Amphetamine
Tablet, Orally Disintegrating · Oral
Uses
Amphetamine extended-release orally disintegrating tablets are a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older [see Clinical Studies ( 14 )] . Limitations of Use The use of amphetamine extended-release orally disintegrating tablets are not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage [see Warnings and Precautions ( 5.5 ), Use in Specific Populations ( 8.4 )] . Amphetamine extended-release orally disintegrating tablets are a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older. ( 1 ) Limitations of Use The use of amphetamine extended-release orally disintegrating tablets are not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage. ( 5.5 , 8.4 )
Dosage and administration
May be taken with or without food. Allow tablet to disintegrate in saliva then swallow. ( 2.2 ) Pediatric patients (ages 6 to 17 years): Starting dose is 6.3 mg once daily in the morning. Maximum dose is 18.8 mg once daily for patients 6 to 12 years, and 12.5 mg once daily for patients 13 to 17 years. ( 2.3 ) Adults: 12.5 mg once daily in the morning. ( 2.4 ) To avoid substitution errors and overdosage, do not substitute for other amphetamine products on a milligram-per-milligram basis because of different amphetamine base compositions and differing pharmacokinetic profiles. ( 2.5 , 5.7 ) 2.1 Pre-treatment Screening Prior to treating patients with amphetamine extended-release orally disintegrating 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 and Precautions ( 5.2 ) ] . the family history and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome before initiating amphetamine extended-release orally disintegrating tablets [see Warnings and Precautions ( 5.9 )] . 2.2 General Administration Information Amphetamine extended-release orally disintegrating tablets may be taken orally with or without food. Individualize the dosage according to the therapeutic needs and response of the patient. Amphetamine extended-release orally disintegrating tablets should be taken as follows: The tablet should remain in the blister pack until the patient is ready to take it. The patient or caregiver should use dry hands to open the blister. Tear along the perforation, bend the blister where indicated and peel back the blister’s labeled backing to take out the tablet. The tablet should not be pushed through the foil. As soon as the blister is opened, the tablet should be removed and placed on the patient’s tongue. The whole tablet should be placed on the tongue and allowed to disintegrate without chewing or crushing. The tablet will disintegrate in saliva so that it can be swallowed. 2.3 Dosage Recommendations in Pediatric Patients The recommended starting dosage is 6.3 mg once daily in the morning. Increase in increments of 3.1 mg or 6.3 mg at weekly intervals. The maximum recommended dose is 18.8 mg daily for patients 6 to 12 years, and 12.5 mg daily for patients 13 to 17 years [see Use in Specific Populations ( 8.3 ) , Clinical Studies ( 14 ) ] . 2.4 Dosage Recommendations in Adults The recommended dose is amphetamine extended-release orally disintegrating tablets 12.5 mg daily. 2.5 Switching from Other Amphetamine Products Patients taking dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate, and amphetamine sulfate extended-release capsules may be switched to amphetamine extended-release orally disintegrating tablets at the equivalent dose taken once daily [see Clinical Pharmacology ( 12.3 )] . Refer to Table 1 for equivalent doses of amphetamine extended-release orally disintegrating tablets and dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate, and amphetamine sulfate extended-release capsules. Dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate, and amphetamine sulfate extended-release capsules are also referred to as mixed salts of a single-entity amphetamine product extended-release capsules (MAS ER). Table 1: Equivalent Doses of Amphetamine Extended-Release Orally Disintegrating Tablets and Dextroamphetamine Sulfate, Dextroamphetamine Saccharate, Amphetamine Aspartate Monohydrate, and Amphetamine Sulfate (Mixed Salts of a Single-Entity Amphetamine Product) Extended-Release Capsules Amphetamine extended-release orally disintegrating tablets 3.1 mg 6.3 mg 9.4 mg 12.5 mg 15.7 mg 18.8 mg Dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate, and amphetamine sulfate extended-release capsules Mixed salts of a single-entity amphetamine product extended-release capsules (MAS ER) 5 mg 10 mg 15 mg 20 mg 25 mg 30 mg If switching from any other amphetamine products, discontinue that treatment, and titrate with amphetamine extended-release orally disintegrating tablets using the titration schedule [see Dosage and Administration ( 2.3 ) , ( 2.4 ) ] . Do not substitute for other amphetamine products on a milligram-per-milligram basis because of different amphetamine base compositions and differing pharmacokinetic profiles [see Warnings and Precautions ( 5.9 )] . 2.6 Dosage Modifications Due to Drug Interactions Agents that alter urinary pH can impact urinary excretion and alter blood levels of amphetamine. Acidifying agents (e.g., ascorbic acid) decrease blood levels, while alkalinizing agents (e.g., sodium bicarbonate) increase blood levels. Adjust amphetamine extended-release orally disintegrating tablets dosage accordingly [see Drug Interactions ( 7.1 )] .
