Lisdexamfetamine Dimesylate Dailymed

1 Indications And Usage

Lisdexamfetamine dimesylate capsules 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:
• •Pediatric patients with ADHD younger than 6 years of age experienced more long-term weight loss than patients 6 years and older[see Use in Specific Populations (8.4)].
• •Lisdexamfetamine dimesylate capsules 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 capsules for the treatment of obesity have not been established [see Warnings and Precautions (5.2)].

Lisdexamfetamine dimesylate capsules 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:
• •Pediatric patients with ADHD younger than 6 years of age experienced more long-term weight loss than patients 6 years and older (8.4)
• •Lisdexamfetamine dimesylate capsules 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 capsules for the treatment of obesity have not been established (5.2)

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 capsules, 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 capsules [see Warnings and Precautions (5.8)].

2.2 General Administration Information

Take lisdexamfetamine dimesylate capsules orally in the morning with or without food; avoid afternoon doses because of the potential for insomnia. Lisdexamfetamine dimesylate capsules may be administered in one of the following ways:

Information for lisdexamfetamine dimesylate capsules:

• •Swallow lisdexamfetamine dimesylate 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.
•  Do not take anything less than one capsule 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 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 m²), the maximum dosage should not exceed 50 mg once daily. In patients with end stage renal disease (ESRD, GFR < 15 mL/min/1.73 m²), the maximum recommended dosage is 30 mg once daily [see Use in Specific Populations ( Error! Hyperlink reference not valid. )].

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 dosage accordingly [see Drug Interactions (7.1)].

• • 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 lisdexamfetamine dimesylate capsules, screen patients for risk factors for developing a manic episode. If new psychotic or manic symptoms occur, consider discontinuing lisdexamfetamine dimesylate capsules. (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 lisdexamfetamine dimesylate capsules 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 lisdexamfetamine dimesylate capsules and initiate supportive treatment (4, 5.7, 10)
• • Motor and Verbal Tics, and Worsening of Tourette’s Syndrome: Before initiating lisdexamfetamine dimesylate capsules, 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

Lisdexamfetamine dimesylate capsules has a high potential for abuse and misuse. The use of lisdexamfetamine dimesylate capsules exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Lisdexamfetamine dimesylate capsules 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 lisdexamfetamine dimesylate capsules, 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 lisdexamfetamine dimesylate capsules, 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 lisdexamfetamine dimesylate capsules in a safe place, preferably locked, and instruct patients to not give lisdexamfetamine dimesylate capsules to anyone else. Throughout lisdexamfetamine dimesylate capsules 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 lisdexamfetamine dimesylate capsules 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 a larger increases.

Monitor all lisdexamfetamine dimesylate capsules-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 lisdexamfetamine dimesylate capsules 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 lisdexamfetamine dimesylate capsules.

5.5 Long-Term Suppression of Growth in Pediatric Patients

CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients.

In a 4-week, placebo-controlled trial of lisdexamfetamine dimesylate capsules in pediatric patients ages 6 to 12 years old with ADHD, there was a dose-related decrease in weight in the lisdexamfetamine dimesylate capsules 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 lisdexamfetamine dimesylate capsules-treated pediatric patients. Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted. Lisdexamfetamine dimesylate capsules are not approved for use in pediatric patients below 6 years of age [see Use in Specific Populations (8.4)].

5.6 Peripheral Vasculopathy, including Raynauds Phenomenon

CNS stimulants, including lisdexamfetamine dimesylate capsules, 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 lisdexamfetamine dimesylate capsules treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for lisdexamfetamine dimesylate capsules-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 lisdexamfetamine dimesylate capsules (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 lisdexamfetamine dimesylate capsules with MAOI drugs is contraindicated [see Contraindications (4)].

Discontinue treatment with lisdexamfetamine dimesylate capsules and any concomitant serotonergic agents immediately if symptoms of serotonin syndrome occur, and initiate supportive symptomatic treatment. If concomitant use of lisdexamfetamine dimesylate capsules with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate lisdexamfetamine dimesylate capsules 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 Tourettes 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 lisdexamfetamine dimesylate capsules, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor lisdexamfetamine dimesylate capsules-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 lisdexamfetamine dimesylate capsules [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 (see Boxed Waning, 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 Hikma Pharmaceuticals USA Inc. at 1-800-962-8364 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%), 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 Lisdexamfetamine dimesylate 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 Lisdexamfetamine dimesylate 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 lisdexamfetamine dimesylate 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 Lisdexamfetamine Dimesylate and Greater than or Equal to Twice the Incidence in Patients Taking Placebo in a 4-Week Clinical Trial (Study 1)

	Lisdexamfetamine Dimesylate	Placebo
	(n=218)	(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 Lisdexamfetamine Dimesylate and Greater than or Equal to Twice the Incidence in Patients Taking Placebo in a 4-Week Clinical Trial (Study 4)

	Lisdexamfetamine Dimesylate	Placebo
	(n=233)	(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 Lisdexamfetamine Dimesylate and Greater than or Equal to Twice the Incidence in Patients Taking Placebo in a 4-Week Clinical Trial (Study 7)

	Lisdexamfetamine Dimesylate	Placebo
	(n=358)	(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 lisdexamfetamine dimesylate and 0% on placebo; decreased libido was observed in 1.4% of subjects on lisdexamfetamine dimesylate and 0% on placebo.

Weight Loss and Slowing Growth Rate in Pediatric Patients with ADHD: In a controlled trial of lisdexamfetamine dimesylate capsules 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 lisdexamfetamine dimesylate, 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 lisdexamfetamine dimesylate capsules 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 lisdexamfetamine dimesylate 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 lisdexamfetamine dimesylate, 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 naturaulic 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 lisdexamfetamine dimesylate capsules, 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 lisdexamfetamine dimesylate-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 lisdexamfetamine dimesylate-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 Lisdexamfetamine dimesylate 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 Lisdexamfetamine dimesylate Treated Patients with BED in Clinical Trials: Adverse reactions reported in the pooled controlled trials in adult patients (Study 11 and 12) treated with lisdexamfetamine dimesylate or placebo are presented in Table 4 below.

Table 4: Adverse Reactions Reported by 2% or More of Adult Patients with BED Taking Lisdexamfetamine Dimesylate and Greater than or Equal to Twice the Incidence in Patients Taking Placebo in 12-Week Clinical Trials (Study 11 and 12)

	Lisdexamfetamine Dimesylate	Placebo
	(N=373)	(N=372)
Dry Mouth	36%	7%
InsomniaIncludes all preferred terms containing the word “insomnia.”	20%	8%
Decreased Appetite	8%	2%
Increased Heart RateIncludes 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 lisdexamfetamine dimesylate capsules. 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.