Amphetamine 6.3 mg Tablet, Orally Disintegrating — NDC 0480-3316-65 (Billing 00480-3316-65)
This is a package of Amphetamine 6.3 mg Tablet, Orally Disintegrating from Teva Pharmaceuticals, Inc., marketed since Dec 2025 and currently FDA-listed; retail pharmacies pay about $16.07 per unit (NADAC). It is this product's only package size.
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 075545
- GCN: 40648
- HICL (First Databank): 043652
- AHFS class code: 28:20.04.00
- RxCUI (RxNorm): 1739803
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Central Nervous System Stimulant class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Amphetamine (Adzenys® ER, Adzenys® XR, Dyanavel® XR, Evekeo®, Evekeo® ODT, others) is used as part of a treatment program to control symptoms of attention deficit hyperactivity disorder (ADHD; more difficulty focusing, controlling actions, and remaining still or quiet than other people who are the same age) in adults and children. Amphetamine (Evekeo®, others) is also used to treat narcolepsy (a sleep disorder that causes excessive daytime sleepiness and sudden attacks of sleep). Amphetamine (Evekeo®, others) is also used for a limited period of time (a few weeks) along with a reduced calorie...
Read the full MedlinePlus article ↗- It depends on the specific product. Most amphetamine products — including Adzenys XR-ODT, Dyanavel XR, and the extended-release orally disintegrating tablets — are approved to trea...
- What conditions is amphetamine actually approved to treat?
- You can take most amphetamine products with or without food — it won't meaningfully change how much you absorb. That said, eating (especially a high-fat meal) can delay when it kic...
- Is it okay to take this with food, or does it have to be on an empty stomach?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Amphetamine — tap one for details:
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $16.073 | $2,893.18 / 180 tablets |
| Medicaid paysCMS SDUD · 12 mo | $16.88 | $3,039.16 / 180 tablets |
| Medicare drug plans payPart D · Q2 2026 | $12.15 | $2,186.14 / 180 tablets |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 00480-3316-65 You're viewing this Main listing | 30 BLISTER PACK in 1 CARTON / 6 TABLET, ORALLY DISINTEGRATING in 1 BLISTER PACK | 2025-12-08 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Amphetamine 6.3 mgthis 00480-3316-65 | Teva | 6 tablets | $16.073 | AB | Availability likely | — |
| Amphetamine Extended-Release 6.3 mg 62542-0010-30 | Neos | 6 tablets | $16.073 | AB | Availability likely | — |
| Adzenys XR-ODT 6.3 mg 70165-0010-30 | Neos | 6 tablets | $19.209 | AB | Availability likely | +20% |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Sep 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Sep 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
Where does this data come from?
IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: ABUSE, MISUSE, AND ADDICTION Amphetamine extended-release orally disintegrating tablets have 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 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, proper storage of the drug, and proper disposal of any unused drug. 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 [see Warnings and Precautions ( 5.1 ), Drug Abuse and Dependence ( 9.2 )] . WARNING: ABUSE, MISUSE AND ADDICTION See full prescribing information for complete boxed warning.
Amphetamine extended-release orally disintegrating tablets have 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 amphetamine extended-release orally disintegrating tablets, can result in overdose and death ( 5.1 , 9.2 , 10 ): 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, proper storage of the drug, and proper disposal of any unused drug.
Throughout treatment, reassess each patient’s risk and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE 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 ▾
2 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 )
2.1Pre-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 )] .
2.2General 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.
2.3Dosage 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 ) ] .
2.4Dosage Recommendations in Adults The recommended dose is amphetamine extended-release orally disintegrating tablets 12.5 mg daily.
2.5Switching 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 sing… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 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 ▾
4 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 Cautions ▾
5 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 )
5.1Abuse, 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.
5.2Risks 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.
5.3Increased 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 increas… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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 .
6.1Clinical 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 ev… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 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 )
7.1Drugs 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.
7.2Drug/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.
🔄 Drug / Laboratory Test Interactions ▾
7.2Drug/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 ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause fetal harm. ( 8.1 ) Lactation: Breastfeeding not recommended. ( 8.2 )
8.1Pregnancy 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.
Whe… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy 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 numb… [Excerpted — this section continues on DailyMed.]
🧒 Pediatric Use ▾
8.4Pediatric 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 ▾
8.5Geriatric Use Amphetamine extended-release orally disintegrating tablets have not been studied in the geriatric population.
