Guanfacine

Guanfacine is used to treat attention deficit hyperactivity disorder (ADHD), as part of a total treatment plan including psychological, educational, and social measures. Unlike other drugs used to treat ADHD, guanfacine is not a stimulant. The exact way that guanfacine works to treat ADHD is unknown. Guanfacine is thought to affect receptors in the parts of the brain that lead to strengthening working memory, reducing distraction, and improving attention and impulse control. Guanfacine may help lessen ADHD symptoms such as being disruptive, inattentive, hyperactive, impulsive, and arguing with adults or losing one's temper.

• Guanfacine is also used to treat high blood pressure (hypertension) and is often given together with other blood pressure medications.
• Guanfacine is available under the following different brand names: Intuniv, and Tenex.

Dosage Forms and Strengths

Tablet (Tenex)

• 1mg
• 2mg

Tablet, extended-release (Intuniv)

• 1mg
• 2mg
• 3mg
• 4mg

Dosage Considerations – Should be Given as Follows:

Hypertension

Adult

Tenex:

• 1 mg orally at bedtime; may increase to 2 mg after 3-4 weeks
• Usual range 0.5-2 mg/day
• Do not exceed 3 mg once/day due to increased risk of adverse effects

Pediatric

Children under 12 years

• Safety and efficacy not established

Children 12 years and older

• Tenex: 1 mg orally at bedtime; may increase to 2-3 mg after 3-4 weeks
• Usual range: 0.5-2 mg/day

Attention Deficit Hyperactivity Disorder, Pediatric

Intuniv:

• Monotherapy for ADHD or adjunct to stimulants

Children under 6 years:

• Safety and efficacy not established

Children 6-18 years

• Intuniv: 1 mg/day orally initially; may adjust dose using increasing increments (not exceeding 1 mg/week)
• 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 is 0.05-0.12 mg/kg/day orally initially 
• Aged 6-12 years: Doses greater than 4 mg/day not evaluated.
• Aged 13-17 years: Doses greater than 7 mg/day not evaluated
• Adjunctive trials with psychostimulants: Doses greater than 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
• Greater than 91 kg: 5-7 mg/day

Heroin Withdrawal (Off-label)

• 0.03-1.75 mg/day orally for 5-15 days

Migraine Prophylaxis (Off-label)

• Initial: 1 mg/day; do not exceed 3 mg/day

Dosage Modifications

Extended-release tablets

• Renal impairment: Dose reduction may be necessary for patients with significant impairment of renal function
• Hepatic impairment: Dose reduction may be necessary for patients with significant impairment of hepatic function

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 recommended 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 the dose to the recommended level

Strong or moderate CYP3A4 inducers

• CYP3A4 inducers significantly reduce guanfacine plasma concentrations and eliminate 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
• Extended-release tablets
  • 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 the dose to the recommended level

Dosing Considerations

• Immediate-release and extended-release formulations are not interchangeable due to differences in bioavailability

Common side effects of guanfacine include:

• Dry mouth
• Drowsiness
• Headache
• Dizziness
• Constipation
• Fatigue
• Abdominal or stomach pain
• Low blood pressure (hypotension)
• Lack of energy
• Impotence
• Lethargy
• Irritability
• Nausea
• Decreased appetite
• Weakness
• Insomnia
• Slow heart rate
• Palpitations
• Confusion
• Depression
• Shortness of breath
• Hair loss
• Dermatitis
• Increased sweating
• Itching
• Indigestion
• Difficulty swallowing
• Slowness of movement
• Leg cramps
• Tiredness
• Weight gain

Serious side effects of guanfacine include:

• Severe dizziness
• Slow heartbeat
• Fainting
• Mental/mood changes (such as depression, hallucinations, or thoughts of suicide)

Other side effects of guanfacine include:

• Dizziness upon standing
• Exfoliation
• Rash
• Joint pain
• Muscle pain

Postmarketing side effects of guanfacine reported include:

• Cardiovascular: Slow heart rate, palpitations, fainting, fast heart rate
• CNS: Paresthesias, vertigo
• GI: Abdominal pain, constipation, diarrhea, indigestion
• Liver/biliary: Abnormal liver function tests
• Musculoskeletal: Joint pain, leg cramps, leg pain, muscle pain
• Psychiatric: Agitation, anxiety, confusion, depression, hallucinations, insomnia, nervousness
• Reproductive: Impotence
• Respiratory: Shortness of breath
• Skin: Alopecia, dermatitis, skin peeling, itching, rash
• Sensory: Blurred vision, alterations in taste
• Urinary: Increased nighttime urination, urinary frequency
• Other: Weakness, chest pain, swelling (edema), feeling unwell (malaise), tremor

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Guanfacine has no known severe interactions with other drugs.
• Serious Interactions of guanfacine include:
  • amisulpride
  • amitriptyline
  • amoxapine
  • clomipramine
  • desipramine
  • dosulepin
  • doxepin
  • imipramine
  • lofepramine
  • maprotiline
  • mianserin
  • mirtazapine
  • nortriptyline
  • protriptyline
  •  trazodone
  • trimipramine
• Guanfacine has moderate interactions with at least 127 different drugs.
• Guanfacine has mild interactions with at least 46 different drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

This medication contains guanfacine. Do not take Intuniv or Tenex if you are allergic to guanfacine or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Pregnancy, lactation

Effects of Drug Abuse

• Hypersensitivity

Short-Term Effects

• See "What Are Side Effects Associated with Using Guanfacine?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Guanfacine?"

Cautions

• Avoid abrupt withdrawal (can result in anxiety, nervousness, and rebound hypertension).
• May cause low blood pressure (hypotension), orthostasis, slow heart rate (bradycardia), and fainting (syncope), use with caution in history of cerebrovascular disease, recent heart attack (myocardial infarction [MI]), severe coronary insufficiency, or syncope.
• Chronic renal/hepatic failure.
• May cause sedation, especially at the start; avoid operating heavy machinery.
• Skin rash with exfoliation reported.
• Avoid concomitant use with other CNS depressants (e.g., alcohol) as they may potentiate central nervous system (CNS) effects.
• The risk of cardiovascular effects may increase when administered concurrently with antihypertensive medications or drugs that affect heart rate.

ADHD

• Low blood pressure (hypotension) is dose-limiting Do not substitute extended-release tablets for immediate-release guanfacine on an mg/mg basis, because 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

• Guanfacine may be acceptable for use during pregnancy. Either animal studies show no risk but human studies are not available or animal studies showed minor risks and human studies were done and showed no risk.
• It is unknown if guanfacine is excreted into breast milk; use caution if breastfeeding.