How can I safely switch an adult patient tolerating guanfacine extended‑release 1 mg for hypertension or ADHD, with normal renal and hepatic function, to clonidine extended‑release 1 mg?

Switching from Guanfacine ER 1 mg to Clonidine ER 1 mg

You can directly switch from guanfacine extended-release 1 mg to clonidine extended-release 1 mg without cross-tapering, starting clonidine the day after stopping guanfacine, because both medications work through the same alpha-2A adrenergic receptor mechanism and guanfacine carries a lower risk of rebound hypertension compared to clonidine. 1, 2

Switching Protocol

Step 1: Discontinue Guanfacine

• Stop guanfacine ER 1 mg abruptly without tapering at this low dose, as the FDA label and clinical trials demonstrate that guanfacine can be discontinued without significant rebound hypertension, particularly at doses ≤1 mg. 3, 4
• Guanfacine exhibits a more gradual return to baseline blood pressure upon discontinuation compared to clonidine's rapid rebound, with only occasional values exceeding baseline. 3
• The elimination half-life of guanfacine averages 17 hours (range 10-30 hours), meaning the drug will clear over 3-5 days. 3

Step 2: Initiate Clonidine ER

• Start clonidine ER 0.1 mg once daily at bedtime the day after stopping guanfacine, not the full 1 mg dose initially. 5, 6
• The ACC/AHA guidelines recommend starting clonidine at 0.1 mg with gradual titration to avoid excessive hypotension and bradycardia. 5
• Titrate clonidine ER by 0.1 mg every 3-7 days based on blood pressure response and tolerability, up to the target dose of 1 mg daily (divided into twice-daily dosing if needed for ADHD, or once-daily for hypertension). 1, 6

Step 3: Cardiovascular Monitoring

• Measure blood pressure and heart rate at baseline (before stopping guanfacine), then 3-5 days after the switch, and at each clonidine dose adjustment. 1, 6
• Monitor for bradycardia (heart rate <60 bpm) and hypotension (systolic BP <90 mmHg), which occur more frequently with clonidine (17.5% bradycardia rate) than guanfacine. 6
• Clonidine causes greater reductions in blood pressure and heart rate than guanfacine at equivalent doses due to lower alpha-2A receptor selectivity. 2, 7

Critical Safety Considerations

Rebound Hypertension Risk

• Clonidine carries a significantly higher risk of rebound hypertension and hypertensive crisis upon abrupt discontinuation compared to guanfacine, requiring mandatory tapering when eventually stopping clonidine. 5, 1, 3
• The ACC/AHA guidelines explicitly state that clonidine must be tapered to avoid hypertensive crisis, whereas guanfacine withdrawal produces milder, more gradual increases in blood pressure. 5, 3
• If clonidine needs to be discontinued in the future, taper by 0.1 mg every 3-7 days rather than stopping abruptly. 1, 6

Comparative Adverse Effect Profiles

• Clonidine causes significantly more sedation, dry mouth, and orthostatic hypotension than guanfacine due to its lower selectivity for alpha-2A receptors and approximately 10-fold higher potency. 2, 7, 8
• Sedation and orthostatic circulatory effects were "considerably more frequent" with clonidine than guanfacine in head-to-head trials. 8
• The ACC/AHA guidelines note that central alpha-2 agonists like clonidine are "generally reserved as last-line because of significant CNS adverse effects, especially in older adults." 5

Common Pitfalls to Avoid

• Do not start clonidine at the full 1 mg dose—this will cause excessive hypotension and sedation. Always start at 0.1 mg and titrate gradually. 5, 6
• Do not assume dose equivalence—clonidine is approximately 10 times more potent than guanfacine, so 1 mg guanfacine does not equal 1 mg clonidine. 2
• Do not abruptly discontinue clonidine in the future without a proper taper, as this carries serious risk of hypertensive crisis that exceeds the risk seen with guanfacine. 5, 1, 3
• Counsel patients that clonidine will cause more sedation than guanfacine, particularly during the first 2-4 weeks, and consider evening dosing to minimize daytime impairment. 1, 2, 8

Indication-Specific Considerations

For Hypertension

• Clonidine 0.1-0.8 mg daily (divided into twice-daily dosing) is the typical range for blood pressure control. 5
• Both medications reduce blood pressure comparably, but guanfacine has a more favorable tolerability profile with once-daily dosing. 7, 8

For ADHD

• Clonidine ER requires twice-daily dosing for optimal ADHD symptom control, unlike guanfacine ER which provides true once-daily coverage. 1, 2
• Both medications have similar effect sizes (approximately 0.7) for ADHD symptoms, but clonidine's greater sedation may limit tolerability. 1, 6
• Therapeutic effects of clonidine appear more rapidly than guanfacine, which requires 2-4 weeks for full benefit. 1, 2