3-Beadside effects

The following adverse reactions are discussed in greater detail in other sections of the labeling: Abuse, Misuse, and Addiction Hypersensitivity to amphetamine products or other ingredients of MYDAYIS Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors Risks to Patients with Serious Cardiac Disease Increased Blood Pressure and Heart Rate Psychiatric Adverse Reactions Long-Term Suppression of Growth in Pediatric Patients Peripheral Vasculopathy, Including Raynaud's Phenomenon Seizures Serotonin Syndrome Motor and Verbal Tics, and Worsening of Tourette's Syndrome Most common adverse reactions in patients with ADHD (incidence ≥5% and at a rate at least twice placebo) are: Pediatrics (13 years and older): insomnia, decreased appetite, decreased weight, irritability, and nausea.

Adults: insomnia, decreased appetite, decreased weight, dry mouth, increased heart rate, and anxiety. To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A., Inc. at 1-877-TAKEDA-7 (1-877-825-3327) 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 clinical practice. MYDAYIS was studied in adults (18 to 55 years) and pediatric patients (13 to 17 years) who met Diagnostic and Statistical Manual of Mental Disorders, 4 th or 5 th editions (DSM-IV-TR ® or DSM-5) criteria for ADHD. The safety data for adults were pooled from three randomized, double-blind, placebo-controlled studies in doses of 12.5 mg to 75 mg per day (1.5 times the maximum recommended dosage). Doses higher than 50 mg per day did not demonstrate additional clinical benefit and are not recommended. The safety data for pediatric patients (13 to 17 years) is from 1 randomized, double-blind, placebo-controlled study of doses of 12.5 mg to 25 mg. The total exposure in patients treated with MYDAYIS totalled 704; this included pediatric patients, 78 adolescent patients and 626 adult patients from multiple well-controlled trials. The duration of use ranged from 4 to 7 weeks. Adverse Reactions Leading to Discontinuation of Treatment In pooled controlled trials of adult patients, 9% (54/626) of MYDAYIS-treated patients discontinued due to adverse reactions compared to 2% (7/328) of placebo-treated patients. The most frequent adverse reactions leading to discontinuation (i.e., leading to discontinuation in at least 1% of MYDAYIS-treated patients and at a rate at least twice that of placebo) were insomnia (2%, n=15), blood pressure increased (2%, n=10), decreased appetite (1%, n=5), and headache (1%, n=4). In a controlled trial including adolescent patients (13 to 17 years), 5% (4/78) of MYDAYIS-treated patients discontinued due to adverse reactions compared to 0% (0/79) of placebo-treated patients. The most frequent adverse reaction leading to discontinuation (i.e., leading to discontinuation in at least 1% of MYDAYIS-treated patients and at a rate at least twice that of placebo) were dizziness (1%, n=1), depression (1%, n=1), abdominal pain upper (1%, n=1), and viral infection (1%, n=1). Adverse Reactions Occurring at an Incidence of ≥2% and at Least Twice Placebo Among MYDAYIS-Treated Adults in Clinical Trials The most common adverse reactions reported in adults were insomnia, decreased appetite, dry mouth, decreased weight, heart rate increased, and anxiety. Table 1 lists the adverse reactions that occurred ≥2% compared to placebo. The most common adverse reaction (insomnia) generally occurred early during treatment with MYDAYIS.

Table 1: Adverse Reactions Reported by 2% or More of Adults Taking MYDAYIS and at Least Twice the Incidence in Patients Taking Placebo in 3 Clinical Trials (4, 6, and 7 Weeks) Body System Adverse Reaction MYDAYIS Includes doses up to 75 mg (1.5 times the maximum recommended dosage). (N = 626) Placebo (N = 328) Nervous System - Anxiety 7% 3% - Feeling Jittery 2% 1% - Agitation 2% 0% - Bruxism 2% 0% Psychiatric Disorders - Insomnia 31% 8% - Depression 3% 0% Metabolism and Nutritional Disorders - Decreased Appetite 30% 4% - Weight Decreased 9% 0% Gastrointestinal System - Dry Mouth 23% 4% - Diarrhea 3% 1% Cardiovascular System - Heart Rate Increased 9% 0% - Palpitations 4% 2% Genitourinary System - Dysmenorrhea Dysmenorrhea was observed in 11 females. 4% 2% - Erectile Dysfunction Erectile dysfunction was observed in 6 males. 2% 1% Adverse Reactions Occurring at an Incidence of 2% or More and at Least Twice Placebo Among MYDAYIS-Treated Adolescents (13 to 17 years) in a 4-Week Clinical Trial The most common adverse reactions reported in adolescents were decreased appetite, nausea, insomnia, abdominal pain upper, irritability, and weight decreased. Table 2 lists the adverse reactions that occurred ≥2% compared to placebo.

Table 2: Adverse Reactions Reported by ≥2% or More of Adolescents Taking MYDAYIS and at Least Twice the Incidence in Patients Taking Placebo in a 4-Week Clinical Trial Body System Adverse Reaction MYDAYIS (N = 78) Placebo (N = 79) Nervous System - Dizziness 4% 0% Metabolism and Nutrition Disorders - Decreased appetite 22% 6% - Weight decreased 5% 1% Psychiatric Disorders - Irritability 6% 3% - Insomnia Insomnia includes terms: initial insomnia, middle insomnia, terminal insomnia and insomnia. 8% 3% Gastrointestinal Disorders - Nausea 8% 4% - Abdominal pain upper 4% 1%

6.2 Adverse

Reactions Associated with the Use of Amphetamines The following adverse reactions have been associated with the use of amphetamines. The following adverse reactions have been identified during postapproval use of amphetamines. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Allergic: Urticaria, rash, hypersensitivity reactions, including angioedema and anaphylaxis. Serious skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.

Cardiovascular: Dyspnea, sudden death. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.

Central Nervous System: Psychotic episodes at recommended doses, overstimulation, restlessness, euphoria, dyskinesia, dysphoria, headache, tics, fatigue, aggression, anger, logorrhea, dermatillomania, and paresthesia (including formication), motor and verbal tics.

Endocrine: Impotence, changes in libido, frequent or prolonged erections.

Eye Disorders: Mydriasis.

Gastrointestinal: Unpleasant taste, constipation, intestinal ischemia. Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis.

Skin: Alopecia.

Vascular Disorders: Raynaud’s phenomenon.