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Alpha-2A Adrenoceptor Agonist (ADHD — Non-Stimulant) Pregnancy: Avoid — limited human data. Alpha-2 agonism reduces foetal heart rate variability in animal studies. Use only if clearly necessary; discuss with obstetrician.

Guanfacine (Extended-Release)

Brand names: Intuniv

Adult dose

Dose: 1–7 mg once daily (adults). Titrate by 1 mg/week based on response and tolerability
Route: Oral (extended-release)
Frequency: Once daily (same time each day — evening preferred to reduce daytime sedation)
Max: 7 mg/day (adults); 4 mg/day (children 6–12 years)
ADHD as monotherapy or adjunct to stimulants. Intuniv XR formulation — do NOT crush, chew, or divide tablet (destroys extended-release matrix). Start 1 mg, increase by 1 mg/week. Avoid taking with high-fat meal (increases guanfacine AUC 75%). Taper when stopping — abrupt withdrawal causes rebound hypertension. Source: BNF 90; MHRA SPC Intuniv.

Paediatric dose

Dose: 6–12 years: 0.05–0.12 mg/kg/day (max 4 mg/day). 13–17 years: 1–7 mg once daily (same as adult mg/day/kg
Route: Oral (extended-release only)
Frequency: Once daily
Max: 4 mg/day (under 13 years); 7 mg/day (13–17 years)
Licensed from 6 years for ADHD. Weight-based dosing in younger children. Clinical effect typically seen at 0.08–0.12 mg/kg. Source: BNF for Children 2024; NICE NG87.

Dose adjustments

Renal

Severe renal impairment: reduce dose — increased exposure. eGFR <15 mL/min: not recommended.

Hepatic

Severe hepatic impairment: reduce dose — increased exposure due to reduced clearance.

Paediatric weight-based calculator

Licensed from 6 years for ADHD. Weight-based dosing in younger children. Clinical effect typically seen at 0.08–0.12 mg/kg. Source: BNF for Children 2024; NICE NG87.

Clinical pearls

  • Non-stimulant ADHD option — key indication: guanfacine is used when stimulants (methylphenidate, lisdexamfetamine) are contraindicated, ineffective, or not tolerated, or when ADHD is comorbid with tics (stimulants worsen tics), anxiety (stimulants may worsen), or in children with significant appetite suppression on stimulants. NICE NG87 recommends guanfacine as second-line after methylphenidate and atomoxetine.
  • Mechanism in ADHD: alpha-2A agonism in prefrontal cortex (PFC) strengthens PFC neural network connectivity. The PFC regulates attention, working memory, and impulse control — function which is impaired in ADHD. Guanfacine enhances PFC function without increasing catecholamine levels systemically (unlike stimulants). Effect is on cognitive function — not euphoriant — explains low abuse potential.
  • Rebound hypertension on withdrawal: abrupt discontinuation of guanfacine causes rebound catecholamine release — hypertensive crisis has been reported. Always taper over at least 1–2 weeks. If patient misses doses, monitor BP. Counsel parents/carers not to suddenly stop in children.
  • Comorbid tic disorder advantage: stimulants can exacerbate tics in ADHD+Tourette syndrome. Guanfacine improves both ADHD symptoms and tic severity — preferred in this comorbid condition. Combined ADHD-tic studies show 35–40% reduction in tic severity alongside ADHD benefit.
  • BP and HR monitoring protocol: check pulse and sitting/standing BP at baseline, 2–4 weeks after each dose change, and 3-monthly when stable. If HR <50 bpm or symptomatic hypotension — dose reduce. If syncope — stop and reassess. Source: BNF 90; BNF for Children 2024; NICE NG87; Sallee et al. Am J Psychiatry 2009 (ADHD trials).

Contraindications

  • Hypersensitivity to guanfacine
  • Symptomatic bradycardia or AV block (alpha-2 agonism reduces heart rate)
  • Hypotension
  • Do not use immediate-release guanfacine formulation — different PK profile and not licensed for ADHD

Side effects

  • Somnolence and fatigue (most common — peak during first 2–4 weeks; usually resolves; take in evening to reduce daytime drowsiness)
  • Hypotension (orthostatic — alpha-2 vasodilation; check standing BP)
  • Bradycardia (alpha-2 agonism reduces sympathetic tone at SA node — monitor HR)
  • Dry mouth, constipation (alpha-2 GI effects)
  • Mood changes, irritability (especially in children — monitor)
  • Rebound hypertension on abrupt withdrawal (taper over ≥1 week)

Interactions

  • Strong CYP3A4 inhibitors (clarithromycin, itraconazole, ketoconazole): increase guanfacine AUC up to 4-fold — reduce guanfacine dose by 50%
  • Strong CYP3A4 inducers (rifampicin, carbamazepine): reduce guanfacine levels — avoid or increase dose
  • Antihypertensives: additive hypotension and bradycardia — monitor BP and HR
  • CNS depressants (alcohol, benzodiazepines, opioids): additive sedation — advise patients
  • High-fat meals: increase guanfacine absorption 75% — take consistently with or without food, not with high-fat meal

Monitoring

  • Blood pressure and heart rate (sitting and standing) at baseline, 2–4 weeks after dose changes, then 3-monthly
  • ADHD symptom rating scales (SNAP-IV, Conners) at 4 weeks, 3 months, then 6-monthly
  • Weight and height (growth monitoring in children — less growth suppression than stimulants)
  • Mood and sleep quality
  • Rebound symptoms if dose missed (monitor BP)

Reference: BNFc; BNF 90; BNF for Children 2024; NICE NG87 (ADHD); Sallee et al. Am J Psychiatry 2009; MHRA SPC Intuniv. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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