Dosing and uses of Intuniv, Tenex (guanfacine)
Adult dosage forms and strengths
tablet (Tenex)
- 1mg
- 2mg
Hypertension
Tenex: 1 mg PO qHS; may increase to 2 mg after 3-4 weeks
Usual range 0.5-2 mg/day
Do not exceed 3 mg qDay due to increased risk of adverse effects
Heroin Withdrawal (Off-label)
0.03-1.75 mg/day PO for 5-15 days
Migraine Prophylaxis (Off-label)
Initial: 1 mg/day; do not exceed 3 mg/day
Fragile X Syndrome (Orphan)
Orphan sponsor
- Watson Laboratories, Inc; 311 Bonnie Circle, PO Box 1900; Corona, CA 91718-1900
Dosage modifications
Strong or moderate CYP3A4 inhibitors
- Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations
- FDA-labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the reommended dose; specific recommendations for immediate-release (IR) guanfacine are not available
- Starting therapy while currently taking CYP3A4 inhibitor: Decrease dose to half the recommended level
- Continuing therapy while adding CYP3A4 inhibitor: Decrease dose to half the recommended level
- Continuing therapy while stopping CYP3A4 inhibitor: Increase dose to recommended level
Strong or moderate CYP3A4 inducers
- CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life
- If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response
- For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered
- Starting therapy while currently taking CYP3A4 inducer: Increase dose up to double the recommended level
- Continuing therapy while adding CYP3A4 inducer: Increase dose up to double the recommended level over 1-2 weeks
- Continuing therapy while stopping CYP3A4 inducer: Increase dose to recommended level
Pediatric dosage forms and strengths
tablet (Tenex)
- 1mg
- 2mg
tablet, extended-release (Intuniv)
- 1mg
- 2mg
- 3mg
- 4mg
Hypertension
<12 years
- Safety and efficacy not established
≥12 years
- Tenex: 1 mg PO qHS; may increase to 2-3 mg after 3-4 weeks
- Usual range: 0.5-2 mg/day
Attention Deficit Hyperactivity Disorder
Intuniv: Monotherapy for ADHD or adjunct to stimulants
<6 years: Safety and efficacy not established
6-18 years
- Intuniv: 1 mg/day PO initially; may adjust dose using increasing increments (not exceeding 1 mg/wk)
- Take once daily, either in the morning or evening, at approximately the same time each day
- To balance the exposure-related potential benefits and risks, the recommended target dose range depending on clinical response and tolerability is0.05-0.12 mg/kg/day PO initially
- Aged 6-12 years: Doses >4 mg/day not evaluated
- Aged 13-17 years: Doses >7 mg/day not evaluated
- Adjunctive trials with psychostimulants: Doses >4 mg/day not evaluated
Target dose range by weight
- 25-33.9 kg: 2-3 mg/day
- 34-41.4 kg: 2-4 mg/day
- 41.5-49.4 kg: 3-5 mg/day
- 49.5-58.4 kg: 3-6 mg/day
- 58.5-91 kg: 4-7 mg/day
- >91 kg: 5-7 mg/day
Dosage modifications
Strong or moderate CYP3A4 inhibitors
- Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations
- FDA-labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the reommended dose; specific recommendations for immediate-release (IR) guanfacine are not available
- Starting therapy while currently taking CYP3A4 inhibitor: Decrease dose to half the recommended level
- Continuing therapy while adding CYP3A4 inhibitor: Decrease dose to half the recommended level
- Continuing therapy while stopping CYP3A4 inhibitor: Increase dose to recommended level
Strong or moderate CYP3A4 inducers
- CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life
- If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response
- For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered
- Starting therapy while currently taking CYP3A4 inducer: Increase dose up to double the recommended level
- Continuing therapy while adding CYP3A4 inducer: Increase dose up to double the recommended level over 1-2 weeks
- Continuing therapy while stopping CYP3A4 inducer: Increase dose to recommended level
Dosing Considerations
Immediate-release and extended-release formulations are not interchangeable due to differences in bioavailability
Tourette Syndrome (Orphan)
Orphan designation for combination of guanfacine and amphetamine to treatment Tourette syndrome
Sponsor
- Genco Sciences, LLC; 1011 Greenwood Avenue; Willmette, Illinois 60091
Intuniv, Tenex (guanfacine) adverse (side) effects
>10%
Xerostomia (10-60%)
Somnolence (5-39%)
Headache (0.2-26%)
