Amphetamineside effects

The following adverse reactions are discussed in greater detail in other sections of the labeling: Abuse, Misuse, and Addiction Hypersensitivity to amphetamine, or other components of DYANAVEL XR 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 Serotonin Syndrome Motor and Verbal Tics, and Worsening of Tourette’s Syndrome Most common adverse reactions observed with amphetamine products: dry mouth, anorexia, weight loss, abdominal pain, nausea, insomnia, restlessness, emotional lability, dizziness, tachycardia To report SUSPECTED ADVERSE REACTIONS, contact Tris Pharma, Inc. at 1-732-940-0358 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. Adverse Reactions in Studies with Other Amphetamine Products in Pediatric Patients and Adults with ADHD Cardiovascular: Palpitations, tachycardia, elevation of blood pressure, sudden death, myocardial infarction. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.

Central Nervous System: Psychotic episodes at recommended doses, overstimulation, restlessness, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, tics, aggression, anger, logorrhea.

Eye Disorders: Vision blurred, mydriasis.

Gastrointestinal: Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances. Anorexia and weight loss may occur as undesirable effects.

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.

Skin: Alopecia. Adverse Reactions in Studies with DYANAVEL XR in Pediatric Patients with ADHD There is limited experience with DYANAVEL XR in controlled trials. Based on this limited experience, the adverse reaction profile of DYANAVEL XR appears similar to other amphetamine extended-release products. The most common (≥2% in the DYANAVEL XR group and greater than placebo) adverse reactions reported in the Phase 3 controlled study conducted with DYANAVEL XR extended-release oral suspension in 108 patients with ADHD (aged 6 to 12 years) were: epistaxis, allergic rhinitis, and upper abdominal pain. Table 1. Common Adverse Reactions Occurring in ≥2% of Patients on DYANAVEL XR Extended-Release Oral Suspension and Greater than Placebo During the Double Blind Phase. Preferred Term DYANAVEL XR (N=52) Placebo (N=48) Respiratory, thoracic and mediastinal disorders Epistaxis 3.8% 0% Rhinitis allergic 3.8% 0% Gastrointestinal disorders Abdominal pain upper 3.8% 2.1%

6.2 Postmarketing

Experience The following adverse reactions have been identified during post approval use of other amphetamine products. 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: palpitations, sudden death, myocardial infarction. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use Central Nervous System: restlessness, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, aggression, anger, logorrhea, and paresthesia (including formication), motor and verbal tics Endocrine: impotence, changes in libido, frequent or prolonged erections Eye Disorders: vision blurred, mydriasis Gastrointestinal: unpleasant taste, constipation, intestinal ischemia, and other gastrointestinal disturbances Musculoskeletal, Connective Tissue, and Bone Disorders: rhabdomyolysis Psychiatric Disorders: dermatillomania, bruxism Skin: alopecia Vascular Disorders: Raynaud’s phenomenon