Motor and Verbal Tics, and Worsening of Tourette's Syndrome [see Warnings and Precautions (5.8)]

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.

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 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 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 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 lisdexamfetamine dimesylate, 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.