Dosage forms and strengths
Amphetamine extended-release orally disintegrating tablets 3.1 mg are light yellow, mottled round tablets debossed with “A17” on one side and plain on the other side. Amphetamine extended-release orally disintegrating tablets 6.3 mg are light yellow, mottled round tablets debossed with “A118” on one side and plain on the other side. Amphetamine extended-release orally disintegrating tablets 9.4 mg are light yellow, mottled round tablets debossed with “A119” on one side and plain on the other side. Amphetamine extended-release orally disintegrating tablets 12.5 mg are light yellow, mottled round tablets debossed with “A285” on one side and plain on the other side. Amphetamine extended-release orally disintegrating tablets 15.7 mg are light yellow, mottled round tablets debossed with “A121” on one side and plain on the other side. Amphetamine extended-release orally disintegrating tablets 18.8 mg are light yellow, mottled round tablets debossed with “A122” on one side and plain on the other side. Extended-release orally disintegrating tablets: 3.1 mg, 6.3 mg, 9.4 mg, 12.5 mg, 15.7 mg, 18.8 mg ( 3 )
Contraindications
Amphetamine extended-release orally disintegrating tablets are contraindicated: In patients known to be hypersensitive to amphetamine, or other components of amphetamine extended-release orally disintegrating tablets. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products [see Adverse Reactions ( 6.2 )] . 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 [see Warnings and Precautions ( 5.7 ), Drug Interactions ( 7.1 )] . Known hypersensitivity to amphetamine products or other ingredients in amphetamine extended-release orally disintegrating tablets. ( 4 ) Use of monoamine oxidase inhibitor (MAOI) or within 14 days of the last MAOI dose. ( 4 )
Warnings and precautions
Risks to Patients with Serious Cardiac Disease: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, or other serious cardiac disease. ( 5.2 ) Increased Blood Pressure and Heart Rate: Monitor blood pressure and pulse. ( 5.3 ) Psychiatric Adverse Reactions: Prior to initiating amphetamine extended-release orally disintegrating tablets, screen patients for risk factors for developing a manic episode. If new psychotic or manic symptoms occur, consider discontinuing amphetamine extended-release orally disintegrating tablets. ( 5.4 ) Long-Term Suppression of Growth in Pediatric Patients: Closely monitor growth (height and weight) in pediatric patients. Pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted. ( 5.5 ) Peripheral Vasculopathy, including Raynaud’s phenomenon: Careful observation for digital changes is necessary during amphetamine extended-release orally disintegrating tablets treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy. ( 5.6 ) Serotonin Syndrome: Increased risk when coadministered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations. If it occurs, discontinue amphetamine extended-release orally disintegrating tablets and initiate supportive treatment. ( 5.7 , 17 ) Motor and Verbal Tics, and Worsening of Tourette’s Syndrome: Before initiating amphetamine extended-release orally disintegrating tablets, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome. Discontinue treatment if clinically appropriate. ( 5.8 ) 5.1 Abuse, Misuse, and Addiction Amphetamine extended-release orally disintegrating tablets have a high potential for abuse and misuse. The use of amphetamine extended-release orally disintegrating tablets exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Amphetamine extended-release orally disintegrating tablets can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse and Dependence ( 9.2 )] . Misuse and abuse of CNS stimulants, including amphetamine extended-release orally disintegrating tablets, can result in overdose and death [see Overdosage ( 10 )] , and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. Before prescribing amphetamine extended-release orally disintegrating 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 extended-release orally disintegrating tablets in a safe place, preferably locked, and instruct patients to not give amphetamine extended-release orally disintegrating tablets to anyone else. Throughout amphetamine extended-release orally disintegrating tablets treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction. 5.2 Risks to Patients with Serious Cardiac Disease Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosage. Avoid amphetamine extended-release orally disintegrating tablets use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. 5.3 Increased Blood Pressure and Heart Rate CNS stimulants cause an increase in blood pressure (mean increase about 2 to 4 mm Hg) and heart rate (mean increase about 3 to 6 bpm). Some patients may have larger increases. Monitor all amphetamine extended-release orally disintegrating tablets-treated patients for potential tachycardia and hypertension. 5.4 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 extended-release orally disintegrating tablets treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or has a history of depressive symptoms or a family history of suicide, bipolar disorder, and depression). New Psychotic or Manic Symptoms CNS stimulants, at the recommended dosage, may cause psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in patients without 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 0.1% of CNS stimulant-treated patients compared to 0% of placebo-treated patients. If such symptoms occur, consider discontinuing amphetamine extended-release orally disintegrating tablets. 5.5 Long-Term Suppression of Growth in Pediatric Patients Amphetamine extended-release orally disintegrating tablets are not approved for use and are not recommended in pediatric patients below 6 years of age [see Use in Specific Population ( 8.4 )] . CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Closely monitor growth (weight and height) in amphetamine extended-release orally disintegrating 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.
