For attention-deficit/hyperactivity disorder (ADHD)

Results from the open-label,
dose-optimization phase*

The open-label, dose-optimization phase was conducted prior to the double-blind, placebo-controlled crossover phase to determine the optimal EVEKEO® CII (amphetamine sulfate tablets, USP) daily dose for ADHD study patients, who were ages 6 to 12 years old1

The Attention-Deficit/Hyperactivity Disorder Rating Scale, Version IV (ADHD-RS-IV) and patient tolerability were used to help determine the optimal dose (see ADHD-RS-IV results)1

The starting dose was 10 mg daily and could be titrated up to 40 mg daily1

Dose Optimization: The Median Dose of EVEKEO Was 20 mg Daily (10 mg BID)1

3530252015105131632161012620 mg0Number of Pediatric Patients by Final EVEKEO DoseFinal Daily EVEKEO Dose (N=105)210 mg15 mg30 mg35 mg40 mg25 mg

EVEKEO noticeably improved the 3 core symptoms of ADHD1

During the open-label, dose-optimization phase, pediatric patients with ADHD were evaluated weekly using the ADHD-RS-IV scale.1

  • This is an investigator-rated measure of the core symptoms of ADHD
  • These symptoms include inattentiveness, hyperactivity, and impulsivity

Starting at week 1, EVEKEO improved ADHD-RS-IV scores at every weekly assessment compared with baseline. At the end of the 8-week open-label phase, EVEKEO had delivered a 68% improvement.1

ADHD-RS-IV: EVEKEO Improved Inattentiveness, Hyperactivity, and Impulsivity From Week 1 Through Week 81

68% Observed Meanimprovementat week 8240302010ScreeningBaselineWeek 1Week 2Week 3Week 4Week 5Week 6Week 7Week 8

EVEKEO was well tolerated, with a low rate of discontinuations due to adverse events1

Of 105 pediatric patients with ADHD in the enrolled safety population of the EVEKEO classroom study, 5 discontinued therapy due to adverse events.1

Open-Label Tolerability Reported in ≥5% of Patients1

Adverse EventEVEKEO
Decreased appetite27.6%
Upper abdominal pain14.3%
Irritability14.3%
Headache13.3%
Upper respiratory tract infection10.5%
Fatigue9.5%
Tachycardia8.6%
Insomnia6.7%
Dry mouth5.7%
Nausea5.7%
Vomiting5.7%
Affect lability5.7%

*Study Design: Results are from a phase 4, multicenter, laboratory classroom study of children ages 6 to 12 years with ADHD published in 2015. The 8-week open-label, dose-optimization phase (N=105) used the Attention-Deficit/Hyperactivity Disorder Rating Scale, Version IV (ADHD-RS-IV) to help assess symptom improvement; 8 of the children were not subsequently randomized and thus were not included in the ADHD-RS-IV assessment. The 2-week, double-blind, randomized, placebo-controlled, crossover phase (N=97) used the Permanent Product Measure of Performance (PERMP) and the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale to evaluate EVEKEO efficacy. Both phases assessed safety and tolerability. The study excluded children with significant psychiatric and medical comorbidities.1,2

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.