Amphetamine Sulfate 5 mg Tablet, 100-count — NDC 63629-2079-1 (Billing 63629-2079-01)

WARNINGS Abuse, Misuse, and Addiction Amphetamine sulfate has a high potential for abuse and misuse. The use of Amphetamine sulfate exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Amphetamine sulfate can be diverted for non-medical use into illicit channels or distribution (see DRUG ABUSE AND DEPENDENCE ).

Misuse and abuse of CNS stimulants, including Amphetamine sulfate, 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 Amphetamine sulfate, 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 Amphetamine sulfate to anyone else. Throughout Amphetamine sulfate 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 are treated with CNS stimulants at the recommended ADHD dosages.

Avoid amphetamine sulfate 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). Monitor all patients for potential tachycardia and hypertension.

Psychiatric Adverse Reactions Exacerbation of Pre-Existing 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 amphetamine sulfate, 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 amphetamine sulfate.

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 amphetamine sulfate-treated pediatric patients treated with CNS stimulants. Pediatric patients not growing or gaining height or 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 seizures, 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 amphetamine sulfate, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon.

Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS Cardiovascular Palpitations, tachycardia, elevation of blood pressure. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use. Central Nervous System Psychotic episodes at recommended doses (rare), overstimulation, restlessness, dizziness, insomnia, euphoria, dyskinesia, dysphoria, tremor, headache, exacerbation of motor and verbal tics and Tourette's syndrome.

Gastrointestinal Dryness of the mouth, unpleasant taste, diarrhea, constipation, intestinal ischemia and other gastrointestinal disturbances. Anorexia and weight loss may occur as undesirable effects when amphetamines are used for other than the anorectic effect. Allergic Urticaria Endocrine Impotence, changes in libido, and frequent or prolonged erections.

Musculoskeletal Rhabdomyolysis

Drug Interactions MAO inhibitors - MAOI antidepressants, as well as a metabolic 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 neurological toxic effects and malignant hyperpyrexia can occur, sometimes with fatal results.

Serotonergic Drugs - The concomitant use of amphetamine sulfate 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 amphetamine sulfate initiation or dosage increase. If serotonin syndrome occurs, discontinue amphetamine sulfate and the concomitant serotonergic drug(s) (see WARNING and PRECAUTIONS ).

CYP2D6 Inhibitors - The concomitant use of amphetamine sulfate and CYP2D6 inhibitors may increase the exposure of amphetamine sulfate 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 amphetamine sulfate initiation and after a dosage increase. If serotonin syndrome occurs, discontinue amphetamine sulfate and the CYP2D6 inhibitor (see WARNING , OVERDOSAGE ).

Examples of CYP2D6 Inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir. Acidifying agents - Gastrointestinal acidifying agents (guanethidine, reserpine, glutamic acid HCl, ascorbic acid, fruit juices, etc.) lower absorption of amphetamines. Urinary acidifying agents (ammonium chloride, sodium acid phosphate, etc.) increase 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.

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 action of amphetamines. Antidepressants tricyclic - Amphetamines may enhance the activity of tricyclic 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.

Antihistamines - Amphetamines may counteract the sedative effect of antihistamines. Antihypertensives - Amphetamines may antagonize the hypotensive effects of antihypertensives. Chlorpromazine - Chlorpromazine blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamine, and can be used to treat amphetamine poisoning.

Ethosuximide - Amphetamines may delay intestinal absorption of ethosuximide. Haloperidol - Haloperidol blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamines. Lithium carbonate - The antiobesity 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 anticonv… [Excerpted — this section continues on DailyMed.]

PRECAUTIONS General Caution is to be exercised in prescribing amphetamines for patients with even mild hypertension. 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 amphetamine sulfate, which can lead to overdose and death, and proper disposal of any unused drug (see WARNINGS , DRUG ABUSE AND DEPENDENCE , and OVERDOSAGE ).

Advise patients to store amphetamine sulfate in a safe place, preferably locked, and instruct patients to not give amphetamine sulfate 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 amphetamine sulfate 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 amphetamine sulfate can elevate blood pressure and heart rate (see WARNINGS ). Psychiatric Adverse Reactions Advise patients that amphetamine sulfate, 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 amphetamine sulfate, 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 amphetamine sulfate 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 amphetamine sulfate.

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 amphetamine sulfate 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 amphetamine sulfate. Instruct the patients to notify their healthcare provider if emergence or worsening of tics or Tourette's syndrome occurs (see WARNINGS ).

Amphetamines may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or vehicle; the patient should therefore be cautioned accordingly.

DRUG ABUSE AND DEPENDENCE Controlled Substance Amphetamine sulfate tablets contain amphetamine, a Schedule II controlled substance. Abuse Amphetamine sulfate has a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction (see WARNINGS ). Amphetamine sulfate 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 amphetamine sulfate, 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 Amphetamine sulfate 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 Amphetamine sulfate include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.

Tolerance Amphetamine sulfate 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).