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Pronunciation
(GWAHN fa seen)
Generic Available (U.S.)
Yes: Excludes extended release tablet
Index Terms
Brand Names: U.S.
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Tablet, immediate release: Management of hypertension
Tablet, extended release: Treatment of attention-deficit/hyperactivity disorder (ADHD) as monotherapy or adjunctive therapy to stimulants
Use: Unlabeled
Tic disorder; Tourette's syndrome
Pregnancy Risk Factor
B
Pregnancy Considerations
Animal studies indicate decreased fetal survival when administered at higher doses than recommended in humans. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the benefits justify the risk to the fetus.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to guanfacine or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Cardiovascular effects: May cause bradycardia, hypotension, orthostasis, and syncope; these effects are more pronounced during the first month of therapy.
• CNS effects: May cause sedation and drowsiness which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Dermatological effects: Skin rash with exfoliation has been reported; discontinue guanfacine and monitor patients who develop a rash.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with severe coronary insufficiency, recent MI, or a history of bradycardia, cardiovascular disease, heart block, hypotension, or syncope. Cautious use is also recommended in patients with conditions that predispose them to syncope (eg, orthostasis, dehydration).
• Cerebrovascular disease: Use with caution in patients with cerebrovascular disease.
• Hepatic impairment: Use with caution in patients with chronic hepatic impairment.
• Renal impairment: Use with caution in patients with chronic renal impairment.
Concurrent drug therapy issues:
• Antihypertensives: Concurrent use with other antihypertensive medications and/or drugs that decrease heart rate may increase the risk of cardiovascular effects (eg, bradycardia, hypotension, syncope).
• CNS depressants: Avoid concomitant use with other CNS depressants and ethanol; effects may be potentiated.
Dosage form specific issues:
• Product interchangeability: Formulations of guanfacine (immediate release versus extended release) are not interchangeable on a mg:mg basis as bioavailability varies.
Other warnings/precautions:
• Abrupt withdrawal: Abrupt discontinuation can result in nervousness, anxiety and rarely, rebound hypertension (occurs 2-4 days after withdrawal). To minimize these effects, taper the dose in decrements of ≤1 mg every 3-7 days.
• ADHD treatment: Appropriate use: Recommended to be used as part of a comprehensive treatment program for attention-deficit disorders; safety and efficacy of long-term use for the treatment of ADHD (>2 years) have not been established (Sallee, 2009).
Adverse Reactions
>10%:
Central nervous system: Somnolence (5% to 45%; dose-related), dizziness (2% to 15%; dose-related), headache (3% to 26%), fatigue (2% to 15%)
Gastrointestinal: Xerostomia (4% to 54%; dose-related), constipation (≤16%; dose-related), abdominal pain (≤11%; dose-related)
1% to 10%:
Cardiovascular: Hypotension (≤10%; dose-related), hypertension (2% to 5%), syncope (1% to 5%), AV block (<2%), bradycardia (<2%), chest pain (<2%), orthostasis (<2%), pallor (<2%), sinus arrhythmias (<2%)
Central nervous system: Insomnia (2% to 12%), fever (8%; Biederman, 2008), irritability (6%), lethargy (2% to 6%)
Gastrointestinal: Vomiting (9%), nausea (≤7%), weight gain (≤7%), appetite decreased (2% to 5%), diarrhea (2% to 5%), stomach discomfort (2% to 5%), dyspepsia (<2%)
Genitourinary: Impotence (≤7%), enuresis (<2%), urinary frequency (<2%)
Hepatic: ALT increased (<2%)
Neuromuscular & skeletal: Weakness (≤7%)
Respiratory: Asthma (<2%)
<1%, postmarketing, and/or case reports: Agitation, alopecia, amnesia, anxiety, arthralgia, blurred vision, confusion, conjunctivitis, depression, dermatitis, diaphoresis, dysphagia, dyspnea, edema, exfoliative dermatitis, hypokinesia, iritis, leg cramps/pain, libido decreased, liver function tests abnormal, malaise, myalgia, nervousness, nocturia, palpitation, paresis, paresthesia, pruritus, purpura, rash, rebound hypertension, rhinitis, seizure, tachycardia, taste perversion, tinnitus, tremor, urinary incontinence, vertigo, vision disturbance
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Antidepressants (Alpha2-Antagonist): May diminish the antihypertensive effect of Alpha2-Agonists. Management: Consider avoiding concurrent use. If these combinations cannot be avoided, monitor for decreased effects of alpha2-agonists if an alpha2-antagonist is initiated/dose increased, or increased effects if an alpha2-antagonist is discontinued/dose decreased. Risk D: Consider therapy modification
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Beta-Blockers: May enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the alpha2-agonist is abruptly withdrawn. Exceptions: Levobunolol; Metipranolol. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of GuanFACINE. Management: Consider increasing the guanfacine dose (within the labeled dosage range) when such a combination is used. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of GuanFACINE. Risk C: Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Divalproex: GuanFACINE may increase the serum concentration of Divalproex. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Iobenguane I 123: Alpha2-Agonists may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May diminish the antihypertensive effect of Alpha2-Agonists. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Tricyclic Antidepressants: May diminish the antihypertensive effect of Alpha2-Agonists. Risk D: Consider therapy modification
Valproic Acid: GuanFACINE may increase the serum concentration of Valproic Acid. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Storage
Immediate release: Store at room temperature between 20°C to 25°C (68°F to 77°F).
