Adverse reactions noted with guanfacine hydrochloride are similar to those of other drugs of the central 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 hydrochloride could not be established, should a rash occur, guanfacine hydrochloride 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 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=60 |
| 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 to 3 mg as follows:
Adeverse Reactions | 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 pateints 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, iritis, vision disturbance Musculoskeletal- leg cramps, hypokinesia
Respiratory- dyspnea
Dermatologic- dermatitis, pruritus, purpura, sweating
Urogenital- testicular disorder, urinary incontinence
Other- malaise, paresthesia, paresis
Adverse reaction reports tend to decrease over time. In an open-label trial of one year's duration, 580 hypertensive subjects were given guanfacine, titrated to achieve goal blood pressure, alone (51%), with diuretic (38%), with beta blocker (3%), with diuretic plus beta blocker (6%), or with diuretic plus vasodilator (2%). The mean daily dose of guanfacine reached was 4.7 mg.
Adverse Reaction | Incidence of adverse reactions at any time during the study n = 580 | Incidence of adversed reactions at end of the one year n = 580 |
| Dry Mouth | 60% | 15% |
| Drowsiness | 33% | 6% |
| Dizziness | 15% | 1% |
| Constipation | 14% | 3% |
| Weakness | 5% | 1% |
| Headache | 4% | 0.2% |
| Insomnia | 5% | 0% |
There were 52 (8.9%) dropouts due to adverse effects in this 1-year trial. The causes were: dry mouth (n = 20), weakness (n = 12), constipation (n = 7), somnolence (n = 3), nausea (n = 3), orthostatic hypotension (n = 2), insomnia (n = 1), rash (n = 1), nightmares (n = 1), headache (n = 1), and depression (n = 1).
