Vyvanse

1 INDICATIONS AND USAGE VYVANSE ® is 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) ] . VYVANSE is 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 VYVANSE 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 ) VYVANSE is 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 VYVANSE for the treatment of obesity have not been established ( 5.2 ) Limitations of Use: The use of VYVANSE 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) ] . VYVANSE is 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 VYVANSE for the treatment of obesity have not been established [see Warnings and Precautions (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 VYVANSE, 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 VYVANSE [see Warnings and Precautions (5.8) ] . 2.2 General Administration Information Take VYVANSE orally in the morning with or without food; avoid afternoon doses because of the potential for insomnia. VYVANSE may be administered in one of the following ways: Information for VYVANSE capsules: Swallow VYVANSE capsules whole, or Open capsules, empty and mix the entire contents with yogurt, water, or orange juice. If the contents of the capsule include any compacted powder, a spoon may be used to break apart the powder. The contents should be mixed until completely dispersed. Consume the entire mixture immediately. It should not be stored. The active ingredient dissolves completely once dispersed; however, a film containing the inactive ingredients may remain in the glass or container once the mixture is consumed. Information for VYVANSE chewable tablets: VYVANSE chewable tablets must be chewed thoroughly before swallowing. VYVANSE capsules can be substituted with VYVANSE 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 capsule or 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 VYVANSE 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 VYVANSE dosage accordingly [see Drug Interactions (7.1) ] .

3 DOSAGE FORMS AND STRENGTHS Capsules: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg ( 3 ) Chewable tablets: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg ( 3 ) VYVANSE ( lisdexamfetamine dimesylate ) capsules: Capsules 10 mg: pink body/pink cap (imprinted with S489 and 10 mg) Capsules 20 mg: ivory body/ivory cap (imprinted with S489 and 20 mg) Capsules 30 mg: white body/orange cap (imprinted with S489 and 30 mg) Capsules 40 mg: white body/blue green cap (imprinted with S489 and 40 mg) Capsules 50 mg: white body/blue cap (imprinted with S489 and 50 mg) Capsules 60 mg: aqua blue body/aqua blue cap (imprinted with S489 and 60 mg) Capsules 70 mg: blue body/orange cap (imprinted with S489 and 70 mg) VYVANSE ( lisdexamfetamine dimesylate ) chewable tablets: Chewable tablets 10 mg: White to off-white round shaped tablet debossed with '10' on one side and 'S489' on the other Chewable tablets 20 mg: White to off-white hexagonal shaped tablet debossed with '20' on one side and 'S489' on the other Chewable tablets 30 mg: White to off-white arc triangular shaped tablet debossed with '30' on one side and 'S489' on the other Chewable tablets 40 mg: White to off-white capsule shaped tablet debossed with '40' on one side and 'S489' on the other Chewable tablets 50 mg: White to off-white arc square shaped tablet debossed with '50' on one side and 'S489' on the other Chewable tablets 60 mg: White to off-white arc diamond shaped tablet debossed with '60' on one side and 'S489' on the other

4 CONTRAINDICATIONS VYVANSE is contraindicated in patients with: Known hypersensitivity to amphetamine products or other ingredients of VYVANSE. 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 VYVANSE ( 4 ) Use with monoamine oxidase (MAO) inhibitor, or within 14 days of the last MAO inhibitor dose ( 4 , 7.1 )

5 WARNINGS AND PRECAUTIONS Risks to Patients with Serious Cardiac Disease: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac 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 VYVANSE, screen patients for risk factors for developing a manic episode. If new psychotic or manic symptoms occur, consider discontinuing VYVANSE. ( 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 VYVANSE 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 co-administered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations. If it occurs, discontinue VYVANSE and initiate supportive treatment. ( 4 , 5.7 , 10 ) Motor and Verbal Tics, and Worsening of Tourette's Syndrome: Before initiating VYVANSE, assess the family history and clinically evaluate patients for tics or Tourette's syndrome. Regularly monitor patients for the emergence or worsening of tics or Tourette's syndrome. Discontinue treatment if clinically appropriate. ( 5.8 ) 5.1 Abuse, Misuse, and Addiction VYVANSE has a high potential for abuse and misuse. The use of VYVANSE exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. VYVANSE 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 VYVANSE, 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 VYVANSE, 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 VYVANSE in a safe place, preferably locked, and instruct patients to not give VYVANSE to anyone else. Throughout VYVANSE treatment, reassess each patient's risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction. 