lisdexamfetamine dimesylate

Indications and Usage ( 1 ) 08/2021 Warnings and Precautions ( 5.5 ) 08/2021 Indications and Usage ( 1 ) 09/2025 Warnings and Precautions ( 5.5 ) 09/2025

1 INDICATIONS AND USAGE Lisdexamfetamine dimesylate chewable tablets are indicated for the treatment of: Attention Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years and older [see Clinical Studies ( 14.1 )] Moderate to severe binge eating disorder (BED) in adults [see Clinical Studies ( 14.2 )] . Limitations of Use : The use of lisdexamfetamine dimesylate chewable tablets 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 )] . Lisdexamfetamine dimesylate chewable tablets are not indicated or recommended for weight loss. Use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events. The safety and effectiveness of lisdexamfetamine dimesylate chewable tablets for the treatment of obesity have not been established [see Warnings and Precautions ( 5.2 )] . Lisdexamfetamine dimesylate chewable tablets are a central nervous system (CNS) stimulant indicated for the treatment of ( 1 ): Attention Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years and older Moderate to severe binge eating disorder (BED) in adults Limitations of Use : The use of lisdexamfetamine dimesylate chewable tablets 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 ) Lisdexamfetamine dimesylate chewable tablets are not indicated for weight loss. Use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events. The safety and effectiveness of lisdexamfetamine dimesylate chewable tablets for the treatment of obesity have not been established. ( 5.2 )

2 DOSAGE AND ADMINISTRATION Indicated Population Initial Dose Titration Schedule Recommended Dose Maximum Dose ADHD (Adults and pediatric patients 6 years and older) ( 2.2 ) 30 mg every morning 10 mg or 20 mg weekly 30 mg to 70 mg per day 70 mg per day BED (Adults) ( 2.3 ) 30 mg every morning 20 mg weekly 50 mg to 70 mg per day 70 mg per day Prior to treatment, assess for presence of cardiac disease ( 2.4 ) Severe renal impairment: Maximum dose is 50 mg/day ( 2.5 ) End stage renal disease (ESRD): Maximum dose is 30 mg/day ( 2.5 ) 2.1 Pretreatment Screening Prior to treating patients with lisdexamfetamine dimesylate chewable 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 lisdexamfetamine dimesylate chewable tablets [see Warnings and Precautions ( 5.8 )] . 2.2 General Administration Information Take lisdexamfetamine dimesylate chewable tablets orally in the morning with or without food; avoid afternoon doses because of the potential for insomnia. Lisdexamfetamine dimesylate chewable tablets may be administered in one of the following ways: Information for l isdexamfetamine dimesylate chewable tablets: Lisdexamfetamine dimesylate chewable tablets must be chewed thoroughly before swallowing. Lisdexamfetamine dimesylate capsules can be substituted with lisdexamfetamine dimesylate chewable tablets on a unit per unit/mg per mg basis (for example, 30 mg capsules for 30 mg chewable tablet) [see Clinical Pharmacology ( 12.3 )] . Do not take anything less than one chewable tablet per day. A single dose should not be divided. 2.3 Dosage for Treatment of ADHD The recommended starting dosage in adults and pediatric patients 6 years and older is 30 mg once daily in the morning. Dosage may be adjusted in increments of 10 mg or 20 mg at approximately weekly intervals up to maximum recommended dosage of 70 mg once daily [see Clinical Studies ( 14.1 )] . 2.4 Dosage for Treatment of Moderate to Severe BED in Adults The recommended starting dosage in adults is 30 mg once daily to be titrated in increments of 20 mg at approximately weekly intervals to achieve the recommended target dose of 50 mg to 70 mg once daily. The maximum recommended dosage is 70 mg once daily [see Clinical Studies ( 14.2 )] . Discontinue lisdexamfetamine dimesylate chewable tablets if binge eating does not improve. 2.5 Dosage in Patients with Renal Impairment In patients with severe renal impairment (GFR 15 to <30 mL/min/1.73 m 2 ), the maximum dosage should not exceed 50 mg once daily. In patients with end stage renal disease (ESRD, GFR <15 mL/min/1.73 m 2 ), the maximum recommended dosage is 30 mg once daily [see Use in Specific Populations ( 8.6 )] . 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 lisdexamfetamine dimesylate chewable tablets dosage accordingly [see Drug Interactions ( 7.1 )] .

