Amphetamine Sulfate Prescribing Information
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.
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.
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
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.
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.
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.
CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder
in patients with a pre-existing psychotic 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).
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.
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
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.
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 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 treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy.
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
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 with MAOI drugs is contraindicated (see
Discontinue treatment with amphetamine sulfate and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of amphetamine sulfate with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate amphetamine sulfate 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.
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. Regularly monitor patients for the emergence or worsening of tics or Tourette's syndrome with amphetamine sulfate, and discontinue treatment if clinically appropriate.
Amphetamine sulfate tablets contain amphetamine, a Schedule II controlled substance.
Amphetamine sulfate has a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction (see
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
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).
Amphetamine sulfate tablets, USP 5 mg and 10 mg are indicated for:
- Narcolepsy
- Attention Deficit-Disorder with Hyperactivityas 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.
- Exogenous Obesityas 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) should be weighed against possible risks inherent in use of the drug, such as those described below.
CLINICAL PHARMACOLOGYAmphetamines 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.
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.
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, USP 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.
Not recommended for children under 3 years of age.
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 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 ).
WARNINGSAbuse, Misuse, and AddictionAmphetamine 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 (seeOVERDOSAGE), 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 DiseaseSudden 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 RateCNS 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 ReactionsExacerbation of Pre-Existing PsychosisCNS 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 DisorderCNS 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 SymptomsCNS 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 PatientsCNS 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).SeizuresThere 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 phenomenonStimulants, 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 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 treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy.
Serotonin SyndromeSerotonin 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. In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 (seeDRUG 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 with MAOI drugs is contraindicated (see
CONTRAINDICATIONS).Discontinue treatment with amphetamine sulfate and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of amphetamine sulfate with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate amphetamine sulfate 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 SyndromeCNS 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. Regularly monitor patients for the emergence or worsening of tics or Tourette's syndrome with amphetamine sulfate, and discontinue treatment if clinically appropriate.
- the family history and clinically evaluate patients for motor or verbal tics or Tourette's syndrome (see ).
WARNINGSAbuse, Misuse, and AddictionAmphetamine 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 (seeOVERDOSAGE), 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 DiseaseSudden 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 RateCNS 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 ReactionsExacerbation of Pre-Existing PsychosisCNS 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 DisorderCNS 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 SymptomsCNS 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 PatientsCNS 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).SeizuresThere 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 phenomenonStimulants, 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 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 treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy.
Serotonin SyndromeSerotonin 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. In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 (seeDRUG 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 with MAOI drugs is contraindicated (see
CONTRAINDICATIONS).Discontinue treatment with amphetamine sulfate and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of amphetamine sulfate with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate amphetamine sulfate 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 SyndromeCNS 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. Regularly monitor patients for the emergence or worsening of tics or Tourette's syndrome with amphetamine sulfate, and discontinue treatment if clinically appropriate.
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.
- Known hypersensitivity to amphetamine products.
- During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crises may result) (see ).
WARNINGSAbuse, Misuse, and AddictionAmphetamine 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 (seeOVERDOSAGE), 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 DiseaseSudden 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 RateCNS 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 ReactionsExacerbation of Pre-Existing PsychosisCNS 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 DisorderCNS 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 SymptomsCNS 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 PatientsCNS 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).SeizuresThere 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 phenomenonStimulants, 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 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 treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy.
Serotonin SyndromeSerotonin 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. In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 (seeDRUG 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 with MAOI drugs is contraindicated (see
CONTRAINDICATIONS).Discontinue treatment with amphetamine sulfate and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of amphetamine sulfate with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate amphetamine sulfate 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 SyndromeCNS 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. Regularly monitor patients for the emergence or worsening of tics or Tourette's syndrome with amphetamine sulfate, and discontinue treatment if clinically appropriate.
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
Amphetamine sulfate tablets contain amphetamine, a Schedule II controlled substance.
Amphetamine sulfate has a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction (see
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
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).
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.
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.
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.
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.
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.
CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder
in patients with a pre-existing psychotic 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).
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.
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
Caution is to be exercised in prescribing amphetamines for patients with even mild hypertension.
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
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
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
Advise patients that amphetamine sulfate can elevate blood pressure and heart rate (see
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
Advise patients that amphetamine sulfate, may cause slowing of growth including weight loss (see
- 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.
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
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
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.
Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.
Mutagenicity studies and long term studies in animals to determine the carcinogenic potential of amphetamine sulfate have not been performed.
Dextroamphetamine sulfate has been shown to have embryotoxic and teratogenic effects when administered to A/Jax mice and C57BL mice in doses approximately 41 times the maximum human dose. Embryotoxic effects were not seen in New Zealand white rabbits given the drug in doses 7 times the human dose nor in rats given 12.5 times the maximum human dose. There are no adequate and well-controlled studies in pregnant women. Amphetamine sulfate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
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.
Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.
Long-term effects of amphetamines in children have not been well established.
Amphetamines are not recommended for use as anorectic agents in children under 12 years of age, or in children under 3 years of age with Attention Deficit Disorder with Hyperactivity described under INDICATIONS AND USAGE.
Clinical experience suggests that in psychotic children, administration of amphetamines may exacerbate symptoms of behavior disturbance and thought disorder.
Data is inadequate to determine whether chronic administration of amphetamines may be associated with growth inhibition; therefore growth should be monitored during treatment. Drug Treatment is not indicated in all cases of Attention Deficit Disorder with Hyperactivity and should be considered only in light of the complete history and evaluation of the child. The decision to prescribe amphetamines should depend on the physician's assessment of the chronicity and severity of the child's symptoms and their appropriateness for his/her age. Prescription should not depend solely on the presence of one or more of the behavioral characteristics.
When these symptoms are associated with acute stress reactions, treatment with amphetamines is usually not indicated.
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.
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 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 treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy.
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
Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.
Mutagenicity studies and long term studies in animals to determine the carcinogenic potential of amphetamine sulfate have not been performed.
Dextroamphetamine sulfate has been shown to have embryotoxic and teratogenic effects when administered to A/Jax mice and C57BL mice in doses approximately 41 times the maximum human dose. Embryotoxic effects were not seen in New Zealand white rabbits given the drug in doses 7 times the human dose nor in rats given 12.5 times the maximum human dose. There are no adequate and well-controlled studies in pregnant women. Amphetamine sulfate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
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.
Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.
Long-term effects of amphetamines in children have not been well established.
Amphetamines are not recommended for use as anorectic agents in children under 12 years of age, or in children under 3 years of age with Attention Deficit Disorder with Hyperactivity described under INDICATIONS AND USAGE.
Clinical experience suggests that in psychotic children, administration of amphetamines may exacerbate symptoms of behavior disturbance and thought disorder.
Data is inadequate to determine whether chronic administration of amphetamines may be associated with growth inhibition; therefore growth should be monitored during treatment. Drug Treatment is not indicated in all cases of Attention Deficit Disorder with Hyperactivity and should be considered only in light of the complete history and evaluation of the child. The decision to prescribe amphetamines should depend on the physician's assessment of the chronicity and severity of the child's symptoms and their appropriateness for his/her age. Prescription should not depend solely on the presence of one or more of the behavioral characteristics.
When these symptoms are associated with acute stress reactions, treatment with amphetamines is usually not indicated.
Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.
Mutagenicity studies and long term studies in animals to determine the carcinogenic potential of amphetamine sulfate have not been performed.
Dextroamphetamine sulfate has been shown to have embryotoxic and teratogenic effects when administered to A/Jax mice and C57BL mice in doses approximately 41 times the maximum human dose. Embryotoxic effects were not seen in New Zealand white rabbits given the drug in doses 7 times the human dose nor in rats given 12.5 times the maximum human dose. There are no adequate and well-controlled studies in pregnant women. Amphetamine sulfate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
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.
Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.
Long-term effects of amphetamines in children have not been well established.
Amphetamines are not recommended for use as anorectic agents in children under 12 years of age, or in children under 3 years of age with Attention Deficit Disorder with Hyperactivity described under INDICATIONS AND USAGE.
Clinical experience suggests that in psychotic children, administration of amphetamines may exacerbate symptoms of behavior disturbance and thought disorder.
Data is inadequate to determine whether chronic administration of amphetamines may be associated with growth inhibition; therefore growth should be monitored during treatment. Drug Treatment is not indicated in all cases of Attention Deficit Disorder with Hyperactivity and should be considered only in light of the complete history and evaluation of the child. The decision to prescribe amphetamines should depend on the physician's assessment of the chronicity and severity of the child's symptoms and their appropriateness for his/her age. Prescription should not depend solely on the presence of one or more of the behavioral characteristics.
When these symptoms are associated with acute stress reactions, treatment with amphetamines is usually not indicated.
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 with MAOI drugs is contraindicated (see
- Known hypersensitivity to amphetamine products.
- During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crises may result) (seeWARNINGS).
Discontinue treatment with amphetamine sulfate and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of amphetamine sulfate with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate amphetamine sulfate 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.
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. Regularly monitor patients for the emergence or worsening of tics or Tourette's syndrome with amphetamine sulfate, and discontinue treatment if clinically appropriate.
Palpitations, tachycardia, elevation of blood pressure. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.
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.
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.
Urticaria
Impotence, changes in libido, and frequent or prolonged erections.
Rhabdomyolysis