Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Dailymed

Warning: Abuse, Misuse, And Addiction

MAS-ER Capsules have a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including MAS-ER Capsules, can result in overdose and death [see Overdosage (10)], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.

Before prescribing MAS-ER Capsules, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug. Throughout MAS-ER Capsule treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction [see Warnings and Precautions (5.1), Drug Abuse and Dependence (9.2)].


WARNING: ABUSE, MISUSE, AND ADDICTION

See full prescribing information for complete boxed warning.

MAS-ER Capsules has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including MAS-ER Capsules, can result in overdose and death (5.1, 9.2, 10):

• Before prescribing MAS-ER Capsules, assess each patient’s risk for abuse, misuse, and addiction.
• Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug.
• Throughout treatment, reassess each patient’s risk and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

• Pediatric patients (ages 6 to 17): 10 mg once daily in the morning. Maximum dose for children 6 to 12 years of age is 30 mg once daily. (2.2, 2.3, 2.4)
• Adults: 20 mg once daily in the morning. (2.5)
• Pediatric patients (ages 6 to 17) with severe renal impairment: 5 mg once daily in the morning. Maximum dose for children 6 to 12 years of age with severe renal impairment is 20 mg once daily. (2.6, 8.6)
• Adults with severe renal impairment: 15 mg once daily in the morning. (2.6, 8.6)
• Patients with ESRD: Not recommended. (2.6, 8.6)

2.1 Pretreatment Screening

Prior to treating patients with MAS-ER Capsules, assess:

• for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions (5.2)].
• the family history and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome before initiating MAS-ER Capsules [see Warnings and Precautions (5.9)].

2.2 General Administration Information

Individualize the dosage according to the therapeutic needs and response of the patient. Administer MAS-ER Capsules at the lowest effective dosage.

Based on bioequivalence data, patients taking divided doses of immediate-release Adderall, (for example, twice daily), may be switched to MAS-ER Capsules at the same total daily dose taken once daily. Titrate at weekly intervals to appropriate efficacy and tolerability as indicated.

MAS-ER 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.

MAS-ER Capsules may be taken orally with or without food.

MAS-ER Capsules should be given upon awakening. Afternoon doses should be avoided because of the potential for insomnia.

2.3Recommended Dosage in Pediatric Patients 6 to 12 Years

In pediatric patients 6 to 12 years of age with ADHD and are either starting treatment for the first time or switching from another medication, start with 10 mg once daily in the morning; daily dosage may be adjusted in increments of 5 mg or 10 mg at weekly intervals. When in the judgment of the clinician a lower initial dose is appropriate, patients may begin treatment with 5 mg once daily in the morning. The maximum recommended dose for children 6 to 12 years of age is 30 mg/day; doses greater than 30 mg/day have not been studied in children. MAS-ER Capsules has not been studied in children under 6 years of age.

2.4 Recommended Dosage in Pediatric Patients 13 to 17 Years

The recommended starting dose for pediatric patients 13 to 17 years of age with ADHD and are either starting treatment for the first time or switching from another medication is 10 mg/day. The dose may be increased to 20 mg/day after one week if ADHD symptoms are not adequately controlled.

2.5 Recommended Dosage in 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.

2.6Dosage in Patients with Renal Impairment

In adult patients with severe renal impairment (GFR 15 to <30 mL/min/1.73 m²), the recommended dose is 15 mg once daily in the morning. In pediatric patients (6 to 17 years of age) with severe renal impairment, the recommended dose is 5 mg once daily. The maximum dose for children 6 to 12 years of age with severe renal impairment is 20 mg once daily. MAS-ER Capsules are not recommended in patients with end stage renal disease (ESRD) (GFR <15 mL/min/1.73 m²) [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.7Dosage Modification Due to Drug Interactions

Agents that alter urinary pH can impact excretion and alter blood levels of amphetamines. Acidifying agents (e.g., ascorbic acid) decrease blood levels; adjust MAS-ER Capsules dosage based on clinical response [see Drug Interactions (7)].

3 Dosage Forms And Strengths

5 mg extended-release capsules: Clear/blue (imprinted M. Amphet Salts 5 mg) 10 mg extended-release capsules: Blue/blue (imprinted M. Amphet Salts 10 mg) 15 mg extended-release capsules: Blue/white (imprinted M. Amphet Salts 15 mg) 20 mg extended-release capsules: Orange/orange (imprinted M. Amphet Salts 20 mg) 25 mg extended-release capsules: Orange/white (imprinted M. Amphet Salts 25 mg) 30 mg extended-release capsules: Natural/orange (imprinted M. Amphet Salts 30 mg)


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

4 Contraindications

MAS-ER Capsules administration is contraindicated in patients:

