Dextroamphetamine Saccharate and Amphetamine Aspartate and Dextroamphetamine Sulfate and Amphetamine Sulfate

WARNING: ABUSE, MISUSE, AND ADDICTION Mixed Salts of a Single Entity Amphetamine Product 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 Mixed Salts of a Single Entity Amphetamine Product, 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 Mixed Salts of a Single Entity Amphetamine Product, 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 Mixed Salts of a Single Entity Amphetamine Product 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 DRUG ABUSE AND DEPENDENCE ).

WARNINGS Abuse, Misuse, and Addiction Mixed Salts of a Single Entity Amphetamine Product has a high potential for abuse and misuse. The use of Mixed Salts of a Single Entity Amphetamine Product exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Mixed Salts of a Single Entity Amphetamine Product 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 Mixed Salts of a Single Entity Amphetamine Product, 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 Mixed Salts of a Single Entity Amphetamine Product, 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 Mixed Salts of a Single Entity Amphetamine Product to anyone else. Throughout Mixed Salts of a Single Entity Amphetamine Product 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 Mixed Salts of a Single Entity Amphetamine Product 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 Mixed Salts of a Single Entity Amphetamine Product-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 preexisting 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 Mixed Salts of a Single Entity Amphetamine Product. 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 Mixed Salts of a Single Entity Amphetamine Product-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 Mixed Salts of a Single Entity Amphetamine Product, 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 dosages 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 Mixed Salts of a Single Entity Amphetamine Product treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for Mixed Salts of a Single Entity Amphetamine Product-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 Mixed Salts of a Single Entity Amphetamine Product. 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 Mixed Salts of a Single Entity Amphetamine Product with MAOI drugs is contraindicated ( see CONTRAINDICATIONS ). Discontinue treatment with Mixed Salts of a Single Entity Amphetamine Product and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Mixed Salts of a Single Entity Amphetamine Product with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate Mixed Salts of a Single Entity Amphetamine Product 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. Assess the family history and clinically evaluate patients for tics or Tourette’s syndrome before initiating Mixed Salts of a Single Entity Amphetamine Product. Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome with Mixed Salts of a Single Entity Amphetamine Product, and discontinue treatment if clinically appropriate.

ADVERSE REACTIONS 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, 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.