Guanfacine

INDICATIONS AND USAGE Guanfacine Tablets, USP are indicated in the management of hypertension. Guanfacine hydrochloride may be given alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

DOSAGE AND ADMINISTRATION The recommended initial dose of guanfacine tablets when given alone or in combination with another antihypertensive drug is 1 mg daily given at bedtime to minimize somnolence. If after 3 weeks to 4 weeks of therapy 1 mg does not give a satisfactory result, a dose of 2 mg may be given, although most of the effect of guanfacine tablets are seen at 1 mg (see CLINICAL PHARMACOLOGY ). Higher daily doses have been used, but adverse reactions increase significantly with doses above 3 mg/day. The frequency of rebound hypertension is low, but it can occur. When rebound occurs, it does so after 2 days to 4 days, which is delayed compared with clonidine hydrochloride. This is consistent with the longer half-life of guanfacine. In most cases, after abrupt withdrawal of guanfacine, blood pressure returns to pretreatment levels slowly (within 2 days to 4 days) without ill effects.

CONTRAINDICATIONS Guanfacine hydrochloride tablets are contraindicated in patients with known hypersensitivity to guanfacine hydrochloride.

ADVERSE REACTIONS Adverse reactions noted with guanfacine hydrochloride are similar to those of other drugs of the central α 2 -adrenoreceptor agonist class: dry mouth, sedation (somnolence), weakness (asthenia), dizziness, constipation, and impotence. While the reactions are common, most are mild and tend to disappear on continued dosing. Skin rash with exfoliation has been reported in a few cases; although clear cause and effect relationships to guanfacine tablets could not be established, should a rash occur, guanfacine tablets should be discontinued and the patient monitored appropriately. In the dose-response monotherapy study described under CLINICAL PHARMACOLOGY , the frequency of the most commonly observed adverse reactions showed a dose relationship from 0.5 mg to 3 mg as follows: Adverse Reaction Placebo n = 59 0.5 mg n = 60 1 mg n = 61 2 mg n = 60 3 mg n = 59 Dry Mouth 0 % 10 % 10 % 42 % 54 % Somnolence 8 % 5 % 10 % 13 % 39 % Asthenia 0 % 2 % 3 % 7 % 3 % Dizziness 8 % 12 % 2 % 8 % 15 % Headache 8 % 13 % 7 % 5 % 3 % Impotence 0 % 0 % 0 % 7 % 3 % Constipation 0 % 2 % 0 % 5 % 15 % Fatigue 2 % 2 % 5 % 8 % 10 % The percent of patients who dropped out because of adverse reactions are shown below for each dosage group. Placebo 0.5 mg 1 mg 2 mg 3 mg Percent dropouts 0 % 2.0 % 5.0 % 13 % 32 % The most common reasons for dropouts among patients who received guanfacine were dry mouth, somnolence, dizziness, fatigue, weakness, and constipation. In the 12-week, placebo-controlled, dose-response study of guanfacine administered with 25 mg chlorthalidone at bedtime, the frequency of the most commonly observed adverse reactions showed a clear dose relationship from 0.5 mg to 3 mg as follows: Adverse Reaction Placebo n = 73 0.5 mg n = 72 1 mg n = 72 2 mg n = 72 3 mg n = 72 Dry Mouth 5 (7 %) 4 (5 %) 6 (8 %) 8 (11 %) 20 (28 %) Somnolence 1 (1 %) 3 (4 %) 0 (0 %) 1 (1 %) 10 (14 %) Asthenia 0 (0 %) 2 (3 %) 0 (0 %) 2 (2 %) 7 (10 %) Dizziness 2 (2 %) 1 (1 %) 3 (4 %) 6 (8 %) 3 (4 %) Headache 3 (4 %) 4 (3 %) 3 (4 %) 1 (1 %) 2 (2 %) Impotence 1 (1 %) 1 (0 %) 0 (0 %) 1 (1 %) 3 (4 %) Constipation 0 (0 %) 0 (0 %) 0 (0 %) 1 (1 %) 1 (1 %) Fatigue 3 (3 %) 2 (3 %) 2 (3 %) 5 (6 %) 3 (4 %) There were 41 premature terminations because of adverse reactions in this study. The percent of patients who dropped out and the dose at which the dropout occurred were as follows: Dose Placebo 0.5 mg 1 mg 2 mg 3 mg Percent dropouts 6.9 % 4.2 % 3.2 % 6.9 % 8.3 % Reasons for dropouts among patients who received guanfacine were: somnolence, headache, weakness, dry mouth, dizziness, impotence, insomnia, constipation, syncope, urinary incontinence, conjunctivitis, paresthesia, and dermatitis. In a second 12-week placebo-controlled combination therapy study in which the dose could be adjusted upward to 3 mg per day in 1-mg increments at 3-week intervals, i.e., a setting more similar to ordinary clinical use, the most commonly recorded reactions were: dry mouth, 47 %; constipation, 16 %; fatigue, 12 %; somnolence, 10 %; asthenia, 6 %; dizziness, 6 %; headache, 4 %; and insomnia, 4 %. Reasons for dropouts among patients who received guanfacine were: somnolence, dry mouth, dizziness, impotence, constipation, confusion, depression, and palpitations. In the clonidine/guanfacine comparison described in CLINICAL PHARMACOLOGY , the most common adverse reactions noted were as follows: Adverse Reactions Guanfacine (n = 279) Clonidine (n = 278) Dry Mouth 30 % 37 % Somnolence 21 % 35 % Dizziness 11 % 8 % Constipation 10 % 5 % Fatigue 9 % 8 % Headache 4 % 4 % Insomnia 4 % 3 % Adverse reactions occurring in 3 % or less of patients in the three controlled trials of guanfacine hydrochloride with a diuretic were: Cardiovascular- bradycardia, palpitations, substernal pain Gastrointestinal- abdominal pain, diarrhea, dyspepsia, dysphagia, nausea CNS- amnesia, confusion, depression, insomnia, libido decrease ENT disorders- rhinitis, taste perversion, tinnitus Eye disorders- conjunctivitis, i …