Side effects
The following adverse reactions are discussed in greater detail in other sections of the labeling: Abuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions ( 5.1 ), and Drug Abuse and Dependence ( 9.2 , 9.3 )] Hypersensitivity to amphetamine, or other components of amphetamine extended-release orally disintegrating tablets [see Contraindications ( 4 )] Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see Contraindications ( 4 ) and Drug Interactions ( 7.1 )] Risks to Patients with Serious Cardiac Disease [see Warnings and Precautions ( 5.2 )] Increased Blood Pressure and Heart Rate [see Warnings and Precautions ( 5.3 )] Psychiatric Adverse Reactions [see Warnings and Precautions ( 5.4 )] Long-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions ( 5.5 )] Peripheral Vasculopathy, including Raynaud’s phenomenon [see Warnings and Precautions ( 5.6 )] Serotonin Syndrome [see Warnings and Precautions ( 5.7 )] Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions ( 5.8 )] Pediatric patients ages 6 to 12 years: Most common adverse reactions (≥5% and with a higher incidence than on placebo) were loss of appetite, insomnia, abdominal pain, emotional lability, vomiting, nervousness, nausea, and fever. ( 6.1 ) Pediatric patients ages 13 to 17 years: Most common adverse reactions (≥5% and with a higher incidence than on placebo) were loss of appetite, insomnia, abdominal pain, weight loss, and nervousness. ( 6.1 ) Adults: Most common adverse reactions ≥5% and with a higher incidence than on placebo were dry mouth, loss of appetite, insomnia, headache, weight loss, nausea, anxiety, agitation, dizziness, tachycardia, diarrhea, asthenia, and urinary tract infections. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of amphetamine extended-release orally disintegrating tablets has been established from adequate and well-controlled studies of single-entity amphetamine product extended-release (MAS ER) capsules [see Clinical Studies ( 14 )] . The adverse reactions of MAS ER capsules in these adequate and well-controlled studies are described below. The premarketing development program for MAS ER included exposures in a total of 1,315 participants in clinical trials (635 pediatric patients, 350 adolescent patients, 248 adult patients, and 82 healthy adult subjects). Of these, 635 patients (ages 6 to 12 years) were evaluated in two controlled clinical studies, one open-label clinical study, and two single-dose clinical pharmacology studies (N=40). Adverse Reactions Leading to Discontinuation of Treatment The most frequent adverse reactions leading to discontinuation of MAS ER in controlled and uncontrolled, multiple-dose clinical trials of pediatric patients ages 6 to 12 years (N=595) were anorexia (loss of appetite) (2.9%), insomnia (1.5%), weight loss (1.2%), emotional lability (1%), and depression (0.7%). In a separate placebo-controlled 4-week study in pediatric patients ages 13 to 17 years with ADHD, five patients (2.1%) discontinued treatment due to adverse events among MAS ER-treated patients (N=233) compared to 0% who received placebo (N=54). The most frequent adverse event leading to discontinuation and considered to be drug-related (i.e., leading to discontinuation in at least 1% of MAS ER-treated patients and at a rate at least twice that of placebo) was insomnia (1.3%, n=3). In one placebo-controlled 4-week study among adults with ADHD with doses 20 mg to 60 mg, 23 patients (12.0%) discontinued treatment due to adverse events among MAS ER-treated patients (N=191) compared to one patient (1.6%) who received placebo (N=64). The most frequent adverse events leading to discontinuation and considered to be drug-related (i.e., leading to discontinuation in at least 1% of MAS ER-treated patients and at a rate at least twice that of placebo) were insomnia (5.2%, n=10), anxiety (2.1%, n=4), nervousness (1.6%, n=3), dry mouth (1.6%, n=3), anorexia (1.6%, n=3), tachycardia (1.6%, n=3), headache (1.6%, n=3), and asthenia (1.0%, n=2). Adverse Reactions Occurring in Clinical Trials Adverse reactions reported in a 3-week clinical trial of pediatric patients 6 to 12 years of age and a 4-week clinical trial in pediatric patients 13 to 17 years of age and adults, respectively, treated with MAS ER or placebo are presented in the tables below.
