5 WARNINGS AND PRECAUTIONS

5.1 Potential for Abuse and Dependence

CNS stimulants, including lisdexamfetamine dimesylate capsules, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Drug Abuse and Dependence (9.2, 9.3)].

5.2 Serious Cardiovascular Reactions

Sudden death, stroke, and myocardial infarction have been reported in adults with CNS stimulant treatment at recommended doses. Sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during lisdexamfetamine dimesylate capsules treatment.

5.3 Blood Pressure and Heart Rate Increases

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). Monitor all 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 mixed/manic episode in patients with bipolar disorder. Prior to initiating 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 recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. If such symptoms occur, consider discontinuing lisdexamfetamine dimesylate capsules. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in 0.1% of CNS stimulant-treated patients compared to 0% in placebo-treated patients.

5.5 Suppression of Growth

CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including lisdexamfetamine dimesylate capsules. 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)].

Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted. Lisdexamfetamine dimesylate capsules is not approved for use in pediatric patients below 6 years of age [see Use in Specific Populations (8.4)].

5.6 Peripheral Vasculopathy, including Raynaud’s Phenomenon

Stimulants, including lisdexamfetamine dimesylate capsules, are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

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.

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)]
• Drug Dependence [see Boxed Warning, Warnings and Precautions (5.1), and Drug Abuse and Dependence (9.2, 9.3)]
• Serious Cardiovascular Reactions [see Warnings and Precautions (5.2)]
• Blood Pressure and Heart Rate Increases [see Warnings and Precautions (5.3)]
• Psychiatric Adverse Reactions [see Warnings and Precautions (5.4)]
• Suppression of Growth [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)]

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 capsules 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 capsules-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 capsules-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 capsules-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 Capsules 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 Capsules 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 capsules 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 capsules and 0% on placebo; decreased libido was observed in 1.4% of subjects on lisdexamfetamine dimesylate capsules 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 capsules, 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 capsules 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 capsules, 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 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 capsules-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 capsules-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 Capsules 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 Capsules 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 capsules or placebo are presented in Table 4 below.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval 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, 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.

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

Lisdexamfetamine dimesylate capsules contains lisdexamfetamine, a prodrug of amphetamine, a Schedule II controlled substance.

9.2 Abuse

CNS stimulants, including lisdexamfetamine dimesylate capsules, other amphetamine-containing products, and methylphenidate have a high potential for abuse. Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. Abuse is characterized by impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Both abuse and misuse may lead to addiction, and some individuals may develop addiction even when taking lisdexamfetamine dimesylate capsules as prescribed.

Signs and symptoms of amphetamine abuse may include increased heart rate, respiratory rate, blood pressure, and/or sweating, dilated pupils, hyperactivity, restlessness, insomnia, decreased appetite, loss of coordination, tremors, flushed skin, vomiting, and/or abdominal pain. Anxiety, psychosis, hostility, aggression, suicidal or homicidal ideation have also been seen. Abusers of CNS stimulants may chew, snort, inject, or use other unapproved routes of administration which can result in overdose and death [see Overdosage (10)].

To reduce the abuse of CNS stimulants, including lisdexamfetamine dimesylate capsules, assess the risk of abuse prior to prescribing. After prescribing, keep careful prescription records, educate patients and their families about abuse and on proper storage and disposal of CNS stimulants. Monitor for signs of abuse while on therapy, and re-evaluate the need for lisdexamfetamine dimesylate capsules use.

Studies of Lisdexamfetamine Dimesylate Capsules in Drug Abusers
A randomized, double-blind, placebo-control, cross-over, abuse liability study in 38 patients with a history of drug abuse was conducted with single-doses of 50, 100, or 150 mg of lisdexamfetamine dimesylate capsules, 40 mg of immediate-release d-amphetamine sulphate (a controlled II substance), and 200 mg of diethylpropion hydrochloride (a controlled IV substance). Lisdexamfetamine dimesylate capsules 100 mg produced significantly less “Drug Liking Effects” as measured by the Drug Rating Questionnaire-Subject score, compared to d-amphetamine 40 mg; and 150 mg of lisdexamfetamine dimesylate capsules demonstrated similar “Drug-Liking Effects” compared to 40 mg of d-amphetamine and 200 mg of diethylpropion.

