DESCRIPTION

Amphetamine Sulfate is a sympathomimetic amino of the amphetamine group. It is a white, odorless crystalline powder. It has a slightly bitter taste. Its solutions are acid to litmus, having a pH of 5.0 to 6.0. It is freely soluble in water and slightly soluble in alcohol.

Each tablet, for oral administration contains 5 mg or 10 mg of amphetamine sulfate, USP. Each tablet also contains the following inactive ingredients: crospovidone, magnesium stearate, silicified microcrystalline cellulose, and stearic acid.

Structural Formula:

CLINICAL PHARMACOLOGY

Amphetamines are non-catecholamine, sympathomimetic amines with CNS stimulant activity. Peripheral actions include elevations of systolic and diastolic blood pressures, and weak bronchodilator, and respiratory stimulant action.

Amphetamine, as the racemic form, differs from dextroamphetamine in a number of ways. The l-isomer is more potent than the d-isomer in cardiovascular activity, but much less potent in causing CNS excitatory effects. The racemic mixture also is less effective as an appetite suppressant when compared to dextroamphetamine. There is neither specific evidence which clearly establishes the mechanism whereby amphetamines produce mental and behavioral effects in children, nor conclusive evidence regarding how those effects relate to the condition of the central nervous system.

Drugs in this class used in obesity are commonly known as "anorectics" or "anorexigenics." It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. Other central nervous system actions or metabolic effects, may be involved, for example. Adult obese subjects instructed in dietary management and treated with "anorectic" drugs lose more weight on the average than these treated with placebo and diet, as determined in relatively short-term clinical trials.

The magnitude of increased weight loss of drug-treated patients over placebo-treated patients is only a fraction of a pound a week. The rate of weight loss is greatest in the first weeks of therapy for both drug and placebo subjects and tends to decrease in succeeding weeks. The origins of the increased weight loss due to the various possible drug effects are not established. The amount of weight loss associated with the use of an "anorectic" drug varies from trial to trial, and the increased weight loss appears to be related in part to variables other than the drug prescribed, such as the physician-investigator, the population treated, and the diet prescribed. Studies do not permit conclusions as to the relative importance of the drug and nondrug factors on weight loss.

The natural history of obesity is measured in years, whereas the studies cited are restricted to few weeks duration; thus, the total impact of drug-induced weight loss over that of diet alone must be considered clinically limited.

INDICATIONS AND USAGE

Amphetamine sulfate tablets, USP, are indicated for:

1.

Narcolepsy

2.

Attention Deficit Disorder with Hyperactivity as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of the syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or not be warranted.

3.

Exogenous Obesity as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction for patients refractory to alternative therapy, e.g., repeated diets, group programs, and other drugs. The limited usefulness of amphetamines (see CLINICAL PHARMACOLOGY) should be weighed against possible risks inherent in use of the drug, such as those described below.

CONTRAINDICATIONS

•

Known hypersensitivity to amphetamine products.

•

During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crises may result) (see WARNINGS).

WARNINGS

Abuse, Misuse, and Addiction

Amphetamine sulfate tablets have a high potential for abuse and misuse. The use of amphetamine sulfate tablets expose 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 tablets, 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 tablets, 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 tablets to anyone else. Throughout amphetamine sulfate tablets 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 tablets 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 tablets, 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 tablets.

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 tablets-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 tablets, 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 and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing 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 amphetamine sulfate tablets treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for 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 co-administration with cytochrome P450 (CYP2D6) inhibitors may also increase the risk with increased exposure to amphetamine sulfate tablets. 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 amphetamine sulfate tablets with MAOI drugs is contraindicated (see CONTRAINDICATIONS).

Discontinue treatment with amphetamine sulfate tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of amphetamine sulfate tablets with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate amphetamine sulfate tablets 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 amphetamine sulfate tablets. Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome with amphetamine sulfate tablets, and discontinue treatment if clinically appropriate.

PRECAUTIONS

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 increased intraocular pressure and glaucoma, motor and verbal tics.

DRUG ABUSE AND DEPENDENCE

Controlled Substance

Amphetamine sulfate tablets contain amphetamine, a Schedule II controlled substance.

Abuse

Amphetamine sulfate tablets have a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction (see WARNINGS). Amphetamine sulfate tablets 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 tablets 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 tablets include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.

Tolerance

Amphetamine sulfate tablets 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).

OVERDOSAGE

Clinical Effects of Overdose

Overdose of CNS stimulants is characterized by the following sympathomimetic effects:

•

Cardiovascular effects including tachyarrhythmias, and hypertension or hypotension. Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop.

•

CNS effects including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur.

•

Life-threatening hyperthermia (temperatures greater than 104°F) and rhabdomyolysis may develop.

Overdose Management

Consider the possibility of multiple drug ingestion. D-amphetamine is not dialyzable. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

DOSAGE AND ADMINISTRATION

Regardless of indication, amphetamine should be administered at the lowest effective dosage and dosage should be individually adjusted. Late evening doses should be avoided because of resulting insomnia.

Narcolepsy

Usual dose is 5 to 60 milligrams per day in divided doses depending on the individual patient response.

Narcolepsy seldom occurs in children under 12 years of age; however, when it does, amphetamine sulfate tablets may be used. The suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until optimal response obtained. In patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until optimal response is obtained. If bothersome adverse reactions appear (e.g., insomnia or anorexia) dosage should be reduced. Give the first dose on awakening; additional doses (5 or 10 mg) at intervals of 4 to 6 hours.

Attention Deficit Disorder with Hyperactivity

Not recommended for children under 3 years of age.

In children from 3 to 5 years of age, start with 2.5 mg daily; daily dosage may be raised in increments of 2.5 mg at weekly intervals until optimal response is obtained.

In children 6 years of age or older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 milligrams per day.

With tablets give first dose on awakening; additional doses (1 to 2) at intervals of 4 to 6 hours.

Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.

Prior to treating patients with amphetamine sulfate tablets 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).

•

the family history and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome (see WARNINGS).

Exogenous Obesity

Usual dosage is up to 30 mg daily, taken in divided doses of 5 to 10 mg, 30 to 60 minutes before meals. Not recommended for this use in children under 12 years of age.

HOW SUPPLIED

Amphetamine sulfate tablets, USP 10mg are white, round, convex tablet, uppers are double crossed scored and debossed "1" on the lower left corner and "0" on the lower right corner, lowers debossed "S" in bottles of 100 tablets with child-resistant closure. 

NDC: 72162-1369-1: 100 Tablets in a BOTTLE.

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15oC and 30oC (59oF and 86oF). [see USP Controlled Room Temperature.] Dispense in a well-closed container, as defined in the USP.

Repackaged/Relabeled by:
Bryant Ranch Prepack, Inc.
Burbank, CA 91504

MEDICATION GUIDE

Dispense with Medication Guide available at:

www.solcohealthcare.com/medguide/amphetamine-tablets.pdf

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 09/2023

Amphetamine Sulfate (CII) Tab 10MG #100