Dizziness (2-15%)
Constipation (2-16%)
Fatigue (2-15%)
Abdominal pain (11%)
1-10%
Hypotension (7%)
Asthenia (2-7%)
Impotence (0-7%)
Lethargy (6%)
Dizziness (6%)
Irritability (6%)
Nausea (3-6%)
Decreased appetite (5%)
Weakness (1-5%)
Insomnia (3-4%)
Bradycardia (3%)
Palpitations (3%)
Confusion (3%)
Depression (3%)
Dyspnea (3%)
Alopecia (3%)
Dermatitis (3%)
Diaphoresis (3%)
Pruritus (3%)
Dyspepsia (3%)
Dysphagia (3%)
Hypokinesia (3%)
Leg cramps (3%)
Frequency not defined
Orthostatic hypotension
Exfoliation
Rash
Arthralgia
Myalgia
Postmarketing Reports
Cardiovascular: Bradycardia, palpitations, syncope, tachycardia
CNS: Paresthesias, vertigo
GI: Abdominal pain, constipation, diarrhea, dyspepsia
Liver/biliary: Abnormal LFTs
Musculoskeletal: Arthralgia, leg cramps, leg pain, myalgia
Psychiatric: Agitation, anxiety, confusion, depression, hallucinations, insomnia, nervousness
Reproductive: Impotence
Respiratory: Dyspnea
Skin: Alopecia, dermatitis, exfoliative dermatitis, pruritus, rash
Sensory: Blurred vision, alterations in taste
Urinary: Nocturia, urinary frequency
Other: Asthenia, chest pain, edema, malaise, tremor
Warnings
Contraindications
Hypersensitivity
Cautions
Avoid abrupt withdrawal (can result in anxiety, nervousness, and rebound hypertension)
May cause hypotension, orthostasis, bradycardia, and syncope, use with caution in history of cerebrovascular disease, recent MI, severe coronary insufficiency, or syncope
Chronic renal/hepatic failure
May cause sedation, especially at start; avoid operating heavy machinery
Skin rash with exfoliation reported
Avoid concomitant use with other CNS depressants (eg, alcohol) as they may potentiate CNS effects
Risk of cardiovascular effects may increase when administered concurrently with antihypertensive medications or drugs that affect heart rate
ADHd
- Hypotension is dose-limiting
- Do not substitute extended-release tablet for immediate-release guanfacine on a mg/mg basis, because of differing pharmacokinetic profiles
- May cause dose-dependent hypotension, bradycardia, and syncope
- Hallucinations reported in children with ADHD treated with guanfacine
Geriatric patients
- May cause adverse CNS effects
- May cause bradycardia and orthostatic hypotension
- Not recommended as routine treatment for hypertension (Beers criteria)
Pregnancy and lactation
Pregnancy category: B
Lactation: Unknown if excreted into breast milk; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Intuniv, Tenex (guanfacine)
Mechanism of action
Selective alpha2-adrenergic receptor agonist causing decreased sympathetic outflow and subsequent decrease in vasomotor tone and heart rate; may preferentially bind postsynaptic alpha2A adrenoreceptors in the prefrontal cortex, which may improve delay-related firing of prefrontal cortex neurons (as a result, behavioral inhibition may be affected); mechanism of action in ADHD is not known
Absorption
Bioavailability: Immediate-release (80-100%); extended-release (58%)
Onset: Initial effect (2 hr); maximum effect (6 hr)
Duration: 24 hr
Peak plasma time: Immediate release (1-4 hr); extended release (4-8 hr)
Distribution
Protein bound: 70%
Vd: 6.3 L/kg
Metabolism
Via CYP3A4 (hepatic)
Metabolites: Glucuronide and sulfate of 3-hydroxy guanfacine, oxidized mercapturic acid derivatives (inactive)
Elimination
Half-life: Immediate release (17 hr); extended release (16 hr)
Dialyzable: HD (No)
Excretion: Urine 80% (unchanged)
Administration
ADHD (extended-release tablet [Intuniv])
Do not administer with high-fat meals due to potential for increased serum levels
Swallow tablets whole; do not crush, chew, or break tablets because this will increase the rate of guanfacine release
If extended-release dose missed, repeat dosage titration based on patient tolerability
Discontinuing: Taper by decrements not exceeding 1 mg q3-7Days to avoid rebound hypertension
Switching from immediate-release tablet
Discontinue immediate-release tablet and titrate with extended-release tablet as described above
Do not substitute for immediate-release guanfacine tablets on a mg-per-mg basis, because of differing pharmacokinetic profiles
Intuniv has significantly reduced peak plasma levels (60% lower), bioavailability (43% lower), and a delayed time to peak levels (3 hr later) compared to those of the same dose of immediate-release guanfacine