3 DOSAGE FORMS AND STRENGTHS Lisdexamfetamine dimesylate chewable tablets : Chewable tablets 10 mg: White or off-white to mottled round shaped tablet debossed with 'm169' on one side and plain on the other side Chewable tablets 20 mg: White or off-white to mottled hexagonal shaped tablet debossed with 'm170' on one side and plain on the other side Chewable tablets 30 mg: White or off-white to mottled arc triangular shaped tablet debossed with 'm171' on one side and plain on the other side Chewable tablets 40 mg: White or off-white to mottled capsule shaped tablet debossed with 'm172' on one side and plain on the other side Chewable tablets 50 mg: White or off-white to mottled arc square shaped tablet debossed with 'm173' on one side and plain on the other side Chewable tablets 60 mg: White or off-white to mottled arc diamond shaped tablet debossed with 'm174' on one side and plain on the other side Chewable tablets: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg ( 3 )

4 CONTRAINDICATIONS Lisdexamfetamine dimesylate chewable tablets are contraindicated in patients with: Known hypersensitivity to amphetamine products or other ingredients of lisdexamfetamine dimesylate chewable tablets. Anaphylactic reactions, Stevens-Johnson Syndrome, angioedema, and urticaria have been observed in postmarketing reports [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 ) and Drug Interactions ( 7.1 )] . Known hypersensitivity to amphetamine products or other ingredients in lisdexamfetamine dimesylate chewable tablets. ( 4 ) Use with monoamine oxidase (MAO) inhibitor, or within 14 days of the last MAO inhibitor dose. ( 4 , 7.1 )

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Known hypersensitivity to amphetamine products or other ingredients of lisdexamfetamine dimesylate [see Contraindications (4)] Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see Contraindications (4) and Drug Interactions (7.1)] Abuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions (5.1), and Drug Abuse and Dependence (9.2, 9.3)] 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)] Most common adverse reactions (incidence ≥5% and at a rate at least twice placebo) in pediatric patients ages 6 to 17 years, and/or adults with ADHD were anorexia, anxiety, decreased appetite, decreased weight, diarrhea, dizziness, dry mouth, irritability, insomnia, nausea, upper abdominal pain, and vomiting. (6.1) Most common adverse reactions (incidence ≥5% and at a rate at least twice placebo) in adults with BED were dry mouth, insomnia, decreased appetite, increased heart rate, constipation, feeling jittery, and anxiety. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Camber Pharmaceuticals, Inc., at 1-866-495-8330 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 practice. Attention Deficit Hyperactivity Disorder The safety data in this section is based on data from the 4-week controlled parallel-group clinical studies of lisdexamfetamine dimesylate in pediatric and adult patients with ADHD [see Clinical Studies (14.1)]. Adverse Reactions Associated with Discontinuation of Treatment in ADHD Clinical Trials In the controlled trial in pediatric patients ages 6 to 12 years (Study 1), 8% (18/218) of lisdexamfetamine dimesylate-treated patients discontinued due to adverse reactions compared to 0% (0/72) of placebo-treated patients. The most frequently reported adverse reactions (1% or more and twice rate of placebo) were ECG voltage criteria for ventricular hypertrophy, tic, vomiting, psychomotor hyperactivity, insomnia, decreased appetite and rash [2 instances for each adverse reaction, i.e., 2/218 (1%)]. Less frequently reported adverse reactions (less than 1% or less than twice rate of placebo) included abdominal pain upper, dry mouth, weight decreased, dizziness, somnolence, logorrhea, chest pain, anger and hypertension. In the controlled trial in pediatric patients ages 13 to 17 years (Study 4), 3% (7/233) of lisdexamfetamine dimesylate-treated patients discontinued due to adverse reactions compared to 1% (1/77) of placebo-treated patients. The most frequently reported adverse reactions (1% or more and twice rate of placebo) were decreased appetite (2/233; 1%) and insomnia (2/233; 1%). Less frequently reported adverse reactions (less than 1% or less than twice rate of placebo) included irritability, dermatillomania, mood swings, and dyspnea. In the controlled adult trial (Study 7), 6% (21/358) of lisdexamfetamine dimesylate-treated patients discontinued due to adverse reactions compared to 2% (1/62) of placebo-treated patients. The most frequently reported adverse reactions (1% or more and twice rate of placebo) were insomnia (8/358; 2%), tachycardia (3/358; 1%), irritability (2/358; 1%), h …