Drug interactions
Acidifying and Alkalinizing Agents: Agents that alter urinary pH can alter blood levels of amphetamine. Acidifying agents can decrease amphetamine blood levels, while alkalinizing agents can increase amphetamine blood levels. Adjust amphetamine extended-release orally disintegrating tablets dosage accordingly. ( 7.1 ) 7.1 Drugs Having Clinically Important Interactions with Amphetamines Table 5: Drugs having clinically important interactions with amphetamines. MAO Inhibitors (MAOI) Clinical Impact MAOI antidepressants slow amphetamine metabolism, increasing amphetamines effect on the release of norepinephrine and other monoamines from adrenergic nerve endings causing headaches and other signs of hypertensive crisis. Toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results. Intervention Do not administer amphetamine extended-release orally disintegrating tablets during or within 14 days following the administration of MAOI [see Contraindications ( 4 )] . Serotonergic Drugs Clinical Impact The concomitant use of amphetamine extended-release orally disintegrating tablets and serotonergic drugs increases the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during amphetamine extended-release orally disintegrating tablets initiation or dosage increase. If serotonin syndrome occurs, discontinue amphetamine extended-release orally disintegrating tablets and the concomitant serotonergic drug(s) [see Warnings and Precautions ( 5.7 )] . Alkalinizing Agents Clinical Impact Increase blood levels and potentiate the action of amphetamine. Intervention Coadministration of amphetamine extended-release orally disintegrating tablets and gastrointestinal alkalinizing agents should be avoided. Acidifying Agents Clinical Impact Lower blood levels and efficacy of amphetamines. Intervention Increase dose based on clinical response. Tricyclic Antidepressants Clinical Impact 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. Intervention Monitor frequently and adjust or use alternative therapy based on clinical response. 7.2 Drug/Laboratory Test Interactions Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.
Use in specific populations
Pregnancy: May cause fetal harm. ( 8.1 ) Lactation: Breastfeeding not recommended. ( 8.2 ) 8.1 Pregnancy Risk Summary Available data from epidemiologic studies and postmarketing reports on the use of amphetamine in pregnant women over decades of use have not identified a drug-associated risk of major birth defects or miscarriage. Neonates exposed to amphetamine in utero are at risk for withdrawal symptoms following delivery. Adverse pregnancy outcomes including premature delivery and low birth weight have been seen in infants born to mothers taking amphetamines during pregnancy (see Clinical Considerations). No apparent effects on morphological development were observed in embryo-fetal development studies, with oral administration of amphetamine to rats and rabbits during organogenesis. However, in a pre- and post-natal development study, amphetamine (d- to l- ratio of 3:1) administered orally to pregnant rats during gestation and lactation caused a decrease in pup survival and a decrease in pup body weight that correlated with a delay in developmental landmarks at clinically relevant doses of amphetamine. In addition, adverse effects on reproductive performance were observed in pups whose mothers were treated with amphetamine. Long-term neurochemical and behavioral effects have also been reported in animal developmental studies using clinically relevant doses of amphetamine ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Amphetamines, such as amphetamine extended-release orally disintegrating tablets, cause vasoconstriction and thereby may decrease placental perfusion. In addition, amphetamines can stimulate uterine contractions, increasing the risk of premature delivery. Infants born to mothers taking amphetamines during pregnancy have an increased risk of premature delivery and low birth weight. Monitor infants born to mothers taking amphetamines for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness. Data Animal Data Amphetamine, in the enantiomer ratio present in amphetamine extended-release orally disintegrating tablets, (d- to l-ratio of 3:1), had no apparent effects on embryofetal morphological development or survival when orally administered to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 6 and 16 mg/kg/day, respectively. These doses are approximately 2 and 12 times, respectively, the maximum recommended human dose (MRHD) for adolescents of 12.5 mg/day (as base), on a mg/m 2 body surface area basis. Fetal malformations and death have been reported in mice following parenteral administration of d-amphetamine doses of 50 mg/kg/day (approximately 10 times the MRHD for adolescents on a mg/m 2 