GUANFACINE- guanfacine hydrochloride tablet
Guanfacine hydrochloride is a centrally acting antihypertensive with α 2 -adrenoceptor agonist properties in tablet form for oral administration.
The chemical name of guanfacine hydrochloride is N -Amidino-2-(2,6-dichlorophenyl) acetamide monohydrochloride and its molecular weight is 282.55. Its structural formula is:
Guanfacine hydrochloride is a white to off-white powder; sparingly soluble in water and alcohol and slightly soluble in acetone.
Each tablet, for oral administration, contains guanfacine hydrochloride equivalent to 1 mg or 2 mg guanfacine. The tablets contain the following inactive ingredients:
1 mg — anhydrous lactose, FD&C Red 40 aluminum lake, microcrystalline cellulose, povidone, stearic acid.
2 mg — anhydrous lactose, D&C Yellow 10 aluminum lake, FD&C Red 40 aluminum lake, microcrystalline cellulose, povidone, stearic acid.
Guanfacine hydrochloride is an orally active antihypertensive agent whose principal mechanism of action appears to be stimulation of central α 2 -adrenergic receptors. By stimulating these 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.
The dose-response relationship for blood pressure and adverse effects of guanfacine given once a day as monotherapy has been evaluated in patients with mild to moderate hypertension. In this study patients were randomized to placebo or to 0.5 mg, 1 mg, 2 mg, 3 mg, or 5 mg of guanfacine. Results are shown in the following table. A useful effect was not observed overall until doses of 2 mg were reached, although responses in white patients were seen at 1 mg; 24 hour effectiveness of 1 mg to 3 mg doses was documented using 24 hour ambulatory monitoring. While the 5 mg dose added an increment of effectiveness, it caused an unacceptable increase in adverse reactions.
|Mean Change S/D* Seated||n= (range)||Placebo||0.5 mg||1 mg||2 mg||3 mg||5 mg|
|*S/D = Systolic/diastolic blood pressure|
Controlled clinical trials in patients with mild to moderate hypertension who were receiving a thiazide-type diuretic have defined the dose-response relationship for blood pressure response and adverse reactions of guanfacine given at bedtime and have shown that the blood pressure response to guanfacine can persist for 24 hours after a single dose. In the 12-week placebo-controlled dose-response study, patients were randomized to placebo or to doses of 0.5, 1, 2, and 3 mg of guanfacine, in addition to 25 mg chlorthalidone, each given at bedtime. The observed mean changes from baseline, tabulated below, indicate the similarity of response for placebo and the 0.5 mg dose. Doses of 1, 2, and 3 mg resulted in decreased blood pressure in the sitting position with no real differences among the three doses. In the standing position there was some increase in response with dose.
|Mean Change||n=||Placebo 63||0.5 mg 63||1 mg 64||2 mg 58||3 mg 59|
|*S/D = Systolic/diastolic blood pressure|
While most of the effectiveness of guanfacine in combination (and as monotherapy in white patients) was present at 1 mg, adverse reactions at this dose were not clearly distinguishable from those associated with placebo. Adverse reactions were clearly present at 2 and 3 mg (see ADVERSE REACTIONS).
In a second 12-week placebo-controlled study of 1, 2, or 3 mg of guanfacine hydrochloride administered with 25 mg of chlorthalidone once daily, a significant decrease in blood pressure was maintained for a full 24 hours after dosing. While there was no significant difference between the 12 and 24 hour blood pressure readings, the fall in blood pressure at 24 hours was numerically smaller, suggesting possible escape of blood pressure in some patients and the need for individualization of therapy.
In a double-blind, randomized trial, either guanfacine or clonidine was given at recommended doses with 25 mg chlorthalidone for 24 weeks and then abruptly discontinued. Results showed equal degrees of blood pressure reduction with the two drugs and there was no tendency for blood pressures to increase despite maintenance of the same daily dose of the two drugs. Signs and symptoms of rebound phenomena were infrequent upon discontinuation of either drug. Abrupt withdrawal of clonidine produced a rapid return of diastolic and especially, systolic blood pressure to approximately pretreatment levels, with occasional values significantly greater than baseline, whereas guanfacine withdrawal produced a more gradual increase to pretreatment levels, but also with occasional values significantly greater than baseline.
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.