• known to be hypersensitive to amphetamine, or other components of MAS-ER Capsules. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products [see Adverse Reactions (6.2)].
• taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs (including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis [see Warnings and Precautions (5.8), Drug Interactions (7.1)]

• Known hypersensitivity or idiosyncrasy to amphetamine (4)
• During or within 14 days following the administration of monoamine oxidase inhibitors (MAOI) (4, 7.1)

5 Warnings And Precautions

• Risks to Patients with Serious Cardiac Disease: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease. (5.2)
• Increased Blood Pressure and Heart Rate: Monitor blood pressure and pulse at appropriate intervals. (5.3)
• Psychiatric Adverse Reactions: Prior to initiating MAS-ER Capsules, screen patients for risk factors for developing a manic episode. If new psychotic or manic symptoms occur, consider discontinuing MAS-ER Capsules. (5.4)
• Long-Term Suppression of Growth in Pediatric Patients: Closely monitor growth (height and weight) in pediatric patients. Pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted. (5.5)
• Seizures: May lower the convulsive threshold. Discontinue in the presence of seizures. (5.6)
• Peripheral Vasculopathy, Including Raynaud’s Phenomenon: Careful observation for digital changes is necessary during MAS-ER Capsule treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy. (5.7)
• Serotonin Syndrome: Increased risk when coadministered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations. If it occurs, discontinue MAS-ER Capsules and initiate supportive treatment. (4, 5.8, 10)
• Motor and Verbal Tics, and Worsening of Tourette’s Syndrome: Before initiating MAS-ER Capsules, 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. Discontinue treatment if clinically appropriate. (5.9)

5.1 Abuse, Misuse, and Addiction

MAS-ER Capsules have a high potential for abuse and misuse. The use of MAS-ER Capsules exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. MAS-ER Capsules can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse and Dependence (9.2)]. Misuse and abuse of CNS stimulants, including MAS-ER Capsules, can result in overdose and death [see Overdosage (10)], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.

Before prescribing MAS-ER Capsules, 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 MAS-ER Capsules in a safe place, preferably locked, and instruct patients to not give MAS-ER Capsules to anyone else. Throughout MAS-ER Capsule treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

5.2 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 stimulants at the recommended ADHD dosage. Avoid MAS-ER Capsule use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.

5.3Increased Blood Pressure and Heart Rate

CNS stimulants may cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 bpm).

Monitor all MAS-ER Capsule-treated patients for hypertension and tachycardia.

5.4Psychiatric Adverse Reactions

Exacerbation of Pre-Existing Psychosis Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with pre-existing psychotic disorder.

Induction of a Manic Episode in Patients with Bipolar Disease CNS stimulants may induce a manic or mixed episode in patients. Prior to initiating MAS-ER Capsule 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 the recommended dosage, 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 to 0% of placebo-treated patients. If such symptoms occur, consider discontinuing MAS-ER Capsules.

5.5Long-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 MAS-ER Capsule-treated pediatric patients treated with CNS stimulants.

In a controlled trial of MAS-ER Capsules 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 and 20 mg MAS-ER Capsules. Higher doses were associated with greater weight loss within the initial 4 weeks of treatment. Chronic use of amphetamines can be expected to cause a similar suppression of growth [see Adverse Reactions (6.1)].

Pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted.

5.6Seizures

There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in the absence of seizures, and very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, MAS-ER Capsules should be discontinued.

5.7Peripheral Vasculopathy, Including Raynauds Phenomenon

CNS stimulants, including MAS-ER Capsules, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, sequelae have included 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 MAS-ER Capsule treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for MAS-ER Capsule-treated patients who develop signs or symptoms of peripheral vasculopathy.

5.8 Serotonin Syndrome

Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as MAOIs, selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort [see Drug Interactions (7.1)]. Amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor inhibition of CYP2D6 metabolism [see Clinical Pharmacology (12.3)]. The potential for a pharmacokinetic interaction exists with the coadministration of CYP2D6 inhibitors which may increase the risk with increased exposure to MAS-ER Capsules. In these situations, consider an alternative nonserotonergic drug or an alternative drug that does not inhibit CYP2D6 [see Drug Interactions (7.1)]. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., 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 MAS-ER Capsules with MAOI drugs is contraindicated [see Contraindications (4)].

Discontinue treatment with MAS-ER Capsules and any concomitant serotonergic agents immediately if symptoms of serotonin syndrome occur, and initiate supportive symptomatic treatment. Concomitant use of MAS-ER Capsules with other serotonergic drugs or CYP2D6 inhibitors should be used only if the potential benefit justifies the potential risk. If clinically warranted, consider initiating MAS-ER Capsules with lower doses, monitoring patients for the emergence of serotonin syndrome during drug initiation or titration, and informing patients of the increased risk for serotonin syndrome.

