg | 1.875 mg | 2.5 mg | 3.125 mg | 3.75 mg | 5 mg | 7.5 mg |
| Total Amphetamine Base Equivalence | 3.13 mg | 4.7 mg | 6.3 mg | 7.8 mg | 9.4 mg | 12.6 mg | 18.8 mg |
+——————————————+————+————-+———–+————-+————+———–+———–+
Mechanism of Action
How This Medicine Works
Adderall contains chemicals that stimulate your brain. We don’t know exactly how it helps with ADHD. The medicine seems to increase certain brain chemicals called norepinephrine and dopamine. This happens by blocking their removal and increasing their release in your brain.
How Your Body Processes This Medicine
Adderall tablets contain two types of amphetamine in a 3 to 1 ratio. When healthy people took a single 10 mg or 30 mg dose without food, the medicine reached its highest level in the blood about 3 hours later. One type of amphetamine left the body faster than the other (9.77 to 11 hours vs. 11.5 to 13.8 hours). When people took 30 mg instead of 10 mg, the amount in their blood was about three times higher.
We don’t know if taking this medicine with food changes how well it works.
How Your Body Breaks Down and Gets Rid of This Medicine
Your body changes amphetamine into other chemicals through several steps. It can be broken down in different parts of the molecule to form chemicals like 4-hydroxyamphetamine, alpha-hydroxy-amphetamine, or norephedrine. Some of these new chemicals are still active in your body. They get broken down further into other substances, and eventually form benzoic acid and hippuric acid.
We don’t know all the enzymes that break down amphetamine, but we know one called CYP2D6 is involved. Since people have different versions of this enzyme, some people may process amphetamine differently than others.
Amphetamine can interfere with an enzyme called monoamine oxidase. Lab tests show it might also interfere with other enzymes, but we’re not sure if this happens in real people.
About half of the amphetamine dose comes out in your urine as breakdown products, and 30% to 40% comes out unchanged. How much comes out in urine depends a lot on how acidic your urine is and how much you urinate. When urine is more basic (alkaline), less amphetamine is removed and it stays in your body longer. When urine is more acidic and you urinate more, more amphetamine is removed quickly.
The amount of amphetamine found in urine can range from 1% to 75% depending on urine acidity. The rest is broken down by your liver. If your liver or kidneys don’t work well, amphetamine might stay in your body longer. Medicines that change how acidic your urine is can also change how quickly amphetamine leaves your body.
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
Adderall
®
tablets contain d-amphetamine and l-amphetamine salts in the ratio of 3:1. Following administration of a single dose 10 or 30 mg of Adderall
®
to healthy volunteers under fasted conditions, peak plasma concentrations occurred approximately 3 hours post-dose for both d-amphetamine and l-amphetamine. The mean elimination half-life (t
1/2
) for d-amphetamine was shorter than the t
1/2
of the l-isomer (9.77 to 11 hours vs. 11.5 to 13.8 hours). The PK parameters (C
max
, AUC
0-inf
) of d-and l-amphetamine increased approximately three-fold from 10 mg to 30 mg indicating dose-proportional pharmacokinetics.
The effect of food on the bioavailability of Adderall
®
has not been studied.
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% to 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 affect 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
].