Guanfacine
Guanfacine
Generic Name
Guanfacine
Brand Names
*Intuniv* for extended‑release; *Tenex* for the immediate‑release formulation) is an alpha‑2A adrenergic agonist used primarily for attention‑deficit/hyperactivity disorder (ADHD) in children and adolescents, and occasionally for hypertension and Tourette syndrome.
Mechanism
- Selective alpha‑2A agonism: preferentially stimulates presynaptic α₂A‑adrenergic receptors in the prefrontal cortex, reducing norepinephrine release.
- Neurotransmitter modulation: ↓ sympathetic tone → ↓ hyperactivity and impulsivity; ↑ working‑memory capacity via frontal‑cortical disinhibition.
- Peripheral effects: vasoconstriction of arteriolar smooth muscle → ↓ mean arterial pressure.
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Pharmacokinetics
| Parameter | Data (adult, oral) |
| Absorption | Rapid; peak plasma concentration (Cₘₐₓ) at ~2–3 h (IR) or ~4–5 h (ER). Oral bioavailability ~70 %. |
| Distribution | Plasma protein binding ~30 %; total volume of distribution ~2.9 L/kg. |
| Metabolism | Hepatic via CYP2D6 and CYP3A4 to inactive metabolites (glucuronides). |
| Elimination | Renal excretion of metabolites and unchanged drug; half‑life 18–20 h (IR) or 19–20 h (ER). |
| Drug interactions | Strong CYP2D6 and CYP3A4 inhibitors (e.g., ketoconazole) ↑ plasma levels; CYP3A4 inducers (e.g., rifampin) ↓ levels. |
> Note: Pediatric dosing often starts at a lower nominal dose due to altered metabolism and greater sensitivity.
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Indications
| Indication | Recommended Use |
| ADHD (children 6–17 y) | Extended‑release formulation, 0.5–4 mg once daily. |
| Tourette syndrome | Adjunctive therapy (≤ 4 mg daily). |
| Hypertension (rare) | Off‑label; short‑acting formulations used for refractory cases. |
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Contraindications
- Contraindications
- Hypersensitivity to guanfacine or excipients.
- Severe bradycardia or conduction abnormalities (e.g., first‑degree AV block).
- Concurrent use of strong CYP2D6 inhibitors (see interaction).
- Warnings
- Cardiovascular: may cause bradycardia, hypotension, orthostatic dizziness.
- CNS: somnolence, fatigue; rare paradoxical agitation.
- Pregnancy: Category C; limited data; risk–benefit assessment needed.
- Concurrent stimulant therapy: may attenuate stimulant‑induced hypertension.
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Dosing
| Formulation | Starting Dose | Titration | Target Dose (Adults) | Adults (Children 6–12 y) | Children (12–17 y) |
| ER (Intuniv®) | 0.5 mg daily | ↑0.5 mg every 1–2 weeks ‑ max 4.0 mg | 1–4 mg | 0.1 mg/kg (max 2 mg) | 0.5 mg |
| IR (Tenex®) | 0.1–0.2 mg twice daily | ↑0.1 mg increments daily | 0.3–3.0 mg/day | 0.007–0.014 mg/kg twice daily | 0.2 mg |
• Administration guidelines
• Take with or after a meal; food does not significantly alter absorption.
• Avoid alcohol and other CNS depressants during titration.
• Taper slowly (¼–½ dose decrement) if discontinuing to prevent rebound hypertension or withdrawal symptoms.
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Adverse Effects
- Common (≥10 % incidence)
- Somnolence, fatigue
- Dry mouth, constipation
- Irritability, mild nausea
- Mild orthostatic hypotension
- Serious (≤1 % incidence)
- Severe bradycardia, hypotension (requires stopping drug)
- Syncope or loss of consciousness
- Acute cardiac events (rare)
- Severe allergic reactions (anaphylaxis)
> Monitoring tip: Watch for paradoxical increases in blood pressure or heart rate when initiating concomitant stimulants.
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Monitoring
| Parameter | Frequency | Rationale |
| Blood pressure & heart rate | Baseline, 1‑2 weeks, 4‑6 weeks, or whenever symptomatic | Detect bradycardia/hypotension |
| Weight, height (children) | Every visit | Growth impact surveillance |
| Efficacy metrics | ADHD rating scales (e.g., Vanderbilt, Conners) | Dose adequacy |
| Laboratory | None required routinely | However, for high doses > 2 mg: consider hepatic panels in CYP450‑altered patients |
| Pregnancy test | In female patients of childbearing potential | Category C evidence |
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Clinical Pearls
- Alpha‑2A selectivity ➜ fewer CNS side effects compared with non‑selective adrenergic agonists (e.g., clonidine).
- ER formulation offers once‑daily dosing, improving adherence in school settings.
- When combined with methylphenidate, guanfacine mitigates stimulant‑induced tachycardia without blunting therapeutic benefit.
- Dose titration is slow (≈ 0.5 mg every 1–2 weeks) to avoid abrupt BP/HR changes.
- In patients with seizure disorders, a gradual taper reduces risk of rebound hypertension that can precipitate seizures.
- Pregnancy safety: limited human data; animal studies show no teratogenicity but still counsel against use if alternatives exist.
- Children < 6 yrs: still under investigation; use with extreme caution.
- Use in the elderly: start at lowest dose; monitor for orthostatic hypotension.
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• Key Take‑away: Guanfacine is an α₂A agonist that enhances prefrontal cortical function in ADHD while exerting antihypertensive effects. Its once‑daily extended‑release regimen improves adherence, and careful BP/HR monitoring ensures safety, especially when co‑prescribed with stimulants or in cardiovascular‑compromised patients.