What is the recommended dosage of Intuniv (guanfacine) when switching from clonidine 0.2mg twice daily (bid)?

Switching from Clonidine 0.2mg BID to Intuniv (Guanfacine Extended-Release)

When switching from clonidine 0.2mg twice daily (total 0.4mg/day) to Intuniv, start with guanfacine 1-2mg once daily at bedtime, then titrate based on response after 3-4 weeks, while tapering clonidine gradually over several days to avoid rebound hypertension. 1, 2

Direct Conversion Considerations

There is no established direct conversion ratio between clonidine and guanfacine, as they differ significantly in potency and pharmacokinetics:

• Guanfacine is approximately 5-10 times less potent than clonidine at alpha-2 receptors, meaning higher milligram doses of guanfacine are needed to achieve similar effects 1
• Guanfacine has a longer half-life (approximately 17 hours) compared to clonidine, allowing once-daily dosing and producing more gradual blood pressure changes 2
• Clonidine 0.4mg/day total dose suggests moderate symptom severity requiring careful transition 1, 3

Recommended Transition Protocol

Step 1: Initiate Guanfacine

• Start guanfacine 1mg once daily at bedtime as the initial dose, which is the FDA-recommended starting dose for most patients 2
• For patients requiring more robust control or those with higher body weight, consider starting at 2mg once daily 1
• Bedtime dosing minimizes somnolence and sedation, which are common adverse effects 1

Step 2: Taper Clonidine Gradually

• Never discontinue clonidine abruptly due to significant risk of rebound hypertension, which can occur 2-4 days after discontinuation 3, 2, 4
• Begin tapering clonidine after 2-3 days of guanfacine initiation to allow guanfacine to reach steady-state levels 2
• Reduce clonidine by 0.1mg every 2-3 days (e.g., 0.2mg BID → 0.1mg BID → 0.1mg once daily → discontinue) 3, 5
• Monitor blood pressure and heart rate twice daily during the taper period for at least 7 days after complete clonidine discontinuation 4, 5

Step 3: Titrate Guanfacine

• Wait 3-4 weeks after reaching the initial guanfacine dose before considering dose adjustments, as therapeutic effects take 2-4 weeks to fully manifest 1, 2
• If response is inadequate at 1mg, increase to 2mg once daily 2
• Most therapeutic effect occurs at 1-2mg daily; doses above 3mg/day significantly increase adverse effects without proportional benefit 2
• Maximum recommended dose is 3-4mg daily, though most patients respond adequately to lower doses 1, 2

Critical Safety Considerations

Rebound Hypertension Risk

• Clonidine withdrawal produces rapid blood pressure increases (especially systolic), typically within 2-3 days, while guanfacine withdrawal is more gradual (3-4 days) 4, 5
• 40-64% of patients experience diastolic blood pressure elevations ≥10mmHg after abrupt alpha-2 agonist discontinuation 5
• Patients on concurrent beta-blockers are at higher risk for severe withdrawal reactions and should have beta-blockers discontinued several days before clonidine tapering 3

Monitoring Parameters

• Blood pressure and heart rate at baseline and twice daily during transition period 4, 5
• Watch for hypotension, bradycardia, somnolence, and sedation, which are more common with clonidine but still occur with guanfacine 1
• Guanfacine causes less sedation and fewer orthostatic effects compared to clonidine, which may improve tolerability 1, 6

Adverse Effect Profile Differences

• Dry mouth occurs in 30% with guanfacine vs. 37% with clonidine 4
• Somnolence occurs in 21% with guanfacine vs. 35% with clonidine (statistically significant difference) 4
• Both agents cause similar rates of constipation, but guanfacine has fewer orthostatic circulatory effects 6, 4

Special Population Considerations

Elderly Patients (≥75 years)

• Start at the lower end of the dosing range (1mg) due to increased risk of orthostatic hypotension, confusion, and falls 3
• Extended monitoring period recommended given higher susceptibility to CNS adverse effects 3

Renal Impairment

• Use lower doses in renal insufficiency, as guanfacine clearance is reduced though plasma levels increase only slightly 2
• Start with 1mg and titrate cautiously in patients with significant renal dysfunction 2

Pregnancy and Breastfeeding

• Guanfacine crosses the placental barrier and is present in breast milk 3
• Monitor breastfed infants for drowsiness and hypotonia if maternal guanfacine therapy is necessary 3

Common Pitfalls to Avoid

• Do not abruptly stop clonidine when starting guanfacine—this is the most critical error and can precipitate hypertensive crisis 3, 2, 4
• Do not expect immediate therapeutic effects—guanfacine requires 2-4 weeks to reach full efficacy, unlike stimulants which work immediately 1
• Do not exceed 3mg/day without clear justification—adverse effects increase significantly above this dose with minimal additional benefit 2
• Do not use sustained-release or delayed-release formulations of other medications during the transition, as absorption may be unpredictable 1