7 DRUG INTERACTIONS Acidifying and Alkalinizing Agents: Agents that alter urinary pH can alter blood levels of amphetamine. Acidifying agents decrease amphetamine blood levels, while alkalinizing agents increase amphetamine blood levels. Adjust lisdexamfetamine dimesylate chewable tablets dosage accordingly. ( 2.6 , 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 lisdexamfetamine dimesylate chewable tablets during or within 14 days following the administration of MAOI [see Contraindications ( 4 )] . Serotonergic Drugs Clinical Impact The concomitant use of lisdexamfetamine dimesylate chewable 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 lisdexamfetamine dimesylate chewable tablets initiation or dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate chewable tablets and the concomitant serotonergic drug(s) [see Warnings and Precautions ( 5.7 )] . CYP2D6 Inhibitors Clinical Impact The concomitant use of lisdexamfetamine dimesylate chewable tablets and CYP2D6 inhibitors may increase the exposure of dextroamphetamine, the active metabolite of lisdexamfetamine dimesylate chewable tablets compared to the use of the drug alone and increase the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during lisdexamfetamine dimesylate chewable tablets initiation and after a dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate chewable tablets and the CYP2D6 inhibitor [see Warnings and Precautions ( 5.7 ) and Overdosage ( 10 )] . Alkalinizing Agents Clinical Impact Urinary alkalinizing agents can increase blood levels and potentiate the action of amphetamine. Intervention Co-administration of lisdexamfetamine dimesylate chewable tablets and urinary alkalinizing agents should be avoided. Acidifying Agents Clinical Impact Urinary acidifying agents can 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 Drugs Having No Clinically Important Interactions with Lisdexamfetamine Dimesylate Chewable Tablets From a pharmacokinetic perspective, no dose adjustment of lisdexamfetamine dimesylate chewable tablets is necessary when lisdexamfetamine dimesylate chewable tablets are co-administered with guanfacine, venlafaxine, or omeprazole. In addition, no dose adjustment of guanfacine or venlafaxine is needed when lisdexamfetamine dimesylate chewable tablets are co-administered [see Clinical Pharmacology ( 12.3 )] . From a pharmacokinetic perspective, no dose adjustment for drugs that are substrates of CYP1A2 (e.g., theophylline, duloxetine, melatonin), CYP2D6 (e.g., atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g., omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g., midazolam, pimozide, simvastatin) is necessary when lisdexamfetamine dimesylate chewable tablets are co-administered [see Clinical Pharmacology ( 12.3 )] .

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 pregnancy outcomes in women exposed to ADHD medications during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/adhd-medications/ . Risk Summary The limited available data from published literature and postmarketing reports on use of lisdexamfetamine dimesylate in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. Adverse pregnancy outcomes, including premature delivery and low birth weight, have been seen in infants born to mothers dependent on amphetamines [see Clinical Considerations] . In animal reproduction studies, lisdexamfetamine dimesylate (a prodrug of d-amphetamine) had no effects on embryo-fetal morphological development or survival when administered orally to pregnant rats and rabbits throughout the period of organogenesis. Pre- and postnatal studies were not conducted with lisdexamfetamine dimesylate. However, amphetamine (d- to l-ratio of 3:1) administration 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 estimated 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 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Amphetamines, such as lisdexamfetamine dimesylate, cause vasoconstriction and thereby may decrease placental perfusion. In addition, amphetamines can stimulate uterine contractions increasing the risk of premature delivery. Infants born to amphetamine-dependent mothers 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 Lisdexamfetamine dimesylate had no apparent effects on embryo-fetal morphological development or survival when administered orally to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 40 and 120 mg/kg/day, respectively. These doses are approximately 5.5 and 33 times, respectively, the maximum recommended human dose (MRHD) of 70 mg/day given to adults, on a mg/m 2 body surface area basis. A study was conducted with amphetamine (d- to l-enantiomer ratio of 3:1) in which pregnant rats received daily oral doses of 2, 6, and 10 mg/kg from gestation day 6 to lactation day 20. 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 body weight was seen at 6 and 10 mg/kg which correlated with delays in developmental landmarks, such as preputial separation and vaginal opening. Increased pup locomotor activity was seen at 10 mg/kg on day 22 postpartum but not at 5 weeks postweaning. 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 giv …