Extended release: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Guanfacine is a selective alpha2A-adrenoreceptor agonist which reduces sympathetic nerve impulses, resulting in reduced sympathetic outflow and a subsequent decrease in vasomotor tone and heart rate. In addition, guanfacine preferentially binds postsynaptic alpha2A-adrenoreceptors in the prefrontal cortex and has been theorized to improve delay-related firing of prefrontal cortex neurons. As a result, underlying working memory and behavioral inhibition are affected; thereby improving symptoms associated with ADHD. Guanfacine is not a CNS stimulant.
Pharmacodynamics/Kinetics
Duration: Antihypertensive effect: 24 hours following single dose
Distribution: Vd: 6.3 L/kg
Protein binding: ~70%
Metabolism: Hepatic via CYP3A4
Bioavailability:
Immediate release: ~80%
Extended release (relative to immediate-release): 58%
Half-life elimination:
Immediate release: ~17 hours (range: 10-30 hours)
Extended release: 16 hours
Time to peak, serum:
Immediate release: 2.6 hours (range: 1-4 hours)
Extended release: ~5 hours
Excretion: Urine (~50% of total dose as unchanged drug)
Dosage
Oral:
Children ≥6 years and Adolescents: ADHD, monotherapy or adjunct to stimulants: Extended release (Intuniv™): Initial: 1 mg once daily; may adjust by increments no larger than 1 mg/week as tolerated, based on clinical response; maximum dose: 4 mg/day. Note: If patient misses 2 or more consecutive doses, repeat titration of dose should be considered.
Note: Clinical response is associated with doses of 0.05-0.08 mg/kg/day. Doses up to 0.12 mg/kg/day may provide additional benefit; however, doses >4 mg/day have not been evaluated.
Children ≥12 years and Adults: Hypertension:Immediate release: 1 mg usually at bedtime, may increase if needed at 3- to 4-week intervals; usual dose range (JNC 7): 0.5-2 mg once daily
Elderly: Hypertension: Consider lower initial doses and titrate to response (Aronow, 2011)
Dosage adjustment in renal impairment: No specific dosage adjustments are recommended by the manufacturer; consider using the lower end of the dosing range in patients with renal impairment.
Hemodialysis: Dialysis clearance is ~15% of total clearance; usual doses are recommended.
Dosage adjustment in hepatic impairment: No specific dosage adjustments are recommended by the manufacturer; however, dosage adjustments may be required.
Administration: Oral
Extended release tablets should not be crushed, broken, or chewed. Formulations (immediate release versus extended release) are not interchangeable. When switching from an immediate release formulation, discontinue that treatment and retitrate using the extended release formulation.
Monitoring Parameters
Heart rate, blood pressure
When used for the treatment of ADHD, thoroughly evaluate for cardiovascular risk. Monitor heart rate, blood pressure (prior to initiation, following dosage adjustments, and periodically thereafter), and consider obtaining ECG prior to initiation (Vetter, 2008).
Dietary Considerations
Extended release tablets: Do not administer with a high-fat meal due to increased exposure.
Patient Education
Avoid excessive alcohol. Do not chew or crush extended release tablet; take with a full glass of water. Maintain adequate hydration, unless instructed to restrict fluid intake. You may experience some drowsiness, dizziness, insomnia, fatigue, or orthostatic hypotension. Report palpitations or chest pain, excessive drowsiness or dizziness, respiratory difficulty, or gastrointestinal changes.
Geriatric Considerations
Because of adverse effects such as CNS depression, dry mouth, and constipation, guanfacine is not considered a drug of choice in the elderly.
Cardiovascular Considerations
Gaunfacine is a more selective alpha2-agonist than clonidine and is not routinely used in clinical practice because of significant and marked hypotension; withdrawal effects rarely occur due to its long half-life.
