EMEDZ.NET

Guanfacine (Intuniv) - Uses, Dose, Side effects, MOA, Brands

Guanfacine is a medication that is primarily used to treat attention deficit hyperactivity disorder (ADHD) and hypertension (high blood pressure). It belongs to a class of drugs known as alpha-2 adrenergic agonists. Guanfacine works by stimulating certain receptors in the brain, leading to a reduction in the release of norepinephrine, a neurotransmitter associated with arousal and stress responses.

In the treatment of ADHD, guanfacine is often used as part of a comprehensive treatment plan that may include behavioral therapy and other interventions. It is believed to have a calming effect and can help improve focus and reduce impulsivity in individuals with ADHD.

For hypertension, guanfacine is used to lower blood pressure by relaxing blood vessels. It is sometimes prescribed in combination with other antihypertensive medications.

Guanfacine (Intuniv) is a prescription medicine that may be used to treat patients with attention-deficit/ hyperactivity disorder and hypertension. It is not a preferred medicine for both these indications.

Guanfacine Uses:

Attention-deficit/hyperactivity disorder (extended release only):
- It is used in the treatment of attention deficit hyperactivity disorder (ADHD) as monotherapy or along with other therapies that include stimulant medications.
Hypertension (immediate-release only):
- Hypertension can also be treated with Guanfacine.

Note: It is not recommended as a first-line treatment of hypertension.

Guanfacine (Intuniv) Dose in Adults

Guanfacine (Intuniv) Dose as alternative agent in the treatment of Hypertension:

The usual starting dose is 0.5 to 1 milligram (mg) taken once a day at bedtime.
Your doctor might increase the dose if necessary, but this adjustment typically happens after 3 to 4 weeks.
The maximum recommended dose is 2 mg once daily at bedtime. It's important not to exceed 3 mg per day, as higher doses can lead to more side effects.

Guanfacine (Intuniv) Dose in Childrens

Note: Both Immediate release and extended release products are not interchangeable because of difference in their pharmacokinetics.

Guanfacine (Intuniv) Dose in the treatment of Attention-deficit/ hyperactivity disorder:

Immediate Release Product:

Children ≥6 years and Adolescents:

If ≤45 kg (about 99 pounds): Start with 0.5 mg once daily at bedtime.
For those >45 kg: Begin with 1 mg once daily at bedtime.
The dosage may be increased every 3 to 4 days, but the maximum daily doses depend on weight.

Extended Release Product (e.g., Intuniv):

Children and Adolescents 6 to 17 years:

Begin with 1 mg once daily, either in the morning or evening.
The dose can be increased gradually by no more than 1 mg per week, aiming for a target dose based on weight ranges.

Suggested fixed target dose range for patients weighing ≥ 25 kg:

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:

Monotherapy (Guanfacine alone):
- Children 6 to 12 years: 4 mg/day
- Adolescents 13 to 17 years: 7 mg/day
Adjunct therapy (with other ADHD medications): 4 mg/day

Missed Doses of Extended Release:

If a patient misses two or more consecutive doses, consider retitrating the dose.

Discontinuation of Extended Release:

Taper the dose by no more than 1 mg every 3 to 7 days.

Dosing Adjustment for Concomitant Medications:

CYP3A4 Inhibitors (can increase guanfacine levels):

If starting guanfacine while on a strong inhibitor, decrease guanfacine dose.
If adding a strong inhibitor, decrease guanfacine dose.
If the inhibitor is stopped, increase guanfacine to the recommended dose.

CYP3A4 Inducers (can decrease guanfacine levels):

If starting guanfacine while on a strong inducer, consider increasing the dose.
If adding an inducer, consider increasing the dose.
If the inducer is stopped, decrease guanfacine dose.

Guanfacine (Intuniv) Dose in the treatment of Hypertension:

In children aged 12 years and adolescents, the typical dose of guanfacine in immediate-release form is:

Start with 1 mg, usually taken at bedtime.
If necessary, the dose may be increased at 3- to 4-week intervals.
The usual daily dosage range is 0.5 to 2 mg.
The maximum daily dose should not exceed 2 mg.

