Introduction
Intuniv (guanfacine) is an extended-release, once-daily formulation approved by the FDA for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6-17 years. Unlike stimulant medications commonly used for ADHD, Intuniv is a selective alpha-2A adrenergic receptor agonist that provides an alternative mechanism for managing ADHD symptoms.
Mechanism of Action
Intuniv exerts its therapeutic effects through selective agonism of postsynaptic alpha-2A adrenergic receptors in the prefrontal cortex. This action enhances noradrenergic neurotransmission, which strengthens working memory, reduces distractibility, and improves behavioral inhibition. The drug modulates intracellular cAMP and hyperpolarizes neurons through potassium channel activation, ultimately enhancing prefrontal cortical regulation of attention and impulse control.
Indications
- FDA-approved for monotherapy treatment of ADHD in pediatric patients 6-17 years
- FDA-approved as adjunctive therapy to stimulant medications for ADHD in pediatric patients 6-17 years
- Off-label uses may include treatment of oppositional defiant disorder, Tourette's syndrome, and anxiety disorders in pediatric populations
Dosage and Administration
Initial dose: 1 mg orally once daily Dose titration: May increase by 1 mg/week based on clinical response and tolerability Maintenance dose: 1-4 mg daily (maximum recommended dose: 4 mg/day) Administration: Swallow whole tablet; do not crush, chew, or break. Administer with or without food, but consistency in administration relative to meals is recommended. Special populations:- Renal impairment: Use with caution in severe impairment
- Hepatic impairment: Use with caution
- Geriatric patients: Not recommended
- Weight-based dosing: Not required
Pharmacokinetics
Absorption: Bioavailability approximately 80%; peak plasma concentrations reached within 4-8 hours Distribution: Volume of distribution ~6 L/kg; 70% protein-bound Metabolism: Primarily metabolized via CYP3A4 system; no active metabolites Elimination: Half-life approximately 18 hours; primarily excreted in urine (50%) and feces (40%) as metabolites Steady-state: Achieved within 4-5 days of consistent dosingContraindications
- Hypersensitivity to guanfacine or any component of the formulation
- Concomitant use with strong CYP3A4 inhibitors or inducers
- Patients with severe hepatic impairment
Warnings and Precautions
Boxed Warning: None Important precautions:- Sedation and somnolence: May impair mental and physical abilities
- Hypotension, bradycardia, and syncope: Monitor heart rate and blood pressure
- Rebound hypertension: May occur with abrupt discontinuation
- CYP3A4 interactions: Significant drug interaction potential
- Pregnancy: Category B - use only if clearly needed
- Lactation: Excreted in breast milk; not recommended
Drug Interactions
Major interactions:- Strong CYP3A4 inhibitors (ketoconazole, clarithromycin): Increase guanfacine concentrations
- Strong CYP3A4 inducers (rifampin, carbamazepine): Decrease guanfacine concentrations
- Antihypertensive agents: Additive hypotensive effects
- CNS depressants: Additive sedative effects
- Contraindicated combinations: Strong CYP3A4 inhibitors/inducers
Adverse Effects
Common (≥5%):- Somnolence/sedation (38%)
- Fatigue (15%)
- Abdominal pain (12%)
- Hypotension (10%)
- Bradycardia (7%)
- Dizziness (6%)
- Syncope (<1%)
- Severe hypotension
- Sinus bradycardia
- AV block
- Hepatic enzyme elevations
Monitoring Parameters
Baseline:- Comprehensive medical history
- Blood pressure and heart rate
- Height and weight
- Liver function tests (if indicated)
- Blood pressure and heart rate at each dose increase and periodically during maintenance
- ADHD symptom assessment using standardized scales
- Sedation/somnolence assessment
- Growth parameters in pediatric patients
- Adherence assessment
- Monitor for rebound hypertension for at least 3-4 days
Patient Education
Key points for patients and caregivers:- Take medication at the same time each day
- Do not crush, chew, or break tablets
- Avoid abrupt discontinuation; taper under medical supervision
- Report dizziness, lightheadedness, or excessive drowsiness
- Rise slowly from sitting or lying positions
- Avoid alcohol and other CNS depressants
- Inform all healthcare providers about Intuniv use
- Store at room temperature away from moisture
- Keep medication in secure location due to potential for misuse
- If missed, take as soon as remembered unless close to next dose
- Do not double doses
References
1. FDA Prescribing Information: Intuniv (guanfacine) extended-release tablets 2. Biederman J, et al. A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics. 2008;121(1):e73-e84. 3. Connor DF, et al. Effects of guanfacine extended release on oppositional symptoms in children aged 6-12 years with attention-deficit hyperactivity disorder and oppositional symptoms. CNS Drugs. 2010;24(9):755-768. 4. Sallee FR, et al. Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2009;48(2):155-165. 5. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Guanfacine. Available from: https://www.clinicalkey.com 6. Lexicomp Online [Internet]. Hudson (OH): Wolters Kluwer Clinical Drug Information. Guanfacine monograph.