| Effexor |
 |
| |
SIDE EFFECTS
Immediate Release Tablets
Associated with Discontinuation of Treatment
Nineteen percent (537/2897) of venlafaxine patients in
phase 2-3 depression studies discontinued treatment due
to an adverse event. The more common events (>1%) associated
with discontinuation and considered to be drug-related
(i.e., those events associated with dropout at a rate
approximately twice or greater for venlafaxine compared
to placebo) are included in TABLE 4.
| TABLE 4 |
| |
Venlafaxine |
Placebo |
| CNS |
| Somnolence |
3% |
1% |
| Insomnia |
3% |
1% |
| Dizziness |
3% |
¾ |
| Nervousness |
2% |
¾ |
| Dry
mouth |
2% |
¾ |
| Anxiety |
2% |
1% |
| Gastrointestinal |
| Nausea |
6% |
1% |
| Urogenital |
| Abnormal
ejaculation* |
3% |
¾ |
| Other |
| Headache |
3% |
1% |
| Asthenia |
2% |
¾ |
| Sweating |
2% |
¾ |
| *
Percentages based on the number of males. |
| ¾
Less than 1% |
Incidence in Controlled Trials
Commonly Observed Adverse Events in Controlled
Clinical Trials: The most commonly observed
adverse events associated with the use of venlafaxine
HCl (incidence of 5% or greater) and not seen at an equivalent
incidence among placebo-treated patients (i.e., incidence
for venlafaxine HCl at least twice that for placebo),
derived from the 1% incidence TABLE 5, were asthenia,
sweating, nausea, constipation, anorexia, vomiting, somnolence,
dry mouth, dizziness, nervousness, anxiety, tremor, and
blurred vision as well as abnormal ejaculation/orgasm
and impotence in men.
Adverse Events Occurring at an Incidence
of 1% or More Among Venlafaxine HCl-Treated Patients:
TABLE 5 enumerates adverse events that occurred
at an incidence of 1% or more, and were more frequent
than in the placebo group, among venlafaxine HCl-treated
patients who participated in short-term (4- to 8-week)
placebo-controlled trials in which patients were administered
doses in a range of 75 to 375 mg/day. TABLE 5 shows the
percentage of patients in each group who had at least
one episode of an event at some time during their treatment.
Reported adverse events were classified using a standard
COSTART-based Dictionary terminology.
The prescriber should be aware that these figures cannot
be used to predict the incidence of side effects in the
course of usual medical practice where patient characteristics
and other factors differ from those which prevailed in the
clinical trials. Similarly, the cited frequencies cannot
be compared with figures obtained from other clinical investigations
involving different treatments, uses and investigators.
The cited figures, however, do provide the prescribing physician
with some basis for estimating the relative contribution
of drug and nondrug factors to the side effect incidence
rate in the population studied.
| TABLE 5 Treatment-Emergent
Adverse Experience Incidence in 4- to 8-Week Placebo-Controlled
Clinical Trials* |
| Body System |
Preferred
Term |
Venlafaxine
HCl (n=1033) |
Placebo
(n=609) |
| Body
as a Whole |
Headache |
25% |
24% |
| Asthenia |
12% |
6% |
| Infection |
6% |
5% |
| Chills |
3% |
¾ |
| Chest
pain |
2% |
1% |
| Trauma |
2% |
1% |
| Cardiovascular |
Vasodilatation |
4% |
3% |
| Increased
blood pressure/hypertension | 2% |
¾ |
| Tachycardia |
2% |
¾ |
| Postural
hypotension |
1% |
¾ |
| Dermatological |
Sweating |
12% |
3% |
| Rash |
3% |
2% |
| Pruritus |
1% |
¾ |
| Gastrointestinal |
Nausea |
37% |
11% |
| Constipation |
15% |
7% |
| Anorexia |
11% |
2% |
| Diarrhea |
8% |
7% |
| Vomiting |
6% |
2% |
| Dyspepsia |
5% |
4% |
| Flatulence |
3% |
2% |
| Metabolic |
Weight
loss |
1% |
¾ |
| Nervous
System |
Somnolence |
23% |
9% |
| Dry
