For the treatment of ADHD in patients 6 years and older

Dyanavel® XR offers
rapid onset and extended efficacy

DYANAVEL XR (amphetamine) significantly improved attention and behavior within as little as 1 hour and lasting through 13 hours post-dose with no return to baseline vs placebo*

DYANAVEL® XR (amphetamine) Extended Release SKAMP Score Efficacy Graph DYANAVEL® XR (amphetamine) Extended Release SKAMP Score Efficacy Graph Mobile
DYANAVEL® XR (amphetamine) Extended Release 1 Hour Onset of Efficacy

DYANAVEL XR was effective at 1 hour vs placebo; P<.0001, as measured by SKAMP1

DYANAVEL® XR (amphetamine) Extended Release Primary Efficacy Endpoint at 4 Hours

The primary efficacy endpoint as measured by change in SKAMP-Combined score at 4 hours; P<.00011

DYANAVEL® XR (amphetamine) Extended Release 13 Hour Efficacy

Improvement (decrease) in SKAMP-Combined score vs placebo was demonstrated for up to 13 hours; P<.00011

  • The primary endpoint, change from pre-dose in SKAMP-Combined score at 4 hours, was statistically significantly improved in the DYANAVEL XR group compared with that in the placebo group: LS mean DYANAVEL XR –8.8; placebo 6.0 (LS mean difference –14.8 [95% CI, –17.9, –11.6; P<.001])1
  • Rapid onset (at 1 hour) and lasting efficacy (to 13 hours post-dose) may help improve ADHD symptoms for patients from morning routine through school day, after-school activities, dinner time, and homework time
  • Significantly improved attention and behavior compared with placebo across all time points
  • Mean SKAMP-Combined scores remained below mean pre-dose score levels (17.3) at each post-dose time point

DYANAVEL XR significantly improved PERMP scores1,2

DYANAVEL® XR (amphetamine) Extended Release Pre- and Post-Dose Efficacy DYANAVEL® XR (amphetamine) Extended Release Pre- and Post-Dose Efficacy Mobile
  • Change in PERMP scores across all measured time points was a secondary endpoint2
  • PERMP is a timed, written test that measures the number of math problems attempted and solved correctly in 10 minutes. A higher PERMP score indicates better performance3
  • PERMP scores (problems attempted and problems correct) were significantly improved with DYANAVEL XR (amphetamine) at all post-dose time points compared with placebo (P<.0001 for both)1,2

PERMP test examples

The PERMP is a validated, time-sensitive, skill-adjusted test consisting of math problems to be completed at multiple time points (administration of serial PERMPs) and is a robust, objective measure of the ability to initiate a task, self-monitor/stay on task, and complete written seatwork. The PERMP does not test for mathematical ability or the ability to learn math because the difficulty of problems is adjusted to the existing math skill level of each participant.2

Shown below are examples of PERMP test results from an actual patient in the clinical study.

dxr-efficacy-image3

*Study details: One-week randomized, double-blind, placebo-controlled laboratory classroom assessment of attention and behavior, scored by teachers and raters using the SKAMP rating scale in children aged 6 to 12 years (N=108) who met DSM-IV criteria for ADHD. Classroom assessment followed a 5-week, open-label dose-optimization period, where subjects initially received 2.5 mg or 5 mg DYANAVEL XR once daily in the morning. The dose was titrated by 2.5 mg to 10 mg every 4 to 7 days until an optimal dose or the maximum dose of 20 mg/day was reached. Key secondary efficacy parameters were onset and duration of clinical effect. The change scores from pre-dose SKAMP-Combined scores at post-dose time points (1, 2, 4, 6, 8, 10, 12, and 13 hours) were used to evaluate key secondary efficacy parameters.

The SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham) rating scale, often used in clinical trials, is a validated rating instrument, used by trained raters to specifically measure the observed classroom manifestations of ADHD. The items of the SKAMP are specific for place, the classroom, and time, a typical class period. The scale’s items describe typical behaviors in a classroom setting, and additional items that describe behaviors associated with ADHD in the classroom. The SKAMP method of assessment has been demonstrated to be a sensitive measure of attention and behavior within a lab classroom setting.4

Cl, confidence interval; DSM-IV, Diagnostic and
Statistical Manual of Mental Disorders,
Fourth Edition; LS, least squares; PERMP, Permanent Product Measure of Performance; SE, standard error.

Important Safety Information

WARNING: ABUSE AND DEPENDENCE

CNS stimulants, including DYANAVEL XR, Quillivant XR, QuilliChew ER, and other amphetamine-containing or methylphenidate-containing products, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy.

