Guanfacine (Intuniv)

Pharmacokinetics of Guanfacine XR (Extended-Release)

Absorption Taking a high-fat meal was found to increase absorption considerably (Tmax = 5-6 hours, IR = 1-4 hours)
Distribution 6.3L/kg
Metabolism Hepatic, oxidation (phase I) and glucuronidation (phase II)
Elimination Excreted by both the liver and the kidney
Half-life • 13-14 hrs in children/adolescents

• 17-18 hours in adults

Guanfacine: Cytochrome P450 Metabolism

Substrate of (Metabolized by) 3A4 (3A5, 2C9, and 2C19)
Induces Does not induce any of the major CYP enzymes
Inhibits Does not inhibit any of the major CYP enzymes

Dosing for Guanfacine

Taper Taper the daily dose no more than 1 mg every 3 to 7 days to reduce the risk of rebound hypertension.
  • Guanfacine comes in oral formulation
  • Blood pressure
  • Heart rate
  • Weight
  • ECG
  • Known hypersensitivity or allergy
  • Precautions advised in those with a history of bradycardia, cardiovascular disease, heart block, hypotension, and syncope
  • QT prolonging drugs (e.g. - quetiapine, quinidine) – since guanfacine XR may cause a decrease in heart rate, concomitant use with QT prolonging drugs is not recommended
  • Beta-blockers may increase risk of rebound hypertensive effect if guanfacine XR is stopped abruptly
  • Anticonvulsants
    • Guanfacine XR may increase serum concentrations of valproic acid
    • Carbamazepine, phenobarbital and phenytoin may increase serum concentrations of guanfacine XR through CYP3A4 induction
  • CYP3A4 inducers or inhibitors (e.g. - rifampin, fluconazole, ritonavir)
    • Inducers may increase serum concentrations of guanfacine XR
    • Inhibitors may decrease serum concentrations of guanfacine XR
  • Guanfacine is associated with a minor QTc prolongation