Guanfacine (Intuniv) Dose in the treatment of Pervasive developmental disorders (PDD) and ADHD:

In children and adolescents aged 5 to 14 years, the dosing of guanfacine in immediate-release form, based on limited available data, is as follows:

Immediate Release Product:

Children and Adolescents 5 to 14 years:
- <25 kg (about 55 pounds): Start with 0.25 mg once daily. Increase the dose as tolerated every 4 days in 0.25 mg/day increments, divided into 2 to 3 doses.
- ≥25 kg (about 55 pounds): Begin with 0.5 mg once daily. Increase the dose as tolerated every 4 days in 0.5 mg/day increments, divided into 2 to 3 doses.
Maximum Daily Dose: 3 mg/day

Additional Information:

Efficacy Results: The efficacy results from limited data show variability. Some studies indicate improvement in hyperactivity scores, while others did not show improvements in certain patient assessment parameters.
Clinical Trials: A 6-week crossover trial in children with ADHD and autism or intellectual disabilities showed improvement in hyperactivity scores for some patients. An 8-week pilot study in children with ADHD and PDD demonstrated improvement in hyperactivity subscale scores, but increased irritability occurred in some patients.
Retrospective Chart Review: In a chart review of pediatric autism spectrum disorders, approximately 24% of patients responded to a mean dose of 2.6 mg/day. Patients with Asperger’s or PDD not otherwise specified (NOS) responded more frequently than those with autistic disorder or comorbidity of mental retardation.

Guanfacine (Intuniv) Dose in the treatment of Tic disorder; Tourette syndrome:

In children and adolescents aged 6 to 16 years, the dosing of guanfacine in immediate-release form, based on limited available data, is as follows:

Immediate Release Product:

Oral Administration:
- Initial: Start with 0.5 mg once daily at bedtime for 3 days.
- Titration: Increase to 0.5 mg twice daily for 4 days.
- Further Titration: Increase to 0.5 mg three times daily for 7 days.
- Maximum Daily Dose: 4 mg/day

Additional Information:

Clinical Studies:
- A double-blind, placebo-controlled study in patients with ADHD and mild to moderate tics reported a final dose range of 1.5 to 3 mg/day in three divided doses. The most common dose was reported as 2.5 mg/day (1 mg in the morning, 0.5 mg at 3 pm, and 1 mg at bedtime). A significant decrease (31%) in tic scores and improvement in teacher-rated ADHD scores were observed after 8 weeks.
- An open-label trial in patients with Tourette’s syndrome and ADHD used similar initial doses and dose titration. The final reported dose range was 0.75 to 3 mg/day in divided doses (2 to 3 times daily). Seven out of 10 patients required a final dose of 1.5 mg/day in divided doses.
- A short 4-week trial in patients with mild chronic tic disorder showed only slight improvement in tic scores after titration to a final dose of 2 mg/day over approximately 3 weeks.

Pregnancy Risk Factor B

Limited information is available about using guanfacine during pregnancy.
It's important to note that untreated chronic maternal hypertension can lead to negative effects on both the fetus and the mother.

Guanfacine use during breastfeeding:

It's not known whether guanfacine is present in breast milk.
The manufacturer advises caution when giving guanfacine to breastfeeding women.
This caution indicates that the potential risks and benefits of using guanfacine while breastfeeding should be carefully considered.

Guanfacine (Intuniv) Dose in Kidney disease:

For the immediate-release form of guanfacine, there are no specific dosage adjustments mentioned in the manufacturer's instructions for people with kidney problems. However, it's generally advised to start with a lower dose in individuals with renal impairment.
If someone is undergoing hemodialysis (a medical process to filter the blood), both the immediate-release and extended-release forms of guanfacine are cleared from the blood at a slow rate during dialysis, accounting for only about 15% of the total clearance.