5.2 Risks to Patients with Serious Cardiac Disease Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosage. Avoid VYVANSE use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. 5.3 Increased Blood Pressure and Heart Rate CNS stimulants cause an increase in blood pressure (mean increase about 2 to 4 mm Hg) and heart rate (mean increase about 3 to 6 bpm). Some patients may have larger increases. Monitor all VYVANSE-treated patients for potential tachycardia and hypertension. 5.4 Psychiatric Adverse Reactions Exacerbation of Pre-existing Psychosis CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder CNS stimulants may induce a manic or mixed episode. Prior to initiating VYVANSE treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, and depression). New Psychotic or Manic Symptoms CNS stimulants, at the recommended dosage, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients compared to 0% of placebo-treated patients. If such symptoms occur, consider discontinuing VYVANSE. 5.5 Long-Term Suppression of Growth in Pediatric Patients VYVANSE is not approved for use and is not recommended in pediatric patients below 6 years of age [see Use in Specific Populations (8.4) ] . CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. In a 4-week, placebo-controlled trial of VYVANSE in pediatric patients ages 6 to 12 years old with ADHD, there was a dose-related decrease in weight in the VYVANSE groups compared to weight gain in the placebo group. Additionally, in studies of another stimulant, there was slowing of the increase in height [see Adverse Reactions (6.1) ] . Closely monitor growth (weight and height) in VYVANSE-treated pediatric patients. Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted. 5.6 Peripheral Vasculopathy, including Raynaud's Phenomenon CNS stimulants, including VYVANSE, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; however, sequelae have included digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing reports and at the therapeutic dosages of CNS stimulants in all age groups throughout the course of treatment. Signs and symptoms generally improved after dosage reduction or discontinuation of the CNS stimulant. Careful observation for digital changes is necessary during VYVANSE treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for VYVANSE-treated patients who develop signs or symptoms of peripheral vasculopathy. 5.7 Serotonin Syndrome Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort [see Drug Interactions (7.1) ] . The co-administration with cytochrome P450 2D6 (CYP2D6) inhibitors may also increase the risk with increased exposure to the active metabolite of VYVANSE (dextroamphetamine). In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 [see Drug Interactions (7.1) ] . Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Concomitant use of VYVANSE with MAOI drugs is contraindicated [see Contraindications (4) ] . Discontinue treatment with VYVANSE and any concomitant serotonergic agents immediately if symptoms of serotonin syndrome occur, and initiate supportive symptomatic treatment. If concomitant use of VYVANSE with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate VYVANSE with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome. 5.8 Motor and Verbal Tics, and Worsening of Tourette's Syndrome CNS stimulants, including amphetamine, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette's syndrome has also been reported [see Adverse Reactions (6.2) ] . Before initiating VYVANSE, assess the family history and clinically evaluate patients for tics or Tourette's syndrome. Regularly monitor VYVANSE-treated patients for the emergence or worsening of tics or Tourette's syndrome, and discontinue treatment if clinically appropriate.

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 VYVANSE [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 Takeda Pharmaceuticals at 1-800-828-2088 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 VYVANSE 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 VYVANSE-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 VYVANSE-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 VYVANSE-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%), hypertension (4/358; 1%), headache (2/358; 1%), anxiety (2/358; 1%), and dyspnea (3/358; 1%). Less frequently reported adverse reactions (less than 1% or less than twice rate of placebo) included palpitations, diarrhea, nausea, decreased appetite, dizziness, agitation, depression, paranoia and