Guanfacine has been approved by the Food and Drug Administration as an adjunct to stimulant medications for the treatment of attention-deficit/hyperactivity disorder in children and adolescents aged 6-17, the manufacturer announced Feb. 28 in a statement.
The extended-release form of the drug, a selective alpha-2A adrenergic receptor agonist, previously had been approved as monotherapy for treating ADHD. Approval of the monotherapy was based on two 8- to 9-week studies, and the adjunctive therapy indication was based on a 9-week study of children and adolescents, according to the prescribing information for guanfacine, marketed as Intuniv by Shire PLC. The 9-week study included 455 patients with ADHD who had a suboptimal response to stimulant treatment. Those who had no response to stimulant therapy were not included in the study.
Patients were randomized to receive a dose of guanfacine or placebo in the morning or evening or placebo in combination with the stimulant they had been receiving, with the dose of guanfacine starting at 1 mg titrated weekly over a 5-week period to a maximum of 4 mg/day, based on tolerability and clinical response. At the end of 9 weeks, the mean reductions in total scores on the ADHD rating scale (ADHD-RS-IV) were significantly greater among those who received the combination than among those who continued on the psychostimulant alone. The prescribing information states that "controlled adjunctive long-term efficacy studies over 9 weeks have not been conducted," and that it is indicated "as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, and social) for patients with this syndrome."
The most common adverse events, reported in 5% or more of patients at a rate of at least twice the placebo rate, were somnolence, fatigue, insomnia, dizziness, and abdominal pain. Most adverse events were mild to moderate, and the four serious adverse events reported in the study – which included syncope and poison ivy – were not considered to be related to the drug, by the investigator, according to the company statement. The discontinuation attributable to side effects was 3% among those on the combination, compared with 1% among those on the stimulant alone, according to the company statement.
Guanfacine is a known antihypertensive, and the labeling cautions about its use with antihypertensive drugs. (It is marketed as an antihypertensive as Tenex, by another manufacturer).
Guanfacine comes in 1-mg, 2-mg, 3-mg and 4-mg extended-release tablets. It should be taken once daily, and should not be taken with high-fat meals, which increases exposure to the drug, according to the prescribing information.