Guanfacine (Intuniv) Dose in Liver disease:

For the immediate-release form of guanfacine, the manufacturer's instructions do not specify any dosage adjustments.
However, individuals with chronic liver (hepatic) impairment should use this medication with caution.
This caution suggests that, in cases of liver problems, it's essential to be careful and possibly consider lower doses or close monitoring, as the liver plays a role in metabolizing medications, and impaired liver function can affect how drugs are processed in the body.

Adverse events have been reported with children and adolescents between 6 and 17 years of age unless otherwise specified.

Common Side Effects of Guanfacine (Intuniv):

Central Nervous System:
- Drowsiness
- Headache
- Fatigue
- Dizziness
- Insomnia
Gastrointestinal:
- Abdominal Pain
- Decreased Appetite

Less Common Side Effects Of Guanfacine (Intuniv):

Cardiovascular:
- Hypotension
- Bradycardia
- Orthostatic Hypotension
- First-Degree Atrioventricular Block
- Sinus Arrhythmia
- Tachycardia
- Syncope
Central Nervous System:
- Irritability
- Lethargy
- Anxiety
- Nightmares
- Emotional Lability
- Agitation
- Depression
- Increased Blood Pressure
- Loss Of Consciousness
Dermatologic:
- Skin Rash
- Pruritus
Endocrine & Metabolic:
- Weight Gain
Gastrointestinal:
- Xerostomia
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Abdominal Distress
- Dyspepsia
- Stomach Discomfort
Genitourinary:
- Urinary Incontinence
Respiratory:
- Asthma
Miscellaneous:
- Fever

Frequency of side effects 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

Contraindications to Guanfacine (Intuniv):

If someone is hypersensitive to guanfacine or any part of the medication, it means they have a strong sensitivity or allergic reaction to it.
This includes being allergic to any of the ingredients in the formulation.

Warnings and precautions

Cardiovascular effects

Guanfacine can affect the heart and blood pressure, leading to potential issues like AV block (a heart rhythm problem), slow heart rate (bradycardia), low blood pressure (hypotension), dizziness upon standing (orthostasis), problems with the heart's natural pacemaker (sinus node dysfunction), and fainting (syncope).
These effects depend on the dosage, and they might be more noticeable in the first month of treatment or worsen when combined with other drugs that affect the sympathetic nervous system.

CNS effects

Guanfacine can have effects on the central nervous system (CNS), such as causing sedation and drowsiness.
This means it may make people feel sleepy or less alert. Because of this, individuals taking guanfacine should be careful when performing activities that require mental alertness, like operating machinery or driving.
It's important for patients to be aware of these potential effects and take precautions to ensure their safety and the safety of others while using guanfacine.

Dermatological effects

Guanfacine can lead to dermatological effects, including the development of a skin rash accompanied by peeling and itching (pruritus).
If a person taking guanfacine notices a rash, it's important to stop using the medication and seek medical attention.
Monitoring is necessary for individuals who develop a rash to ensure that any potential complications or reactions are addressed promptly.

Cardiovascular disease

Guanfacine should be used cautiously in individuals with cardiovascular disease.
This includes people with severe problems in the blood supply to the heart (coronary insufficiency), those who recently had a heart attack (MI), or a history of slow heart rate (bradycardia), heart block, low blood pressure (hypotension), or fainting (syncope).
Additionally, caution is advised for individuals with conditions that make them more likely to faint, such as orthostasis (dizziness upon standing) or dehydration.

Cerebrovascular disease

Guanfacine should be used with caution in individuals who have cerebrovascular disease, which involves issues with blood vessels supplying the brain.

Hepatic impairment

Guanfacine should be used carefully in individuals with chronic liver (hepatic) impairment.
If the liver is not working well, adjustments in the dosage of guanfacine may be needed, especially in cases of severe impairment.