🆘 Overdosage ▾
10 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
12.3Pharmacokinetics Absorption Following a single, 18.8 mg oral dose of amphetamine extended-release orally disintegrating tablets in 40 healthy adult subjects in a crossover study under fasting conditions, d-amphetamine mean (±SD) peak plasma concentrations of 44.9 (±8.9) ng/mL occurred at a median time of 5.0 hours after dosing, and l-amphetamine mean (±SD) peak plasma concentrations of 14.5 (+ 3.0 ng/mL occurred at a median time of 5.25 hours after dosing (Figure 1). Figure 1: Mean Concentration of D-Amphetamine and L-Amphetamine vs Time for Amphetamine Extended-Release Orally Disintegrating Tablets (18.8 mg) and Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules (MAS ER 30 mg) in the Fasted State The single dose pharmacokinetics of d-amphetamine under fed conditions are summarized (Table 6) from studies in healthy adults following an oral dose of 18.8 mg amphetamine extended-release orally disintegrating tablets.
Table 6: d-Amphetamine PK Parameters (mean + SD) after Amphetamine Extended-Release Orally Disintegrating Tablets 18.8 mg PK parameter Adults Fasted Adults Fed a T max (hr) b 5.00 (3.00 to 12.00) 7.00 (3.00 to 16.00) T 1/2 (hr) 11.25±2.0 11.33±2.0 C max (ng/ml) 44.9±8.9 36.3±6.9 AUC inf (hr*ng/mL) 876.9±182.4 856.3±166.1 a A high-fat meal was consumed 30 minutes prior to drug administration b Data presented as median (range) A single dose of amphetamine extended-release orally disintegrating tablets 18.8 mg provided comparable plasma concentration profiles of both d-amphetamine and l-amphetamine to mixed salts of a single-entity amphetamine product extended-release capsules (MAS ER) 30 mg.
The mean elimination half-life for d-amphetamine is 11 hours in adults and 9 to 10 hours in pediatric patients aged 6 to 12 years. For l-amphetamine, the mean elimination half-life in adults is 14 hours and 10 to 11 hours in pediatric patients aged 6 to 12 years. Mean weight-normalized clearance values for d-amphetamine and l-amphetamine decreased slightly with an increase in age.
Food Effect Food does not affect the extent of absorption of d-amphetamine and l-amphetamine but caused a 19% reduction in C max . Food also prolonged the median t max by approximately 2.0 hours for d-amphetamine and by 2.5 hours for l-amphetamine after administration of amphetamine extended-release orally disintegrating tablets. These changes are not considered clinically significant.
Alcohol Effect In an in vitro alcohol-induced dose dumping study, a substantial increase in amphetamine release occurred in the presence of 40% alcohol but not with 5%, 10% and 20% alcohol. Elimination Metabolism and Excretion Amphetamine is reported to be oxidized at the 4 position of the benzene ring to form 4-hydroxyamphetamine, or on the side chain α or β carbons to form alpha-hydroxy-amphetamine or norephedrine, respectively. Norephedrine and 4-hydroxy-amphetamine are both active and each is subsequently oxidized to form 4-hydroxy-norephedrine.
Alpha-hydroxy-amphetamine undergoes deamination to form phenylacetone, which ultimately forms benzoic acid and its glucuronide and the glycine conjugate hippuric acid. Although the enzymes involved in amphetamine metabolism have not been clearly defined, CYP2D6 is known to be involved with formation of 4-hydroxy-amphetamine. Since CYP2D6 is genetically polymorphic, population variations in amphetamine metabolism are a possibility.
Amphetamine is known to inhibit monoamine oxidase, whereas the ability of amphetamine and its metabolites to inhibit various P450 isozymes and other enzymes has not been adequately elucidated. In vitro exper… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism 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 / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING 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].
📋 Description ▾
11 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
💬 Information for Patients ▾
17 PATIENT COUNSELING 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 re… [Excerpted — this section continues on DailyMed.]
💬 Medication Guide ▾
MEDICATION GUIDE Amphetamine (am fet' a meen) Extended-Release Orally Disintegrating Tablets, CII What is the most important information I should know about amphetamine extended-release orally disintegrating tablets? Amphetamine extended-release orally disintegrating tablets may cause serious side effects, including: Abuse, misuse, and addiction. Amphetamine extended-release orally disintegrating tablets have a high chance for abuse and misuse and may lead to substance use problems, including addiction.
