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GuanFACINE

Medically reviewed by Drugs.com. Last updated on Sep 2, 2020.

Pronunciation

(GWAHN fa seen)

Index Terms

  • Guanfacine HCl
  • Guanfacine Hydrochloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Tenex: 1 mg [DSC] [contains fd&c red #40 aluminum lake]

Tenex: 2 mg [DSC] [contains fd&c yellow #10 aluminum lake]

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

Brand Names: U.S.

  • Intuniv
  • Tenex [DSC]

Pharmacologic Category

  • Alpha2-Adrenergic Agonist
  • Antihypertensive

Pharmacology

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.

Absorption

Readily absorbed.

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)

Metabolism

Hepatic via CYP3A4. Approximately 50% of clearance is hepatic.

Excretion

Urine (~50% [40% to 75% of dose] as unchanged drug)

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

Duration of Action

Antihypertensive effect: 24 hours following single dose

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

Protein Binding

~70%

Special Populations: 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.

Special Populations: Children

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).

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]).

Contraindications

Hypersensitivity to guanfacine or any component of the formulation

Dosing: Adult

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.

Dosing: Geriatric

Immediate release: Refer to adult dosing. In the management of hypertension, consider lower initial doses and titrate to response (Aronow 2011).

Dosing: Pediatric

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 mental retardation (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.

Administration

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.

Dietary Considerations

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

Storage

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).

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Alcohol (Ethyl): May enhance the CNS depressant effect of GuanFACINE. Avoid combination

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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. 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. Consider therapy modification

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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. 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. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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. 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. 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. 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. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to concomitant therapy when possible. If concomitant therapy cannot be avoided, monitor for reduced clinical effects of the CYP3A4 substrate. Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. 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. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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

Fexinidazole [INT]: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole [INT]. 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. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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. Consider therapy modification

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. 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. Consider therapy modification

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. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. 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 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. Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May diminish the antihypertensive effect of Alpha2-Agonists. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. 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. Consider therapy modification

Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. 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. Consider therapy modification

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Valproate Products: GuanFACINE may increase the serum concentration of Valproate Products. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. 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. Consider therapy modification

Test Interactions

May lead to false-positive aldosterone/renin ratio (ARR) (Funder 2016).

Adverse Reactions

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

Warnings/Precautions

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).

Monitoring Parameters

Heart rate, blood pressure

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).

Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2017]):

Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%: Target blood pressure <130/80 mm Hg is recommended.

Confirmed hypertension without markers of increased ASCVD risk: Target blood pressure <130/80 mm Hg may be reasonable.

Pregnancy Considerations

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).

Patient Education

What is this drug used for?

• It is used to treat high blood pressure.

• It is used to treat attention deficit problems with hyperactivity.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Constipation

• Fatigue

• Dry mouth

• Loss of strength and energy

• Irritability

• Nausea

• Vomiting

• Trouble sleeping

• Abdominal pain

• Lack of appetite

• Headache

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe dizziness

• Passing out

• Slow heartbeat

• Abnormal heartbeat

• Sexual dysfunction

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.