Guanfacine ER

• ADHD (Attention-Deficit/Hyperactivity Disorder)
• Pediatric ADHD
• Non-Stimulant ADHD Treatment
• Adjunctive ADHD Therapy

Guanfacine extended-release is a selective alpha-2A adrenergic receptor agonist used for the treatment of attention-deficit/hyperactivity disorder (ADHD). This non-stimulant medication works in the prefrontal cortex to improve attention, working memory, and behavioral inhibition without the abuse potential associated with stimulant medications.

Mechanism of Action

Guanfacine is a selective alpha-2A adrenergic receptor agonist. In the prefrontal cortex, stimulation of post-synaptic alpha-2A receptors strengthens working memory, improves attention regulation, and enhances behavioral inhibition—core deficits in ADHD. The prefrontal cortex regulates attention, behavior, and emotion through networks that are modulated by catecholamine signaling. By directly stimulating alpha-2A receptors, guanfacine mimics the effects of norepinephrine on these networks, improving prefrontal cortex function. This mechanism is distinct from guanfacine's antihypertensive effect, which is mediated through presynaptic alpha-2 receptors in the brainstem that reduce sympathetic outflow.

Available Formulations

Guanfacine extended-release is available as tablets in 1 mg, 2 mg, 3 mg, and 4 mg strengths. The tablets should be swallowed whole and should not be crushed, chewed, or broken, as this destroys the extended-release mechanism. This formulation is distinct from immediate-release guanfacine tablets, which are primarily used for hypertension. The extended-release tablets should be taken at the same time each day.

Medical Uses

Guanfacine extended-release is FDA-approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in patients aged 6-17 years. It can be used as monotherapy or as adjunctive therapy to stimulant medications. It is particularly useful for patients who cannot tolerate stimulants, those with comorbid anxiety, tic disorders, or sleep difficulties, or when stimulant response is suboptimal.

Dosing Guidelines

Treatment should begin at 1 mg once daily and increased in increments of no more than 1 mg per week, depending on clinical response and tolerability. The recommended target dose range is 0.05-0.12 mg/kg/day. Maximum recommended doses vary by weight. When discontinuing, taper the dose in decrements of no more than 1 mg every 3-7 days to minimize rebound hypertension. The tablets can be taken with or without food but should not be taken with high-fat meals, which increase absorption.

Important Safety Information

Guanfacine extended-release causes dose-dependent decreases in blood pressure and heart rate; patients should be monitored regularly. Somnolence and sedation occur commonly and may impair mental alertness and motor coordination. Patients should not operate heavy machinery or drive until they know how the medication affects them. Syncope has been reported. Treatment should not be discontinued abruptly due to risk of rebound hypertension. Use with caution in patients with hypotension, bradycardia, heart block, or other cardiovascular conditions.

Drug Interactions

Strong CYP3A4 inhibitors (ketoconazole) and inducers (rifampin) significantly affect guanfacine levels; dose adjustments are required. CYP3A4 inhibitors may increase levels (consider dose reduction); CYP3A4 inducers may decrease levels (consider dose increase). Other CNS depressants and alcohol may increase sedation. Caution with antihypertensive medications due to additive effects. Valproic acid increases guanfacine exposure.

Special Populations

There are no adequate studies in pregnant women. Animal studies showed no teratogenicity but some developmental effects. Use during pregnancy only if clearly needed. Guanfacine is excreted in breast milk; caution is advised. Safety and efficacy have been established in pediatric patients aged 6-17 years. Guanfacine ER has not been studied systematically in adults for ADHD; immediate-release formulations are used off-label. Elderly patients typically use immediate-release for hypertension. Patients with significant renal or hepatic impairment may require dose reduction.