Philadelphia — Shire plc, a global specialty biopharmaceutical company, has announced that the U.S. Food and Drug Administration (FDA) approved the use of once-daily Intuniv (guanfacine) extended-release tablets as adjunctive therapy to stimulants for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents ages 6 to 17 as part of a total treatment program.
The approval is based on results from a nine-week placebo-controlled study of Intuniv when given in combination with a stimulant, in children and adolescents with ADHD.1
"This approval of Intuniv for treating ADHD as adjunctive therapy to a stimulant offers physicians a new treatment option for children and adolescents with ADHD who are having a suboptimal response to their current stimulant therapy," said Robert Findling, MD, Director of Child & Adolescent Psychiatry at University Hospitals Case Medical Center and Professor of Psychiatry & Pediatrics at Case Western Reserve University School of Medicine, a lead investigator for the study.
"In this study, the once-daily dosing of Intuniv was effective when taken in the morning or the evening, giving physicians flexibility when it comes to treating their patients with ADHD," Findling added.
Intuniv is indicated for the treatment of ADHD as monotherapy and as adjunctive therapy to stimulant medications in children and adolescents ages 6 to 17. The effectiveness of Intuniv for more than nine weeks has not been systematically evaluated.
The physician electing to use Intuniv for extended periods should periodically reevaluate its long-term usefulness for the individual patient. Intuniv is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, and social).1
Intuniv is the only once-daily ADHD medication approved for administration as adjunctive therapy to stimulants. Intuniv a nonstimulant, is a selective alpha-2A agonist.1
During the nine-week, multicenter, double-blind, randomized, placebo-controlled study, patients (N=455) experiencing a suboptimal response to stimulant treatment for ADHD received a morning or evening dose of Intuniv (1 mg, 2 mg, 3 mg, or 4 mg) or placebo in combination with their prescribed dose of a stimulant.2
Clinicians using the ADHD-RS-IV, which includes both hyperactive/impulsive and inattentive subscales, reported significant reductions in total scores from baseline at end point for patients receiving Intuniv and stimulant when Intuniv was dosed either in the morning or evening, compared with placebo and stimulant.2
Suboptimal response was defined as treatment with a stable dose of stimulant for at least four weeks with improvement, yet persistence of mild to moderate ADHD symptoms in the opinion of the investigator (defined as an ADHD-RS-IV total score of at least 24, Clinical Global Impressions-Severity of Illness scale score of at least three). Patients with no response to stimulants prior to study enrollment were excluded from participating in this study.2
The most commonly observed adverse reactions (incidence greater than or equal to 5 percent and at least twice the rate for placebo) in this adjunctive trial were: somnolence, fatigue, insomnia, dizziness, and abdominal pain.1
The majority of events were mild or moderate in severity and no unique events were observed with Intuniv given with a stimulant compared with those reported historically for either treatment alone.2
Three percent of patients receiving Intuniv plus stimulant discontinued from the study due to adverse events, compared to 1 percent in the placebo plus stimulant group.1
Four serious adverse events (SAEs) were reported in the study and included syncope, mixed disturbance of emotions (similar to behaviors prior to study start), poison ivy, and a nonintentional overdose in a sibling of a study participant. All SAEs were considered by the investigator to be unrelated to Intuniv.2
"This approval marks a significant development in our ADHD portfolio—one that may help to address symptoms that many children with ADHD may experience while on stimulant treatment," said Michael Yasick, Senior Vice President of Shire's ADHD Business Unit.
"We understand that every child is unique, and it is our goal to offer treatment options for ADHD in a variety of situations, whether a child could benefit from treatment with a stimulant, nonstimulant, or both."
Intuniv is available in four doses—1 mg, 2 mg, 3 mg, and 4 mg.(1) Intuniv should be taken once a day.(1) The active ingredient in Intuniv is guanfacine. Intuniv is not a central nervous system (CNS) stimulant or a controlled substance.(1) It is not likely to cause dependence or be abused.1
1. INTUNIV [package insert], Wayne, PA: Shire US Inc.; 02/2011.
2. Wilens T, Bukstein OG, Cutler AJ, Findling RL, Youcha S, White C, Rubin J. A multicenter placebo controlled study of extended-release guanfacine coadministered with stimulants in the treatment of ADHD: Effects on overall, morning, and evening ADHD assessments. Paper presented at: American Academy of Child and Adolescent Psychiatry Annual Meeting; October 28, 2010; New York, NY.
3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Revision (DSM-IV-TR ®). Washington, DC: American Psychiatric Association; 2000:85-93.
4. Pliszka S and the AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894-921.
5. Centers for Disease Control and Prevention. Increasing prevalence of parent reported attention deficit/hyperactivity disorder among children -- United States, 2004 and 2007. Morb Mortal Weekly Rep (MMWR). 2010;59(44):1439-1443.