AGE
Symptoms
Post-marketing reports of guanfacine overdosage indicate that hypotension, drowsiness, lethargy, and bradycardia have been observed following overdose. Initial hypertension may develop early and may be followed by hypotension. Similar symptoms have been described in voluntary reports to the American Association of Poison Control Center’s National Poison Data System. Miosis of the pupils may be noted on examination No fatal overdoses of guanfacine have been reported in published literature. .
Treatment
Consult a Certified Poison Control Center by calling 1-800-222-1222 for up to date guidance and advice.
Management of INTUNIV overdose should include monitoring for and the treatment of initial hypertension, if that occurs, as well as hypotension, bradycardia, lethargy and respiratory depression. Children and adolescents who develop lethargy should be observed for the development of more serious toxicity including coma, bradycardia and hypotension for up to 24 hours, due to the possibility of delayed onset hypotension. ®
11 DESCRIPTION
INTUNIV is a once-daily, extended-release formulation of guanfacine hydrochloride (HCl) in a matrix tablet formulation for oral administration only. The chemical designation is N-amidino-2-(2,6-dichlorophenyl) acetamide monohydrochloride. The molecular formula is C H Cl N O·HCl corresponding to a molecular weight of 282.55. The chemical structure is: ®9923
spd503-chemical-stucture
Guanfacine HCl is a white to off-white crystalline powder, sparingly soluble in water (approximately 1 mg/mL) and alcohol and slightly soluble in acetone. The only organic solvent in which it has relatively high solubility is methanol (>30 mg/mL). Each tablet contains guanfacine HCl equivalent to 1 mg, 2 mg, 3 mg, or 4 mg of guanfacine base. The tablets also contain hypromellose, methacrylic acid copolymer, lactose, povidone, crospovidone, microcrystalline cellulose, fumaric acid, and glyceryl behenate. In addition, the 3mg and 4mg tablets also contain green pigment blend PB-1763.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Guanfacine is a central alpha -adrenergic receptor agonist. Guanfacine is not a central nervous system (CNS) stimulant. The mechanism of action of guanfacine in ADHD is not known. 2A
12.2 Pharmacodynamics
Guanfacine is a selective central alpha -adrenergic receptor agonist in that it has a 15-20 times higher affinity for this receptor subtype than for the alpha or alpha subtypes. 2A2B2C
Guanfacine is a known antihypertensive agent. By stimulating central alpha -adrenergic receptors, guanfacine reduces sympathetic nerve impulses from the vasomotor center to the heart and blood vessels. This results in a decrease in peripheral vascular resistance and a reduction in heart rate. 2A
Effects on Height, Weight, and Body Mass Index (BMI)
Patients taking INTUNIV demonstrated similar growth compared to normative data. Patients taking INTUNIV had a mean increase in weight of 0.5 kg (1 lb) compared to those receiving placebo over a comparative treatment period. Patients receiving INTUNIV for at least 12 months in open-label studies gained an average of 8 kg (17 lbs) in weight and 8 cm (3 in) in height. The height, weight, and BMI percentile remained stable in patients at 12 months in the long-term studies compared to when they began receiving INTUNIV . ®®®®
Effect on ECG
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