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Guanfacine Side Effects

Please note - some side effects for Guanfacine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).


Side Effects of Guanfacine - for the Consumer

Guanfacine

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Guanfacine:

Constipation; dizziness; drowsiness; dry mouth; tiredness.

Seek medical attention right away if any of these SEVERE side effects occur when using Guanfacine:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); changes in heartbeat; inability to have sex; pounding in the chest.

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Guanfacine Side Effects - for the Professional

Guanfacine

Adverse reactions noted with Guanfacine are similar to those of other drugs of the central α2 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 could not be established, should a rash occur, Guanfacine should be discontinued and the patient monitored appropriately.

In the dose-response monotherapy study described underCLINICAL PHARMACOLOGY, the frequency of the most commonly observed adverse reactions showed a dose relationship from 0.5 to 3 mg as follows:

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 inCLINICAL PHARMACOLOGY, the most common adverse reactions noted were as follows:

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).

Postmarketing Experience: 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.

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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Side Effects by Body System

General

Guanfacine is generally well-tolerated. In a study of 580 hypertensive patients, only 7% withdrew due to adverse side effects. In addition, most side effects were mild, dose-related, and resolved over time.

Nervous system

Nervous system side effects include fatigue or a sedative effect and dizziness in 33% and 15% of patients, respectively. After one year of therapy, the incidence of these side effects falls to 6% and 1%, respectively. Headaches occur in less than 5% of patients.

Gastrointestinal

Gastrointestinal problems include dry mouth in up to 60% of patients. Constipation has been associated with the use of this drug in 14% of patients. After one year of therapy the incidence of dry mouth and constipation averages 15% and 3%, respectively.

Cardiovascular

Cardiovascular side effects include orthostatic hypotension and palpitations, each of which is rare. There is limited, indirect (ECG) evidence of left ventricular hypertrophy resolution after guanfacine therapy.

Genitourinary

Genitourinary complaints in male patients are limited to impotence, which is associated with higher doses (daily doses of 3 mg or more).

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More resources:

Cerner Multum guanfacine

MedFacts Guanfacine

Micromedex Guanfacine - Includes detailed dosage instructions.

FDA Guanfacine

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