Side Effects of Guanfacine Extended Release
The most common side effects of guanfacine extended release are somnolence (sedation), headache, fatigue, dry mouth, dizziness, irritability, upper abdominal pain, and bradycardia/hypotension, with most adverse effects being mild to moderate and often resolving within the first few weeks of treatment. 1, 2
Most Frequent Adverse Effects
Neurological and Sedation-Related
- Somnolence/sedation is the most common side effect, occurring in 18.7-50.7% of patients depending on dose and study population 3, 4, 5
- Headache occurs in approximately 20-22% of patients 3, 4, 5
- Fatigue affects 11-24% of patients 3, 4, 5
- Dizziness is reported in 5-15% of patients, with higher rates at higher doses 6, 4
- Sedation-related adverse effects (somnolence, sedation, hypersomnia combined) can affect up to 62.5% of patients but typically emerge within the first 2 weeks and most resolve before treatment completion 4, 5
Gastrointestinal Effects
- Upper abdominal pain occurs in 11.8-25.3% of patients 3, 5
- Dry mouth is common, particularly at higher doses (28-54% in dose-response studies) 6
- Constipation affects 5-16% of patients, with dose-dependent increases 1, 6
- Nausea occurs in >5% of patients 4
Cardiovascular Effects
- Modest decreases in blood pressure and heart rate are common, though typically not clinically significant 1, 4
- Bradycardia and hypotension can occur, requiring monitoring during dose adjustments 1, 2
- Mean heart rate and blood pressure decrease as dose increases, then return toward baseline during maintenance and tapering phases 4
Other Common Effects
Dose-Dependent Pattern
- Side effects demonstrate clear dose-response relationships, with higher doses (3-4 mg) associated with substantially higher rates of dry mouth (54%), somnolence (39%), and constipation (15%) compared to lower doses 6
- The FDA label shows dropout rates increase dramatically with dose: 2% at 0.5 mg, 5% at 1 mg, 13% at 2 mg, and 32% at 3 mg 6
Time Course and Resolution
- Most sedation-related adverse effects emerge within the first 2 weeks of treatment and generally resolve by study end or before the taper period 4, 5
- Approximately 63.5% of sedation/somnolence events resolve prior to the taper period 5
- Evening administration is generally preferable to minimize daytime somnolence and fatigue that could interfere with school performance 2, 7
Critical Safety Warnings
Discontinuation Effects
- Guanfacine must never be abruptly discontinued—it requires tapering by 1 mg every 3-7 days to avoid rebound hypertension 1, 2
- While rebound hypertension is less common with extended-release formulations compared to immediate-release, tapering is still mandatory 7
Cardiovascular Monitoring
- Baseline blood pressure and heart rate should be obtained before initiation 2
- Cardiovascular parameters should be monitored during dose adjustments 1, 2
- Patients should contact their healthcare provider immediately if they experience chest pain, very slow heart rate, or irregular heartbeat 2
Less Common but Serious Effects
- Hallucinations and psychotic symptoms are uncommon but can occur (though this is more commonly associated with stimulants) 1
- Skin rash with exfoliation has been reported in rare cases; if rash occurs, guanfacine should be discontinued 6
- Allergic reactions and cardiac conduction abnormalities are potential concerns requiring monitoring 2
Practical Clinical Considerations
- Treatment effects are delayed, typically requiring 2-4 weeks before observing clinical benefits, unlike stimulants which work immediately 2, 7
- Most adverse effects are mild to moderate in severity and rarely lead to discontinuation when appropriately managed 4
- When used as adjunctive therapy with stimulants, the safety profile remains acceptable, with the most common adverse events being upper abdominal pain, fatigue, irritability, headache, and somnolence 3
- If multiple doses are accidentally missed, patients should not restart at full dose without medical guidance 2