ADVERSE REACTIONS
Adverse reactions noted with guanfacine are similar to those of other drugs of the central α 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.
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Skin rash with exfoliation has been reported in a few cases; although clear cause and effect relationships to guanfacine could not be established, should a rash occur, guanfacine should be discontinued and the patient monitored appropriately.
In the dose-response monotherapy study described under, the frequency of the most commonly observed adverse reactions showed a dose relationship from 0.5 to 3 mg as follows:
CLINICAL PHARMACOLOGY
|
Adverse
|
Placebo
|
0.5 mg
|
1 mg
|
2 mg
|
3 mg
|
|
Reaction
|
n=59
|
n=60
|
n=61
|
n=60
|
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% |
5% |
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:
| |
Placebo
|
0.5 mg
|
1 mg
|
2 mg
|
3 mg
|
|
Adverse Reaction
|
n = 73
|
n = 72
|
n = 72
|
n = 72
|
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, the most common adverse reactions noted were as follows:
CLINICAL PHARMACOLOGY
| |
Guanfacine
|
Clonidine
|
|
Adverse Reactions
|
(n=279)
|
(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 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
|
Incidence of adverse reactions
at end of one year
|
| |
n=580
|
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).
An open-label postmarketing study involving 21,718 patients was conducted to assess the safety of guanfacine (as the hydrochloride) 1 mg/day given at bedtime for 28 days. Guanfacine was administered with or without other antihypertensive agents. Adverse events reported in the postmarketing study at an incidence greater than 1% included dry mouth, dizziness, somnolence, fatigue, headache, and nausea. The most commonly reported adverse events in this study were the same as those observed in controlled clinical trials.
Postmarketing Experience:
Less frequent, possibly guanfacine-related events observed in the postmarketing study and/or reported spontaneously include:
BODY AS A WHOLE: asthenia, chest pain, edema, malaise, tremor
CARDIOVASCULAR: bradycardia, palpitations, syncope, tachycardia
CENTRAL NERVOUS SYSTEM: paresthesias, vertigo
EYE DISORDERS: blurred vision
GASTROINTESTINAL SYSTEM: abdominal pain, constipation, diarrhea, dyspepsia
LIVER AND BILIARY SYSTEM: abnormal liver function tests
MUSCULOSKELETAL SYSTEM: arthralgia, leg cramps, leg pain, myalgia
PSYCHIATRIC: agitation, anxiety, confusion, depression, insomnia, nervousness
REPRODUCTIVE SYSTEM, MALE: impotence
RESPIRATORY SYSTEM: dyspnea
SKIN AND APPENDAGES: alopecia, dermatitis, exfoliative dermatitis, pruritus, rash
SPECIAL SENSES: alterations in taste
URINARY SYSTEM: nocturia, urinary frequency
Rare, serious disorders with no definitive cause and effect relationship to guanfacine have been reported spontaneously and/or in the postmarketing study. These events include acute renal failure, cardiac fibrillation, cerebrovascular accident, congestive heart failure, heart block, and myocardial infarction.
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REPORTS OF SUSPECTED GUANFACINE SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Guanfacine. The information is not vetted and should not be considered as verified clinical evidence.
Possible Guanfacine side effects / adverse reactions in 10 year old female
Reported by a consumer/non-health professional from United States on 2011-10-31
Patient: 10 year old female
Reactions: Confusional State, Swelling Face, Dyspepsia, Swollen Tongue, Coordination Abnormal, Blood Pressure Decreased, Complex Partial Seizures
Suspect drug(s):
Guanfacine
Administration route: Oral
Indication: Abnormal Behaviour
Start date: 2009-11-13
End date: 2009-12-14
Guanfacine
Dosage: 1/2 tablet 3 times daily
Administration route: Oral
Start date: 2009-12-15
End date: 2010-02-01
Possible Guanfacine side effects / adverse reactions in 10 year old female
Reported by a consumer/non-health professional from United States on 2011-11-17
Patient: 10 year old female
Reactions: Confusional State, Swelling Face, Swollen Tongue, Dyspepsia, Sedation, Coordination Abnormal, Complex Partial Seizures, Blood Pressure Decreased
Suspect drug(s):
Guanfacine
Administration route: Oral
Indication: Abnormal Behaviour
Start date: 2009-11-13
End date: 2009-12-14
Guanfacine
Dosage: 1/2 tablet 3 times daily
Administration route: Oral
Start date: 2009-12-15
End date: 2010-02-01
Possible Guanfacine side effects / adverse reactions in 10 year old female
Reported by a consumer/non-health professional from United States on 2011-12-02
Patient: 10 year old female
Reactions: Confusional State, LIP Swelling, Chest Discomfort, Swelling Face, Dyspnoea, Swollen Tongue, Fatigue, Syncope, Dyspepsia, Sedation, Dizziness, Coordination Abnormal, Complex Partial Seizures, Blood Pressure Decreased
Suspect drug(s):
Guanfacine
Dosage: 1/2 tablet 3 times daily
Administration route: Oral
Start date: 2009-12-15
End date: 2010-02-01
Guanfacine
Administration route: Oral
Indication: Abnormal Behaviour
Start date: 2009-11-13
End date: 2009-12-14
Guanfacine
Administration route: Oral
Indication: Autism
Start date: 2009-11-13
End date: 2009-12-14
Guanfacine
Administration route: Oral
Indication: Aggression
Start date: 2009-11-13
End date: 2009-12-14
Guanfacine
Dosage: 1/2 tablet 3 times daily
Administration route: Oral
Start date: 2009-12-15
End date: 2010-02-01
Guanfacine
Dosage: 1/2 tablet 3 times daily
Administration route: Oral
Start date: 2009-12-15
End date: 2010-02-01
Guanfacine
Administration route: Oral
Indication: Autism Spectrum Disorder
Start date: 2009-11-13
End date: 2009-12-14
Guanfacine
Dosage: 1/2 tablet 3 times daily
Administration route: Oral
Start date: 2009-12-15
End date: 2010-02-01
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