Note: Manufacturer labeling states immediate-release and extended-release products are not interchangeable on a mg-per-mg basis due to differences in pharmacokinetic profiles.
Attention-deficit/hyperactivity disorder (ADHD):
Note: Use is suggested in patients who are intolerant of or lacked a response to stimulants; an adequate stimulant trial of at least 6 weeks suggested prior to initiating guanfacine; not typically used first-line (AAP [Wolraich 2019]; NICE 2018). Guanfacine may be an optimal selection for patients with tics or Tourette syndrome comorbidity (AAN [Pringsheim 2019]; NICE 2018) or if stimulant diversion or misuse is a concern. May be used as monotherapy or as adjunctive with ongoing stimulant (AAP [Wolraich 2019]; NICE 2018). Dosing is different for patients with autism spectrum disorder and ADHD comorbidity; see "Autism spectrum disorder (ASD) and ADHD (comorbidity)."
Immediate-release product: Limited data available (Dopheide 2009; Pliszka 2007):
Children ≥6 years and Adolescents:
≤45 kg: Oral: Initial: 0.5 mg once daily at bedtime; may titrate every 3 to 4 days in 0.5 mg/day increments to 0.5 mg twice daily, then 0.5 mg three times daily, then 0.5 mg four times daily; maximum daily dose: Patient weight 27 to 40.5 kg: 2 mg/day; 40.5 to 45 kg: 3 mg/day.
>45 kg: Oral: Initial: 1 mg once daily at bedtime; may titrate every 3 to 4 days in 1 mg/day increments to 1 mg twice daily, then 1 mg three times daily, then 1 mg four times daily; maximum daily dose: 4 mg/day.
Extended-release product (eg, Intuniv):
Children and Adolescents 6 to 17 years: Oral: Initial: 1 mg once daily administered at the same time of day (in the morning or evening); may titrate dose by no more than 1 mg/week increments based upon response and as tolerated to the recommended target dose range: 0.05 to 0.12 mg/kg/day or 1 to 7 mg/day. Target range based on data from monotherapy trials to balance the exposure (dose)-related potential benefits and risks (hypotension, bradycardia, and sedative effects). In clinical monotherapy trials, initial clinical response was associated with doses of 0.05 to 0.08 mg/kg once daily; increased efficacy was seen with increasing mg/kg doses; doses up to 0.12 mg/kg once daily have shown benefit when tolerated. In adjunctive therapy trials with stimulant medication, doses of 0.05 to 0.12 mg/kg/day produced optimal clinical response in the majority of patients.
Suggested fixed target dose range for patients weighing ≥25 kg: All doses administered once daily at the same time (either in the morning or evening) not to exceed age-based maximum daily doses:
25 to 33.9 kg: 2 to 3 mg/day.
34 to 41.4 kg: 2 to 4 mg/day.
41.5 to 49.4 kg: 3 to 5 mg/day.
49.5 to 58.4 kg: 3 to 6 mg/day.
58.5 to 91 kg: 4 to 7 mg/day.
>91 kg: 5 to 7 mg/day.
Maximum daily doses: Doses above the following have not been evaluated:
Monotherapy: Children 6 to 12 years: 4 mg/day; Adolescents: 13 to 17 years: 7 mg/day.
Adjunct therapy (with psychostimulants): 4 mg/day.
Conversion from immediate-release guanfacine to the extended-release product: Discontinue the immediate-release product; initiate the extended-release product at the doses recommended above.
Missed doses of extended release: If patient misses ≥2 consecutive doses, repeat titration of dose should be considered.
Discontinuation of extended release: Taper dose by no more than 1 mg every 3 to 7 days.
Autism spectrum disorder (ASD) and ADHD (comorbidity): Limited data available; efficacy results variable:
Children and Adolescents 5 to 14 years: Immediate-release product:
<25 kg: Oral: Initial: 0.25 mg once daily, increase dose as tolerated every 4 days in 0.25 mg/day increments in 2 to 3 divided doses; maximum daily dose: 3 mg/day (Scahill 2006).
≥25 kg: Oral: Initial: 0.5 mg once daily, increase dose as tolerated every 4 days in 0.5 mg/day increments in 2 to 3 divided doses; maximum daily dose: 3 mg/day (Handen 2008; Scahill 2006).
