Guanfacine extended-release tablets (Intuniv): Selective alpha2a-adrenergic receptor agonist approved for the treatment of ADHD

Guanfacine is a selective alpha_2a-adrenergic receptor agonist that was approved on September 2, 2009, for the treatment of attention-deficit/hyperactivity disorder (ADHD). Guanfacine's mechanism of action for this indication is unknown.

Efficacy. The efficacy of this agent for the treatment of ADHD was assessed in 2 placebo-controlled trials in patients aged 6 to 17 years. In the first study, patients were treated with guanfacine 2, 3, or 4 mg or placebo once/d for 8 weeks. In the second study, patients were treated with guanfacine 1, 2, 3, or 4 mg/d or placebo once/d for 9 weeks. Guanfacine doses were titrated by ≤1 mg/wk. The signs and symptoms of ADHD were evaluated once/wk using the clinician-administered and clinician-scored ADHD Rating Scale-IV. The primary outcome was change in mean ADHD-RS score. In both studies, the mean reductions in ADHD-RS scores were significant among guanfacine-treated patients versus placebo-treated patients.

Safety. Guanfacine treatment may cause decreases in blood pressure and heart rate, which can lead to syncope. Heart rate and blood pressure should be assessed before therapy initiation, after dose increases, and periodically during therapy. This agent should be used with caution in patients with a history of hypotension, heart block, bradycardia, cardiovascular disease, syncope, orthostatic hypotension, or dehydration. This agent should be used with caution in patients being treated concomitantly with antihypertensive agents or other drugs that reduce blood pressure or heart rate or increase the risk of syncope. Somnolence and sedation were commonly reported adverse events in clinical trials. This agent should not be used in patients concomitantly taking other guanfacine-containing medications. The most common adverse events associated with guanfacine treatment include somnolence/sedation, abdominal pain, dizziness, hypotension/decreased blood pressure, dry mouth, and constipation.

Dosing. This agent should be initiated at a dose of 1 mg/d, with dose titrations of ≤1 mg/wk. The dose should be maintained within the range of 1 to 4 mg/d depending on clinical response and tolerability. Tablets should not be administered with high-fat meals and should not be crushed, chewed, or broken before they are swallowed. Extended-release tablets should not be substituted for immediate-release tablets on a mg-mg basis. The efficacy of this agent for long-term use (>9 wk) has not been evaluated in clinical trials; therefore, healthcare professionals should periodically re-evaluate the long-term usefulness of this agent for individual patients. When therapy with guanfacine is discontinued, the dose should be tapered by ≤1 mg every 3 to 7 days.