What are the recommended starting doses, titration schedules, and maximum doses of guanfacine for adult hypertension, pediatric attention‑deficit/hyperactivity disorder, and dose adjustments for elderly or patients with hepatic or renal impairment?

Guanfacine Dosing Guidelines

Adult Hypertension

For adult hypertension, guanfacine should be initiated at 0.5–1 mg once daily at bedtime, with a maximum dose of 2 mg daily. 1

Starting Dose and Titration

• Begin with 0.5–1 mg once daily at bedtime 1
• The 1 mg bedtime dose is the lowest therapeutically effective dose when added to a diuretic, producing a 14/13 mm Hg decrease in blood pressure 2
• Titrate gradually based on blood pressure response 1
• Maximum dose: 2 mg daily 1

Important Considerations for Hypertension

• Guanfacine is generally reserved as a last-line agent for hypertension due to significant CNS adverse effects (sedation, dry mouth, orthostatic hypotension), especially in older adults 1
• Never discontinue abruptly—taper gradually to avoid rebound hypertension and potential hypertensive crisis 1
• Doses of 2–3 mg daily show no additional efficacy over 1 mg but increase side effects 2

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Pediatric ADHD (Ages 6–17 Years)

For pediatric ADHD, initiate guanfacine extended-release at 1 mg once daily in the evening, titrate by 1 mg weekly based on response and tolerability, targeting 0.05–0.12 mg/kg/day with a maximum of 7 mg daily. 3, 4

Starting Dose

• 1 mg once daily (evening administration strongly preferred) 3, 4
• FDA-approved for children and adolescents aged 6–17 years only 3
• Not approved for children under 6 years; behavioral therapy is first-line for preschool-aged children (4–5 years) 3

Titration Schedule

• Increase by 1 mg per week based on response and tolerability 3
• Target dose range: 0.05–0.12 mg/kg/day or 1–7 mg/day 3, 4
• Maximum dose: 7 mg daily (some jurisdictions specify 6 mg) 3, 4
• Weight-adjusted doses >0.08 mg/kg but ≤0.12 mg/kg may provide additional clinical benefits if tolerated 5

Timing and Onset

• Evening administration is strongly preferred to minimize daytime somnolence and fatigue, which are the most common adverse effects 3, 4
• Provides "around-the-clock" symptom control with once-daily dosing 3, 4
• Therapeutic effects require 2–4 weeks to become apparent, unlike stimulants which work immediately 3, 4

Monitoring Requirements

• Obtain baseline blood pressure and heart rate before initiation 3
• Monitor cardiovascular parameters at each dose adjustment and periodically during maintenance 3
• Expected decreases: 1–4 mm Hg in blood pressure and 1–2 bpm in heart rate 3
• Screen for personal or family history of cardiac conditions (Wolff-Parkinson-White syndrome, sudden death, hypertrophic cardiomyopathy, long QT syndrome) 3

Position in Therapy

• Second-line treatment after stimulants due to smaller effect sizes (approximately 0.7 vs 1.0 for stimulants) 3
• May be preferred as first-line when ADHD co-occurs with: sleep disorders, tic disorders, substance use risk, or when stimulants have failed or caused intolerable adverse effects 3
• FDA-approved for adjunctive therapy with stimulants, allowing lower stimulant doses while maintaining efficacy 3

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Dose Adjustments for Special Populations

Elderly Patients

• Use with extreme caution in elderly patients who are more susceptible to hypotensive effects and CNS adverse effects 1
• Central alpha-2 agonists like guanfacine are not recommended in older adults unless other antihypertensives have failed, due to risk of depression, bradycardia, and orthostatic hypotension 1
• Consider lower starting doses and slower titration 1

Hepatic Impairment

• No specific dosing adjustments are provided in the major guidelines 1
• Exercise caution and monitor closely for adverse effects 1

Renal Impairment

• No specific dosing adjustments are provided in the major guidelines for guanfacine 1
• Unlike gabapentin and pregabalin, which require dose reduction in renal insufficiency, guanfacine dosing recommendations do not specify renal adjustments 1
• Monitor blood pressure and cardiovascular parameters closely 1

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Critical Safety Warnings

Discontinuation Protocol

Guanfacine must NEVER be stopped abruptly—taper by 1 mg every 3–7 days to avoid rebound hypertension. 3, 6

• Abrupt cessation can cause marked catecholamine rise, anxiety, and potentially hypertensive crisis 6
• This applies regardless of dose, duration of treatment, or indication 6
• Tapering is required even after short-term (≈4 weeks) low-dose (1 mg) courses 6
• Although guanfacine extended-release may have less rebound hypertension than immediate-release formulations, tapering is still mandatory 4, 7

Common Adverse Effects

• Somnolence/sedation (most frequent—typically mild-to-moderate and lessens with continued treatment) 3
• Headache (20.5% of patients) and fatigue (15.2% of patients) 3
• Dry mouth, dizziness, irritability, abdominal pain 3
• Constipation (5–16%, dose-dependent) 3
• Hypotension and bradycardia (monitor during dose adjustments) 3

Serious but Rare Adverse Effects

• Hallucinations and psychotic symptoms (uncommon but can occur) 3
• Cardiac conduction abnormalities (monitor ECG if indicated) 3
• Prolonged QTc interval (reported in overdose cases) 8

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Drug Interactions

CYP3A4 Interactions

• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) may increase guanfacine levels—consider dose reduction and monitor closely 3
• CYP3A4 inducers (e.g., rifampin, phenytoin) may decrease guanfacine levels—may require dose increase 3

CNS Depressants

• Exercise caution with phenothiazines, barbiturates, benzodiazepines, alcohol due to additive sedative effects 3
• Monitor for excessive somnolence, hypotension, and bradycardia when combining with other sedating medications (e.g., trazodone) 3

Combination with Stimulants

• FDA-approved for adjunctive use with stimulants in ADHD 3
• Monitor for opposing cardiovascular effects: stimulants increase heart rate and blood pressure, while guanfacine decreases both 3
• Combination allows for lower stimulant dosages, potentially reducing stimulant-related adverse effects 3

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Practical Implementation Algorithm

For ADHD in Children/Adolescents (6–17 years):

1. Obtain baseline: blood pressure, heart rate, cardiac history screening 3
2. Start: 1 mg once daily in the evening 3
3. Titrate: increase by 1 mg weekly to target 0.05–0.12 mg/kg/day (max 7 mg) 3
4. Monitor: blood pressure and heart rate at each dose adjustment 3
5. Wait: 2–4 weeks at optimal dose before assessing full therapeutic response 3
6. Combine with behavioral interventions for optimal outcomes 3

For Adult Hypertension:

1. Start: 0.5–1 mg once daily at bedtime (preferably with a diuretic) 1, 2
2. Titrate: gradually based on blood pressure response 1
3. Maximum: 2 mg daily 1
4. Reserve as last-line due to CNS adverse effects 1

When Discontinuing:

1. Never stop abruptly 3, 6
2. Taper by 1 mg every 3–7 days 3, 6
3. Monitor blood pressure and heart rate throughout taper 6