Drug Interactions The potential for increased sedation when guanfacine hydrochloride is given with other CNS-depressant drugs should be appreciated. The administration of guanfacine concomitantly with a known microsomal enzyme inducer (phenobarbital or phenytoin) to two patients with renal impairment reportedly resulted in significant reductions in elimination half-life and plasma concentration. In such cases, therefore, more frequent dosing may be required to achieve or maintain the desired hypotensive response. Further, if guanfacine is to be discontinued in such patients, careful tapering of the dosage may be necessary in order to avoid rebound phenomena (see Rebound above). Anticoagulants Ten patients who were stabilized on oral anticoagulants were given guanfacine, 1 - 2 mg/day, for 4 weeks. No changes were observed in the degree of anticoagulation. In several well-controlled studies, guanfacine was administered together with diuretics with no drug interactions reported. In the long-term safety studies, guanfacine hydrochloride was given concomitantly with many drugs without evidence of any interactions. The principal drugs given (number of patients in parentheses) were: cardiac glycosides (115), sedatives and hypnotics (103), coronary vasodilators (52), oral hypoglycemics (45), cough and cold preparations (45), NSAIDs (38), antihyperlipidemics (29), antigout drugs (24), oral contraceptives (18), bronchodilators (13), insulin (10), and beta blockers (10). Drug/Laboratory Test Interactions No laboratory test abnormalities related to the use of guanfacine hydrochloride have been identified.

DESCRIPTION Guanfacine hydrochloride, USP is a centrally acting antihypertensive with α 2 -adrenoceptor agonist properties in tablet form for oral administration. The chemical name of guanfacine hydrochloride, USP is N -Amidino-2-(2,6-dichlorophenyl) acetamide monohydrochloride and its molecular weight is 282.55. Its structural formula is: Guanfacine hydrochloride, USP 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, USP 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 chemical structure

OVERDOSAGE Signs and Symptoms: Drowsiness, lethargy, bradycardia and hypotension have been observed following overdose with guanfacine. A 25-year-old female intentionally ingested 60 mg. She presented with severe drowsiness and bradycardia of 45 beats/minute. Gastric lavage was performed and an infusion of isoproterenol (0.8 mg in 12 hours) was administered. She recovered quickly and without sequelae. A 28-year-old female who ingested 30 mg to 40 mg developed only lethargy, was treated with activated charcoal and a cathartic, was monitored for 24 hours, and was discharged in good health. A 2-year-old male weighing 12 kg who ingested up to 4 mg of guanfacine developed lethargy. Gastric lavage (followed by activated charcoal and sorbitol slurry via NG tube) removed some tablet fragments within 2 hours after ingestion, and vital signs were normal. During 24-hour observation in ICU, systolic pressure was 58 and heart rate 70 at 16 hours post-ingestion. No intervention was required, and the child was discharged fully recovered the next day. Treatment of Overdosage: Gastric lavage and supportive therapy as appropriate. Guanfacine is not dialyzable in clinically significant amounts (2.4%).

HOW SUPPLIED Guanfacine tablets, USP are available in the following dosing strengths (expressed in equivalent amounts of guanfacine): 1 mg- round, blue, uncoated tablets, debossed with Λ on one side and plain on other side. They are supplied as follows: 5 Bottles of 30, NDC 72888-123-30 Bottles of 100, NDC 72888-123-01 Bottles of 500, NDC 72888-123-05 Bottles of 1,000, NDC 72888-123-00 2 mg- round, white, uncoated tablets, debossed with Λ on one side and plain on other side. They are supplied as follows: 6 Bottles of 30, NDC 72888-124-30 Bottles of 100, NDC 72888-124-01 Bottles of 500, NDC 72888-124-05 Bottles of 1,000, NDC 72888-124-00 Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container. All the brands are trademarks of their respective owners. Distributed By: Advagen Pharma Ltd., East Windsor, NJ 08520, USA Manufactured by: Rubicon Research Limited Thane 421506, India. Rev. 12/2025