ST LOUIS (MD Consult) - On September 3, 2009, Shire announced that the US Food and Drug Administration has approved Intuniv (guanfacine) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6 to 17 years. Once-daily Intuniv is expected to be available in US pharmacies in November 2009 and will be manufactured in 4 dosage strengths (1, 2, 3, and 4 mg).
Intuniv is a nonscheduled, selective, α-2A receptor agonist and has no known potential for abuse or dependence. Although the drug's mechanism of action is unknown, it is speculated that Intuniv is able to directly engage receptors found in the prefrontal cortex of the brain. Scientists believe that stimulation of the postsynaptic α-2A receptors may strengthen working memory, reduce susceptibility to distraction, improve attention regulation, improve behavioral inhibition, and enhance impulse control.
The efficacy of Intuniv for the treatment of ADHD was established in 2 similarly designed clinical trials in children and adolescents aged 6 to 17 years whose conditions met the Diagnostic and Statistical Manual of Mental Disorders—IV's criteria for ADHD. The first pivotal trial was a phase 3, double-blind, parallel-group trial, in which investigators randomly assigned 345 study patients to receive either placebo or a fixed 2-mg, 3-mg, or 4-mg once-daily dose of Intuniv during an 8-week period. The second pivotal trial was a phase 3, double-blind, parallel-group trial, in which investigators randomly assigned 324 patients to receive either placebo or a fixed 1-mg, 2-mg, 3-mg, or 4-mg once-daily dose of Intuniv during a 9-week period, with the 1-mg dose assigned only to children who weighed <50 kg (110 lbs).
In both trials, doses of Intuniv were increased in increments of 1 mg per week, and investigators evaluated participants' signs and symptoms of ADHD on a once-weekly basis using the clinician administered and scored ADHD Rating Scale-IV (ADHD-RS-IV), a scale frequently used in ADHD clinical trials that assesses hyperactive, impulsive, and inattentive symptoms. The primary outcome was the change in total ADHD-RS-IV scores from baseline to end point in both studies.
Results from both trials demonstrated statistically significant improvements in ADHD-RS-IV scores in patients taking Intuniv, beginning 1 to 2 weeks after patients began receiving the drug. In the first pivotal trial, the mean reduction in ADHD-RS-IV total scores at end point were –16.7 for Intuniv compared with –8.9 for placebo (P < .0001), the mean reduction in ADHD-RS-IV total scores in the second pivotal trial were –19.6 for Intuniv and –12.2 for placebo (P = .0040).
Frank A. Lopez, MD, a neurodevelopmental pediatrician in private practice at Children's Developmental Center in Winter Park, Fla, made this comment about Intuniv's efficacy: "In clinical trials, Intuniv, a selective α-2A receptor agonist, significantly reduced ADHD symptoms across a full day as measured by parents at 6 PM, 8 PM, and 6 AM the next morning. This is important because children with ADHD require symptom control at home, school, and during after school activities."
Safety data from these trials showed that adverse events reported by participants receiving Intuniv were generally mild to moderate in severity. Treatment-related adverse events that were reported more frequently than 10% included somnolence (32%), headache (26%), fatigue (18%), upper abdominal pain (14%), and sedation (13%). Small to modest changes in blood pressure, pulse rate, and electrocardiographic parameters were observed.
The manufacturer warns that Intuniv should be used with caution in patients who have experienced hypotension, bradycardia, heart block or syncope or who may have a condition that predisposes them to syncope. Caution is also advised in prescribing Intuniv for patients who are treated concomitantly with antihypertensives or other drugs that can reduce blood pressure or heart rate, or with medications that can increase the risk of syncope. Heart rate and blood pressure should be measured before therapy initiation, after dose increases, and periodically while on therapy. Patients should be advised to avoid becoming dehydrated or overheated.
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