Guanfacine - Drug Monograph

Introduction

Guanfacine is a centrally acting alpha-2A adrenergic receptor agonist approved by the FDA for the treatment of attention-deficit/hyperactivity disorder (ADHD) and hypertension. Originally developed as an antihypertensive agent, guanfacine has gained significant recognition for its neuropsychiatric applications, particularly in pediatric and adult ADHD management. It is available in immediate-release (Guanfacine HCl) and extended-release (Guanfacine ER) formulations, with the extended-release version specifically approved for ADHD treatment.

Mechanism of Action

Guanfacine selectively agonizes postsynaptic alpha-2A adrenergic receptors in the prefrontal cortex. This action enhances noradrenergic neurotransmission, leading to strengthened working memory, reduced distraction, improved attention regulation, and enhanced behavioral inhibition. Unlike stimulant medications, guanfacine does not directly affect dopamine neurotransmission. Its antihypertensive effects result from reduction in sympathetic outflow from the central nervous system, leading to decreased peripheral vascular resistance and heart rate.

Indications

• Extended-release formulation: Treatment of ADHD as monotherapy and as adjunctive therapy to stimulant medications in children and adolescents 6-17 years old
• Immediate-release formulation: Management of hypertension

• Tourette syndrome
• Oppositional defiant disorder
• PTSD-related hyperarousal symptoms
• Aggression and emotional dysregulation in autism spectrum disorder
• Opioid withdrawal symptoms

Dosage and Administration

• Initial dose: 1 mg once daily
• May increase by 1 mg weekly to target dose of 0.05-0.12 mg/kg/day
• Maximum dose: 4 mg daily for children and adolescents
• Administer once daily at same time each day, with or without food

• Initial dose: 1 mg once daily at bedtime
• Maintenance dose: 1-3 mg once daily
• Maximum dose: 3 mg daily

• Renal impairment: Use with caution; dose adjustment recommended
• Hepatic impairment: Contraindicated in severe hepatic impairment
• Geriatric patients: Initiate at lower doses due to increased sensitivity
• Pediatric patients: Approved for ADHD in children ≥6 years

Pharmacokinetics

Contraindications

• Hypersensitivity to guanfacine or any component of the formulation
• Severe hepatic impairment
• Concomitant use with strong CYP3A4 inhibitors or inducers (for extended-release formulation)

Warnings and Precautions

• Sedation and somnolence: Common, especially during initial treatment
• Hypotension and bradycardia: Monitor heart rate and blood pressure
• Rebound hypertension: May occur with abrupt discontinuation
• QT prolongation: Monitor in patients with cardiac conditions
• Hepatic impairment: Use caution in moderate impairment; contraindicated in severe impairment
• Pregnancy: Category B - use only if clearly needed
• Breastfeeding: Excreted in human milk; use caution

Drug Interactions

• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin): Increase guanfacine concentrations
• Strong CYP3A4 inducers (carbamazepine, rifampin): Decrease guanfacine concentrations
• Antihypertensives: Additive hypotensive effects
• CNS depressants: Additive sedative effects
• Alcohol: Increased sedative effects

• Valproic acid: May increase guanfacine concentrations
• Other alpha-2 agonists: Additive effects

Adverse Effects

• Somnolence/sedation (up to 40%)
• Fatigue (15-20%)
• Abdominal pain (10-15%)
• Hypotension (5-10%)
• Bradycardia (5-8%)
• Dry mouth (5-8%)
• Dizziness (5-8%)

• Syncope
• Severe hypotension
• Sinus bradycardia
• AV block
• Hallucinations
• Manic symptoms
• Allergic reactions

Monitoring Parameters

• Comprehensive medical history
• Blood pressure and heart rate
• Height and weight (pediatric patients)
• ECG if cardiac risk factors present
• Liver function tests

• Blood pressure and heart rate at each dose adjustment and periodically during maintenance
• Sedation/somnolence assessment
• Growth parameters in pediatric patients (every 3-6 months)
• ADHD symptom assessment using standardized scales
• Adverse effect profile

• Cardiac monitoring if symptoms suggest bradycardia or hypotension
• Liver function tests if hepatic impairment suspected

Patient Education

• Take medication at the same time each day
• Do not crush, chew, or break extended-release tablets
• Avoid abrupt discontinuation; taper under medical supervision
• Be aware of potential sedation; avoid driving or operating machinery until effects are known
• Monitor for signs of hypotension (dizziness, lightheadedness)
• Report any fainting episodes or significant changes in heart rate
• Avoid alcohol and other CNS depressants
• Inform all healthcare providers about guanfacine use
• Keep medication out of reach of children

• Store at room temperature (20-25°C/68-77°F)
• Keep in original container with lid tightly closed
• Protect from moisture

References

1. FDA Prescribing Information: Intuniv (guanfacine) extended-release tablets 2. Bello NT. Clinical utility of guanfacine extended release in the treatment of ADHD in children and adolescents. Patient Prefer Adherence. 2015;9:877-885 3. Hirota T, Schwartz S, Correll CU. Alpha-2 agonists for attention-deficit/hyperactivity disorder in youth: a systematic review and meta-analysis of monotherapy and add-on trials to stimulant therapy. J Am Acad Child Adolesc Psychiatry. 2014;53(2):153-173 4. Stahl SM. Mechanism of action of alpha-2A adrenergic agonists in attention-deficit/hyperactivity disorder with a focus on guanfacine extended release. J Child Adolesc Psychopharmacol. 2015;25(5):372-379 5. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Guanfacine; [updated 2023] 6. Lexicomp Online [Internet]. Hudson (OH): Wolters Kluwer Clinical Drug Information. Guanfacine; [updated 2023] 7. American Academy of Pediatrics. ADHD: Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics. 2019;144(4):e20192528