restlessness. Adverse Reactions Occurring at an Incidence of ≥5% or More Among VYVANSE Treated Patients with ADHD in Clinical Trials The most common adverse reactions (incidence ≥5% and at a rate at least twice placebo) reported in pediatric patients ages 6 to 17 years, and/or adults were anorexia, anxiety, decreased appetite, decreased weight, diarrhea, dizziness, dry mouth, irritability, insomnia, nausea, upper abdominal pain, and vomiting. Adverse Reactions Occurring at an Incidence of 2% or More Among VYVANSE Treated Patients with ADHD in Clinical Trials Adverse reactions reported in the controlled trials in pediatric patients ages, 6 to 12 years (Study 1), pediatric patients ages 13 to 17 years (Study 4), and adult patients (Study 7) treated with VYVANSE or placebo are presented in Tables 1, 2 and 3 below. Table 1 Adverse Reactions Reported by 2% or More of Pediatric Patients Ages 6 to 12 Years with ADHD Taking VYVANSE and Greater than or Equal to Twice the Incidence in Patients Taking Placebo in a 4-Week Clinical Trial (Study 1) VYVANSE (n=218) Placebo (n=72) Decreased Appetite 39% 4% Insomnia 22% 3% Abdominal Pain Upper 12% 6% Irritability 10% 0% Vomiting 9% 4% Weight Decreased 9% 1% Nausea 6% 3% Dry Mouth 5% 0% Dizziness 5% 0% Affect lability 3% 0% Rash 3% 0% Pyrexia 2% 1% Somnolence 2% 1% Tic 2% 0% Anorexia 2% 0% Table 2 Adverse Reactions Reported by 2% or More of Pediatric Patients Ages 13 to 17 Years with ADHD Taking VYVANSE and Greater than or Equal to Twice the Incidence in Patients Taking Placebo in a 4-Week Clinical Trial (Study 4) VYVANSE (n=233) Placebo (n=77) Decreased Appetite 34% 3% Insomnia 13% 4% Weight Decreased 9% 0% Dry Mouth 4% 1% Palpitations 2% 1% Anorexia 2% 0% Tremor 2% 0% Table 3 Adverse Reactions Reported by 2% or More of Adult Patients with ADHD Taking VYVANSE and Greater than or Equal to Twice the Incidence in Patients Taking Placebo in a 4-Week Clinical Trial (Study 7) VYVANSE (n=358) Placebo (n=62) Decreased Appetite 27% 2% Insomnia 27% 8% Dry Mouth 26% 3% Diarrhea 7% 0% Nausea 7% 0% Anxiety 6% 0% Anorexia 5% 0% Feeling Jittery 4% 0% Agitation 3% 0% Increased Blood Pressure 3% 0% Hyperhidrosis 3% 0% Restlessness 3% 0% Decreased Weight 3% 0% Dyspnea 2% 0% Increased Heart Rate 2% 0% Tremor 2% 0% Palpitations 2% 0% In addition, in the adult population erectile dysfunction was observed in 2.6% of males on VYVANSE and 0% on placebo; decreased libido was observed in 1.4% of subjects on VYVANSE and 0% on placebo. Weight Loss and Slowing Growth Rate in Pediatric Patients with ADHD In a controlled trial of VYVANSE in pediatric patients ages 6 to 12 years (Study 1), mean weight loss from baseline after 4 weeks of therapy was -0.9, -1.9, and -2.5 pounds, respectively, for patients receiving 30 mg, 50 mg, and 70 mg of VYVANSE, compared to a 1 pound weight gain for patients receiving placebo. Higher doses were associated with greater weight loss with 4 weeks of treatment. Careful follow-up for weight in pediatric patients ages 6 to 12 years who received VYVANSE over 12 months suggests that consistently medicated pediatric patients (i.e., treatment for 7 days per week throughout the year) have a slowing in growth rate, measured by body weight as demonstrated by an age- and sex-normalized mean change from baseline in percentile, of -13.4 over 1 year (average percentiles at baseline and 12 months were 60.9 and 47.2, respectively). In a 4-week controlled trial of VYVANSE in pediatric patients ages 13 to 17 years, mean weight loss from baseline to endpoint was -2.7, -4.3, and -4.8 lbs., respectively, for patients receiving 30 mg, 50 mg, and 70 mg of VYVANSE, compared to a 2.0 pound weight gain for patients receiving placebo. Careful follow-up of weight and height in pediatric patients ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated pediatric patients over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated pediatric patients ages 7 to 13 years (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. In a controlled trial of amphetamine (d- to l-enantiomer ratio of 3:1) in pediatric patients ages 13 to 17 years, mean weight change from baseline within the initial 4 weeks of therapy was -1.1 pounds and -2.8 pounds, respectively, for patients receiving 10 mg and 20 mg of amphetamine. Higher doses were associated with greater weight loss within the initial 4 weeks of treatment [see Warnings and Precautions (5.5) ] . Weight Loss in Adults with ADHD In the controlled adult trial (Study 7), mean weight loss after 4 weeks of therapy was 2.8 pounds, 3.1 pounds, and 4.3 pounds, for patients receiving final doses of 30 mg, 50 mg, and 70 mg of VYVANSE, respectively, compared to a mean weight gain of 0.5 pounds for patients receiving placebo. Binge Eating Disorder The safety data in this section is based on data from two 12-week parallel group, flexible-dose, placebo-controlled studies in adults with BED [see