Guanfacine 2 mg Tablet, 100-count — NDC 27241-243-01 (Billing 27241-0243-01)

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… [Excerpted — this section continues on DailyMed.]

PRECAUTIONS General Like other antihypertensive agents, guanfacine hydrochloride should be used with caution in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease, or chronic renal or hepatic failure. Sedation Guanfacine tablets, like other orally active central α 2 -adrenergic agonists, causes sedation or drowsiness, especially when beginning therapy. These symptoms are dose-related (see ADVERSE REACTIONS ).

When guanfacine tablets are used with other centrally active depressants (such as phenothiazines, barbiturates, or benzodiazepines), the potential for additive sedative effects should be considered. Rebound Abrupt cessation of therapy with orally active central α 2 -adrenergic agonists may be associated with increases (from depressed on-therapy levels) in plasma and urinary catecholamines, symptoms of “nervousness and anxiety” and, less commonly, increases in blood pressure to levels significantly greater than those prior to therapy.

Information for Patients Patients who receive guanfacine tablets should be advised to exercise caution when operating dangerous machinery or driving motor vehicles until it is determined that they do not become drowsy or dizzy from the medication. Patients should be warned that their tolerance for alcohol and other CNS depressants may be diminished. Patients should be advised not to discontinue therapy abruptly.

Laboratory Tests In clinical trials, no clinically relevant laboratory test abnormalities were identified as causally related to drug during short-term treatment with guanfacine hydrochloride. Drug Interactions The potential for increased sedation when guanfacine tablets are 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 mg/day to 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 tablets were 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. Carcinogenesis, Mutagenesis, Impairment of Fertility No carcinogenic effect was observed in studies of 78 weeks in mice at doses more than 150 times the maximum recommended human dose and 102 weeks in rats at doses more than 100 times the maximum recommended human dose.

In a variety of test models, guanfacine was not mutagenic. No adverse effects were observed in fertility studies in male and female rats. Pregnancy Administration of guanfacine to rats at 70 times the maximum recommended human dose and to rabbits at 20 times the maximum recommended human dose resulted in no evidence of harm to the fetus.

Higher doses (100 and 200 times the maximum recommended human dose in rabbits and rats respectively) were associated with reduced fetal survival and maternal to… [Excerpted — this section continues on DailyMed.]

DRUG ABUSE AND DEPENDENCE No reported abuse or dependence has been associated with the administration of guanfacine hydrochloride. 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 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 %).