Dosing based on a double-blind, placebo-controlled, 6-week crossover trial conducted in children with ADHD and autism or intellectual disabilities (n=11; age: 5 to 9 years); five of 11 patients showed improvement in hyperactivity scores; other patient assessment parameters did not show improvements (Handen 2008). In an open-label, 8-week pilot study in children with ADHD and ASD (n=25; mean age: 9 years; range: 5 to 14 years), patients showed improvement in parent- and teacher-rated hyperactivity subscale scores; increased irritability occurred in 7 patients; the authors note that patients with ASD may be more sensitive to irritability-type adverse effects (Scahill 2006). A retrospective chart review of pediatric ASD (n=80; age: 3 to 18 years) reported ~24% of patients responded to mean dose of 2.6 mg/day; the authors noted using Diagnostic and Statistical Manual of Mental Disorders criteria at the time of the trial, patients with Asperger syndrome or Pervasive Developmental Disorder not otherwise specified (PDD-NOS) responded more frequently than those with autistic disorder or comorbidity of intellectual disability (Posey 2004).
Hypertension: Note: Although FDA approved for hypertension, pediatric consensus guidelines do not include guanfacine as a therapeutic option; use has been replaced by other agents (AAP [Flynn 2017]).
Children ≥12 years and Adolescents: Immediate-release product: Oral: 1 mg usually at bedtime; may increase, if needed, at 3- to 4-week intervals; usual range: 0.5 to 2 mg/day; maximum daily dose: 2 mg/day.
Tic disorder; Tourette syndrome: Limited data available; efficacy results variable: Compared to placebo, guanfacine is possibly more likely to reduce tic severity (AAN [Pringsheim 2019]); however, other trials have not conferred similar results using extended-release guanfacine for chronic tic disorder (Murphy 2017); in patients with ADHD as a comorbidity, greater efficacy has been shown (AACAP [Murphy 2013]; AAN [Pringsheim 2019]).
Children and Adolescents 6 to 16 years: Immediate-release product: Oral: Initial: 0.5 mg once daily at bedtime for 3 days, then 0.5 mg twice daily for 4 days, then 0.5 mg 3 times daily for 7 days; further upward titration based on clinical response to maximum daily dose: 4 mg/day (Scahill 2001); twice-daily dosing may be effective for some patients (Chappell 1995; Cummings 2002).
Dosing based on a double-blind, placebo-controlled study in patients with ADHD and mild to moderate tics (n=34; mean age: 10.4 years; range: 7 to 14 years); reported final dose range: 1.5 to 3 mg/day in 3 divided doses with the most common dose reported was 2.5 mg/day (ie, 1 mg in morning, 0.5 mg at 3 pm, and 1 mg at bedtime); a statistically significant decrease (31%) in tic scores and improvement in teacher-rated ADHD scores was reported after 8 weeks (Scahill 2001). A small open-label trial of patients with Tourette syndrome and ADHD (n=10; age range: 8 to 16 years) used similar initial doses and dose titration (0.5 mg increments every 3 to 4 days); final reported dose range: 0.75 to 3 mg/day in divided doses (2 to 3 times daily); seven of 10 patients required a final dose of 1.5 mg/day in divided doses (Chappell 1995). A short 4-week trial evaluating 24 patients (age range: 6 to 16 years) with mild chronic tic disorder showed only slight improvement in tic scores after titration (over approximately 3 weeks) to a final dose of 2 mg/day (Cummings 2002).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Immediate release: Children ≥12 years and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, the lower end of the dosing range is recommended in patients with renal impairment; use with caution, as ~50% of the dose (40% to 75% of dose) is excreted as unchanged drug in urine.
Extended release (Intuniv): Children ≥6 years and Adolescents: There are no dosage adjustments provided in manufacturer's labeling (has not been studied); however, dosage adjustments may be necessary in patients with significant renal impairment.
Hemodialysis: Immediate release or extended release: Dialysis clearance is low (~15% of total clearance).
Immediate release: Children ≥12 years and Adolescents: There are no specific dosage adjustments provided in the manufacturer's labeling; however, use with caution in chronic hepatic impairment; consider dosage reduction.
Extended release (Intuniv): Children ≥6 years and Adolescents: There are no dosage adjustments provided in manufacturer's labeling (has not been studied); however, dosage adjustments may be necessary in patients with significant hepatic impairment.
(For additional information see "Guanfacine: Drug information")
Hypertension (alternative agent): Immediate release: Oral: Initial: 0.5 to 1 mg once daily at bedtime; may increase as needed after 3 to 4 weeks up to 2 mg once daily at bedtime (ACC/AHA [Whelton 2017]). Note: Adverse reactions increase significantly with doses above 3 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Immediate release: There are no specific dosage adjustments provided in the manufacturer’s labeling; however, the lower end of the dosing range is recommended in patients with renal impairment.
Hemodialysis: Immediate release or extended release: Dialysis clearance is low (~15% of total clearance).