5.9Motor and Verbal Tics, and Worsening of Tourettes Syndrome

CNS stimulants, including amphetamine, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette’s syndrome has also been reported [see Adverse Reactions (6.2)].

Before initiating MAS-ER Capsules, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor MAS-ER Capsule-treated patients for the emergence or worsening of tics or Tourette’s syndrome, and discontinue treatment if clinically appropriate.

6 Adverse Reactions

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Abuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions (5.1), Drug Abuse and Dependence (9.2, 9.3)]
• Risks to Patients with Serious Cardiac Disease [see Warnings and Precautions (5.2)]
• Increased Blood Pressure and Heart Rate [see Warnings and Precautions (5.3)]
• Psychiatric Adverse Reactions [see Warnings and Precautions (5.4)]
• Long-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions (5.5)]
• Seizures [see Warnings and Precautions (5.6)]
• Peripheral Vasculopathy, including Raynaud’s Phenomenon [see Warnings and Precautions (5.7)]
• Serotonin Syndrome [see Warnings and Precautions (5.8)]
• Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions (5.9)]

• Pediatric patients ages 6 to 12: Most common adverse reactions (≥5% and with a higher incidence than on placebo) were loss of appetite, insomnia, abdominal pain, emotional lability, vomiting, nervousness, nausea, and fever. (6.1)
• Pediatric patients ages 13 to 17: Most common adverse reactions (≥5% and with a higher incidence than on placebo) were loss of appetite, insomnia, abdominal pain, weight loss, and nervousness. (6.1)
• Adults: Most common adverse reactions ≥5% and with a higher incidence than on placebo were dry mouth, loss of appetite, insomnia, headache, weight loss, nausea, anxiety, agitation, dizziness, tachycardia, diarrhea, asthenia, and urinary tract infections. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-800-828-2088 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The premarketing development program for MAS-ER Capsules included exposures in a total of 1,315 participants in clinical trials (635 pediatric patients, 350 adolescent patients, 248 adult patients, and 82 healthy adult subjects). Of these, 635 patients (ages 6 to 12) were evaluated in two controlled clinical studies, one open-label clinical study, and two single-dose clinical pharmacology studies (N=40). Safety data on all patients are included in the discussion that follows. Adverse reactions were assessed by collecting adverse reactions, results of physical examinations, vital signs, weights, laboratory analyses, and ECGs.

Adverse reactions during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of reactions into a smaller number of standardized event categories. In the tables and ulings that follow, COSTART terminology has been used to classify reported adverse reactions.

The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type uled.

Adverse Reactions Leading to Discontinuation of Treatment

In two placebo-controlled studies of up to 5 weeks duration among children with ADHD, 2.4% (10/425) of MAS-ER Capsule-treated patients discontinued due to adverse reactions (including three patients with loss of appetite, one of whom also reported insomnia) compared to 2.7% (7/259) receiving placebo.

The most frequent adverse reactions leading to discontinuation of MAS-ER Capsules in controlled and uncontrolled, multiple-dose clinical trials of children (N=595) were anorexia (loss of appetite) (2.9%), insomnia (1.5%), weight loss (1.2%), emotional lability (1%), and depression (0.7%). Over half of these patients were exposed to MAS-ER Capsules for 12 months or more.

In a separate placebo-controlled 4 week study in adolescents with ADHD, five patients (2.1%) discontinued treatment due to adverse events among MAS-ER Capsule-treated patients (N=233) compared to none who received placebo (N=54). The most frequent adverse event leading to discontinuation and considered to be drug-related (i.e., leading to discontinuation in at least 1% of MAS-ER Capsule-treated patients and at a rate at least twice that of placebo) was insomnia (1.3%, n=3).

In one placebo-controlled 4 week study among adults with ADHD with doses 20 to 60 mg, 23 patients (12.0%) discontinued treatment due to adverse events among MAS-ER Capsule-treated patients (N=191) compared to one patient (1.6%) who received placebo (N=64). The most frequent adverse events leading to discontinuation and considered to be drug-related (i.e., leading to discontinuation in at least 1% of MAS-ER Capsule-treated patients and at a rate at least twice that of placebo) were insomnia (5.2%, n=10), anxiety (2.1%, n=4), nervousness (1.6%, n=3), dry mouth (1.6%, n=3), anorexia (1.6%, n=3), tachycardia (1.6%, n=3), headache (1.6%, n=3), and asthenia (1.0%, n=2).

Adverse Reactions Occurring in Controlled Trials

Adverse reactions reported in a 3 week clinical trial of children and a 4 week clinical trial in adolescents and adults, respectively, treated with MAS-ER Capsules or placebo are presented in the tables below.

