For attention-deficit/hyperactivity disorder (ADHD)

Studied in pediatric ADHD
patients with both inattentive and hyperactivity/impulsivity symptoms

4 out of 5 pediatric patients with ADHD in the EVEKEO classroom study had combined-type ADHD1

EVEKEO® CII (amphetamine sulfate tablets, USP) was assessed for efficacy and safety in a double-blind, randomized, phase 4, laboratory classroom study with pediatric ADHD patients. The patients were aged 6-12 years old and of different genders and race/ethnicities (see baseline characteristics below). In the study, more than 80% of the patients had multiple symptoms across the ADHD presentation spectrum (ie, inattention, hyperactivity, impulsivity).1,2

Classroom Study Design1

4 Weeks

Screening
Phase
N=107

8 Weeks

Open-label,
Dose-Optimization Phase
N=105

2 Weeks

Randomized,
Double-blind,
Crossover Phase
N=97

A phase 4, multicenter, laboratory classroom study of children ages 6 to 12 years with ADHD with results published in 2015. The total enrolled safety population was 105 children; 8 of the children were not randomized and thus not included in the ADHD-RS-IV assessment. The study excluded children with significant psychiatric and medical comorbidities.1,2

Baseline Characteristics1,2

8-Week, Dose-Optimization Phase2-Week, Randomized, Double-blind,
Crossover Phase (1 Week Each)
Characteristicn (%)
(N=97*)
EVEKEO/Placebo
n (%)
(n=47)
Placebo/EVEKEO
n (%)
(n=50)

Age, mean ± SD, years

6-7
8-10
11-12
9.6±1.86
16 (16.5)
44 (45.4)
37 (38.1)
9.6±1.97
7 (14.9)
22 (46.8)
18 (38.3)
9.6±1.78
9 (18.0)
22 (44.0)
19 (38.8)

Gender

Male
Female
59 (60.8)
38 (39.2)
29 (61.7)
18 (38.3)
30 (60.0)
20 (40.0)

Race

White
Black/African American
Asian
Other
58 (59.8)
33 (34.0)
1 (1.0)
5 (5.1)
30 (63.8)
13 (27.7)
1 (2.1)
3 (6.4)
28 (56.0)
20 (40.0)
0
2 (4.0)

Ethnicity

Hispanic/Latino
Non-Hispanic/Latino
31 (32.0)
66 (68.0)
15 (31.9)
32 (68.1)
16 (32.0)
34 (68.0)

ADHD type

Inattentive
Hyperactive/Impulsive
Combined
18 (18.6)
0
79 (81.4)
9 (19.1)
0
38 (80.9)
9 (18.0)
0
41 (82.0)
*Total enrolled safety population was 105 children; 8 of the children were not randomized.

References: 1. Childress AC, Brams M, Cutler AJ, et al. The efficacy and safety of Evekeo, racemic amphetamine sulfate, for treatment of attention-deficit/hyperactivity disorder symptoms: a multicenter, dose-optimized, double-blind, randomized, placebo-controlled crossover laboratory classroom study. J Child Adolesc Psychopharmacol. 2015;25(5):402-414. 2. Data on file. Arbor Pharmaceuticals, LLC.

IMPORTANT SAFETY INFORMATION

Evekeo is a federally controlled substance (CII) with a high risk of abuse or dependence. Prolonged use may lead to drug dependence and must be avoided. Subjects may obtain Evekeo for illegal non-therapeutic use or distribution to others, and therefore it should be prescribed or dispensed sparingly.

INDICATION

Evekeo® (amphetamine sulfate tablets, USP) is a prescription medicine for the treatment of narcolepsy, attention deficit disorder with hyperactivity as an integral part of a total treatment program and exogenous obesity as a short term adjunct in a regimen of weight reduction.

IMPORTANT SAFETY INFORMATION

Evekeo is a federally controlled substance (CII) with a high risk of abuse or dependence. Prolonged use may lead to drug dependence and must be avoided. Subjects may obtain Evekeo for illegal non-therapeutic use or distribution to others, and therefore it should be prescribed or dispensed sparingly.


Misuse of Evekeo may cause sudden death and serious cardiovascular adverse events.

Contraindications

Evekeo is contraindicated in patients:

  • with a history of advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines
  • that are tense or agitated
  • with a history of drug abuse
  • taking or who have taken monoamine oxidase inhibitor (MAOI) within 14 days. Hypertensive crises may result.

Warnings and Precautions

Sudden death has been reported in children and adolescents with structural cardiac abnormalities or other serious heart problems in association with CNS stimulant treatment at usual doses. Sudden death, stroke and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Stimulant medications can cause an increase in blood pressure (mean increase about 2-4 mmHg) and heart rate (mean increase about 3-6 bpm). All patients should be monitored for larger changes in heart rate and blood pressure.


Children, adolescents, or adults who are being considered for treatment with Evekeo should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease. Patients developing any signs of heart problems such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease while taking Evekeo should undergo a prompt cardiac evaluation.


Stimulants may exacerbate symptoms in patients with pre-existing psychotic disorder or in patients with new or worsening bipolar disorder. Treatment emergent psychotic or manic symptoms can occur in children or adolescents such as hallucinations, delusional thinking, or mania. Aggressive behavior or hostility is also often observed in children and adolescents taking medications for ADHD and should be monitored for the appearance of, or worsening of aggressive behavior or hostility.


Stimulants have been associated with long-term suppression of growth in pediatric patients. Growth should be monitored during treatment with Evekeo, and patients not growing or gaining height or weight as expected may need to have their treatment interrupted.


Stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.


Stimulants used to treat ADHD 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 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 ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.


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 MAOIs, SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort. See DRUG INTERACTIONS in the prescribing information for all Evekeo interactions. The potential for a pharmacokinetic interaction exists with the co-administration of CYP2D6 inhibitors which may increase the risk with increased exposure to Evekeo. In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6.


Serotonin syndrome symptoms may include mental status changes, autonomic instability, neuromuscular symptoms, seizures, and/or gastrointestinal symptoms. Concomitant use of Evekeo with MAOI drugs is contraindicated. Discontinue treatment with Evekeo and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Evekeo with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate Evekeo 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.


Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

Adverse Reactions

The most common side effects reported with Evekeo treatment include palpitations, tachycardia, hypertension, cardiomyopathy (with chronic use), overstimulation, restlessness, dizziness, insomnia, euphoria, dyskinesia, dysphoria, tremor, headache, exacerbation of phonic tics and Tourette's syndrome, dry mouth, unpleasant taste, constipation, gastrointestinal disturbances, anorexia and weight loss, urticaria, impotence, changes in libido, frequent or prolonged erections, and rhabdomyolysis.


You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For additional safety information, consult the Evekeo full Prescribing Information and Medication Guide.