What are the dosing, titration, monitoring, and discontinuation recommendations for guanfacine in adult hypertension and in pediatric and adult attention‑deficit/hyperactivity disorder?

Guanfacine Dosing, Titration, Monitoring, and Discontinuation

Dosing Guidelines

Start guanfacine extended-release at 1 mg once daily in the evening, titrate by 1 mg per week based on response and tolerability, targeting a weight-adjusted dose of 0.05–0.12 mg/kg/day (maximum 7 mg/day for ADHD, up to 9 mg/day studied in adolescents). 1, 2, 3

Initial Dosing

• Starting dose: 1 mg once daily 1, 2
• Timing: Evening administration is strongly preferred to minimize daytime somnolence and fatigue 1, 2
• Available strengths: 1,2,3, and 4 mg tablets 2

Titration Schedule

• Increase by 1 mg weekly based on clinical response and tolerability 1
• Target range: 0.05–0.12 mg/kg/day or 1–7 mg/day 1, 2
• Weight-adjusted doses >0.08 mg/kg but ≤0.12 mg/kg may provide additional clinical benefits if tolerated 3
• For adolescents weighing >70 kg, doses up to 9 mg/day have been studied and may be considered 3

ADHD-Specific Dosing

• Pediatric ADHD (ages 6–17): 1–7 mg/day, adjusted to approximately 0.1 mg/kg as a general guideline 1, 2
• Therapeutic onset: Expect 2–4 weeks before observing clinical benefits, unlike stimulants which work immediately 1, 2
• Monitor ADHD symptoms systematically at each dose adjustment using parent and teacher reports 1

Hypertension Dosing (Adult)

• Guanfacine is FDA-approved for hypertension in adolescents and adults 4
• Central alpha-2 agonists like guanfacine are reserved as last-line agents for hypertension due to significant CNS adverse effects, especially in older adults 1

Monitoring Requirements

Obtain baseline blood pressure and heart rate before initiating guanfacine, then monitor cardiovascular parameters at each dose adjustment and periodically during maintenance therapy. 1

Cardiovascular Monitoring

• Baseline: Measure blood pressure and heart rate before starting treatment 1
• During titration: Check vital signs at each dose adjustment 1
• Expected changes: Decreases of 1–4 mm Hg in systolic and diastolic blood pressure, and 1–2 bpm in heart rate 1, 5
• Dose-dependent effects: Blood pressure and heart rate decrease as dose increases, then return toward baseline during maintenance and tapering phases 5

Cardiac Screening

• Screen for personal or family history of cardiac conditions including Wolf-Parkinson-White syndrome, unexplained fainting, sudden cardiac death, hypertrophic cardiomyopathy, and long QT syndrome 1
• Patients should contact their healthcare provider immediately if they experience chest pain, very slow heart rate, or irregular heartbeat 1

Symptom Monitoring

• Use standardized rating scales (e.g., ADHD-RS-IV) to track symptom improvement 5
• Monitor for common adverse effects: somnolence (most frequent), headache, fatigue, sedation, dizziness, irritability, upper abdominal pain, nausea, constipation (5–16%), and dry mouth 1, 5, 6
• Most somnolence-related adverse events emerge within the first 2 weeks and generally resolve by study end 5, 6

Special Monitoring Considerations

• Pregnancy: Use with caution due to limited safety data; one small study showed 20% of infants had low birth weight 1
• Elderly patients: Exercise caution due to increased susceptibility to hypotensive effects 1
• Drug interactions: Assess for CYP3A4 inhibitors/inducers and CNS depressants 1

Discontinuation Protocol

Never abruptly stop guanfacine—taper by 1 mg every 3–7 days to avoid rebound hypertension. 1

Tapering Schedule

• Reduce dose by 1 mg every 3–7 days until discontinuation is complete 1
• This tapering schedule is mandatory to prevent rebound hypertension 1
• If multiple doses are accidentally missed, do not restart at full dose without medical guidance 1

Rebound Hypertension Risk

• Although guanfacine extended-release may have less rebound hypertension than immediate-release formulations, tapering is still recommended to minimize potential withdrawal effects 2, 7
• In a study of healthy young adults, abrupt cessation of guanfacine ER up to 4 mg/day did not produce clinically significant BP elevation compared to taper-down, but clinical practice still recommends tapering 7
• The risk of rebound hypertension is lower with guanfacine than with clonidine, but tapering remains the standard of care 1

Key Clinical Considerations

Efficacy Profile

• Effect sizes for ADHD symptoms range from 0.43–0.70 compared to placebo (medium range) 1, 5
• Stimulant medications have larger effect sizes (approximately 1.0) and remain first-line treatment 1
• Guanfacine is generally positioned as second-line after stimulants due to smaller effect sizes 1, 2

Preferred First-Line Scenarios

Guanfacine may be preferred as first-line treatment when ADHD co-occurs with:

• Sleep disorders (evening dosing addresses both ADHD and insomnia) 1
• Tic disorders or Tourette syndrome 1
• Substance use risk (non-controlled medication status) 1
• Oppositional symptoms or disruptive behavior disorders 1

Combination Therapy

• Guanfacine ER and clonidine ER are the only FDA-approved medications for adjunctive use with stimulants 1
• Combination therapy allows for lower stimulant doses while maintaining efficacy 1
• Monitor for opposing cardiovascular effects when combining with stimulants (stimulants increase BP/HR, guanfacine decreases both) 1

Common Pitfalls to Avoid

• Do not expect immediate results: Counsel families that 2–4 weeks are required for therapeutic effects 1, 2
• Do not dose in the morning: Evening administration minimizes daytime sedation 1, 2
• Do not stop abruptly: Always taper to prevent rebound hypertension 1
• Do not use in children <6 years: Guanfacine is FDA-approved only for ages 6–17 years for ADHD 1