basis) or greater to pregnant animals. Administration of these doses was also associated with severe maternal toxicity. A study was conducted in which pregnant rats received daily oral doses of amphetamine (d- to l-enantiomer ratio of 3:1, the same as in amphetamine extended-release orally disintegrating tablets) of 2, 6, and 10 mg/kg from gestation day 6 to lactation day 20. These doses are approximately 0.8, 2, and 4 times the MRHD for adolescents of 12.5 mg/day (as base), on a mg/m 2 basis. All doses caused hyperactivity and decreased weight gain in the dams. A decrease in pup survival was seen at all doses. A decrease in pup bodyweight was seen at 6 and 10 mg/kg which correlated with delays in developmental landmarks. Increased pup locomotor activity was seen at 10 mg/kg on day 22 postpartum but not at 5 weeks post-weaning. When pups were tested for reproductive performance at maturation, gestational weight gain, number of implantations, and number of delivered pups were decreased in the group whose mothers had been given 10 mg/kg. A number of studies in rodents indicate that prenatal or early postnatal exposure to amphetamine (d- or d, l-), at doses similar to those used clinically, can result in long-term neurochemical and behavioral alterations. Reported behavioral effects include learning and memory deficits, altered locomotor activity, and changes in sexual function. 8.2 Lactation Risk Summary Based on limited case reports in published literature, amphetamine (d- or d, l-) is present in human milk at relative infant doses of 2% to 13.8% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.9 and 7.5. There are no reports of adverse effects on the breastfed infant. Long-term neurodevelopmental effects on infants from amphetamine exposure are unknown. It is possible that large dosages of amphetamine might interfere with milk production, especially in women whose lactation is not well established. Because of the potential for serious adverse reactions in nursing infants, advise patients that breastfeeding is not recommended during treatment with amphetamine extended-release orally disintegrating tablets. 8.4 Pediatric Use The safety and effectiveness have been established in pediatric patients with ADHD ages 6 to 17 years of age in three adequate and well-controlled clinical trials of up to 4 weeks in duration [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12 ), Clinical Studies ( 14 )] . The safety and effectiveness of amphetamine extended-release orally disintegrating tablets have not been established in pediatric patients below the age of 6 years. In studies evaluating extended-release amphetamine products, patients 4 to <6 years of age had higher systemic amphetamine exposures than those observed in older pediatric patients at the same dosage.
Pregnancy
8.1 Pregnancy Risk Summary Available data from epidemiologic studies and postmarketing reports on the use of amphetamine in pregnant women over decades of use have not identified a drug-associated risk of major birth defects or miscarriage. Neonates exposed to amphetamine in utero are at risk for withdrawal symptoms following delivery. Adverse pregnancy outcomes including premature delivery and low birth weight have been seen in infants born to mothers taking amphetamines during pregnancy (see Clinical Considerations). No apparent effects on morphological development were observed in embryo-fetal development studies, with oral administration of amphetamine to rats and rabbits during organogenesis. However, in a pre- and post-natal development study, amphetamine (d- to l- ratio of 3:1) administered orally to pregnant rats during gestation and lactation caused a decrease in pup survival and a decrease in pup body weight that correlated with a delay in developmental landmarks at clinically relevant doses of amphetamine. In addition, adverse effects on reproductive performance were observed in pups whose mothers were treated with amphetamine. Long-term neurochemical and behavioral effects have also been reported in animal developmental studies using clinically relevant doses of amphetamine ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Amphetamines, such as amphetamine extended-release orally disintegrating tablets, cause vasoconstriction and thereby may decrease placental perfusion. In addition, amphetamines can stimulate uterine contractions, increasing the risk of premature delivery. Infants born to mothers taking amphetamines during pregnancy have an increased risk of premature delivery and low birth weight. Monitor infants born to mothers taking amphetamines for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness. Data Animal Data Amphetamine, in the enantiomer ratio present in amphetamine extended-release orally disintegrating tablets, (d- to l-ratio of 3:1), had no apparent effects on