Table 1: Adverse Reactions Reported by 2% or More of Children (6 to 12 Years Old) Receiving MAS-ER Capsules with Higher Incidence Than on Placebo in a 584 Patient Clinical Study

Body System	Preferred Term	MAS-ER Capsules (n=374)	Placebo (n=210)
General	Abdominal Pain (stomachache)	14%	10%
	Fever	5%	2%
	Infection	4%	2%
	Accidental Injury	3%	2%
	Asthenia (fatigue)	2%	0%
Digestive System	Loss of Appetite	22%	2%
	Vomiting	7%	4%
	Nausea	5%	3%
	Dyspepsia	2%	1%
Nervous System	Insomnia	17%	2%
	Emotional Lability	9%	2%
	Nervousness	6%	2%
	Dizziness	2%	0%
Metabolic/Nutritional	Weight Loss	4%	0%

Table 2: Adverse Reactions Reported by 5% or More of Adolescents (13 to 17 Years Old) Weighing ≤ 75 kg/165 lbs Receiving MAS-ER Capsules with Higher Incidence Than Placebo in a 287 Patient Clinical Forced Weekly-Dose Titration StudyIncluded doses up to 40 mg.

Body System	Preferred Term	MAS-ER Capsules (n=233)	Placebo (n=54)
Note: The following reactions did not meet the criterion for inclusion in Table 2 but were reported by 2 to 4% of adolescent patients receiving MAS-ER Capsules with a higher incidence than patients receiving placebo in this study: accidental injury, asthenia (fatigue), dry mouth, dyspepsia, emotional lability, nausea, somnolence, and vomiting.
General	Abdominal Pain (stomachache)	11%	2%
Digestive System	Loss of AppetiteDose-related adverse reactions.	36%	2%
Nervous System	Insomnia	12%	4%
	Nervousness	6%	6%Appears the same due to rounding.
Metabolic/Nutritional	Weight Loss	9%	0%

Table 3: Adverse Reactions Reported by 5% or More of Adults Receiving MAS-ER Capsules with Higher Incidence Than on Placebo in a 255 Patient Clinical Forced Weekly-Dose Titration StudyIncluded doses up to 60 mg.

Body System	Preferred Term	MAS-ER Capsules (n=191)	Placebo (n=64)
Note: The following reactions did not meet the criterion for inclusion in Table 3 but were reported by 2 to 4% of adult patients receiving MAS-ER Capsules with a higher incidence than patients receiving placebo in this study: infection, photosensitivity reaction, constipation, tooth disorder (e.g., teeth clenching, tooth infection), emotional lability, libido decreased, somnolence, speech disorder (e.g., stuttering, excessive speech), palpitation, twitching, dyspnea, sweating, dysmenorrhea, and impotence.
General	Headache	26%	13%
	Asthenia	6%	5%
Digestive System	Dry Mouth	35%	5%
	Loss of Appetite	33%	3%
	Nausea	8%	3%
	Diarrhea	6%	0%
Nervous System	Insomnia	27%	13%
	Agitation	8%	5%
	Anxiety	8%	5%
	Dizziness	7%	0%
	Nervousness	13%	13%Appears the same due to rounding.
Cardiovascular System	Tachycardia	6%	3%
Metabolic/Nutritional	Weight Loss	10%	0%
Urogenital System	Urinary Tract Infection	5%	0%

Hypertension

In a controlled 4 week outpatient clinical study of adolescents with ADHD, isolated systolic blood pressure elevations ≥15 mmHg were observed in 7/64 (11%) placebo-treated patients and 7/100 (7%) patients receiving MAS-ER Capsules 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%) MAS-ER Capsule-treated patients. Similar results were observed at higher doses [see Warnings and Precautions (5.2)].

In a single-dose pharmacokinetic study in 23 adolescents with ADHD, isolated increases in systolic blood pressure (above the upper 95% CI for age, gender, and stature) were observed in 2/17 (12%) and 8/23 (35%), subjects administered 10 and 20 mg MAS-ER Capsules, 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 postdose and, not associated with symptoms.

6.2Adverse Reactions Associated with the Use of Amphetamine, MAS-ER Capsules, or Adderall

The following adverse reactions have been identified during postapproval use of amphetamine, MAS-ER Capsules, or Adderall. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Allergic: Urticaria, rash, hypersensitivity reactions including angioedema and anaphylaxis. Serious skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.

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

Central Nervous System: Psychotic episodes at recommended doses, overstimulation, restlessness, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, motor and verbal tics, aggression, anger, logorrhea, dermatillomania, paresthesia (including formication), and bruxism.

Endocrine: Impotence, changes in libido, frequent or prolonged erections.

Eye Disorders: Vision blurred, mydriasis.

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

Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis.

Skin: Alopecia.

Vascular Disorders: Raynaud's phenomenon.