Immediate release: There are no dosage adjustments provided in the manufacturer’s labeling; however, use with caution in chronic hepatic impairment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 1 mg, 2 mg
Tablet Extended Release 24 Hour, Oral:
Intuniv: 1 mg, 2 mg, 3 mg, 4 mg
Generic: 1 mg, 2 mg, 3 mg, 4 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release 24 Hour, Oral:
Intuniv XR: 1 mg, 2 mg, 3 mg, 4 mg
Oral:
Immediate release: Take at bedtime to minimize somnolence.
Extended release: Take at the same time each day (either morning or evening); swallow tablet whole with water, milk, or other liquid; do not crush, break, or chew; do not administer with high-fat meal.
Oral: IR tablets are usually given at bedtime to minimize somnolence. Formulations (immediate release versus extended release) are not interchangeable.
Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Do not cut, crush, or chew. Switch to IR formulation. Dose adjustment may be necessary since bioavailability of the IR formulation differs from extended release.
Immediate release: Store at 20°C to 25°C (68°F to 77°F).
Extended release: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).
Immediate release: Management of hypertension alone or in combination with other hypertensive agents, especially thiazide-type diuretics (FDA approved ages ≥12 years and adults); has also been used for the treatment of attention-deficit/hyperactivity disorder (ADHD), tic disorder or Tourette syndrome with or without ADHD, and autism spectrum disorder with ADHD comorbidity.
Note: Although FDA approved for hypertension, pediatric consensus guidelines do not include guanfacine as a therapeutic option; use has been replaced by other agents (AAP [Flynn 2017]).
Extended release: Treatment of ADHD as monotherapy or adjunctive therapy with stimulant medication (FDA approved in ages 6 to 17 years).
GuanFACINE may be confused with guaiFENesin, guanabenz, guanidine
Intuniv may be confused with Invega
Tenex may be confused with Entex, Xanax
Beers Criteria: Guanfacine is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to high risk of CNS adverse effects and risk of bradycardia and orthostatic hypotension associated with central alpha blockers; not recommended as routine treatment for hypertension (Beers Criteria [AGS 2019]).
Pharmacy Quality Alliance (PQA): Guanfacine is identified as a high-risk medication in patients 65 years and older on the PQA’s Use of High-Risk Medications in the Elderly (HRM) performance measure, a safety measure used by the Centers for Medicare and Medicaid Services (CMS) for Medicare plans (PQA 2017).
Tenex [U.S.] may be confused with Kinex brand name for biperiden [Mexico]
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse events occurred with children and adolescents 6 to 17 years of age unless otherwise specified.
>10%:
Central nervous system: Drowsiness (28% to 57%), headache (16% to 28%), fatigue (10% to 22%), dizziness (4% to 16%), insomnia (2% to 13%)
Gastrointestinal: Abdominal pain (8% to 19%), decreased appetite (5% to 15%)
1% to 10%:
Cardiovascular: Hypotension (4% to 9%), bradycardia (2% to 5%), orthostatic hypotension (1% to 5%), first-degree atrioventricular block (≥2%), sinus arrhythmia (≥2%), tachycardia (≥2%), syncope (1% to ≥2%)
Central nervous system: Irritability (5% to 8%), lethargy (3% to 8%), anxiety (2% to 5%), nightmares (3% to 4%), emotional lability (2% to 3%), agitation (≥2%), depression (≥2%), increased blood pressure (≥2%), loss of consciousness (children: ≥2%)
Dermatologic: Skin rash (2% to 3%), pruritus (2%)
Endocrine & metabolic: Weight gain (2% to 3%)
Gastrointestinal: Xerostomia (3% to 8%), nausea (5% to 7%), vomiting (2% to 7%), diarrhea (2% to 6%), constipation (2% to 4%), abdominal distress (≥2%), dyspepsia (≥2%), stomach discomfort (≥2%)
Genitourinary: Urinary incontinence (2% to 5%)
Respiratory: Asthma (≥2%)
Miscellaneous: Fever (8%; Biederman 2008)
Frequency not defined:
Cardiovascular: Atrioventricular block, chest pain, hypertension
Central nervous system: Seizure
Dermatologic: Pallor
Genitourinary: Urinary frequency
Hepatic: Increased serum ALT
Hypersensitivity: Hypersensitivity reaction
Neuromuscular & skeletal: Weakness
<1%, postmarketing, and/or case reports: Alopecia, arthralgia, blurred vision, confusion, dermatitis, dysgeusia, dyspnea, edema, erectile dysfunction, exfoliative dermatitis, hallucination, hypertensive encephalopathy (with abrupt discontinuation), leg cramps, leg pain, malaise, myalgia, palpitations, paresthesia, rebound hypertension (with abrupt discontinuation), sedation, tremor, vertigo
Hypersensitivity to guanfacine or any component of the formulation
Concerns related to adverse effects:
• Cardiovascular effects: May cause atrioventricular (AV) block, bradycardia, hypotension, orthostasis, sinus node dysfunction, and syncope; these effects are dose-dependent, more pronounced during the first month of therapy, or may worsen especially when used with other sympatholytic drugs. Monitor vital signs frequently in patients with cardiac conduction abnormalities or those concomitantly treated with other sympatholytic drugs.
• CNS effects: May cause sedation and drowsiness which may impair physical or mental abilities; in extended-release formulation trials of pediatric patients, sedation prevalence peaked in the week the target dose was reached, and then decreased (Huss 2019); patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).
• Dermatological effects: Skin rash with exfoliation and pruritus have 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. Dosage adjustment may be necessary in severe impairment.
• Renal impairment: Use with caution in patients with chronic renal impairment. Dosage adjustment may be necessary in severe impairment.
Dosage form specific issues:
• Product interchangeability: Formulations of guanfacine (immediate release versus extended release) are not interchangeable on a mg to mg basis because bioavailability, Cmax, and Tmax vary.
Other warnings/precautions:
• Discontinuation of therapy: Increased heart rate and rebound hypertension have been reported with abrupt discontinuation; hypertensive encephalopathy has also been reported. Increased risk of rebound hypertension may occur in children with GI illnesses and vomiting. Concomitant stimulant use may increase blood pressure if guanfacine is abruptly stopped. To minimize these effects, taper the dose in decrements of ≤1 mg every 3 to 7 days and monitor blood pressure and pulse following dosage reduction/discontinuation.
• 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).
Prior to treatment with medications for attention-deficit/hyperactivity disorder (ADHD), the American Heart Association and the American Academy of Pediatrics recommend that all children and adolescents diagnosed with ADHD have a thorough cardiovascular assessment, including patient and family health histories, evaluation of all medications used (prescribed and over-the-counter), and a physical examination focused on cardiovascular disease risk factors. An ECG is not mandatory but is reasonable to consider prior to stimulant medication therapy. Prompt evaluation and appropriate referral and testing, if warranted, should occur if any cardiac symptoms are present (Vetter 2008).
These recommendations are based upon 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). Note: In older clinical data, ECG abnormalities and 4 cases of sudden cardiac death were reported in children receiving clonidine (a less selective alpha2-agonist) with methylphenidate; reduce dose of methylphenidate by 40% when used concurrently with clonidine; consider ECG monitoring. However, more recent (published after 2001) multicenter trials have not reported serious cardiovascular outcomes or events in medically screened children and adolescents receiving concomitant clonidine and psychostimulant therapy; the most frequent reported adverse effects with combination therapy were drowsiness, dizziness, and somnolence (Wilens 2012). A double-blind, placebo-controlled trial of 461 pediatric patients (age: 6 to 17 years) examining the effect of the addition of extended-release guanfacine to current psychostimulant therapy did not report any cardiovascular adverse events; in this trial, the most common (>10% incidence) treatment emergent adverse effects were headache, somnolence, fatigue, and dizziness (Wilens 2012). Further studies are needed to examine the long-term safety and efficacy of guanfacine in combination with psychostimulants.
When discontinuing guanfacine ADHD therapy, an increase in blood pressure has been observed in children and adolescents (6 to 17 years); increases in mean systolic and diastolic blood pressure of ~3 mm Hg and 1 mm Hg, respectively, above baseline were reported; monitor vital signs.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Alcohol (Ethyl): May enhance the CNS depressant effect of GuanFACINE. Risk X: Avoid combination
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Beta-Blockers: Alpha2-Agonists may enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Risk D: Consider therapy modification
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May decrease the serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a moderate CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a strong CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider therapy modification
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. 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 (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. 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 the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mirtazapine: May diminish the antihypertensive effect of Alpha2-Agonists. Management: Consider avoiding concurrent use. If the combination cannot be avoided, monitor for decreased effects of alpha2-agonists if mirtazapine is initiated/dose increased, or increased effects if mirtazapine is discontinued/dose decreased. Risk D: Consider therapy modification
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May diminish the therapeutic effect of Alpha2-Agonists. Risk C: Monitor therapy
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Tricyclic Antidepressants: May diminish the antihypertensive effect of Alpha2-Agonists. Management: Consider avoiding this combination. If used, monitor for decreased effects of the alpha2-agonist. Exercise great caution if discontinuing an alpha2-agonist in a patient receiving a TCA. Risk D: Consider therapy modification
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valproate Products: GuanFACINE may increase the serum concentration of Valproate Products. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Grapefruit juice/products: Guanfacine serum concentrations may be increased when taken with grapefruit juice/products. Management: Consider reducing guanfacine dose by 50% when taking grapefruit juice/products concomitantly; monitor for increased effects/toxicity.
