Once-daily tab for children with ADHD

Product: Intuniv

Company: Shire

Pharmacologic class: Central α2A-agonist

Active ingredient: Guanfacine (as HCl) 1 mg, 2 mg, 3 mg, 4 mg; extended-release tabs.

Indication: Attention- deficit hyperactivity disorder (ADHD) in patients aged 6-17 years.

Pharmacology: This product is an extended-release, matrix tablet formulation of the selective α2A-adrenergic receptor agonist, guanfacine, which is also available in an immediate-release form for treating hypertension (Tenex, from PDL Bio-Pharma). By stimulating α2A-adrenergic receptors, guanfacine reduces sympathetic output from the vasomotor centers of the brain to the heart and vasculature. Its mechanism of action in treating ADHD is not known. Immediate-release guanfacine and Intuniv have different pharmacokinetic characteristics. The extent of absorption and the maximum blood levels reached with Intuniv are lower compared with those parameters for immediate-release guanfacine products.

Clinical trials: The efficacy of Intuniv was studied in two trials in patients aged 6-17 years with ADHD. Study 1, which involved 345 patients, was an eight-week, double-blind, placebo-controlled, parallel-group study that evaluated Intuniv at fixed once-daily doses of 2 mg, 3 mg, and 4 mg. Study 2, a nine-week trial with 324 patients, was similar but it included Intuniv at a dose of 1 mg as well as the other doses. In both studies, patients were randomized to a fixed dose after titration; patients weighing <25 kg were excluded. The signs and symptoms of ADHD were evaluated once weekly using the ADHD Rating Scale-IV (ADHD-RS), a clinician- administered score that includes both inattentive and hyperactive/impulsive subscales. For both studies, the primary outcome measure was the change from base-line to end point in mean ADHD-RS scores.

At end point, the mean reductions in ADHD-RS scores were significantly greater for Intuniv compared with placebo in both studies. A dose- response efficacy was evident, especially when data were examined on a weight-adjusted basis. Clinical improvements were seen beginning at doses ranging from 0.05-0.08 mg/kg/day, with additional benefit seen at doses up to 0.12 mg/kg/day. Adults and children: Swallow whole with water, milk, or other liquid. Do not give with high-fat meals. <6 years: not recommended. 6-17 years: initially 1 mg once daily; titrate by 1 mg/day at one-week intervals; usual maximum 4 mg once daily. Improvements seen at doses of 0.05-0.08 mg/kg/day. Doses up to 0.12 mg/kg/day may provide additional benefit. Re-evaluate periodically. Withdraw gradually (by 1 mg every 3-7 days). <18 years: not established.

Contraindications: Concomitant use with other forms of guanfacine.

Precautions: Do not substitute with other forms of guanfacine on a mg-mg basis. Concomitant antihypertensives, other risks for hypotension, syncope, bradycardia, cardiovascular disease. Monitor heart rate, BP. Dehydration. Elevated temperature. Renal or hepatic impairment. Pregnancy (Cat. B). Nursing mothers.

Interactions: May be potentiated by CYP3A4/5 inhibitors (e.g., ketoconazole). May be antagonized by CYP3A4 inducers (e.g., rifampin). May potentiate valproic acid. Additive effects with other antihypertensives, central nervous system depressants (e.g., benzodiazepines, antipsychotics, barbiturates).

Adverse reactions: Somnolence, sedation, abdominal pain, dizziness, hypotension, dry mouth, constipation, bradycardia.

How supplied: Tabs—100

For more information, call 800.828.2088 or visit www.Intuniv.com.

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