embryofetal morphological development or survival when orally administered to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 6 and 16 mg/kg/day, respectively. These doses are approximately 2 and 12 times, respectively, the maximum recommended human dose (MRHD) for adolescents of 12.5 mg/day (as base), on a mg/m 2 body surface area basis. Fetal malformations and death have been reported in mice following parenteral administration of d-amphetamine doses of 50 mg/kg/day (approximately 10 times the MRHD for adolescents on a mg/m 2 basis) or greater to pregnant animals. Administration of these doses was also associated with severe maternal toxicity. A study was conducted in which pregnant rats received daily oral doses of amphetamine (d- to l-enantiomer ratio of 3:1, the same as in amphetamine extended-release orally disintegrating tablets) of 2, 6, and 10 mg/kg from gestation day 6 to lactation day 20. These doses are approximately 0.8, 2, and 4 times the MRHD for adolescents of 12.5 mg/day (as base), on a mg/m 2 basis. All doses caused hyperactivity and decreased weight gain in the dams. A decrease in pup survival was seen at all doses. A decrease in pup bodyweight was seen at 6 and 10 mg/kg which correlated with delays in developmental landmarks. Increased pup locomotor activity was seen at 10 mg/kg on day 22 postpartum but not at 5 weeks post-weaning. When pups were tested for reproductive performance at maturation, gestational weight gain, number of implantations, and number of delivered pups were decreased in the group whose mothers had been given 10 mg/kg. A number of studies in rodents indicate that prenatal or early postnatal exposure to amphetamine (d- or d, l-), at doses similar to those used clinically, can result in long-term neurochemical and behavioral alterations. Reported behavioral effects include learning and memory deficits, altered locomotor activity, and changes in sexual function.
Pediatric use
8.4 Pediatric Use The safety and effectiveness have been established in pediatric patients with ADHD ages 6 to 17 years of age in three adequate and well-controlled clinical trials of up to 4 weeks in duration [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12 ), Clinical Studies ( 14 )] . The safety and effectiveness of amphetamine extended-release orally disintegrating tablets have not been established in pediatric patients below the age of 6 years. In studies evaluating extended-release amphetamine products, patients 4 to <6 years of age had higher systemic amphetamine exposures than those observed in older pediatric patients at the same dosage. Pediatric patients 4 to <6 years of age also had a higher incidence of adverse reactions, including weight loss. Long-Term Growth Suppression Growth should be monitored during treatment with stimulants, including amphetamine extended-release orally disintegrating tablets, in pediatric patients aged 6 to 17 years who are not growing or gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions ( 5.5 )] . Juvenile Animal Data In a juvenile developmental study, rats received daily oral doses of amphetamine (d to l enantiomer ratio of 3:1, the same as in amphetamine extended-release orally disintegrating tablets) of 2, 6, or 20 mg/kg on days 7 to 13 of age; from day 14 to approximately day 60 of age these doses were given twice daily for total daily doses of 4, 12, or 40 mg/kg. The latter doses are approximately 0.6, 2, and 6 times the maximum recommended human dose for children of 18.8 mg/day (as base), on a mg/m 2 basis. Post dosing hyperactivity was seen at all doses; motor activity measured prior to the daily dose was decreased during the dosing period but the decreased motor activity was largely absent after an 18 day drug-free recovery period. Performance in the Morris water maze test for learning and memory was impaired at the 40 mg/kg dose, and sporadically at the lower doses, when measured prior to the daily dose during the treatment period; no recovery was seen after a 19 day drug-free period. A delay in the developmental milestones of vaginal opening and preputial separation was seen at 40 mg/kg but there was no effect on fertility.
Geriatric use
8.5 Geriatric Use Amphetamine extended-release orally disintegrating tablets have not been studied in the geriatric population.
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 hallucination. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur. Life-threatening hyperthermia (temperatures greater than 104ºF) and rhabdomyolysis may develop. Overdose Management Consider the possibility of multiple drug ingestion. The pharmacokinetic profile of amphetamine extended-release orally disintegrating tablets should be considered when treating patients with overdose. D-amphetamine is not dialyzable. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.