Misuse and abuse of amphetamine extended-release orally disintegrating tablets, other amphetamine containing medicines, and methylphenidate containing medicines, can lead to overdose and death. The risk of overdose and death is increased with higher doses of amphetamine extended-release orally disintegrating tablets or when it is used in ways that are not approved, such as snorting or injection. Your healthcare provider should check you or your child’s risk for abuse, misuse, and addiction before starting treatment with amphetamine extended-release orally disintegrating tablets and will monitor you or your child during treatment.
Amphetamine extended-release orally disintegrating tablets may lead to physical dependence after prolonged use, even if taken as directed by your healthcare provider. Do not give amphetamine extended-release orally disintegrating tablets to anyone else. See “What is amphetamine extended-release orally disintegrating tablets?” for more information.
Keep amphetamine extended-release orally disintegrating tablets in a safe place and properly dispose of any unused medicine. See “How should I store amphetamine extended-release orally disintegrating tablets?” for more information. Tell your healthcare provider if you or your child have ever abused or been dependent on alcohol, prescription medicines, or street drugs.
Risks for people with serious heart disease. Sudden death has happened in people who have heart defects or other serious heart disease. Your healthcare provider should check you or your child carefully for heart problems before starting amphetamine extended-release orally disintegrating tablets.
Tell your healthcare provider if you or your child has any heart problems, heart disease, or heart defects. Call your healthcare provider or go to the nearest hospital emergency room right away if you or your child has any signs of heart problems such as chest pain, shortness of breath, or fainting while taking amphetamine extended-release orally disintegrating tablets. Increased blood pressure and heart rate.
Your healthcare provider should check you or your child’s blood pressure and heart rate regularly during treatment with amphetamine extended-release orally disintegrating tablets. Mental (Psychiatric) problems: All Patients new or worse behavior and thought problems new or worse bipolar illness new psychotic symptoms (such as hearing voices, believing things that are not true, are suspicious) or new manic symptoms. Tell your healthcare provider about any mental problems you or your child have, or about a family history of suicide, bipolar illness, or depression.
Call your healthcare provider right away if you or your child have any new or worsening mental symptoms or problems while taking amphetamine extended-release orally disintegrating tablets, especially seeing or hearing things that are not real, believing things that are not real, or are suspicious. What are amphetamine extended-release orally disintegrating tablets? Amphetamine extended-release orally disintegrating tablets is a central nervous system (CNS) stimulant prescription medicine.
It is used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). Amphetamine extended-release orally disintegrating tablets may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD. Amphetamine extended-release orally disintegrating tablets are not recommended for use in children under 6 years of age wi… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Absorption Following a single, 18.8 mg oral dose of amphetamine extended-release orally disintegrating tablets in 40 healthy adult subjects in a crossover study under fasting conditions, d-amphetamine mean (±SD) peak plasma concentrations of 44.9 (±8.9) ng/mL occurred at a median time of 5.0 hours after dosing, and l-amphetamine mean (±SD) peak plasma concentrations of 14.5 (+ 3.0 ng/mL occurred at a median time of 5.25 hours after dosing (Figure 1). Figure 1: Mean Concentration of D-Amphetamine and L-Amphetamine vs Time for Amphetamine Extended-Release Orally Disintegrating Tablets (18.8 mg) and Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules (MAS ER 30 mg) in the Fasted State The single dose pharmacokinetics of d-amphetamine under fed conditions are summarized (Table 6) from studies in healthy adults following an oral dose of 18.8 mg amphetamine extended-release orally disintegrating tablets.
Table 6: d-Amphetamine PK Parameters (mean + SD) after Amphetamine Extended-Release Orally Disintegrating Tablets 18.8 mg PK parameter Adults Fasted Adults Fed a T max (hr) b 5.00 (3.00 to 12.00) 7.00 (3.00 to 16.00) T 1/2 (hr) 11.25±2.0 11.33±2.0 C max (ng/ml) 44.9±8.9 36.3±6.9 AUC inf (hr*ng/mL) 876.9±182.4 856.3±166.1 a A high-fat meal was consumed 30 minutes prior to drug administration b Data presented as median (range) A single dose of amphetamine extended-release orally disintegrating tablets 18.8 mg provided comparable plasma concentration profiles of both d-amphetamine and l-amphetamine to mixed salts of a single-entity amphetamine product extended-release capsules (MAS ER) 30 mg.
The mean elimination half-life for d-amphetamine is 11 hours in adults and 9 to 10 hours in pediatric patients aged 6 to 12 years. For l-amphetamine, the mean elimination half-life in adults is 14 hours and 10 to 11 hours in pediatric patients aged 6 to 12 years. Mean weight-normalized clearance values for d-amphetamine and l-amphetamine decreased slightly with an increase in age.
