Guanfacine: Drug information

For additional information see "Guanfacine: Patient drug information" and "Guanfacine: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table

Brand Names: US

Intuniv

Brand Names: Canada

APO-Guanfacine XR;
Intuniv XR;
JAMP-Guanfacine XR

Pharmacologic Category

Alpha₂-Adrenergic Agonist;
Antihypertensive

Dosing: Adult

Hypertension

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 (Ref). 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.

Dosing: Kidney Impairment: Adult

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).

Dosing: Hepatic Impairment: Adult

Immediate release: There are no dosage adjustments provided in the manufacturer’s labeling; however, use with caution in chronic hepatic impairment.

Dosing: Older Adult

Use is not recommended as a routine treatment of hypertension (Ref).

Immediate release: Refer to adult dosing. In the management of hypertension, consider lower initial doses and titrate to response (Ref).

Dosing: Pediatric

(For additional information see "Guanfacine: Pediatric drug information")

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

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 (Ref). Guanfacine may be an optimal selection for patients with tics or Tourette syndrome comorbidity (Ref) or if stimulant diversion or misuse is a concern. May be used as monotherapy or as adjunctive with ongoing stimulant (Ref). 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 (Ref):

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 and ADHD

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 (Ref).

≥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 (Ref).

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 (Ref). 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 (Ref). 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 (Ref).

Hypertension

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 (Ref).

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.

Tourette syndrome, tic disorder

Tourette syndrome, Tic disorder: Limited data available; efficacy results variable: Compared to placebo, guanfacine is possibly more likely to reduce tic severity (Ref); however, other trials have not conferred similar results using extended-release guanfacine for chronic tic disorder (Ref); in patients with ADHD as a comorbidity, greater efficacy has been shown (Ref).

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 (Ref); twice-daily dosing may be effective for some patients (Ref).

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 (Ref). 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 (Ref). 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 (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

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).

Dosing: Hepatic Impairment: Pediatric

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.

Adverse Reactions (Significant): Considerations

Cardiovascular effects

Cardiovascular effects including atrioventricular (AV) block, bradycardia, hypotension, orthostatic hypotension, sinoatrial nodal rhythm disorder, and syncope may occur with guanfacine use in all ages (Ref).

Mechanism : Dose-related; related to the pharmacologic action (ie, stimulates alpha-2 adrenergic receptors resulting in decreased sympathetic activity leading to decreased heart rate, peripheral resistance, cardiac output, and blood pressure) (Ref).

Onset: Varied; occur most often in the first month of therapy and are usually transient. Tolerance to hypotensive effect develops with continued use (Ref).

Risk factors

• History of bradycardia, hypotension, or syncope

• Dehydration

• Cardiovascular disease (Ref)

• Cardiac conduction abnormalities (Ref)

• Concomitant use of sympatholytic medications (eg, beta blockers, alpha blockers, mixed α,β-blockers)

• Concurrent antihypertensives

CNS effects

CNS effects including drowsiness, insomnia, sedated state, and headache have been reported in adult and pediatric patients (Ref). Sedation and drowsiness may impair physical or mental abilities. Although not life-threatening, these effects commonly result in nonadherence and/or discontinuation of therapy (Ref).

Mechanism : Dose-related; related to the pharmacologic action (ie, activates alpha-2 adrenoreceptors which inhibits the release of norepinephrine [needed for arousal]), CNS effects result when norepinephrine is not present (Ref).

Onset: Intermediate; occurs early in treatment (ie, first few weeks after initiation) and with dose increases; transient and usually resolve with continued use (Ref).

Risk factors:

• Higher doses

• Concomitant treatment with medications with sedative effects (eg, antihistamines, centrally active depressants such phenothiazines, barbiturates, benzodiazepines)

• Concomitant alcohol use

Withdrawal syndrome/rebound Hypertension

Withdrawal syndrome including symptoms resembling nervousness and anxiety (eg, increased heart rate), and rebound hypertension may occur with abrupt discontinuation of guanfacine in all ages (Ref).

Mechanism : Withdrawal; result of excessive plasma catecholamine levels, “catecholamine surge”.

Onset: Rapid; Gradual increase back to baseline pretreatment blood pressures after drug discontinuation; blood pressure readings significantly above pretreatment readings have also been reported (Ref).

Risk factors:

• Higher doses (Ref)

• Longer duration of treatment (Ref)

• Abrupt discontinuation of guanfacine (eg, medication nonadherence, vomiting [abrupt inability to absorb oral dosage forms]) (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Immediate release:

>10%:

Gastrointestinal: Constipation (2% to 15%), xerostomia (10% to 54%)

Nervous system: Dizziness (12% to 15%), drowsiness (5% to 39%) (table 1)Drowsiness (Immediate Release), headache (3% to 13%) (table 2)Headache (Immediate Release)

**Guanfacine: Adverse Reaction: Drowsiness (Immediate Release)**
Drug (Guanfacine)	Placebo	Dose	Dosage Form	Indication	Number of Patients (Guanfacine)	Number of Patients (Placebo)
39%	8%	3 mg daily	Immediate-release tablets	Mild to moderate hypertension	59	59
13%	8%	2 mg daily	Immediate-release tablets	Mild to moderate hypertension	60	59
10%	8%	1 mg daily	Immediate-release tablets	Mild to moderate hypertension	61	59
5%	8%	0.5 mg daily	Immediate-release tablets	Mild to moderate hypertension	60	59

**Guanfacine: Adverse Reaction: Headache (Immediate Release)**
Drug (Guanfacine)	Placebo	Dose	Dosage Form	Indication	Number of Patients (Guanfacine)	Number of Patients (Placebo)
13%	8%	1 mg	Immediate-release tablets	Mild to moderate hypertension	61	59
8%	8%	0.5 mg daily	Immediate-release tablets	Mild to moderate hypertension	60	59
7%	8%	2 mg	Immediate-release tablets	Mild to moderate hypertension	60	59
3%	8%	3 mg daily	Immediate-release tablets	Mild to moderate hypertension	59	59

1% to 10%:

Genitourinary: Impotence (3% to 7%)

Nervous system: Asthenia (2% to 7%), fatigue (5% to 10%)

Extended release (adverse events occurred with children and adolescents 6 to 17 years of age unless otherwise specified):

>10%:

Gastrointestinal: Abdominal pain (8% to 19%), decreased appetite (5% to 15%) (van Stralen 2021)

Nervous system: Dizziness (4% to 16%), drowsiness (28% to 57%; including sedated state) (table 3)Drowsiness (Extended Release), fatigue (10% to 22%), headache (16% to 28%) (table 4)Headache (Extended Release), insomnia (6% to 13%) (table 5)

**Guanfacine: Adverse Reaction: Drowsiness (Extended Release)**
Drug (Guanfacine)	Placebo	Population	Dose	Dosage Form	Indication	Number of Patients (Guanfacine)	Number of Patients (Placebo)	Comments
57%	15%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	107	112	Morning dose
54%	23%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	157	155	N/A
54%	15%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	114	112	Evening dose
51%	11%	Children and adolescents	4 mg daily	Extended-release tablets	Attention-deficit/hyperactivity disorder	151	149	N/A
38%	11%	Children and adolescents	3 mg daily	Extended-release tablets	Attention-deficit/hyperactivity disorder	151	149	N/A
30%	11%	Children and adolescents	2 mg daily	Extended-release tablets	Attention-deficit/hyperactivity disorder	150	149	N/A
28%	11%	Children and adolescents	1 mg daily	Extended-release tablets	Attention-deficit/hyperactivity disorder	61	149	N/A

**Guanfacine: Adverse Reaction: Headache (Extended Release)**
Drug (Guanfacine)	Placebo	Population	Dose	Dosage Form	Indication	Number of Patients (Guanfacine)	Number of Patients (Placebo)	Comments
28%	19%	Children and adolescents	4 mg daily	Extended-release tablets	Attention-deficit/hyperactivity disorder	151	149	N/A
27%	18%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	157	155	N/A
26%	19%	Children and adolescents	1 mg daily	Extended-release tablets	Attention-deficit/hyperactivity disorder	61	149	N/A
25%	19%	Children and adolescents	2 mg daily	Extended-release tablets	Attention-deficit/hyperactivity disorder	150	149	N/A
18%	11%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	107	112	Morning dose
16%	19%	Children and adolescents	3 mg daily	Extended-release tablets	Attention-deficit/hyperactivity disorder	151	149	N/A
16%	11%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	114	112	Evening dose

**Guanfacine: Adverse Reaction: Insomnia (Extended Release)**
Drug (Guanfacine)	Placebo	Population	Dose	Dosage Form	Indication	Number of Patients (Guanfacine)	Number of Patients (Placebo)	Comments
13%	6%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	157	155	N/A
8%	6%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	107	112	Morning dose
6%	6%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	114	112	Evening dose

1% to 10%:

Cardiovascular: Bradycardia (5%) (table 6)Bradycardia (Extended Release), first-degree atrioventricular block (≥2%), hypotension (4% to 9%) (table 7)Hypotension (Extended Release), increased blood pressure (≥2%), orthostatic hypotension (1% to 5%) (table 8), sinoatrial nodal rhythm disorder (≥2%), syncope (≥1%), tachycardia (≥2%)

