Mixed Salts of a Single-entity Amphetamine Product Capsules

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Drug Dependence [see BOXED WARNING, WARNINGS AND PRECAUTIONS, and Drug Abuse and Dependence]
• Hypersensitivity to amphetamine products or other ingredients of MYDAYIS [see CONTRAINDICATIONS]
• Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see CONTRAINDICATIONS and DRUG INTERACTIONS]
• Serious Cardiovascular Reactions [see WARNINGS AND PRECAUTIONS]
• Blood Pressure and Heart Rate Increases [see WARNINGS AND PRECAUTIONS]
• Psychiatric Adverse Reactions [see WARNINGS AND PRECAUTIONS]
• Long-Term Suppression of Growth [see WARNINGS AND PRECAUTIONS]
• Peripheral Vasculopathy, including Raynaud's phenomenon [see WARNINGS AND PRECAUTIONS]
• Seizures [see WARNINGS AND PRECAUTIONS]
• Serotonin Syndrome [see WARNINGS AND PRECAUTIONS]

Clinical Trial 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, 4th or 5th 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 [see Clinical Studies].

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* (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
	Dysmenorrhea1	4%	2%
	Erectile Dysfunction2	2%	1%
*Includes doses up to 75 mg (1.5 times the maximum recommended dosage). 1 Dysmenorrhea was observed in 11 females 2 Erectile dysfunction was observed in 6 males

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*	8%	3%
Gastrointestinal disorders
Nausea	8%	4%
Abdominal pain upper	4%	1%
*Insomnia includes terms: initial insomnia, middle insomnia, terminal insomnia and insomnia.

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 post approval 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.

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).

Eye Disorders: Mydriasis.

Gastrointestinal: Unpleasant taste, constipation.

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

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

Skin: Alopecia.

Vascular Disorders: Raynaud's phenomenon.

Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis.