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:
-
Immediate release:
- Oral: Initially it can be given as 0.5 to 1 mg once a day at bedtime. It may be increased as needed after 3 to 4 weeks up to 2 mg once daily at bedtime.
- Note: Adverse reactions can increase drastically with doses above 3 mg/day.
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:
- ≤45 kg: Oral:
- Initially, it can be given as 0.5 mg once a day at bedtime. It can be titrated every 3 to 4 days in 0.5 mg/day increments to 0.5 mg twice a day, then 0.5 mg three times daily, then 0.5 mg four times daily.
- The maximum daily dose is according to patient weight. For 27 to 40.5 kg: 2 mg/day and for 40.5 to 45 kg: 3 mg/day
- >45 kg: Oral:
- Initially, it can be given as 1 mg once a day at bedtime. It can be titrated up every 3 to 4 days in 1 mg/day increments to 1 mg twice a day, then 1 mg three times daily, then 1 mg four times a day.
- The maximum daily dose is 4 mg/day.
- ≤45 kg: Oral:
-
-
Extended-release product (eg, Intuniv):
- Children and Adolescents 6 to 17 years:
- Oral: Initially 1 mg once a day administered at the same time of day (in the morning or evening).
- It may be titrated up to dose by no more than 1 mg/week increments based upon response and as tolerated to the recommended target dose range which is 0.05 to 0.12 mg/kg/day or 1 to 7 mg/day.
- The target range based on data from monotherapy trials to balance the exposure (dose)-related potential benefits and risks (bradycardia, hypotension, and sedation).
- In clinical monotherapy trials, initial clinical response was associated with doses of 0.05 to 0.08 mg/kg once daily. Increased effects were 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 are given once a day, either in morning or evening not exceeding the maximum daily dose allowed.
- 25 to 33.9 kg:
- 2 to 3 mg/day
- 34 to 41.4 kg:
- 2 to 4 mg/day
- 5 to 49.4 kg:
- 3 to 5 mg/day
- 5 to 58.4 kg:
- 3 to 6 mg/day
- 5 to 91 kg:
- 4 to 7 mg/day
- >91 kg:
- 5 to 7 mg/day
- Maximum daily doses: Above mentioned doses are not evaluated in studies.
- Monotherapy:
- Children 6 to 12 years:
- 4 mg/day.
- In adolescents of 13 to 17 years: 7 mg/day
- Children 6 to 12 years:
- Adjunct therapy (with psychostimulants):
- 4 mg/day
- Monotherapy:
-
-
Conversion from immediate release guanfacine to the extended release product:
- Discontinue the immediate release product. Start the extended release product at the doses recommended as described above.
-
Missed doses of extended release:
- If patient misses two or more consecutive doses, repeat titration of dose should be considered.
-
Discontinuation of extended release:
- Taper dose by no more than 1 mg every week.
-
Dosing adjustment for concomitant CYP3A4 inhibitors/inducers with extended release:
- Strong CYP3A4 inhibitors:
- If initiating guanfacine while taking a strong 3A4 inhibitor, decrease guanfacine dose to 50% the recommended target dose .
- If continuing guanfacine and adding a strong CYP3A4 inhibitor, decrease guanfacine dose by 50% the recommended target dose.
- If the strong CYP3A4 inhibitor is discontinued, increase guanfacine to the recommended target dose.
- Strong CYP3A4 inducers:
- If initiating guanfacine while taking a strong CYP3A4 inducer, consider enhancing the dose up to double the recommended target dose.
- If continuing guanfacine and adding a strong CYP3A4 inducer, consider increasing guanfacine dose up to double the recommended target dose over 1 to 2 weeks.
- If the strong CYP3A4 inducer is stopped, decrease guanfacine dose to recommended target dose over 1 to 2 weeks.
- Strong CYP3A4 inhibitors:
- Children and Adolescents 6 to 17 years:
Guanfacine (Intuniv) Dose in the treatment of Hypertension:
-
Children ≥12 years and Adolescents:
- Immediate release product: Oral:
- 1 mg usually at bedtime. It can be increased, if needed, at 3- to 4-week intervals.
- Usual range is 0.5 to 2 mg/day.
- Maximum daily dose is 2 mg/day
- Immediate release product: Oral:
Guanfacine (Intuniv) Dose in the treatment of Pervasive developmental disorders (PDD) and ADHD:
-
Children and Adolescents 5 to 14 years:
-
Immediate release product:
- <25 kg: Oral:
- Initial: 0.25 mg once a day, increase dose as tolerated every 4 days in 0.25 mg/day increments in 2 to 3 divided doses.
- The maximum daily dose is 3 mg/day (Scahill 2006)
- ≥25 kg: Oral:
- Initially 0.5 mg once a day.
- The dose can be increased as tolerated every 4 days in 0.5 mg/day increments in 2 to 3 divided doses.
- The maximum daily dose is 3 mg/day.
