Adzenys XR-ODT

Indications and Usage ( 1 ) 09/2025 Warnings and Precautions ( 5.5 ) 09/2025

1. INDICATIONS AND USAGE ADZENYS XR-ODT is 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 ADZENYS XR-ODT is 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)] . ADZENYS XR-ODT is 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 ADZENYS XR-ODT is 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)

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 ) 2.1 Pre-treatment Screening Prior to treating patients with ADZENYS XR-ODT, 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 ADZENYS XR-ODT [see Warnings and Precautions (5.9) ]. 2.2 General Administration Information ADZENYS XR-ODT may be taken orally with or without food. Individualize the dosage according to the therapeutic needs and response of the patient. ADZENYS XR-ODT 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 ADZENYS XR-ODT 12.5 mg daily. 2.5 Switching from Other Amphetamine Products Patients taking ADDERALL XR may be switched to ADZENYS XR-ODT at the equivalent dose taken once daily [see Clinical Pharmacology (12.3) ]. Refer to Table 1 for equivalent doses of ADZENYS XR-ODT and ADDERALL XR. ADDERALL XR (dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate, and amphetamine sulfate extended-release capsules) is also referred to as mixed salts of a single-entity amphetamine product extended-release capsules (MAS ER). Table 1: Equivalent Doses of ADZENYS XR-ODT and ADDERALL XR (Mixed Salts of a Single-Entity Amphetamine Product) Extended-Release Capsules ADZENYS XR-ODT Amphetamine extended-release orally disintegrating tablets 3.1 mg 6.3 mg 9.4 mg 12.5 mg 15.7 mg 18.8 mg ADDERALL XR 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 ADZENYS XR-ODT 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 ADZENYS XR-ODT dosage accordingly …

3. DOSAGE FORMS AND STRENGTHS ADZENYS XR-ODT 3.1 mg Amphetamine extended release orally disintegrating tablet: round, orange to light orange mottled (debossed A1 on one side) ADZENYS XR-ODT 6.3 mg Amphetamine extended release orally disintegrating tablet: round, orange to light orange mottled (debossed A2 on one side) ADZENYS XR-ODT 9.4 mg Amphetamine extended release orally disintegrating tablet: round, orange to light orange mottled (debossed A3 on one side) ADZENYS XR-ODT 12.5 mg Amphetamine extended release orally disintegrating tablet: round, orange to light orange mottled (debossed A4 on one side) ADZENYS XR-ODT 15.7 mg Amphetamine extended release orally disintegrating tablet: round, orange to light orange mottled (debossed A5 on one side) ADZENYS XR-ODT 18.8 mg Amphetamine extended release orally disintegrating tablet: round, orange to light orange mottled (debossed A6 on one 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 )

4. CONTRAINDICATIONS ADZENYS XR-ODT is contraindicated: In patients known to be hypersensitive to amphetamine, or other components of ADZENYS XR-ODT. 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 a 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 ADZENYS XR-ODT. ( 4 ) Use of monoamine oxidase inhibitor (MAOI) or within 14 days of the last MAOI dose. ( 4 )

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 ADZENYS XR-ODT [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 Neos Therapeutics, Inc. at 1-888-319-1789 or http://www.adzenysxrodt.com 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 ADZENYS XR-ODT 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 1315 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) com …

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 ADZENYS XR-ODT 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 ADZENYS XR-ODT during or within 14 days following the administration of MAOI [see Contraindications (4) ]. Serotonergic Drugs Clinical Impact The concomitant use of ADZENYS XR-ODT 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 ADZENYS XR-ODT initiation or dosage increase. If serotonin syndrome occurs, discontinue ADZENYS XR-ODT 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 Co-administration of ADZENYS XR-ODT 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.

8. USE IN SPECIFIC POPULATIONS Pregnancy: May cause fetal harm. ( 8.1 ) Lactation: Breastfeeding not recommended. ( 8.2 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors outcomes in women exposed to ADHD medications, including ADZENYS XR-ODT, during pregnancy. Healthcare providers are encouraged to advise patients to register by contacting the National Pregnancy Registry for ADHD Medication at 1-866-961-2388 or online at www.womensmentalhealth.org/pregnancyregistry. 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 ADZENYS XR-ODT, 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 ADZENYS XR-ODT, (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/m2 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/m2 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 ADZENYS XR-ODT) 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/m2 basis. All doses caused hyperactivity and decreased weight gain in the dams. A decrease in pup survival w …

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.

11. DESCRIPTION ADZENYS XR-ODT (amphetamine extended-release orally disintegrating tablet) contains 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 ADZENYS XR-ODT 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: C 9 H 13 N MW 135.21 ADZENYS XR-ODT is an extended-release orally disintegrating tablet containing 50% immediate-release and 50% delayed-release amphetamine for once daily dosing. ADZENYS XR-ODT also contains the following inactive ingredients: Mannitol, Crospovidone, Microcrystalline Cellulose, Methacrylic Acid, Sodium Polystyrene Sulfonate, Citric Acid, Fructose, Orange Flavor, Colloidal Silicon Dioxide, Triethyl Citrate, Sucralose, Lake Blend Orange, Magnesium Stearate, and Polyethylene Glycol 3350. Structural Formula

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 ADZENYS XR-ODT should be considered when treating patients with overdose. Damphetamine is not dialyzable. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

16. HOW SUPPLIED/STORAGE AND HANDLING How Supplied ADZENYS XR-ODT 3.1 mg extended release orally disintegrating tablet: round, orange to light orange mottled (debossed A1 on one side), carton containing 5 blister cards of 6 tablets each, for a total of 30 tablets, NDC 70165-005-30 ADZENYS XR-ODT 6.3 mg extended release orally disintegrating tablet: round, orange to light orange mottled (debossed A2 on one side), carton containing 5 blister cards of 6 tablets each, for a total of 30 tablets, NDC 70165-010-30 ADZENYS XR-ODT 9.4 mg extended release orally disintegrating tablet: round, orange to light orange mottled (debossed A3 on one side), carton containing 5 blister cards of 6 tablets each, for a total of 30 tablets, NDC 70165-015-30 ADZENYS XR-ODT 12.5 mg extended release orally disintegrating tablet: round, orange to light orange mottled (debossed A4 on one side), carton containing 5 blister cards of 6 tablets each, for a total of 30 tablets, NDC 70165-020-30 ADZENYS XR-ODT 15.7 mg extended release orally disintegrating tablet: round, orange to light orange mottled (debossed A5 on one side), carton containing 5 blister cards of 6 tablets each, for a total of 30 tablets, NDC 70165-025-30 ADZENYS XR-ODT 18.8 mg extended release orally disintegrating tablet: round, orange to light orange mottled (debossed A6 on one side), carton containing 5 blister cards of 6 tablets each, for a total of 30 tablets, NDC 70165-030-30 Storage Store at 20°C to 25o C (68°F to 77o F). Excursions permitted to 15-30o C (59-86o F) [see USP Controlled Room Temperature] Store ADZENYS XR-ODT blister packages in the rigid, plastic travel case provided after removal from the carton. To obtain additional travel cases, patients and health care professionals can call Neos Therapeutics, Inc., at 1-888-236-6816.