EVEKEO ODT SIDE EFFECTS

SIDE EFFECTS

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

• Abuse and Dependence
• Hypersensitivity to amphetamine, or other components of EVEKEO ODT
• Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors
• Serious Cardiovascular Reactions
• Blood Pressure and Heart Rate Increases
• Psychiatric Adverse Reactions
• Seizures
• Long-Term Suppression of Growth
• Peripheral Vasculopathy, including Raynaud’s Phenomenon
• Serotonin Syndrome.

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. Study 1 was conducted with EVEKEO tablets (i.e., not the ODT formulation) in children ages 6 to 12 years who met Diagnostic and Statistical Manual of Mental Disorders, 4^th edition, Text Revision (DSM-IV-TR) criteria for ADHD. This study began with an 8-week, open-label, dose-optimization phase followed by a 2-week double-blind, placebo-controlled, randomized, crossover phase. Adverse reactions reported in > 5% of patients (N=105; doses of 10 to 40 mg/day) during the open-label phase included: decreased appetite (28%), infections (22%), abdominal pain (15%), irritability (14%), headache (13%), nausea (6%), vomiting (6%), affect lability (includes mood swings; 9%), tachycardia (9%), insomnia (10%), fatigue (10%),and dry mouth (6%). During the open-label phase, six patients discontinued due to adverse reactions: irritability (n=3), affect lability (n=1), initial insomnia (n=1), and rash (n=1). Table 1 lists the adverse reactions reported during the double-blind, cross-over phase. No patient discontinued the study for an adverse reaction during the double-blind crossover phase. Because of the trial design (an initial 8-week, open-label, active treatment phase), the adverse reaction rates described in the double-blind phase are lower than expected in clinical practice.

Table 1: Adverse Reactions Reported in ≥ 2%, and > Placebo, of EVEKEO-Treated Pediatric Patients (6 to 12 Years) During the Double-Blind Cross-Over Weeks. ^a

Postmarketing Experience

The following adverse reactions have been associated 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: 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, irritability, restlessness, dizziness, insomnia, euphoria, mood swings, aggression, anger, logorrhea, dermatillomania, dyskinesia, dysphoria, tremor, fatigue, headache, exacerbation of motor and phonic tics and Tourette’s syndrome

Gastrointestinal: Dry mouth, unpleasant taste, constipation, nausea, other gastrointestinal disturbances, anorexia, and weight loss.

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

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

Skin: Alopecia.

Vascular Disorders: Raynaud’s phenomenon.

Musculoskeletal: Rhabdomyolysis.

SRC: NLM .