- <25 kg: Oral:
-
Guanfacine (Intuniv) Dose in the treatment of Tic disorder; Tourette syndrome:
Greater efficacy was shown in patients with ADHD comorbidity:
-
Children and Adolescents 6 to 16 years:
-
Immediate release product:
- Oral: Initial: 0.5 mg once a day at bedtime for 3 days, then 0.5 mg twice a day for 4 days, then 0.5 mg 3 times daily for 7 days.
- More upward titration based on clinical response to maximum daily dose: 4 mg/day.
- Twice daily dosing may be effective for some patients.
- The reported final dose range is 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 the morning, 0.5 mg at 3 pm, and 1 mg at bedtime).
- For Tourette’s syndrome and ADHD, the final reported dose range is 0.75 to 3 mg/day in divided doses (2 to 3 times daily).
-
Pregnancy Risk Factor B
- Studies regarding Guanfacine use in pregnancy showed limited data.
- Chronic maternal hypertension, if left untreated, had poor outcomes for the mother, infant, and even the fetus.
- If treatment for hypertension or attention-deficit/hyperactivity disorder during pregnancy is needed, other agents are recommended.
Guanfacine use during breastfeeding:
- It is unclear whether Guanfacine is secreted into breast milk.
- Guanfacine should not be given to women who are breastfeeding.
Guanfacine (Intuniv) Dose in Kidney disease:
-
Immediate release:
- There are no particular dose adjustments provided in the manufacturer’s labeling.
- However, the lower end of the dosing range should be given in patients with renal impairment.
-
Hemodialysis:
- Dialysis clearance is low for both immediate release or extended release. (~15% of total clearance).
Guanfacine (Intuniv) Dose in Liver disease:
-
Immediate release:
- There are no dosage adjustments provided in the manufacturer’s labeling but use with caution in chronic hepatic impairment.
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):
- It is possible to develop hypersensitivity to guanfacine and any component of the formulation.
- This makes it absolutely contraindicated.
Warnings and precautions
-
Cardiovascular effects
- It can cause hypotension, orthostasis and atrioventricular block.
- These effects can be dose dependent and more severe during the first month. They may also worsen if combined with other sympatholytic medications.
- Patients with abnormal cardiac conduction or patients receiving other sympatholytic drugs should monitor their vital signs regularly.
-
CNS effects
- It can also cause somnolence or drowsiness, which can affect your mental and physical abilities.
- It is important to warn patients against performing tasks that require mental alertness, such as driving heavy machinery or operating heavy machinery.
-
Dermatological effects
- Exfoliation, pruritus and skin rash are common. Monitor patients who have skin reactions to guanfacine and stop using it.
-
Cardiovascular disease
- Patients with severe coronary disease, MI, recent MI, bradycardia or other cardiovascular conditions, as well as patients who have had heart attack, hypotension, bradycardia or any other type of syncope, should be cautious.
- Patients with predisposing conditions to syncope such as orthostasis or dehydration should be advised to use caution.
-
Cerebrovascular disease
- Patients with Cerebrovascular Events should exercise caution.
-
Hepatic impairment
- Patients with chronic hepatic impairment should be cautious. In severe cases of impairment, dose adjustment may be necessary.
-
Renal impairment
- Patients with ESRD should be cautious. In severe impairment, dose adjustment is necessary.
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
- Blood pressure
ADHD:
- Thoroughly evaluate for cardiovascular risk.
- Monitor heart rate, blood pressure (prior to initiation, following dosage adjustments, and periodically thereafter).
- Consider obtaining ECG prior to initiation.
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 enough.
How to administer Guanfacine (Intuniv)?
- Oral: Immediate-release tablets are usually given at night to minimize drowsiness.
- Formulations (immediate-release and extended-release) are not interchangeable.
Mechanism of action of Guanfacine (Intuniv):
- 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.
- Guanfacine preferentially binds postsynaptic alpha-2A-adrenoreceptors in the prefrontal cortex and has been theoretically shown to improve delay-related firing of prefrontal cortex neurons.
- This causes impairments in working memory and behavior inhibition.
- This improves ADHD symptoms. Guanfacine does not act as a CNS stimulant.
Notice:
-
- Doses of the same mg are administered at an extended-release product with a lower peak serum concentration (60%) and AUC (43%) than the immediate-release formulation.
Absorption:
- Readily absorbed.
Duration of antihypertensive effect:
- 24 hours following a single dose
Protein binding:
- About 70%
Metabolism:
- Hepatic via CYP3A4.
- Approximately 50% of clearance is hepatic.
Bioavailability:
- Immediate-release: about 80%
- Extended-release (relative to immediate-release): 58%
Half-life elimination:
- Immediate release:
- about 17 hours (range: 10 to 30 hours)
- Extended-release:
- Children ≥6 years: 14.4 hours.
- Adolescents: 18 hours
- 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.
- Adults: 4 to 8 hours
Excretion:
- Urine (about 50% as unchanged drug) 40% to 75% of the dose.
International Brand Names of Guanfacine:
- Intuniv
- Intuniv XR
- Tenex
- Dipresan
- Estulic
- Hipertensal
Guanfacine Brand Names in Pakistan:
No Brands Available in Pakistan.
.png)