ADHD: Cardiovascular evaluation: In an effort to reduce the rate of sudden cardiac death especially in pediatric patients receiving stimulant medications for the treatment of attention-deficit/hyperactivity disorder (ADHD), the American Heart Association (AHA) issued a statement in April 2008 (Vetter, 2008) recommending that all children diagnosed with ADHD who may be candidates for stimulant medications have a thorough cardiovascular assessment (including a combination of a thorough medical history, family history, and physical examination with the intent to identify risk factors for sudden death) prior to initiation of drug therapy. Although not mandatory, physicians should consider obtaining an ECG. These recommendations are based on the Food and Drug Administration (FDA) reports of serious cardiovascular adverse events (including sudden death) in patients (both children and adults) taking usual doses of stimulant medications. Most of these patients were found to have underlying structural heart disease (eg, hypertrophic obstructive cardiomyopathy). Stimulant medications theoretically increase cardiovascular risk due to potential effects on blood pressure elevation and increased heart rate. These effects have generally been considered clinically insignificant in most children, however, may be detrimental in certain patients with underlying cardiovascular disease. None of the medications have been shown to cause heart conditions or proven to have caused sudden cardiac death.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Drowsiness is common; may cause insomnia or dizziness, may rarely cause confusion or depression
Mental Health: Effects on Psychiatric Treatment
Concurrent use with psychotropics may produce additive sedation and dry mouth; TCAs may decrease the hypotensive effect of guanfacine
Mental Health: Child/Adolescent Considerations
Efficacy of guanfacine extended release was not significant when studied in children and adolescents ≤17 years of age with attention-deficit/hyperactivity disorder (ADHD). Generally, not considered a first-line treatment due to lower efficacy rates compared to stimulants; however, guanfacine extended release should be considered when stimulants are ineffective or poorly tolerated. It is more selective for the alpha2A receptor compared to clonidine and therefore has less sedation and dizziness than clonidine.
Biederman J, Melmed RD, Patel A, et al, "A Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine Extended Release in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder," Pediatrics, 2008, 121(1):e73-84.
Cinnamon Bidwell L, Dew RE, and Kollins SH, "Alpha-2 Adrenergic Receptors and Attention-Deficit/Hyperactivity Disorder," Curr Psychiatry Rep, 2010, 12(5):366-73.
Handen BL, Sahl R, and Hardan AY, "Guanfacine in Children With Autism and/or Intellectual Disabilities," J Dev Behav Pediatr, 2008, 29(4):303-8.
Scahill L, Chappell PB, Kim YS, et al, "A Placebo-Controlled Study of Guanfacine in the Treatment of Children With Tic Disorders and Attention Deficit Hyperactivity Disorder," Am J Psychiatry, 2001, 158(7):1067-74.
Nursing: Physical Assessment/Monitoring
Use with caution in presence or risk of cardiovascular disease, cerebrovascular disease, chronic hepatic or renal impairment, or any condition that may predispose to syncope. Assess potential for interactions with other CNS depressants. Do not discontinue abruptly; taper decreasing dose in decrements.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral: 1 mg, 2 mg
Tenex®: 1 mg, 2 mg
Tablet, extended release, oral:
Intuniv™: 1 mg, 2 mg, 3 mg, 4 mg
Pricing: U.S. (www.drugstore.com)
Tablet, 24-hour (Intuniv)
1 mg (30): $183.98
2 mg (30): $187.98
3 mg (30): $188.99
4 mg (30): $183.98
Tablets (Guanfacine HCl)
1 mg (30): $20.99
2 mg (30): $25.99
References
Aronow WS, Fleg JL, Pepine CJ, et al, “ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents,” Circulation, 2011, 123(21):2434-506.
Bassarath L, "Medication Strategies in Childhood Aggression: A Review," Can J Psychiatry, 2003, 48(6):367-73.
Biederman J, Melmed RD, Patel A, et al, “A Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine Extended Release in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder,” Pediatrics, 2008, 121(1):e73-84.
Biederman J, Melmed RD, Patel A, et al, "Long-Term, Open-Label Extension Study of Guanfacine Extended Release in Children and Adolescents With ADHD," CNS Spectr, 2008, 13(12):1047-55.
Chappell PB, Riddle MA, Scahill L, et al, Guanfacine Treatment of Comorbid Attention-Deficit Hyperactivity Disorder and Tourette's Syndrome: Preliminary Clinical Experience," J Am Acad Child Adolesc Psychiatry, 1995, 34(9):1140-6.
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Cummings DD, Singer HS, Krieger M, et al, " Neuropsychiatric Effects of Guanfacine in Children With Mild Tourette Syndrome: A Pilot Study," Clin Neuropharmacol, 2002, 25(6):325-32.
Kaplan NM and Sever PS, “Combination Therapy: A Key to Comprehensive Patient Care,” Am J Hypertens, 1997, 10(7 Pt 2):127S.
Moser M and Black HR, “The Role of Combination Therapy in the Treatment of Hypertension,” Am J Hypertens, 1998, 11(6 Pt 2):73S-8S, 95S-100S.
Sallee FR, Lyne A, Wigal T, et al, “Long-Term Safety and Efficacy of Guanfacine Extended Release in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder,” J Child Adolesc Psychopharmacol, 2009, 19(3):215-26.
Sallee FR, McGough J, Wigal T, et al, “Guanfacine Extended Release in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: A Placebo-Controlled Trial,” J Am Acad Child Adolesc Psychiatry, 2009, 48(2):155-65.
Scahill L, Chappell PB, Kim YS, et al, "A Placebo-Controlled Study of Guanfacine in the Treatment of Children With Tic Disorders and Attention Deficit Hyperactivity Disorder," Am J Psychiatry, 2001, 158(7):1067-74.
Vetter VL, Elia J, Erickson CH, et al, “Cardiovascular Monitoring of Children and Adolescents With Heart Disease Receiving Stimulant Drugs. A Scientific Statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing,” Circulation, 2008, 117:2407-23.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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