12.1 Mechanism of Action Lisdexamfetamine is a prodrug of dextroamphetamine. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The exact mode of therapeutic action in ADHD and BED is not known.

11 DESCRIPTION Lisdexamfetamine dimesylate, a CNS stimulant, is for once-a-day oral administration. The chemical designation for lisdexamfetamine dimesylate is (2S)-2,6-diamino- N -[(1S)-1-methyl-2-phenylethyl] hexanamide dimethanesulfonate. The molecular formula is C 17 H 33 N 3 O 7 S 2 , which corresponds to a molecular weight of 455.59. The chemical structure is: Lisdexamfetamine dimesylate is a white to off-white powder that is soluble in water (986 mg/mL). Lisdexamfetamine dimesylate chewable tablets contain 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, and 60 mg of lisdexamfetamine dimesylate (equivalent to 5.8 mg, 11.6 mg, 17.3 mg, 23.1 mg, 28.9 mg, and 34.7 mg of lisdexamfetamine). Inactive ingredients: Microcrystalline cellulose and guar gum, croscarmellose sodium, mannitol, sucralose, natural grape flavor, colloidal silicon dioxide, and magnesium stearate. Natural grape flavor contains maltodextrin, modified food starch (tapioca/waxy maize), natural flavor, triglycerides (medium chain), citric acid, tartaric acid and sodium benzoate. chemical structure

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 hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur. Life-threatening hyperthermia (temperatures greater than 104°F) and rhabdomyolysis may develop. Overdose Management Consider the possibility of multiple drug ingestion. The pharmacokinetic profile of lisdexamfetamine dimesylate chewable tablets should be considered when treating patients with overdose. Lisdexamfetamine and d-amphetamine are 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 16.1 How Supplied Lisdexamfetamine dimesylate chewable tablets are available as follows: 10 mg – Each white to off-white, round tablet, debossed with L10 on one side and TV on the other side contains 10 mg of lisdexamfetamine dimesylate (equivalent to 5.8 mg lisdexamfetamine). Tablets are supplied in bottles of 100 (NDC 0480-9737-01) with a child-resistant closure. 20 mg - Each white to off-white, hexagonal tablet, debossed with L20 on one side and TV on the other side contains 20 mg of lisdexamfetamine dimesylate (equivalent to 11.6 mg lisdexamfetamine). Tablets are supplied in bottles of 100 (NDC 0480-9738-01) with a child-resistant closure. 30 mg - Each white to off-white, triangular tablet, debossed with L30 on one side and TV on the other side contains 30 mg of lisdexamfetamine dimesylate (equivalent to 17.3 mg lisdexamfetamine). Tablets are supplied in bottles of 100 (NDC 0480-9739-01) with a child-resistant closure. 40 mg - Each white to off-white, capsule shaped tablet, debossed with L40 on one side and TV on the other side contains 40 mg of lisdexamfetamine dimesylate (equivalent to 23.1 mg lisdexamfetamine). Tablets are supplied in bottles of 100 (NDC 0480-9741-01) with a child-resistant closure. 50 mg - Each white to off-white, square tablet, debossed with L50 on one side and TV on the other side contains 50 mg of lisdexamfetamine dimesylate (equivalent to 28.9 mg lisdexamfetamine). Tablets are supplied in bottles of 100 (NDC 0480-9742-01) with a child-resistant closure. 60 mg - Each white to off-white, diamond shaped tablet, debossed with L60 on one side and TV on the other side contains 60 mg of lisdexamfetamine dimesylate (equivalent to 34.7 mg lisdexamfetamine). Tablets are supplied in bottles of 100 (NDC 0480-9744-01) with a child-resistant closure. 16.2 Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP. Keep this and all medications out of the reach of children.