Dextroamphetamine Saccharate And Amphetamine Aspartate And Dextroamphetamine Sulfate And Amphetamine Sulfate
Dextroamphetamine Saccharate And Amphetamine Aspartate And Dextroamphetamine Sulfate And Amphetamine Sulfate Prescribing Information
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 (
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 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 (
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 (
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.
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.
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.
CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic 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).
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.
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 (
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.
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, 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 (
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 (
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.
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.
Mixed Salts of a Single Entity Amphetamine Product, contains amphetamine, a Schedule II controlled substance.
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 (
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 healthcare 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 Mixed Salts of a Single Entity Amphetamine Product, can result in overdose and death (
Mixed Salts of a Single Entity Amphetamine Product 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 Mixed Salts of a Single Entity Amphetamine Product include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.
Mixed Salts of a Single Entity Amphetamine Product 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).
Mixed Salts of a Single Entity Amphetamine Product are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and Narcolepsy.
Regardless of indication, amphetamines should be administered at the lowest effective dosage, and dosage should be individually adjusted according to the therapeutic needs and response of the patient. Late evening doses should be avoided because of the resulting insomnia.
In patients known to be hypersensitive to amphetamine, or other components of Mixed Salts of a Single Entity Amphetamine Product. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products (
Palpitations, tachycardia, elevation of blood pressure, sudden death, myocardial infarction. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.
Patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs (including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis (
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 (
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.
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.
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.
CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic 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).
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.
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 (
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.
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, 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 (
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 (
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.
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.
Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Do not administer Mixed Salts of a Single Entity Amphetamine Product concomitantly or within 14 days after discontinuing MAOI (
The concomitant use of Mixed Salts of a Single Entity Amphetamine Product 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 Mixed Salts of a Single Entity Amphetamine Product initiation or dosage increase. If serotonin syndrome occurs, discontinue Mixed Salts of a Single Entity Amphetamine Product and the concomitant serotonergic drug(s) (
The concomitant use of Mixed Salts of a Single Entity Amphetamine Product and CYP2D6 inhibitors may increase the exposure of Mixed Salts of a Single Entity Amphetamine Product 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 Mixed Salts of a Single Entity Amphetamine Product initiation and after a dosage increase. If serotonin syndrome occurs, discontinue Mixed Salts of a Single Entity Amphetamine Product and the CYP2D6 inhibitor (
Lower blood levels and efficacy of amphetamines. Increase dose based on clinical response. Examples of acidifying agents include gastrointestinal acidifying agents and urinary acidifying agents.
Adrenergic blockers are inhibited by amphetamines.
Increase blood levels and potentiate the action of amphetamine. Co-administration of Mixed Salts of a Single Entity Amphetamine Product and gastrointestinal alkalinizing agents should be avoided. Examples of alkalinizing agents include gastrointestinal alkalinizing agents and urinary alkalinizing agents.
May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Monitor frequently and adjust or use alternative therapy based on clinical response.
Amphetamines may antagonize the hypotensive effects of antihypertensives.
Chlorpromazine blocks dopamine and norepinephrine receptors, thus inhibiting the central stimulant effects of amphetamines, and can be used to treat amphetamine poisoning.
Amphetamines may delay intestinal absorption of ethosuximide.
Haloperidol blocks dopamine receptors, thus inhibiting the central stimulant effects of amphetamines.
The anorectic and stimulatory effects of amphetamines may be inhibited by lithium carbonate.
Amphetamines potentiate the analgesic effect of meperidine.
Amphetamines enhance the adrenergic effect of norepinephrine.
Amphetamines may delay intestinal absorption of phenytoin; coadministration of phenytoin may produce a synergistic anticonvulsant action.
In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.
Amphetamines inhibit the hypotensive effect of veratrum alkaloids.
Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Do not administer Mixed Salts of a Single Entity Amphetamine Product concomitantly or within 14 days after discontinuing MAOI (
The concomitant use of Mixed Salts of a Single Entity Amphetamine Product 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 Mixed Salts of a Single Entity Amphetamine Product initiation or dosage increase. If serotonin syndrome occurs, discontinue Mixed Salts of a Single Entity Amphetamine Product and the concomitant serotonergic drug(s) (
The concomitant use of Mixed Salts of a Single Entity Amphetamine Product and CYP2D6 inhibitors may increase the exposure of Mixed Salts of a Single Entity Amphetamine Product 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 Mixed Salts of a Single Entity Amphetamine Product initiation and after a dosage increase. If serotonin syndrome occurs, discontinue Mixed Salts of a Single Entity Amphetamine Product and the CYP2D6 inhibitor (
Lower blood levels and efficacy of amphetamines. Increase dose based on clinical response. Examples of acidifying agents include gastrointestinal acidifying agents and urinary acidifying agents.
Adrenergic blockers are inhibited by amphetamines.
Increase blood levels and potentiate the action of amphetamine. Co-administration of Mixed Salts of a Single Entity Amphetamine Product and gastrointestinal alkalinizing agents should be avoided. Examples of alkalinizing agents include gastrointestinal alkalinizing agents and urinary alkalinizing agents.
May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Monitor frequently and adjust or use alternative therapy based on clinical response.
Amphetamines may antagonize the hypotensive effects of antihypertensives.
Chlorpromazine blocks dopamine and norepinephrine receptors, thus inhibiting the central stimulant effects of amphetamines, and can be used to treat amphetamine poisoning.
Amphetamines may delay intestinal absorption of ethosuximide.
Haloperidol blocks dopamine receptors, thus inhibiting the central stimulant effects of amphetamines.
The anorectic and stimulatory effects of amphetamines may be inhibited by lithium carbonate.
Amphetamines potentiate the analgesic effect of meperidine.
Amphetamines enhance the adrenergic effect of norepinephrine.
Amphetamines may delay intestinal absorption of phenytoin; coadministration of phenytoin may produce a synergistic anticonvulsant action.
In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.
Amphetamines inhibit the hypotensive effect of veratrum alkaloids.
Palpitations, tachycardia, elevation of blood pressure, sudden death, myocardial infarction. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.
Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Do not administer Mixed Salts of a Single Entity Amphetamine Product concomitantly or within 14 days after discontinuing MAOI (
In patients known to be hypersensitive to amphetamine, or other components of Mixed Salts of a Single Entity Amphetamine Product. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products (
Patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs (including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis (
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 (
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.
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.
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.
CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic 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).
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.
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 (
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.
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, 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 (
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 (
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.
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.