**Guanfacine: Adverse Reaction: Bradycardia (Extended Release)**
Drug (Guanfacine)	Placebo	Population	Dose	Dosage Form	Indication	Number of Patients (Guanfacine)	Number of Patients (Placebo)
5%	0%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	157	155

**Guanfacine: Adverse Reaction: Hypotension (Extended Release)**
Drug (Guanfacine)	Placebo	Population	Dose	Dosage Form	Indication	Number of Patients (Guanfacine)	Number of Patients (Placebo)	Comments
9%	3%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	157	155	N/A
8%	3%	Children and adolescents	1 mg daily	Extended-release tablets	Attention-deficit/hyperactivity disorder	61	149	N/A
8%	3%	Children and adolescents	4 mg daily	Extended-release tablets	Attention-deficit/hyperactivity disorder	151	149	N/A
7%	3%	Children and adolescents	3 mg daily	Extended-release tablets	Attention-deficit/hyperactivity disorder	151	149	N/A
6%	0%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	107	112	Morning dose
5%	3%	Children and adolescents	2 mg daily	Extended-release tablets	Attention-deficit/hyperactivity disorder	150	149	N/A
4%	0%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	114	112	Evening dose

**Guanfacine: Adverse Reaction: Orthostatic Hypotension (Extended Release)**
Drug (Guanfacine)	Placebo	Population	Dose	Dosage Form	Indication	Number of Patients (Guanfacine)	Number of Patients (Placebo)
5%	2%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	157	155
1%	0%	Children and adolescents	1 mg to 4 mg daily	Extended-release tablets	Attention-deficit/hyperactivity disorder	513	149

Dermatologic: Pruritus (2%), skin rash (2% to 3%)

Endocrine & metabolic: Weight gain (2% to 3%)

Gastrointestinal: Abdominal distress (2%), constipation (2% to 4%), diarrhea (2% to 6%), dyspepsia (≥2%), nausea (5% to 7%), stomach discomfort (2%), vomiting (2% to 7%), xerostomia (3% to 8%)

Genitourinary: Urinary incontinence (2% to 5%)

Nervous system: Agitation (≥2%), anxiety (5%) (table 9)Anxiety (Extended Release), depression (≥2%), emotional lability (2% to 3%), irritability (5% to 8%), lethargy (3% to 8%), loss of consciousness (children: ≥2%), nightmares (3% to 4%)

**Guanfacine: Adverse Reaction: Anxiety (Extended Release)**
Drug (Guanfacine)	Placebo	Population	Dose	Dosage Form	Indication	Number of Patients (Guanfacine)	Number of Patients (Placebo)
5%	3%	Children and adolescents	Flexible dose	Extended-release tablets	Attention-deficit/hyperactivity disorder	157	155

Respiratory: Asthma (≥2%)

Miscellaneous: Fever (8%) (Biederman 2008)

Frequency not defined:

Cardiovascular: Atrioventricular block

Dermatologic: Pallor

Hepatic: Increased serum alanine aminotransferase

Hypersensitivity: Hypersensitivity reaction

Nervous system: Asthenia, seizure

Postmarketing (all formulations):

Cardiovascular: Acute myocardial infarction, cardiac fibrillation, chest pain, edema, heart block, heart failure, hypertensive encephalopathy (with abrupt discontinuation), palpitations, rebound hypertension (with abrupt discontinuation) (Martinez-Raga 2013)

Dermatologic: Alopecia, dermatitis, exfoliative dermatitis

Gastrointestinal: Dysgeusia

Genitourinary: Erectile dysfunction, nocturia, urinary frequency

Hepatic: Abnormal hepatic function tests

Nervous system: Cerebrovascular accident, confusion, hallucination, malaise, nervousness, paresthesia, tremor, vertigo

Neuromuscular & skeletal: Arthralgia, lower extremity pain, lower limb cramp, myalgia

Ophthalmic: Blurred vision

Renal: Acute kidney injury

Respiratory: Dyspnea

Contraindications

Hypersensitivity to guanfacine or any component of the formulation

Warnings/Precautions

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.

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, C_max, and T_max vary.

Other warnings/precautions:

• 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).

Warnings: Additional Pediatric Considerations

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).

Dosage Forms: US

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

Generic Equivalent Available: US

Yes

Pricing: US

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

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

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

Generic: 1 mg, 2 mg, 3 mg, 4 mg

Administration: Adult

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.

Administration: Pediatric

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.

Use: Labeled Indications

Attention-deficit/hyperactivity disorder (extended release only): Treatment of attention-deficit/hyperactivity disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications.

Hypertension (immediate release only): Management of hypertension. Note: Not recommended for the initial treatment of hypertension (ACC/AHA [Whelton 2017]).