Clinical Studies 14.2 ] . Patients with cardiovascular risk factors other than obesity and smoking were excluded. Adverse Reactions Associated with Discontinuation of Treatment in BED Clinical Trials In controlled trials of patients ages 18 to 55 years, 5.1% (19/373) of VYVANSE-treated patients discontinued due to adverse reactions compared to 2.4% (9/372) of placebo-treated patients. No single adverse reaction led to discontinuation in 1% or more of VYVANSE-treated patients. Less commonly reported adverse reactions (less than 1% or less than twice rate of placebo) included increased heart rate, headache, abdominal pain upper, dyspnea, rash, insomnia, irritability, feeling jittery and anxiety. Adverse Reactions Occurring at an Incidence of 5% or More and At Least Twice Placebo Among VYVANSE Treated Patients with BED in Clinical Trials The most common adverse reactions (incidence ≥5% and at a rate at least twice placebo) reported in adults were dry mouth, insomnia, decreased appetite, increased heart rate, constipation, feeling jittery, and anxiety. Adverse Reactions Occurring at an Incidence of 2% or More and At Least Twice Placebo Among VYVANSE Treated Patients with BED in Clinical Trials Adverse reactions reported in the pooled controlled trials in adult patients (Study 11 and 12) treated with VYVANSE or placebo are presented in Table 4 below. Table 4 Adverse Reactions Reported by 2% or More of Adult Patients with BED Taking VYVANSE and Greater than or Equal to Twice the Incidence in Patients Taking Placebo in 12-Week Clinical Trials (Study 11 and 12) VYVANSE (N=373) Placebo (N=372) Dry Mouth 36% 7% Insomnia Includes all preferred terms containing the word "insomnia." 20% 8% Decreased Appetite 8% 2% Increased Heart Rate Includes the preferred terms "heart rate increased" and "tachycardia." 7% 1% Feeling Jittery 6% 1% Constipation 6% 1% Anxiety 5% 1% Diarrhea 4% 2% Decreased Weight 4% 0% Hyperhidrosis 4% 0% Vomiting 2% 1% Gastroenteritis 2% 1% Paresthesia 2% 1% Pruritus 2% 1% Upper Abdominal Pain 2% 0% Energy Increased 2% 0% Urinary Tract Infection 2% 0% Nightmare 2% 0% Restlessness 2% 0% Oropharyngeal Pain 2% 0% 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of VYVANSE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events are as follows: cardiomyopathy, mydriasis, diplopia, difficulties with visual accommodation, blurred vision, eosinophilic hepatitis, anaphylactic reaction, hypersensitivity, dyskinesia, dysgeusia, motor and verbal tics, bruxism, depression, dermatillomania, alopecia, aggression, Stevens-Johnson Syndrome, chest pain, angioedema, urticaria, seizures, libido changes, frequent or prolonged erections, constipation, rhabdomyolysis, and intestinal ischemia.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied VYVANSE ( lisdexamfetamine dimesylate ) capsules: VYVANSE capsules 10 mg: pink body/pink cap (imprinted with S489 and 10 mg), bottles of 100, NDC 59417-101-10 VYVANSE capsules 20 mg: ivory body/ivory cap (imprinted with S489 and 20 mg), bottles of 100, NDC 59417-102-10 VYVANSE capsules 30 mg: white body/orange cap (imprinted with S489 and 30 mg), bottles of 100, NDC 59417-103-10 VYVANSE capsules 40 mg: white body/blue green cap (imprinted with S489 and 40 mg), bottles of 100, NDC 59417-104-10 VYVANSE capsules 50 mg: white body/blue cap (imprinted with S489 and 50 mg), bottles of 100, NDC 59417-105-10 VYVANSE capsules 60 mg: aqua blue body/aqua blue cap (imprinted with S489 and 60 mg), bottles of 100, NDC 59417-106-10 VYVANSE capsules 70 mg: blue body/orange cap (imprinted with S489 and 70 mg), bottles of 100, NDC 59417-107-10 VYVANSE ( lisdexamfetamine dimesylate ) chewable tablets: VYVANSE chewable tablets 10 mg: White to off-white round shaped tablet debossed with '10' on one side and 'S489' on the other, bottles of 100, NDC 59417-115-01 VYVANSE chewable tablets 20 mg: White to off-white hexagonal shaped tablet debossed with '20' on one side and 'S489' on the other, bottles of 100, NDC 59417-116-01 VYVANSE chewable tablets 30 mg: White to off-white arc triangular shaped tablet debossed with '30' on one side and 'S489' on the other, bottles of 100, NDC 59417-117-01 VYVANSE chewable tablets 40 mg: White to off-white capsule shaped tablet debossed with '40' on one side and 'S489' on the other, bottles of 100, NDC 59417-118-01 VYVANSE chewable tablets 50 mg: White to off-white arc square shaped tablet debossed with '50' on one side and 'S489' on the other, bottles of 100, NDC 59417-119-01 VYVANSE chewable tablets 60 mg: White to off-white arc diamond shaped tablet debossed with '60' on one side and 'S489' on the other, bottles of 100, NDC 59417-120-01 16.2 Storage and Handling Dispense in a tight, light-resistant container as defined in the USP. Store at room temperature, 20°C to 25°C (68°F to 77°F). Excursions permitted between 15°C and 30°C (59°F to 86°F) [see USP Controlled Room Temperature] .