A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Tenex Side Effects, and Drug Interactions - Guanfacine
Tenex Side Effects, and Drug Interactions - Guanfacine
SIDE EFFECTS
Adverse reactions noted with guanfacine are similar to those of
other drugs of the central
a2-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 guanfacine
could not be established, should rash occur, guanfacine should be
discontinued monitored appropriately.
In a 12-week placebo-controlled, dose-response study of guanfacine
administered with 25mg chlorthalidone
at bedtime, the frequency of the mast 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 CLINICAL
PHARMACOLOGY, the most common adverse reactions noted were:
|
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 |
-
|
3%
|
Adverse reactions occurring were 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
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 41mg.
|
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 |
| MUSCULO-SKELETAL 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.
DRUG ABUSE AND DEPENDENCE
No reported abuse or
dependence has been
associated with the administration of guanfacine .
DRUG INTERACTIONS
The potential for
increased sedation
when guanfacine is given with other CNS-depressant drug
should be appreciated. The administration
of guanfacine concomitantly with 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 PRECAUTIONS:
Rebound).
TCAs decrease the hypotensive effect of guanfacine.
Noncardioselective beta-blockers (nadolol,porpranolol,timolol) may exacerbate rebound hypertension when guanfacine is withdrawn. The beta-blocker should be withdrawn first. The gradual withdrawal of guafacine or a cardioselective beta-blocker could be substituted.
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 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).
Laboratory Test
In clinical trials,
no clinically relevant laboratory test
abnormalities were identified as causally related to drug
during short-term treatment with guanfacine.
Drug/Laboratory Test Interactions
No laboratory test abnormalities
related to the use of guanfacine have been identified.
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