What are the considerations and dosing guidelines for Tenex (guanfacine) in patients with Attention Deficit Hyperactivity Disorder (ADHD) or hypertension?

Guanfacine (Tenex) Dosing and Considerations for ADHD and Hypertension

Extended-release guanfacine is an effective non-stimulant medication for ADHD with a medium effect size (0.7), while immediate-release guanfacine is primarily used for hypertension treatment with dosing typically starting at 1 mg daily at bedtime. 1, 2

Mechanism of Action

• Guanfacine is an alpha-2A adrenergic receptor agonist that enhances noradrenergic neurotransmission 1
• For hypertension, it works by activating central nervous system alpha-adrenoreceptors, reducing sympathetic outflow and vascular tone 3

Dosing Guidelines for ADHD

Extended-Release Guanfacine (Intuniv)

• Available in tablet form with doses of 1,2,3, and 4 mg 1
• Dosing should be weight-based with once-daily administration (approximately 0.1 mg/kg as a general rule) 1
• FDA-approved for ADHD treatment in children and adolescents 1
• Can be used as monotherapy or as adjunctive therapy with stimulant medications 1
• Treatment effects typically observed after 2-4 weeks (unlike stimulants which work more rapidly) 1

Immediate-Release Guanfacine (Tenex) for ADHD

• Often used off-label for ADHD treatment 4
• Dosing must be more frequent than the extended-release formulation
• Less commonly used for ADHD than the extended-release formulation due to need for multiple daily dosing 4

Dosing Guidelines for Hypertension

Immediate-Release Guanfacine (Tenex)

• Initial dose: 1 mg daily given at bedtime to minimize somnolence 2
• If inadequate response after 3-4 weeks, dose may be increased to 2 mg 2
• Most therapeutic effect is seen at 1 mg 2
• Higher doses (above 3 mg/day) significantly increase adverse reactions 2
• Can be used as monotherapy or in combination with other antihypertensive medications 2

Cardiovascular Monitoring

• Guanfacine may decrease heart rate and blood pressure 1
• Obtain personal and family cardiac history before initiating therapy 1
• Consider performing ECG and possible referral to a pediatric cardiologist if cardiac risk factors are present 1
• Monitor vital signs regularly during treatment 1

Common Adverse Effects

• Somnolence/sedation (most common) - occurs in up to 38.6% of patients 5
• Fatigue (15.2%) 5
• Headache (20.5%) 5
• Dry mouth 1
• Dizziness 1
• Irritability 1
• Hypotension 1
• Abdominal pain 1

Special Considerations

Pregnancy and Breastfeeding

• Limited data on guanfacine use during pregnancy 1
• One small study (n=30) using guanfacine for hypertension in preeclampsia showed no congenital malformations, though 20% of infants had low birth weight 1
• No published studies on guanfacine use while breastfeeding 1
• Alternative agents would be preferred during pregnancy and breastfeeding due to limited safety data 1

Discontinuation

• Rebound hypertension can occur after abrupt discontinuation 1
• Always taper guanfacine gradually rather than stopping suddenly 1
• In extended-release formulations, studies suggest abrupt cessation may be better tolerated than with immediate-release formulations, though tapering is still recommended 6

Comparative Efficacy

• Non-stimulants like guanfacine have medium effect sizes (approximately 0.7) compared to stimulants (approximately 1.0) 1
• Guanfacine is generally considered second-line therapy after stimulants for ADHD 1
• Meta-analysis shows guanfacine is significantly more effective than placebo for ADHD treatment (RR 1.78,95% CI: 1.59-2.01) 5

Advantages of Guanfacine

• "Around-the-clock" effects unlike stimulants which may wear off 1
• Not a controlled substance 1
• May be preferred first-line in patients with comorbid substance use disorders, disruptive behavior disorders, tic disorders, or sleep disorders 1
• Can be used as adjunctive therapy with stimulants when stimulant monotherapy is insufficient 1
• Evening administration may be preferable due to sedative effects 1

Clinical Pearls

• For hypertension treatment, tolerance may develop after 3-4 months, requiring dose adjustment or addition of a diuretic 7
• Once-daily dosing (for extended-release) improves medication adherence 1
• When used for ADHD, evening administration is generally preferred due to sedative effects 1
• Avoid use with CYP3A4 inhibitors which can increase guanfacine levels 1
• Caution in patients with history of bradycardia, heart block, or cardiovascular disease 1