Renal impairment

Guanfacine should be used cautiously in individuals with chronic kidney (renal) impairment.
If the kidneys are not functioning well, adjustments in the dosage of guanfacine may be necessary, especially in cases of severe impairment.

Guanfacine: Drug Interaction

Risk Factor C (Monitor therapy)
Alfuzosin	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Amphetamines	May diminish the antihypertensive effect of Antihypertensive Agents.
Antipsychotic Agents (Second Generation [Atypical])	Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).
Barbiturates	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Benperidol	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Bradycardia-Causing Agents	May enhance the bradycardic effect of other Bradycardia-Causing Agents.
Bretylium	May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents.
Brexanolone	CNS Depressants may enhance the CNS depressant effect of Brexanolone.
Brigatinib	May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Brimonidine (Topical)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Bromopride	May enhance the CNS depressant effect of CNS Depressants.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CNS Depressants	May enhance the adverse/toxic effect of other CNS Depressants.
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Dexmethylphenidate	May diminish the therapeutic effect of Antihypertensive Agents.
Diazoxide	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Dimethindene (Topical)	May enhance the CNS depressant effect of CNS Depressants.
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.
Dronabinol	May enhance the CNS depressant effect of CNS Depressants.
DULoxetine	Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine.
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Esketamine	May enhance the CNS depressant effect of CNS Depressants.
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Herbs (Hypertensive Properties)	May diminish the antihypertensive effect of Antihypertensive Agents.
Herbs (Hypotensive Properties)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
HydrOXYzine	May enhance the CNS depressant effect of CNS Depressants.
Hypotension-Associated Agents	Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.
Ivabradine	Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine.
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
Lacosamide	Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide.
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Levodopa-Containing Products	Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products.
Lofexidine	May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Lormetazepam	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
Methylphenidate	May diminish the antihypertensive effect of Antihypertensive Agents.
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
Midodrine	May enhance the bradycardic effect of Bradycardia-Causing Agents.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Molsidomine	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
Naftopidil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nicergoline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nicorandil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nitroprusside	Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside.
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Pentoxifylline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Pholcodine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine.
Phosphodiesterase 5 Inhibitors	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Piribedil	CNS Depressants may enhance the CNS depressant effect of Piribedil.
Pramipexole	CNS Depressants may enhance the sedative effect of Pramipexole.
Prostacyclin Analogues	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Quinagolide	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
ROPINIRole	CNS Depressants may enhance the sedative effect of ROPINIRole.
Rotigotine	CNS Depressants may enhance the sedative effect of Rotigotine.
Rufinamide	May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
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.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Selective Serotonin Reuptake Inhibitors	CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.
Serotonin/Norepinephrine Reuptake Inhibitors	May diminish the antihypertensive effect of Alpha2-Agonists.
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Terlipressin	May enhance the bradycardic effect of Bradycardia-Causing Agents.
Tetrahydrocannabinol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Tofacitinib	May enhance the bradycardic effect of Bradycardia-Causing Agents.
Trimeprazine	May enhance the CNS depressant effect of CNS Depressants.
Valproate Products	GuanFACINE may increase the serum concentration of Valproate Products.
Yohimbine	May diminish the antihypertensive effect of Antihypertensive Agents.
Risk Factor D (Consider therapy modification)
Amifostine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered.
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. Exceptions: Levobunolol; Metipranolol.
Blonanserin	CNS Depressants may enhance the CNS depressant effect of Blonanserin.
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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.
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. Exceptions are discussed in separate monographs.
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.
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating guanfacine in a patient taking a moderate CYP3A4 inducer. Increase guanfacine dose gradually over 1 to 2 weeks if initiating a moderate CYP3A4 inducer in a patient already taking guanfacine.
CYP3A4 Inducers (Strong)	May decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating guanfacine in a patient taking a strong CYP3A4 inducer. Increase guanfacine dose gradually over 1 to 2 weeks if initiating strong CYP3A4 inducer therapy in a patient already taking guanfacine.
CYP3A4 Inhibitors (Moderate)	May increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination.
CYP3A4 Inhibitors (Strong)	May increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination.
Dabrafenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
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. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
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.
Flunitrazepam	CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.
HYDROcodone	CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone 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.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
Methotrimeprazine	CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established.
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.
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.
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.
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.
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.
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.
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.
Pitolisant	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant.
Siponimod	Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia.
Sodium Oxybate	May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated.
St John's Wort	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
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.
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.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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.
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.
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 Factor X (Avoid combination)
Alcohol (Ethyl)	May enhance the CNS depressant effect of GuanFACINE.
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Bromperidol	May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol.
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
Thalidomide	CNS Depressants may enhance the CNS depressant effect of Thalidomide.