Description
Amphetamine extended-release orally disintegrating tablets contain a 3 to 1 ratio of d- to l-amphetamine, a central nervous system stimulant. The labeled strengths reflect the amount of amphetamine base in amphetamine extended-release orally disintegrating tablets whereas the strengths of the (mixed salts of a single-entity amphetamine) products are in terms of the amount of amphetamine salts. Table 1 in Section 2.5 details the equivalent amounts of active ingredient in these products. Structural Formula: Amphetamine extended-release orally disintegrating tablets is an extended-release orally disintegrating tablet containing 45% immediate-release and 55% delayed-release amphetamine for once daily dosing. Amphetamine extended-release orally disintegrating tablets also contain the following inactive ingredients: citric acid, colloidal silicon dioxide, crospovidone, fructose, magnesium stearate, mannitol, methacrylic acid and ethyl acrylate copolymer, microcrystalline cellulose, pineapple flavor, sodium polystyrene sulfonate, sucralose, povidone K-30, talc, triethyl citrate and yellow iron oxide. 1
Mechanism of action
12.1 Mechanism of Action Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action in ADHD is not known. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.
How supplied
How Supplied Amphetamine extended-release orally disintegrating tablets 3.1 mg are light yellow, mottled round tablets debossed with “A17” on one side and plain on the other side and supplied as: Carton containing 5 blister cards of 6 tablets each, for a total of 30 tablets NDC 0480-3315-65. Amphetamine extended-release orally disintegrating tablets 6.3 mg are light yellow, mottled round tablets debossed with “A118” on one side and plain on the other side and supplied as: Carton containing 5 blister cards of 6 tablets each, for a total of 30 tablets NDC 0480-3316-65. Amphetamine extended-release orally disintegrating tablets 9.4 mg are light yellow, mottled round tablets debossed with “A119” on one side and plain on the other side and supplied as: Carton containing 5 blister cards of 6 tablets each, for a total of 30 tablets NDC 0480-3317-65. Amphetamine extended-release orally disintegrating tablets 12.5 mg are light yellow, mottled round tablets debossed with “A285” on one side and plain on the other side and supplied as: Carton containing 5 blister cards of 6 tablets each, for a total of 30 tablets NDC 0480-3318-65. Amphetamine extended-release orally disintegrating tablets 15.7 mg are light yellow, mottled round tablets debossed with “A121” on one side and plain on the other side and supplied as: Carton containing 5 blister cards of 6 tablets each, for a total of 30 tablets NDC 0480-3319-65. Amphetamine extended-release orally disintegrating tablets 18.8 mg are light yellow, mottled round tablets debossed with “A122” on one side and plain on the other side and supplied as: Carton containing 5 blister cards of 6 tablets each, for a total of 30 tablets NDC 0480-3320-65. Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Abuse, Misuse, and Addiction Educate patients and their families about the risks of abuse, misuse, and addiction of amphetamine extended-release orally disintegrating tablets, which can lead to overdose and death, and proper disposal of any unused drug [see Warnings and Precautions ( 5.1 ), Drug Abuse and Dependence ( 9.2 ), Overdosage ( 10) ] . Advise patients to store amphetamine extended-release orally disintegrating tablets in a safe place, preferably locked, and instruct patients to not give amphetamine extended-release orally disintegrating tablets to anyone else. Dosage and Administration Instructions Provide the following instructions on administration to the patient: The tablet should remain in the blister pack until the patient is ready to take it. The patient or caregiver should use dry hands to open the blister. Tear along the perforation, bend the blister where indicated and peel back the blister’s labeled backing to take out the tablet. The tablet should not be pushed through the foil. As soon as the blister is opened, the tablet should be removed and placed on the patient’s tongue. The whole tablet should be placed on the tongue and allowed to disintegrate without chewing or crushing. The tablet will disintegrate in saliva so that it can be swallowed. Risks to Patients with Serious Cardiac Disease Advise patients that there are potential risks to patients with serious cardiac disease, including sudden death, with amphetamine extended-release orally disintegrating tablets use. Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease [see Warnings and Precautions ( 5.2 )] . Increased Blood Pressure and Heart Rate Instruct patients that amphetamine extended-release orally disintegrating tablets can cause elevations of their blood pressure and pulse rate [see Warnings and Precautions ( 5.3 )] . Psychiatric Adverse Reactions Advise patients that amphetamine extended-release orally disintegrating tablets, at recommended doses, may cause psychotic symptoms or mania [see Warnings and Precautions ( 5.4) ] . Long-Term Suppression of Growth Advise patients that amphetamine extended-release orally disintegrating tablets may cause slowing of growth and weight loss [see Warnings and Precautions ( 5.5 )] . Circulation problems in Fingers and Toes [Peripheral vasculopathy, including Raynaud’s phenomenon] Instruct patients beginning treatment with amphetamine extended-release orally disintegrating tablets 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 extended-release orally disintegrating tablets. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients [see Warnings and Precautions ( 5.6 )] . Serotonin Syndrome Caution patients about the risk of serotonin syndrome with concomitant use of amphetamine extended-release orally disintegrating tablets and other serotonergic drugs including SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular MAOIs, both those intended to treat psychiatric disorders and also others such as linezolid [see Contraindications ( 4 ), Warnings and Precautions ( 5.7 ) and Drug Interactions ( 7.1 )] . Advise patients to contact their healthcare provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome. Motor and Verbal Tics, and Worsening of Tourette’s Syndrome Advise patients that motor and verbal tics and worsening of Tourette’s syndrome may occur during treatment with amphetamine extended-release orally disintegrating tablets. Instruct patients to notify their healthcare provider if emergence of new tics or worsening of tics or Tourette’s syndrome occurs [see Warnings and Precautions ( 5.8) ] . Concomitant Medications Advise patients to notify their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs because there is a potential for interactions [see Drug Interactions ( 7.1 )] . Pregnancy Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with amphetamine extended-release orally disintegrating tablets. Advise patients of the potential fetal effects from the use of amphetamine extended-release orally disintegrating tablets during pregnancy [see Use in Specific Populations ( 8.1 )] . Lactation Advise patients not to breastfeed if they are taking amphetamine extended-release orally disintegrating tablets [see Use in Specific Populations ( 8.2 )] . Alcohol Advise patients to avoid alcohol while taking amphetamine extended-release orally disintegrating tablets. Consumption of alcohol while taking amphetamine extended-release orally disintegrating tablets may result in a more rapid release of the dose of amphetamine [see Clinical Pharmacology ( 12 )] . For more information call Teva at 1-888-838-2872. Manufactured For: Teva Pharmaceuticals Parsippany, NJ 07054 Iss. 9/2025
Label text from the FDA structured product label by Teva Pharmaceuticals, Inc. (revised Sep 1, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Amphetamine in 6 products
Amphetamine NDC products (6)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0480-3315 | Amphetamine 3.1 mg/1 Tablet, Orally Disintegrating | Teva Pharmaceuticals, Inc. | ANDA · DEA CII |
| 0480-3316 | Amphetamine 6.3 mg/1 Tablet, Orally Disintegrating | Teva Pharmaceuticals, Inc. | ANDA · DEA CII |
| 0480-3317 | Amphetamine 9.4 mg/1 Tablet, Orally Disintegrating | Teva Pharmaceuticals, Inc. | ANDA · DEA CII |
| 0480-3318 | Amphetamine 12.5 mg/1 Tablet, Orally Disintegrating | Teva Pharmaceuticals, Inc. | ANDA · DEA CII |
| 0480-3319 | Amphetamine 15.7 mg/1 Tablet, Orally Disintegrating | Teva Pharmaceuticals, Inc. | ANDA · DEA CII |
| 0480-3320 | Amphetamine 18.8 mg/1 Tablet, Orally Disintegrating | Teva Pharmaceuticals, Inc. | ANDA · DEA CII |
Frequently asked questions
What is Amphetamine used for?
Amphetamine extended-release orally disintegrating tablets are a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older [see Clinical Studies ( 14 )] . Limitations of Use The use of amphetamine extended-release orally disintegrating tablets are not recommended in pediatric patients younger than 6 years of…
What are the side effects of Amphetamine?
The following adverse reactions are discussed in greater detail in other sections of the labeling: Abuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions ( 5.1 ), and Drug Abuse and Dependence ( 9.2 , 9.3 )] Hypersensitivity to amphetamine, or other components of amphetamine extended-release orally disintegrating tablets [see Contraindications ( 4 )] Hypertensive Crisis When… See the full label for the complete list.
Who makes Amphetamine?
Amphetamine is listed by 1 labeler in the FDA NDC directory, including Teva Pharmaceuticals, Inc..