Guanfacine

246.09326

246.09

249-442-8

30OMY4G3MK

DTXSID9046944

C61779

C02AC02|C - Cardiovascular system

2925290090

81.5

1.7

Solid

1.5±0.1 g/cm3

226 °C

424.9ºC at 760 mmHg

210.8ºC

1.635

1.39e-01 g/L

Refrigerator

2E-07mmHg at 25°C

148.9 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

P264, P270, P301+P310, P321, P330, P405, P501

H301

|Danger|H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P321, P330, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

The oral LD50 in rats is 142mg/kg and 15.3mg/kg in mice. The subcutaneous LD50 in rats is 114mg/kg and 46mg/kg in mice. Patients experiencing and overdose may present with hypotension, drowsiness, lethargy, and bradycardia. Overdose should be managed by first calling local poison control. Patients may require intravenous saline to maintain blood pressure.

In the multiple clinical trials of guanfacine in adolescents and children with ADHD there were no reports of serum enzyme elevations or in instances of clinically apparent liver injury. Furthermore, despite widescale use of the agent for both hypertension and ADHD, there have been no reports of clinically apparent liver injury attributable to guanfacine. Thus, significant liver injury from guanfacine must be quite rare, if it exists at all.

Guanfacine is approximately 70% protein bound in serum.

Guanfacine is indicated alone or as an adjunct with stimulants to treat ADHD.|Treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents 6 to 17 years old for whom stimulants are not suitable, not tolerated or have been shown to be ineffective.Intuniv must be used as a part of a comprehensive ADHD treatment programme, typically including psychological, educational and social measures.

Guanfacine is a selective alpha-adrenergic receptor agonist used for the treatment of hypertension and attention deficit hyperactivity disorder (ADHD) in adults and children. Guanfacine has not been linked to serum enzyme elevations during treatment or to cases of acute, clinically apparent liver injury.

Antihypertensive Agents

Guanfacine is a selective alpha-2A adrenergic receptor agonist but it is unclear how this translates to the treatment of ADHD. It has a long duration of action as it is given once daily and a wide therapeutic window as fatal overdoses have not been described in literature. Patients should be counselled regarding the risk of hypotension, bradycardia, and syncope.

Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS. (See all compounds classified as Adrenergic alpha-2 Receptor Agonists.)|Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)

Guanfacine is 80% orally bioavailable. 1mg immediate release oral guanfacine reaches a C_max of 2.5±0.6ng/mL with a T_max of 3.0h and an AUC of 56±15ng\*h/mL. 1mg extended release oral guanfacine reaches a C_max of 1.0±0.3ng/mL with a T_max of 6.0h and an AUC of 32±9ng\*h/mL. In adults, a 4mg oral extended release dose reaches a C_max of 3.58±1.39ng/mL with a T_max of 5.5h; in children, a 2mg oral extended relsease dose reaches a C_max of 2.6±1.03ng/mL with a T_max of 4.98h; in adolescents, a 2mg oral extended release dose reaches a C_max of 1.7±0.43ng/mL with a T_max of 4.96h.|Guanfacine is 57.0±32.0% eliminated in the urine in patients with normal renal function. Patients with a glomerular filtration rate (GFR) of 10-30mL/min eliminate 14.0±9.0% of a dose in the urine, while patients with a GFR of <1mL/min eliminate 7.5±2.4% of a dose in the urine.|Guanfacine has a volume of distribution of 6.3L/kg.|Guanfacine has a total body cleraance of 360±262mL/min and a renal clearance of 233±245mL/min in patients with normal renal function. Patients with a glomerular filtration rate (GFR) of 10-30mL/min had a total body clearance of 308±274mL/min and a renal clearance of 34±22mL/min. Patients with a GFR of <1mL/min had a total body clearance of 257±187mL/min and a renal clearance of 18±15mL/min.

Guanfacine is oxidized by CYP3A4 to it's main metabolite, 3-hydroxyguanfacine. 3-hydroxyguanfacine is then either glucuronidated or sulphated.

Guanfacine has a half life of 17 hours, but this may range from 10-30 hours. The half life is largely independant of renal function.

Guanfacine is a selective alpha-2A adrenergic receptor agonist, which reduces the effects of the sympathetic nervous system on the heart and circulatory system. The link between guanfacine’s molecular mechanism and it’s effect on the treatment of ADHD has not been determined.

BS 100 141

Human drugs -> Intuniv -> EMA Drug Category|Antiadrenergic agents, centrally acting, Antihypertensives -> Human pharmacotherapeutic group