  • DYANAVEL XR (amphetamine), Quillivant XR (methylphenidate HCI), and QuilliChew ER (methylphenidate HCI) are contraindicated:

    • in patients known to be hypersensitive to amphetamine, methylphenidate, or other components of DYANAVEL XR, Quillivant XR, and QuilliChew ER. Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been reported.

    • in patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs, because of risk of hypertensive crisis.

  • Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, and other serious cardiac problems. Sudden death, stroke, and myocardial infarction have been reported in adults treated with CNS stimulants at recommended doses. Sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems when taking CNS stimulants at recommended doses for ADHD. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during treatment with DYANAVEL XR, Quillivant XR, and QuilliChew ER.

  • CNS stimulants cause increase in blood pressure (mean increase approximately 2 to 4 mm Hg) and heart rate (mean increase about 3 to 6 bpm). Monitor all patients for tachycardia and hypertension.

  • CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder. They may induce a mixed/manic episode in patients with bipolar disorder. Assess for presence of bipolar disorder prior to initiating treatment. At recommended doses, stimulants may cause psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania, in patients without prior history of psychotic illness or mania. If such symptoms occur, consider discontinuing DYANAVEL XR, Quillivant XR, or QuilliChew ER.

  • CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients with ADHD; monitor weight and height during treatment with DYANAVEL XR, Quillivant XR, and QuilliChew ER. Treatment may need to be interrupted in children not growing or gaining weight as expected.

  • CNS stimulants are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; very rare sequelae include digital ulceration and/or soft tissue breakdown. Careful observation for digital changes is necessary during treatment with ADHD stimulants.

  • Cases of painful and prolonged penile erections and priapism have been reported with methylphenidate products. Immediate medical attention should be sought if signs or symptoms of prolonged penile erections or priapism are observed.

  • Serotonin syndrome risk is increased when DYANAVEL XR is co-administered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), MAOIs, and during overdosage situations. If it occurs, discontinue DYANAVEL XR and any concomitant serotonergic agents immediately, and initiate supportive treatment.

  • QuilliChew ER contains phenylalanine, a component of aspartame, and can be harmful to patients with phenylketonuria (PKU).

  • Most common adverse reactions observed with amphetamine products: dry mouth, anorexia, weight loss, abdominal pain, nausea, insomnia, restlessness, emotional lability, dizziness, and tachycardia.

  • Based on limited experience with DYANAVEL XR in controlled trials, 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 in 108 patients with ADHD (aged 6 to 12 years) were: epistaxis (DYANAVEL XR 4%, placebo 0%), allergic rhinitis (4%, 0%) and upper abdominal pain (4%, 2%).

  • Based on accumulated data from other methylphenidate products, the most common (≥5% and twice the rate of placebo) adverse reactions are: appetite decreased, insomnia, nausea, vomiting, dyspepsia, abdominal pain, weight decreased, anxiety, dizziness, irritability, affect lability, tachycardia, blood pressure increased.

  • There is limited experience with Quillivant XR and QuilliChew ER in controlled trials.

    • Quillivant XR: The most common (≥2% in the Quillivant XR group and greater than placebo) adverse reactions reported in the Phase 3 controlled study conducted in 45 ADHD patients (ages 6 to 12 years) in Quillivant XR compared to placebo were affect lability (9% Quillivant XR, 2% placebo), excoriation (4%, 0%), initial insomnia (2%, 0%), tic (2%, 0%), decreased appetite (2%, 0%), vomiting (2%, 0%), motion sickness (2%, 0%), eye pain (2%, 0%), and rash (2%, 0%).

    • QuilliChew ER: The most common (≥2% in the QuilliChew ER group and greater than placebo) adverse reactions reported in the Phase 3 controlled study conducted in 90 pediatric subjects (ages 6 to 12 years) in QuilliChew ER compared to placebo were decreased appetite (2.4% QuilliChew ER, 0% placebo), aggression (2.4%, 0%), emotional poverty (2.4%, 0%), nausea (2.4%, 0%), headache (2.4%, 0%), and weight decreased (2.4%, 0%).

  • DYANAVEL XR, Quillivant XR, and QuilliChew ER use during pregnancy may cause fetal harm.

  • Breastfeeding is not recommended during treatment with DYANAVEL XR, Quillivant XR, or QuilliChew ER.

INDICATION

DYANAVEL XR, Quillivant XR, and QuilliChew ER are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older.

See Full Prescribing Information for DYANAVEL XR, Quillivant XR, and QuilliChew ER, including Boxed Warning about Abuse and Dependence.