Extended-release tablets: Do not administer with a high-fat meal due to increased exposure.
Information related to guanfacine use during pregnancy is limited (Karesoja 1981; Philipp 1980). In one study of 30 women treated with guanfacine for hypertension during pregnancy, the majority (n=25) experience sedation; dry mouth and dizziness were also reported (Philipp 1980).
Chronic maternal hypertension may increase the risk of birth defects, low birth weight, preterm delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to duration and severity of maternal hypertension. Untreated hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, myocardial infarction, preeclampsia, stroke, and delivery complications (ACOG 203 2019).
Agents other than guanfacine are more commonly used to treat hypertension in pregnancy (ACOG 203 2019; ESC [Regitz-Zagrosek 2018]). Females with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]).
If treatment for attention-deficit/hyperactivity disorder (ADHD) during pregnancy is needed, other agents are preferred (Ornoy 2018).
Heart rate, blood pressure, consider ECG monitoring in patients with history of heart disease or concurrent use of medications affecting cardiac conduction.
Attention-deficit/hyperactivity disorder (ADHD): Evaluate patients for cardiac disease prior to initiation of therapy for ADHD with thorough medical history, family history, and physical exam; consider ECG; perform ECG and echocardiogram if findings suggest cardiac disease; promptly conduct cardiac evaluation in patients who develop chest pain, unexplained syncope, or any other symptom of cardiac disease during treatment.
Guanfacine is a selective alpha2A-adrenoreceptor agonist that 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.
Note: When dosed at same mg dose, the extended-release product has a lower peak serum concentration (60% lower) and AUC (43% lower) compared with the immediate-release formulation.
Absorption: Readily absorbed.
Duration: Antihypertensive effect: 24 hours following single dose
Distribution: Vd:
Immediate release: 6.3 L/kg
Extended release: Vd (apparent): Children ≥6 years: 23.7 L/kg; Adolescent: 19.9 L/kg (Boellner 2007)
Protein binding: ~70%
Metabolism: Hepatic via CYP3A4. Approximately 50% of clearance is hepatic.
Bioavailability:
Immediate release: ~80%
Extended release (relative to immediate release): 58%
Half-life elimination:
Immediate release: ~17 hours (range: 10 to 30 hours)
Extended release: Children ≥6 years: 14.4 hours; Adolescents: 18 hours (Boellner 2007); Adults: 18 ± 4 hours
Time to peak, serum:
Immediate release: 2.6 hours (range: 1 to 4 hours)
Extended release: Children ≥6 years and Adolescents: 5 hours (Boellner 2007); Adults: 4 to 8 hours
Excretion: Urine (~50% [40% to 75% of dose] as unchanged drug)
Renal function impairment: In patients with renal impairment, clearance is reduced; plasma levels are only slightly increased. In patients on hemodialysis, dialysis clearance was ~15% of total clearance.
Pediatric: Exposure to guanfacine was slightly higher in children (6 to 12 years of age) compared with adolescents (13 to 17 years of age); data suggest this difference corresponds with patient weight rather than age; clinical significance is not defined (Tsuda 2019).
Guanfacine is a more selective alpha2-agonist than clonidine; therefore, has less sedation and dizziness associated with use than clonidine; withdrawal effects less commonly occur due to its longer half-life.
Medications used to treat attention-deficit/hyperactivity disorder (ADHD) should be part of a total treatment program that may include other components, such as psychological, educational, and social measures. Long-term usefulness of guanfacine for the treatment of ADHD should be periodically re-evaluated in patients receiving the drug for extended periods of time.
Tablet, 24-hour (guanFACINE HCl ER Oral)
1 mg (per each): $10.49
2 mg (per each): $10.49
3 mg (per each): $10.49
4 mg (per each): $10.49
Tablet, 24-hour (Intuniv Oral)
1 mg (per each): $11.66
2 mg (per each): $11.66
3 mg (per each): $11.66
4 mg (per each): $11.66
Tablets (guanFACINE HCl Oral)
1 mg (per each): $0.87 - $1.27
2 mg (per each): $1.18 - $2.01
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