GUANFACINE HYDROCHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Selective alpha-2A adrenergic receptor agonist, reducing sympathetic outflow from the CNS, decreasing peripheral vascular resistance and heart rate.
| Metabolism | Primarily hepatic via CYP3A4 |
| Excretion | Renal excretion accounts for approximately 80% of the dose (40-50% unchanged, remainder as metabolites); fecal elimination is about 20%. |
| Half-life | Terminal elimination half-life is 17 hours (range 10–30 hours) in healthy adults; extends to 24–36 hours in chronic kidney disease. |
| Protein binding | Approximately 70% bound to albumin. |
| Volume of Distribution | 6.3 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Immediate-release: 80–100%; extended-release: 58–60% (relative to immediate-release, due to slow absorption and first-pass metabolism). |
| Onset of Action | Immediate-release: 30–60 minutes; extended-release: 4–8 hours. |
| Duration of Action | Immediate-release: 8–12 hours; extended-release: 24 hours (once-daily dosing). |
Immediate-release: 0.5-2 mg orally once daily at bedtime, titrated from 0.5 mg/day. Extended-release (ER): 1-4 mg orally once daily at bedtime, titrated from 1 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No specific GFR-based dose adjustment required for mild to moderate impairment. For severe impairment (GFR <30 mL/min), consider reducing dose by 50% or increasing dosing interval; use with caution. |
| Liver impairment | Child-Pugh class A: no adjustment. Child-Pugh class B: reduce dose by 50%. Child-Pugh class C: reduce dose by 75% or use alternative agent; contraindicated in severe impairment. |
| Pediatric use | For ADHD: immediate-release 0.5-2 mg/day in divided doses; start 0.5 mg/day, titrate by 0.5 mg increments weekly. Extended-release: 1-4 mg once daily; start 1 mg/day. Weight-based not established; use age-based. |
| Geriatric use | Start at lowest dose (immediate-release: 0.5 mg/day; ER: 1 mg/day). Titrate slowly. Increased sensitivity to hypotensive and sedative effects; monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects Abrupt discontinuation can cause rebound hypertension and nervousness.
| Breastfeeding | Excreted into breast milk; M/P ratio approximately 1.3. Milk levels low relative to maternal dose; caution in breastfeeding infants, especially those with renal impairment or concurrent antihypertensives. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Second and third trimesters: Associated with reduced uterine blood flow and fetal bradycardia; use only if benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Common Effects | ADHD |
| Serious Effects |
["Hypersensitivity to guanfacine or any component","Use with other alpha-2 agonists","Severe bradycardia or heart block"]
| Precautions | ["Rebound hypertension with abrupt discontinuation","Sedation and dizziness","Bradycardia and heart block","QT interval prolongation","Hepatic impairment"] |
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| Monitor maternal blood pressure and heart rate. Fetal heart rate monitoring during labor if used near term. Assess for signs of neonatal hypotension or bradycardia post-delivery. |
| Fertility Effects | No known impairment of fertility in humans; animal studies show no adverse effects on mating or conception. |