Medication Safety Issues

Sound-alike/look-alike issues:

GuanFACINE may be confused with guaiFENesin, guanabenz, guanidine

Intuniv may be confused with Invega

Tenex may be confused with Entex, Xanax

Older Adult: High-Risk Medication:

Beers Criteria: Guanfacine is identified in the Beers Criteria as a potentially inappropriate medication to be avoided for the treatment of hypertension in patients 65 years and older due to high risk of CNS adverse effects and risk of bradycardia and orthostatic hypotension associated with central alpha agonists (Beers Criteria [AGS 2023]).

International issues:

Tenex [US] may be confused with Kinex brand name for biperiden [Mexico]

Metabolism/Transport Effects

Substrate of CYP3A4 (major), OCT1, OCT2; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

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

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. 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: CNS Depressants may enhance the CNS depressant effect of Doxylamine. 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

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. 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

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

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). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider therapy modification

Grapefruit Juice: May increase the serum concentration of GuanFACINE. Management: Advise patients to avoid or limit grapefruit juice consumption while taking guanfacine. In patients who regularly consume grapefruit juice, reduce the extended-release guanfacine dose by 50%. Monitor for guanfacine toxicities with combined use. Risk D: Consider therapy modification

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. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Iloperidone: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Isocarboxazid: May enhance the antihypertensive effect of Antihypertensive Agents. Risk X: Avoid combination

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy

Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. 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-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. 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

Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Loxapine: CNS Depressants may enhance the CNS depressant effect of Loxapine. Risk D: Consider therapy modification

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

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

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

Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. 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

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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

Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. 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

Urapidil: Antihypertensive Agents may enhance the hypotensive effect of Urapidil. 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

Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification

Food Interactions

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.

Reproductive Considerations

Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be continued in patients trying to conceive. Guanfacine is not considered a preferred agent for use in pregnant patients; consider transitioning to a preferred agent in patients planning to become pregnant (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).

Pregnancy Considerations

Outcome data related to guanfacine use during pregnancy are 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 is associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019).

Patients with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]). When treatment of chronic hypertension is initiated during pregnancy, agents other than guanfacine may be preferred (ACOG 2019; ESC [Cífková 2020]; ESC [Regitz-Zagrosek 2018]; SOGC [Magee 2022]).

Because there are limited data related to the use of guanfacine in pregnancy (Cohen 2023; Ornoy 2021), discontinue guanfacine for the treatment of attention deficit/hyperactivity disorder (ADHD) during pregnancy (Ornoy 2021). Data collection to monitor pregnancy and infant outcomes following exposure to ADHD medications is ongoing. Health care providers are encouraged to enroll patients exposed to Intuniv during pregnancy in the National Pregnancy Registry for ADHD Medications (866-961-2388).

Breastfeeding Considerations

It is not known if guanfacine is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Infants exposed to guanfacine via breast milk should be monitored for lethargy, poor feeding, and sedation.

Dietary Considerations

Extended-release tablets: Do not administer with a high-fat meal due to increased exposure.

Monitoring Parameters

Heart rate, blood pressure, mental alertness

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).

Mechanism of Action

Guanfacine is a selective alpha_2A-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 alpha_2A-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.

Pharmacokinetics (Adult Data Unless Noted)

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: V_d:

Immediate release: 6.3 L/kg

Extended release: V_d (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)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: 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).

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AT) Austria: Intuniv;
(AU) Australia: Intuniv;
(BE) Belgium: Estulic | Intuniv;
(BG) Bulgaria: Intuniv;
(CH) Switzerland: Intuniv;
(CZ) Czech Republic: Intuniv;
(DE) Germany: Intuniv;
(EE) Estonia: Intuniv;
(ES) Spain: Intuniv;
(FI) Finland: Intuniv;
(FR) France: Intuniv;
(GB) United Kingdom: Intuniv;
(HU) Hungary: Estulic;
(ID) Indonesia: Estulic;
(IE) Ireland: Intuniv;
(JP) Japan: Intuniv;
(LT) Lithuania: Estulic | Intuniv;
(LU) Luxembourg: Estulic | Intuniv;
(LV) Latvia: Estulic;
(MA) Morocco: Estulic;
(NL) Netherlands: Intuniv;
(NO) Norway: Intuniv;
(PH) Philippines: Estulic;
(PL) Poland: Estulic | Intuniv;
(PR) Puerto Rico: Guanfacine | Guanfacine er | Guanfacine extended release | Guanfacine HCL | Tenex;
(QA) Qatar: Intuniv;
(RU) Russian Federation: Estulic;
(SE) Sweden: Entulic | Intuniv;
(SK) Slovakia: Estulic;
(TN) Tunisia: Estulic;
(TR) Turkey: Arislow er | Estulic;
(UA) Ukraine: Estulic

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Guanfacine: Drug information