Food Effect Food does not affect the extent of absorption of d-amphetamine and l-amphetamine but caused a 19% reduction in C max . Food also prolonged the median t max by approximately 2.0 hours for d-amphetamine and by 2.5 hours for l-amphetamine after administration of amphetamine extended-release orally disintegrating tablets. These changes are not considered clinically significant.
Alcohol Effect In an in vitro alcohol-induced dose dumping study, a substantial increase in amphetamine release occurred in the presence of 40% alcohol but not with 5%, 10% and 20% alcohol. Elimination Metabolism and Excretion Amphetamine is reported to be oxidized at the 4 position of the benzene ring to form 4-hydroxyamphetamine, or on the side chain α or β carbons to form alpha-hydroxy-amphetamine or norephedrine, respectively. Norephedrine and 4-hydroxy-amphetamine are both active and each is subsequently oxidized to form 4-hydroxy-norephedrine.
Alpha-hydroxy-amphetamine undergoes deamination to form phenylacetone, which ultimately forms benzoic acid and its glucuronide and the glycine conjugate hippuric acid. Although the enzymes involved in amphetamine metabolism have not been clearly defined, CYP2D6 is known to be involved with formation of 4-hydroxy-amphetamine. Since CYP2D6 is genetically polymorphic, population variations in amphetamine metabolism are a possibility.
Amphetamine is known to inhibit monoamine oxidase, whereas the ability of amphetamine and its metabolites to inhibit various P450 isozymes and other enzymes has not been adequately elucidated. In vitro experiments with human microsomes indicate minor inhibition of CYP2D6 by amphetamine and minor inhibition of CYP1A2, 2D6, and 3A4 by one or more metabolites. However, due to the probability of auto-inhibition and the lack of information on the concentration of these metabolites relative to in vivo concentrations, no predications regarding the potential for amphetamine or it… [Excerpted — this section continues on DailyMed.]
🔬 Clinical Studies ▾
6.1Clinical 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. Table 2: Adverse Reactions Reported by 2% or More of Pediatric Patients (6 to 12 years old) Receiving MAS ER with Higher Incidence than on Placebo in a 584-Patient Clinical Study Body System Adverse Reaction MAS ER (n=374) Placebo (n=210) General Abdominal Pain (stomachache) Fever Infection Accidental Injury Asthenia (fatigue) 14% 5% 4% 3% 2% 10% 2% 2% 2% 0% Digestive System Loss of Appetite Vomiting Nausea Dyspepsia 22% 7% 5% 2% 2% 4% 3% 1% Nervous System Insomnia Emotional Lability Nervousness Dizziness 17% 9% 6% 2% 2% 2% 2% 0% Metabolic/Nutritional Weight Loss 4% 0% Table 3: Adverse Reactions Reported by 5% or More of Pediatric Patients (13 to 17 Years Old) Weighing ≤ 75kg Receiving MAS ER with Higher Incidence than Placebo in a 287 Patient Clinical Forced Weekly-Dose Titration Study* Body System Preferred Term MAS ER (n=233) Placebo (n=54) General Abdominal Pain (stomachache) 11% 2% Digestive System Loss of Appetite a 36% 2% Nervous System Insomnia a 12% 4% Metabolic/Nutritional Weight Loss a 9% 0% * Included doses up to 40 mg a Dose-related adverse reactions Note: The following reactions did not m… [Excerpted — this section continues on DailyMed.]
🔒 Drug Abuse and Dependence ▾
9 DRUG ABUSE AND DEPENDENCE
9.1Controlled Substance Amphetamine extended-release orally disintegrating tablets contain amphetamine, a Schedule II controlled substance.
9.2Abuse Amphetamine extended-release orally disintegrating tablets have a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction [see Warnings and Precautions ( 5.1 )] . Amphetamine extended-release orally disintegrating tablets can be diverted for non-medical use into illicit channels or distribution. Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect.
Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.
Misuse and abuse of amphetamine 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 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.
9.3Dependence Physical Dependence Amphetamine extended-release orally disintegrating tablets may produce physical dependence. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of CNS stimulants including amphetamine extended-release orally disintegrating tablets include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.
Tolerance Amphetamine extended-release orally disintegrating tablets may produce tolerance. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
🔒 Controlled Substance ▾
9.1Controlled Substance Amphetamine extended-release orally disintegrating tablets contain amphetamine, a Schedule II controlled substance.
