guanfacine

Guanfacine is a medication that belongs to the drug class alpha2 adrenergic agents, used to treathigh blood pressure(hypertension) in adults and children, andattention deficit hyperactivity disorder(ADHD) in children. Guanfacine works on the central nervous system to reducehypertension, and in the treatment ofADHD, it helps reduce impulsive, irritable and hyperactive behaviors and improves concentration and working memory.

Guanfacine stimulates protein molecules known as alpha2 adrenergic receptors in the nerve cells of the sympathetic nervous system, which regulatesheartrate,官网地址bwin, respiratory rate and pupil size. Stimulation of alpha2 receptors decreases the sympathetic nervous system activity, which results in the lowering of blood pressure and slowing down of the heart rate.

The exact mechanism of guanfacine in ADHD is not clear. Guanfacine’s effects on the alpha2 receptors in the central nervous system may produce calming effects, reducing inattentive, hyperactive and impulsive behaviors.

The uses of guanfacine include:

Adult:

FDA-approved:

• Hypertension

Off-label:

• Heroinwithdrawal
• Migraineprophylaxis

Orphan designation:

• Fragile X syndrome, a genetic condition that affects brain development

Pediatric:

FDA-approved:

• Hypertension
• ADHD

Orphan designation:

• Tourette’s syndrome, a nervous system disorder that causesticsand involuntary sounds

• Do not use in patients who are hypersensitive to guanfacine or any of its components
• Measure heart rate and blood pressure before starting guanfacine therapy and continue monitoring periodically, especially following dose increases
• Guanfacine can causelow blood pressure(hypotension), slow heart rate (bradycardia),hypotensionfrom position change (orthostatic) andfainting(syncope); use with caution in patients with a history ofhypotension,heart block心动过缓,cardiovascular diseaseand syncope
• Use with caution in patients treated simultaneously with antihypertensives or otherdrugsthat can reduce blood pressure or heart rate or increase the risk of syncope
• Guanfacine can cause sedation and drowsiness; concurrent use with other central nervous system (CNS) depressants such asbarbiturates,benzodiazepinesoralcoholcan have an additive effect; use with caution
• Guanfacine can impair mental and physical abilities; caution patients to avoid hazardous activities
• Use guanfacine with caution in patients with cerebrovascular disease and impairedliveror kidney function
• Guanfacine is not recommended as routine treatment of hypertension in geriatric patients
• Hallucinationshave been reported inchildren with ADHDtreated with guanfacine
• Do not substitute extended-release tablet for immediate-release guanfacine on an mg/mg basis, because of differing pharmacokinetic profiles
• Avoid abrupt discontinuation of guanfacine; can cause rebound hypertension,anxietyand nervousness

Common side effects of guanfacine include:

• Drowsiness (somnolence)
• Headache
• Fatigue
• Dizziness
• Sleeplessness(insomnia)
• Abdominal pain
• Dry mouth(xerostomia)
• Constipation
• Decreased appetite

Less common side effects of guanfacine include:

• Nausea
• Vomiting
• Diarrhea
• Abdominal discomfort
• Indigestion(dyspepsia)
• Weight gain
• Low blood pressure(hypotension)
• Slow heart rate (bradycardia)
• Fainting(syncope)
• Atrioventricular (AV) block
• 心律不齐(窦arrhythmia)
• Rapid heart rate (tachycardia)
• Blood pressure drop when standing from sitting or lying down (orthostatic hypertension)
• Increase in blood pressure
• High blood pressure(hypertension)
• Chest pain
• Irritability
• Lethargy
• Anxiety
• Agitation
• Mood swings(emotional lability)
• Depression
• Nightmares
• Loss of consciousness(children)
• Weakness(asthenia)
• Fever
• Asthma
• Urinary incontinence
• Urinary frequency
• Elevated liver enzyme ALT
• Skinrash
• Itching(pruritus)
• Pallor
• Hypersensitivity reaction

Rare side effects of guanfacine include:

• Joint pain(arthralgia)
• Muscle pain(myalgia)
• Leg cramps
• Leg pain
• Feeling unwell (malaise)
• Blurred vision
• Confusion
• Hair loss(alopecia)
• Dermatitis
• Exfoliative dermatitis, a severe form of skin reaction
• Swelling (edema)
• Hallucination
• Sedation
• Tremor
• Vertigo
• Abnormal skin sensations (paresthesia)
• Taste perversion (dysgeusia)
• Shortness of breath(dyspnea)
• Erectile dysfunction
• Palpitation
• Rebound hypertension (with abrupt discontinuation)
• Hypertensiveencephalopathy(with abrupt discontinuation)

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet (Tenex)

• 1mg
• 2mg

Tablet, extended-release (Intuniv)

• 1mg
• 2mg
• 3mg
• 4mg

Adult:

Hypertension

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

Heroin Withdrawal (Off-label)

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

MigraineProphylaxis (Off-label)

• Initial: 1 mg/day; do not exceed 3 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 co-administered, 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 dose to recommended level

Strong or moderate CYP3A4 inducers

• CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life
• If co-administered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response
• 多动症患者,fda批准的标签ER guanfacine recommends that, if co-administered, 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

Discontinuation of therapy

• To minimize risk of rebound hypertension upon discontinuation, taper total daily dose in decrements of no more than 1 mg every 3 to 7 days; blood pressure and heart rate should be monitored when reducing dose or discontinuing therapy; follow patients closely for rebound hypertension if abrupt discontinuation occurs (especially with concomitant stimulant use)

Pediatric:

Hypertension

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多动Disorder

Intuniv only

Monotherapy for ADHD or adjunct tostimulants

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

Dosage Modifications

Extended-release tablets

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

Strong or moderate CYP3A4 inhibitors

• Strong or moderate CYP3A4 inhibitors (e.g.,ketoconazole) significantly increase guanfacine plasma concentrations
• 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 (e.g.,carbamazepine) significantly reduce guanfacine plasma concentrations and elimination half-life
• If co-administered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response
• 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: Decrease dose to recommended level over 1-2 weeks

Dosing Considerations

• Immediate-release and extended-release formulations are not interchangeable due to differences in bioavailability
• If switching from immediate-release guanfacine, discontinue treatment; titrate with extended-release tablets following recommended schedule

Discontinuation of extended-release guanfacine

• Following discontinuation of extended-release tablets, patients may experience increases in blood pressure and heart rate
• Monitor blood pressure and pulse when reducing dose or discontinuing treatment
• Taper daily dose in decrements of no more than 1 mg every 3-7 days to minimize the risk of rebound hypertension

• Symptoms of guanfacine overdose include lethargy, drowsiness, hypotension and bradycardia.
• 嗜睡患者应监测for development of more serious symptoms due to the possibility of delayed onset hypotension. Treatment includes gastric lavage, activated charcoal and supportive treatment.

Inform your doctor of all medications you are currently taking, who can advise you on any possibledrug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Guanfacine has no known severe interactions with other drugs.
• Serious Interactions of guanfacine include:
  • amitriptyline
  • cobicistat
  • fexinidazole
  • iobenguane I 131
  • lorlatinib
  • metoclopramide鼻内
  • mifepristone
  • mirtazapine
  • nortriptyline
  • ropeginterferon alfa 2b
• Guanfacine has moderate interactions with at least 139 different drugs.
• Guanfacine has mild interactions with at least 43 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription andover-the-countermedications you use, as well as the dosage for each, and keep a list of the information.

Check with your doctor or health care provider if you have any questions about the medication.

• Animal studies do not show any evidence of fetal harm from guanfacine use duringpregnancy, however, there are no well-controlled studies inpregnantwomen; use if clearly needed.
• Guanfacine is not recommended in the treatment of acute hypertension associated with toxemia ofpregnancy.
• It is not known if guanfacine is present inbreast milk; use with caution innursingmothers.

• Take guanfacine exactly as prescribed
• In case of overdose, seek immediate medical help or contactPoison ControlCenter.
• Keep guanfacine safely out of reach of children
• Do not drink alcohol while on treatment with guanfacine; it can have additive effects
• Inform the doctor if you are taking any other antihypertensive or central nervous system depressant medications
• Do not engage in activities such as driving or operating dangerous machinery while taking guanfacine until it is clear that the drug does not make you dizzy or drowsy