Adult: As monotherapy or in combination with other antihypertensive agents (e.g. thiazide diuretics): As conventional tab: Initially, 1 mg daily at bedtime. May be increased to 2 mg daily after 3-4 weeks, if necessary. Max: 3 mg daily. Elderly: Initiate at the lower end of the dosing range. Child: ≥12 years Same as adult dose.
Child: 6-17 years As monotherapy or adjunctive therapy in patients for whom stimulants are not suitable, not tolerated, or ineffective: As extended-release tab: Initially, 1 mg once daily, may be adjusted in increments of not more than 1 mg per week. Max: 6-12 years 4 mg daily; 13-17 years 7 mg daily. Maintenance: 0.05-0.12 mg/kg daily. Dose must be individualised based on patient's response and tolerability. Dosage recommendations may vary among individual products and between countries (refer to specific product guidelines).
Special Patient Group
Patients taking CYP3A4 and CYP3A5 inhibitors: Dose reduction of guanfacine is recommended.
Renal Impairment
Hypertension:
Initiate at the lower end of the dosing range.
Administration
May be taken with or without food. ER tab: Swallow whole & do not crush/chew/break. Do not take w/ high-fat meal.
Special Precautions
Patient with severe coronary insufficiency, recent MI; history of hypotension, heart block, bradycardia, CV disease, history of syncope or conditions which may predispose them to syncope (e.g. dehydration), history of QT prolongation, risk factors for torsade de pointes (e.g. heart block, hypokalaemia); cerebrovascular disease. Avoid abrupt withdrawal. Guanfacine conventional tab and extended-release tab should not be interchanged on a mg/mg basis because of differing pharmacokinetic profiles. Renal and hepatic impairment. Children and elderly. Pregnancy and lactation. Concomitant therapy with other antihypertensives and moderate and strong CYP3A4 and CYP3A5 inhibitors.
Adverse Reactions
Significant: CV effects (including syncope, bradycardia, hypotension, orthostatic hypotension, sinoatrial nodal rhythm disorder, AV block), CNS effects (e.g. headache, drowsiness, sedation, insomnia), aggressive behaviour or hostility (often in children and adolescents with ADHD), increased BMI (particularly in children and adolescents), withdrawal syndrome (e.g. nervousness, anxiety, rebound hypertension). Cardiac disorders: Chest pain. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation, abdominal pain, stomach discomfort, dry mouth. General disorders and administration site conditions: Fatigue, asthenia, fever, irritability. Investigations: Increased weight. Metabolism and nutrition disorders: Decreased appetite. Nervous system disorders: Somnolence, headache, sedation, dizziness, lethargy, convulsion, syncope. Psychiatric disorders: Depression, anxiety, insomnia, nightmares, affect lability, middle insomnia. Renal and urinary disorders: Enuresis. Reproductive system and breast disorders: Impotence. Respiratory, thoracic and mediastinal disorders: Asthma. Skin and subcutaneous tissue disorders: Rash, pruritus. Potentially Fatal: Suicide-related events including suicidal ideation, attempts, and completed suicide).
This drug may cause dizziness and somnolence, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor heart rate, blood pressure (prior to treatment initiation, after dose adjustment, and periodically thereafter); mental alertness. ADHD: Consider ECG prior to initiation. Evaluate thoroughly for CV risk.
Overdosage
Symptoms: Drowsiness, lethargy, bradycardia, initial hypertension, respiratory depression, and hypotension. Paediatric patients who develop lethargy should be observed for the development of more serious toxicity (e.g. coma) for up to 24 hours due to the possibility of delayed onset of these symptoms. Management: Supportive treatment. Perform gastric lavage if ingestion is recent. Administration of activated charcoal may be considered.
Drug Interactions
Additive hypotensive effects with diuretics. Additive pharmacodynamic effects with other antihypertensives, CNS depressants (e.g. antipsychotics, barbiturates, benzodiazepines, hypnotics, sedatives), and other QT prolongation medications. Decreased elimination half-life and serum concentration with phenobarbital and phenytoin. Increased plasma concentrations with moderate and strong CYP3A4 and CYP3A5 inhibitors. Decreased rate and extent of exposure with CYP3A4 inducers (e.g. rifampicin, efavirenz). May increase serum concentration of valproic acid.
Food Interaction
Increased exposure with high-fat meal (extended-release tab). Increased plasma concentrations with grapefruit juice. Additive sedative effect with alcohol.
Lab Interference
May result in false-positive aldosterone/renin ratio (ARR).
Action
Description: Mechanism of Action: Guanfacine, a phenylacetyl-guanidine derivative, is a selective α2A-adrenoreceptor agonist. It reduces sympathetic nerve impulses from the vasomotor centre to the heart and blood vessels, thus resulting in a decrease in peripheral vascular resistance, renal vascular resistance, blood pressure, and heart rate. Additionally, it binds to postsynaptic α2A-adrenoreceptors in the prefrontal cortex and has been theorised to enhance prefrontal cortex neurons, thereby improving symptoms associated with attention deficit hyperactivity disorder (ADHD). Duration: Antihypertensive effect: 24 hours (as conventional tab). Pharmacokinetics: Absorption: Readily absorbed from the gastrointestinal tract. Bioavailability: Approx 80%. Time to peak plasma concentration: Conventional tab: 2.6 hours (range: 1-4 hours); Extended-release tab: 4-8 hours. Distribution: Extensively distributed in tissues. Plasma protein binding: Approx 70%. Metabolism: Metabolised in the liver via CYP3A4/5-mediated oxidation to form the inactive 3-hydroxy derivative (major metabolite), which undergoes subsequent sulfation and glucuronidation. Excretion: Via urine (approx 80%; 40-75% as unchanged drug). Elimination half-life: Conventional tab: Approx 17 hours (range: 10-30 hours); Extended-release tab: Approx 18 ± 4 hours.
Chemical Structure
Guanfacine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3519, Guanfacine. https://pubchem.ncbi.nlm.nih.gov/compound/Guanfacine. Accessed Mar. 22, 2024.
C02AC02 - guanfacine ; Belongs to the class of imidazoline receptor agonists, centrally-acting antiadrenergic agents. Used in the treatment of hypertension.
References
Anon. Guanfacine. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 05/02/2024.Anon. Guanfacine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/10/2023.Buckingham R (ed). Guanfacine Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/10/2023.Guanfacine Hydrochloride Tablet (Amneal Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 05/02/2024.Guanfacine Tablet, Extended-Release (Slate Run Pharmaceuticals, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 05/02/2024.Guanfacine. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 05/10/2023.Intuniv 2 mg Prolonged-release Tablets (Takeda Pharmaceuticals International AG Ireland Branch). MHRA. https://products.mhra.gov.uk. Accessed 07/02/2024.Intuniv Tablet, Extended Release (Takeda Pharmaceuticals America, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 05/10/2023.Joint Formulary Committee. Guanfacine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/10/2023.
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