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No evidence of carcinogenicity was found in studies in which d,l-amphetamine (enantiomer ratio of 1:1) was administered to mice and rats in the diet for 2 years at doses of up to 30 mg/kg/day in male mice, 19 mg/kg/day in female mice, and 5 mg/kg/day in male and female rats. These doses are approximately 2.4, 1.5, and 0.8 times, respectively, the maximum recommended human dose for children of 18.8 mg/day (as base), on a mg/m 2 body surface area basis.
Mutagenesis Amphetamine, in the enantiomer ratio present in amphetamine extended-release orally disintegrating tablets (d- to l-ratio of 3:1), was not clastogenic in the mouse bone marrow micronucleus test in vivo and was negative when tested in the E. coli component of the Ames test in vitro . d,l-Amphetamine (1:1 enantiomer ratio) has been reported to produce a positive response in the mouse bone marrow micronucleus test, an equivocal response in the Ames test, and negative responses in the in vitro sister chromatid exchange and chromosomal aberration assays.
Amphetamine, in the enantiomer ratio present in amphetamine extended-release orally disintegrating tablets (d- to l-ratio of 3:1), did not adversely affect fertility or early embryonic development in the rat at doses of up to 20 mg/kg/day [approximately 8 times the maximum recommended human dose for adolescents of 12.5 mg/day (as base), on a mg/m 2 body surface area basis].
13.2Animal Toxicology and/or Pharmacology Acute administration of high doses of amphetamine (d- or d, l-) has been shown to produce long-lasting neurotoxic effects, including irreversible nerve fiber damage, in rodents. The significance of these findings to humans is unknown.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No evidence of carcinogenicity was found in studies in which d,l-amphetamine (enantiomer ratio of 1:1) was administered to mice and rats in the diet for 2 years at doses of up to 30 mg/kg/day in male mice, 19 mg/kg/day in female mice, and 5 mg/kg/day in male and female rats. These doses are approximately 2.4, 1.5, and 0.8 times, respectively, the maximum recommended human dose for children of 18.8 mg/day (as base), on a mg/m 2 body surface area basis.
Mutagenesis Amphetamine, in the enantiomer ratio present in amphetamine extended-release orally disintegrating tablets (d- to l-ratio of 3:1), was not clastogenic in the mouse bone marrow micronucleus test in vivo and was negative when tested in the E. coli component of the Ames test in vitro . d,l-Amphetamine (1:1 enantiomer ratio) has been reported to produce a positive response in the mouse bone marrow micronucleus test, an equivocal response in the Ames test, and negative responses in the in vitro sister chromatid exchange and chromosomal aberration assays.
Amphetamine, in the enantiomer ratio present in amphetamine extended-release orally disintegrating tablets (d- to l-ratio of 3:1), did not adversely affect fertility or early embryonic development in the rat at doses of up to 20 mg/kg/day [approximately 8 times the maximum recommended human dose for adolescents of 12.5 mg/day (as base), on a mg/m 2 body surface area basis].
📄 Recent Major Changes ▾
Indications and Usage ( 1 ) 09/2025 Warnings and Precautions ( 5.5 ) 09/2025
📄 Package Label / Principal Display Panel ▾
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 0480-3315-65 Amphetamine Extended-Release Orally Disintegrating Tablets CII 3.1 mg Do not crush or chew tablets PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 (5 x 6) Unit-Dose Tablets 1
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 0480-3316-65 Amphetamine Extended-Release Orally Disintegrating Tablets CII 6.3 mg Do not crush or chew tablets PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 (5 x 6) Unit-Dose Tablets 1
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 0480-3317-65 Amphetamine Extended-Release Orally Disintegrating Tablets CII 9.4 mg Do not crush or chew tablets PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 (5 x 6) Unit-Dose Tablets 1
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 0480-3318-65 Amphetamine Extended-Release Orally Disintegrating Tablets CII 12.5 mg Do not crush or chew tablets PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 (5 x 6) Unit-Dose Tablets 1
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 0480-3319-65 Amphetamine Extended-Release Orally Disintegrating Tablets CII 15.7 mg Do not crush or chew tablets PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 (5 x 6) Unit-Dose Tablets 1
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 0480-3320-65 Amphetamine Extended-Release Orally Disintegrating Tablets CII 18.8 mg Do not crush or chew tablets PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 (5 x 6) Unit-Dose Tablets 1