Intravenous administration of 50 mg lisdexamfetamine dimesylate to individuals with a history of drug abuse produced positive subjective responses on scales measuring "Drug Liking", "Euphoria", "Amphetamine Effects", and "Benzedrine Effects" that were greater than placebo but less than those produced by an equivalent dose (20 mg) of intravenous d-amphetamine.

9.3 Dependence

Physical Dependence
Lisdexamfetamine dimesylate capsules may produce physical dependence from continued therapy. Physical dependence is a state of adaptation manifested by a withdrawal syndrome produced by abrupt cessation, rapid dose reduction, or administration of an antagonist. Withdrawal symptoms after abrupt cessation following prolonged high-dosage administration of CNS stimulants include extreme fatigue and depression.

Tolerance
Lisdexamfetamine dimesylate capsules may produce tolerance from continued therapy. Tolerance is a state of adaptation in which exposure to a specific dose of a drug results in a reduction of the drug’s desired and/or undesired effects over time.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

Carcinogenesis
Carcinogenicity studies of lisdexamfetamine dimesylate have not been performed. No evidence of carcinogenicity was found in studies in which d-, l-amphetamine (enantiomer ratio of 1:1) was administered to mice and rats in the diet for 2 years at doses of up to 30 mg/kg/day in male mice, 19 mg/kg/day in female mice, and 5 mg/kg/day in male and female rats.

Mutagenesis
Lisdexamfetamine dimesylate was not clastogenic in the mouse bone marrow micronucleus test in vivo and was negative when tested in the E.coli and S. typhimurium components of the Ames test and in the L5178Y/TK+/- mouse lymphoma assay in vitro.

Impairment of Fertility
Amphetamine (d- to l-enantiomer ratio of 3:1) did not adversely affect fertility or early embryonic development in the rat at doses of up to 20 mg/kg/day.

13.2 Animal Toxicology and/or Pharmacology

Acute administration of high doses of amphetamine (d- or d, l-) has been shown to produce long-lasting neurotoxic effects, including irreversible nerve fiber damage, in rodents. The significance of these findings to humans is unknown.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Lisdexamfetamine dimesylate capsules:

• Lisdexamfetamine dimesylate capsules 10 mg: Hard Gelatin Capsule Shell Size "3" Pink Opaque Cap imprinted with AC in Black ink and Pink Opaque body imprinted with 10 in black ink filled with White to Off-white powder.
Bottles of 100 NDC 43602-306-01

• Lisdexamfetamine dimesylate capsules 20 mg: Hard Gelatin Capsule Shell Size "3" Ivory Opaque Cap imprinted with AC in Black ink and Ivory Opaque body imprinted with 20 in black ink filled with White to Off-white powder.
Bottles of 60 NDC 43602-307-60
Bottles of 500 NDC 43602-307-05

• Lisdexamfetamine dimesylate capsules 30 mg: Hard Gelatin Capsule Shell Size "3" Orange Opaque Cap imprinted with AC in Black ink and White Opaque body imprinted with 30 in black ink filled with White to Off-white powder.
Bottles of 60 NDC 43602-308-60
Bottles of 500 NDC 43602-308-05

• Lisdexamfetamine dimesylate capsules 40 mg: Hard Gelatin Capsule Shell Size "3" Blue Green Opaque Cap imprinted with AC in Black ink and White Opaque body imprinted with 40 in black ink filled with White to Off-white powder.
Bottles of 60 NDC 43602-309-60
Bottles of 500 NDC 43602-309-05

• Lisdexamfetamine dimesylate capsules 50 mg: Hard Gelatin Capsule Shell Size "3" Blue Opaque Cap imprinted with AC in Black ink and White Opaque body imprinted with 50 in black ink filled with White to Off-white powder.
Bottles of 60 NDC 43602-310-60
Bottles of 500 NDC 43602-310-05

• Lisdexamfetamine dimesylate capsules 60 mg: Hard Gelatin Capsule Shell Size "2" Aqua Blue Opaque Cap imprinted with AC in Black ink and Aqua Blue Opaque body imprinted with 60 in black ink filled with White to Off-white powder.
Bottles of 60 NDC 43602-311-60
Bottles of 500 NDC 43602-311-05

• Lisdexamfetamine dimesylate capsules 70 mg: Hard Gelatin Capsule Shell Size "2" White Opaque Cap imprinted with AC in Black ink and Blue Transparent body imprinted with 70 in black ink filled with White to Off-white powder.
Bottles of 60 NDC 43602-312-60
Bottles of 500 NDC 43602-312-05

16.2 Storage and Handling

Dispense in a tight, light-resistant container as defined in the USP.

