グアンファシン

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals

1mg/mL

1.39e-01 g/L

Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

213-216

225 - 227 °C

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

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

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P260, P264, P270, P273, P280, P301+P316, P318, P319, P321, P330, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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.

◉ Summary of Use during Lactation

◈ What is guanfacine?

Guanfacine

0.02

0.1

The recommended initial dose of guanfacine hydrochloride when given alone or in combination with another antihypertensive drug is 1 mg daily given at bedtime to minimize somnolence.

Data used to generate the benchmarks include the following: Lowest Daily Dose (LDD): 1 mg/day, Lowest Therapeutic Dose (LTD): 0.01 mg/kg-day, and Screening Dose: 0.000004 mg/kg-day.

31-Jul-14

C02AC02

C - Cardiovascular system

QC - Cardiovascular system

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.

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.

30OMY4G3MK

GUANFACINE

Mechanisms of Action [MoA] - Adrenergic alpha2-Agonists

Established Pharmacologic Class [EPC] - Central alpha-2 Adrenergic Agonist

Guanfacine is a Central alpha-2 Adrenergic Agonist. The mechanism of action of guanfacine is as an Adrenergic alpha2-Agonist.

GUANFACINE

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.

Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.

Guanfacine is 80% orally bioavailable. 1mg immediate release oral guanfacine reaches a Cmax of 2.5±0.6ng/mL with a Tmax of 3.0h and an AUC of 56±15ng\*h/mL. 1mg extended release oral guanfacine reaches a Cmax of 1.0±0.3ng/mL with a Tmax of 6.0h and an AUC of 32±9ng\*h/mL. In adults, a 4mg oral extended release dose reaches a Cmax of 3.58±1.39ng/mL with a Tmax of 5.5h; in children, a 2mg oral extended relsease dose reaches a Cmax of 2.6±1.03ng/mL with a Tmax of 4.98h; in adolescents, a 2mg oral extended release dose reaches a Cmax of 1.7±0.43ng/mL with a Tmax 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.