Monitoring parameters:

Heart Rate and Blood Pressure

ADHD Treatment:

Thorough Evaluation: Before starting guanfacine for ADHD, healthcare providers should carefully assess the individual's cardiovascular risk.
Monitoring: Regularly check heart rate and blood pressure, especially before beginning the medication, after adjusting the dosage, and at periodic intervals afterward.
ECG Consideration: In some cases, it may be a good idea to get an electrocardiogram (ECG) before starting guanfacine (Vetter 2008).

Hypertension Management (Based on ACC/AHA Guidelines 2017):

Confirmed Hypertension with Known CVD or 10-year ASCVD Risk ≥10%:
- Recommended Target Blood Pressure: Less than 130/80 mm Hg.
Confirmed Hypertension without Increased ASCVD Risk Markers:
- Reasonable Target Blood Pressure: Less than 130/80 mm Hg may be considered.

These guidelines provide direction for managing blood pressure in individuals with hypertension, taking into account cardiovascular disease (CVD) and a person's 10-year risk of atherosclerotic cardiovascular disease (ASCVD). Regular monitoring and adherence to these targets help guide the use of guanfacine for ADHD and hypertension.

How to administer Guanfacine (Intuniv)?

Timing:
- Immediate-Release Tablets: Typically administered at bedtime to reduce drowsiness (somnolence).
Formulation Note:
- Immediate Release vs. Extended Release: It's important to note that the immediate-release and extended-release formulations of guanfacine are not interchangeable. Each has its specific characteristics, and switching between them should only be done under the guidance of a healthcare professional.

Mechanism of action of Guanfacine (Intuniv):

Guanfacine is a medication that works by reducing certain nerve signals in the body.
It specifically targets alpha-adrenoreceptors, leading to a decrease in heart rate and a relaxing effect on blood vessels.
Guanfacine also binds to receptors in the prefrontal cortex of the brain, which is linked to attention and behavior control.
This action is thought to improve the firing of neurons in this area, affecting working memory and behavioral inhibition.
This, in turn, helps to manage symptoms associated with Attention-Deficit/Hyperactivity Disorder (ADHD).
It's important to note that guanfacine is not a stimulant for the central nervous system.
Additionally, the extended-release form of guanfacine, when taken at the same dose as the immediate-release form, results in a lower peak concentration in the blood and a lower overall exposure to the medication.

Absorption:

Readily absorbed.

Duration of Antihypertensive Effect:

Lasts up to 24 hours following a single dose.

Distribution:

Immediate Release:
- Volume of Distribution: 6.3 L/kg.
Extended Release:
- Children (≥6 years): 23.7 L/kg.
- Adolescents: 19.9 L/kg (Boellner 2007).

Protein Binding:

Approximately 70%.

Metabolism:

Hepatic metabolism primarily through CYP3A4.
About 50% of clearance occurs in the liver.

Bioavailability:

Immediate Release: Approximately 80%.
Extended Release: 58% relative to immediate release.

Half-life Elimination:

Immediate Release: About 17 hours (range: 10 to 30 hours).
Extended Release:
- Children (≥6 years): 14.4 hours.
- Adolescents: 18 hours (Boellner 2007).
- Adults: 16 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.