Store at room temperature, 20ºC to 25ºC (68ºF to 77ºF). Excursions permitted between 15ºC and 30ºC (59 to 86ºF) [see USP Controlled Room Temperature].

Disposal
Comply with local laws and regulations on drug disposal of CNS stimulants. Dispose of remaining, unused, or expired lisdexamfetamine dimesylate capsules by a medicine take-back program.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Controlled Substance Status/High Potential for Abuse and Dependence
Advise patients that lisdexamfetamine dimesylate capsules is a controlled substance and it can be abused and lead to dependence and not to give lisdexamfetamine dimesylate capsules to anyone else [see Drug Abuse and Dependence (9.1, 9.2, and 9.3)]. Advise patients to store lisdexamfetamine dimesylate capsules in a safe place, preferably locked, to prevent abuse. Advise patients to dispose of remaining, unused, or expired lisdexamfetamine dimesylate capsules by a medicine take-back program.

Serious Cardiovascular Risks
Advise patients that there is a potential serious cardiovascular risk including sudden death, myocardial infarction, stroke, and hypertension with lisdexamfetamine dimesylate capsules use. Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease [see Warnings and Precautions (5.2)].

Hypertension and Tachycardia
Instruct patients that lisdexamfetamine dimesylate capsules can cause elevations of their blood pressure and pulse rate and they should be monitored for such effects.

Psychiatric Risks
Advise patients that lisdexamfetamine dimesylate capsules at recommended doses may cause psychotic or manic symptoms even in patients without prior history of psychotic symptoms or mania [see Warnings and Precautions (5.4)].

Suppression of Growth
Advise patients that lisdexamfetamine dimesylate capsules may cause slowing of growth including weight loss [see Warnings and Precautions (5.5)].

Impairment in Ability to Operate Machinery or Vehicles
Advise patients that lisdexamfetamine dimesylate capsules may impair their ability to engage in potentially dangerous activities such as operating machinery or vehicles. Instruct patients to find out how lisdexamfetamine dimesylate capsules will affect them before engaging in potentially dangerous activities [see Adverse Reactions (6.1, 6.2)].

Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud’s phenomenon]
Instruct patients beginning treatment with lisdexamfetamine dimesylate capsules about the risk of peripheral vasculopathy, including Raynaud’s phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change from pale, to blue, to red. Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes. Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking lisdexamfetamine dimesylate capsules. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients [see Warnings and Precautions (5.6)].

Serotonin Syndrome
Caution patients about the risk of serotonin syndrome with concomitant use of lisdexamfetamine dimesylate capsules and other serotonergic drugs including SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular MAOIs, both those intended to treat psychiatric disorders and also others such as linezolid [see Contraindications (4), Warnings and Precautions (5.7) and Drug Interactions (7.1)]. Advise patients to contact their healthcare provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome.

Concomitant Medications
Advise patients to notify their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs because there is a potential for interactions [see Drug Interactions (7.1)].

Pregnancy
Advise patients of the potential fetal effects from the use of lisdexamfetamine dimesylate capsules during pregnancy. Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with lisdexamfetamine dimesylate capsules [see Use in Specific Populations (8.1)].

Lactation
Advise women not to breastfeed if they are taking lisdexamfetamine dimesylate capsules [see Use in Specific Populations (8.2)].

Administration Instructions

• Advise patients to take the capsules whole or empty and mix the entire contents with yogurt, water, or orange juice. Advise patients to consume the mixture immediately and not to store for future use [see Dosage and Administration (2.2)].

Manufactured by:
Ascent Pharmaceuticals, Inc.
Central Islip, NY 11722

Rev: 08/23

For more information call 1-855-221-1622.

The trademarks referenced herein are owned by their respective companies.