What are the dosing guidelines for immediate‑release guanfacine for hypertension and extended‑release guanfacine for ADHD?

Guanfacine Dosing Guidelines

For ADHD, start guanfacine extended-release at 1 mg once daily (preferably in the evening), titrate by 1 mg weekly based on response and tolerability, targeting a weight-adjusted dose of 0.05-0.12 mg/kg/day with a maximum of 4-7 mg/day. 1

Extended-Release Guanfacine for ADHD

Starting Dose and Titration Schedule

• Begin with 1 mg once daily, administered in the evening to minimize daytime somnolence 1, 2
• Increase by 1 mg per week based on clinical response and tolerability 1
• Target dose range: 0.05-0.12 mg/kg/day or 1-7 mg/day absolute maximum 1
• Weight-adjusted doses >0.08 mg/kg but ≤0.12 mg/kg may provide additional clinical benefits if tolerated 3

Timing of Administration

• Evening administration is strongly preferred due to the high frequency of somnolence and fatigue as adverse effects 1, 2
• Morning administration is equally effective if evening dosing causes issues, as demonstrated in randomized trials showing equivalent efficacy regardless of timing 2
• Once-daily dosing provides "around-the-clock" symptom control lasting approximately 24 hours 1

Critical Dosing Considerations

• Therapeutic effects require 2-4 weeks to become apparent, unlike stimulants which work immediately 1, 4
• Extended-release formulation is not substitutable on a mg-for-mg basis with immediate-release guanfacine due to different pharmacokinetics 5
• Doses of 1-4 mg/day are FDA-approved for children and adolescents aged 6-17 years 5, 2

Immediate-Release Guanfacine for Hypertension

Adult Hypertension Dosing

• Starting dose: 1 mg once daily at bedtime 1
• Titrate gradually based on blood pressure response
• Maximum dose: typically 3 mg/day for hypertension (lower than ADHD dosing)

Important caveat: Central alpha-2 agonists like guanfacine are generally reserved as last-line antihypertensive therapy due to significant CNS adverse effects, particularly in older adults 6

Essential Monitoring Requirements

Cardiovascular Monitoring

• Obtain baseline blood pressure and heart rate before initiating treatment 1
• Monitor vital signs at each dose adjustment and periodically during maintenance therapy 1
• Expect modest decreases: 1-4 mmHg in blood pressure and 1-2 bpm in heart rate 1
• Screen for personal or family history of cardiac conditions including Wolf-Parkinson-White syndrome, sudden death, hypertrophic cardiomyopathy, and long QT syndrome 1

Symptom Monitoring

• Systematically assess ADHD symptoms at each dose adjustment using parent and teacher reports 1
• Monitor for common adverse effects: somnolence (44%), headache (20.5%), fatigue (15.2%), dry mouth, dizziness, and constipation (5-16%) 1, 2

Critical Safety Warnings

Discontinuation Protocol

• Never abruptly discontinue guanfacine—must be tapered to avoid rebound hypertension 1, 4
• Taper by 1 mg every 3-7 days when discontinuing treatment 1, 6
• Abrupt cessation can cause hypertensive crisis, particularly with higher doses 7

Contraindications and Precautions

• Avoid in patients with baseline bradycardia (heart rate <60 bpm) or hypotension (systolic BP <90 mmHg) 1
• Use with caution in patients with cardiovascular disease, autonomic dysfunction, or orthostatic hypotension 1
• Exercise caution with CNS depressants (benzodiazepines, alcohol, phenothiazines) due to additive sedative effects 1
• CYP3A4 inhibitors/inducers may require dose adjustments 1

Special Clinical Scenarios

Adjunctive Therapy with Stimulants

• Guanfacine extended-release is FDA-approved for adjunctive use with stimulants 1
• This combination allows for lower stimulant dosages while maintaining efficacy and potentially reducing stimulant-related adverse effects 1
• Monitor for opposing cardiovascular effects: stimulants increase blood pressure/heart rate while guanfacine decreases both 1

Preferred First-Line Scenarios

While stimulants remain first-line for ADHD due to superior effect sizes (1.0 vs 0.7 for guanfacine), guanfacine should be strongly preferred as initial treatment when ADHD co-occurs with: 1

• Sleep disturbances or insomnia
• Tic disorders
• Substance use risk (non-controlled medication status)
• Stimulant intolerance or contraindications

Pediatric Weight-Based Considerations

• Children exhibit higher plasma concentrations than adolescents at equivalent doses due to lower body weight 8
• For adolescents weighing >70 kg, doses may need to exceed 4 mg/day to achieve target weight-adjusted dosing of 0.12 mg/kg 3
• The 0.1 mg/kg rule of thumb provides a practical starting point for dose estimation 4

Common Pitfalls to Avoid

• Do not expect immediate results—counsel families that 2-4 weeks are required for therapeutic effects 1
• Do not combine guanfacine with clonidine—both work through the same alpha-2A mechanism and combination increases sedation and cardiovascular risks without evidence of superior efficacy 6
• Do not crush or split extended-release tablets—discuss with pharmacy about appropriate liquid formulations if needed 1
• Do not restart at full dose after missing multiple doses—contact healthcare provider for guidance on safe resumption 1