mouth |
22% |
11% |
| Dizziness |
19% |
7% |
| Insomnia |
18% |
10% |
| Nervousness |
13% |
6% |
| Anxiety |
6% |
3% |
| Tremor |
5% |
1% |
| Abnormal
dreams |
4% |
3% |
| Hypertonia |
3% |
2% |
| Paresthesia |
3% |
2% |
| Libido
decreased |
2% |
¾ |
| Agitation |
2% |
¾ |
| Confusion |
2% |
1% |
| Thinking
abnormal |
2% |
1% |
| Depersonalization |
1% |
¾ |
| Depression |
1% |
¾ |
| Urinary
retention |
1% |
¾ |
| Twitching |
1% |
¾ |
| Respiration |
Yawn |
3% |
¾ |
| Special
Senses |
Blurred
vision |
6% |
2% |
| Taste
perversion |
2% |
¾ |
| Tinnitus |
2% |
¾ |
| Mydriasis |
2% |
¾ |
| Urogenital
System |
Abnormal
ejaculation/orgasm |
12%† |
¾† |
| Impotence |
6%† |
¾† |
| Urinary
frequency |
3% |
2% |
| Urination
impaired |
2% |
¾‡ |
| Orgasm
disturbance |
2%‡ |
¾‡ |
| Menstrual
disorder |
1%‡ |
¾‡ |
| *
Events reported by at least 1% of patients treated
with venlafaxine HCl are included, and are rounded
to the nearest %. Events for which the venlafaxine
HCl incidence was equal to or less than placebo are
not listed in the table, but included the following:
abdominal pain, pain, back pain, flu syndrome, fever,
palpitation, increased appetite, myalgia, arthralgia,
amnesia, hypesthesia, rhinitis, pharyngitis, sinusitis,
cough increased, urinary tract infection, and dysmenorrhea.‡ |
| ¾
Incidence less than 1%. |
| †
Incidence based on number of male patients. |
| ‡
Incidence based on number of female patients. |
Dose Dependency of Adverse Events
A comparison of adverse event rates in a fixed-dose study
comparing venlafaxine hydrochloride 75, 225, and 375 mg/day
with placebo revealed a dose dependency for some of the
more common adverse events associated with venlafaxine
hydrochloride use, as shown in TABLE 6. The rule for including
events was to enumerate those that occurred at an incidence
of 5% or more for at least one of the venlafaxine groups
and for which the incidence was at least twice the placebo
incidence for at least one venlafaxine hydrochloride group.
Tests for potential dose relationships for these events
(Cochran-Armitage Test, with a criterion of exact 2-sided
p-value £ 0.05) suggested a dose-dependency for
several adverse events in this list, including chills,
hypertension, anorexia, nausea, agitation, dizziness,
somnolence, tremor, yawning, sweating, and abnormal ejaculation.
| TABLE 6 Treatment-Emergent
Adverse Experience Incidence in a Dose Comparison
Trial |
| Body System/Preferred Term |
|
Venlafaxine HCl (mg/day) |
|
Placebo
(n=92) |
75
(n=89) |
225
(n=89) |
375
(n=88) |
| Body as
a Whole |
| Abdominal
pain |
3.3% |
3.4% |
2.2% |
8.0% |
| Asthenia |
3.3% |
16.9% |
14.6% |
14.8% |
| Chills |
1.1% |
2.2% |
5.6% |
6.8% |
| Infection |
2.2% |
2.2% |
5.6% |
2.3% |
| Cardiovascular
System |
| Hypertension |
1.1% |
1.1% |
2.2% |
4.5% |
| Vasodilatation |
0.0% |
4.5% |
5.6% |
2.3% |
| Digestive
System |
| Anorexia |
2.2% |
14.6% |
13.5% |
17.0% |
| Dyspepsia |
2.2% |
6.7% |
6.7% |
4.5% |
| Nausea |
14.1% |
32.6% |
38.2% |
58.0% |
| Vomiting |
1.1% |
7.9% |
3.4% |
6.8% |
| Nervous
System |
| Agitation |
0.0% |
1.1% |
2.2% |
4.5% |
| Anxiety |
4.3% |
11.2% |
4.5% |
2.3% |
| Dizziness |
4.3% |
19.1% |
22.5% |
23.9% |
| Insomnia |
9.8% |
22.5% |
20.2% |
13.6% |
| Libido
decreased |
1.1% |
2.2% |
1.1% |
5.7% |
| Nervousness |
4.3% |
21.3% |
13.5% |
12.5% |
| Somnolence |
4.3% |
16.9% |
18.0% |
26.1% |
| Tremor |
0.0% |
1.1% |
2.2% |
10.2% |
| Respiratory
System |
| Yawn |
0.0% |
4.5% |
5.6% |
8.0% |
| Skin and
Appendages |
| Sweating |
5.4% |
6.7% |
12.4% |
19.3% |
| Special
Senses |
| Abnormality
of accommodation |
0.0% |
9.1% |
7.9% |
5.6% |
| Urogenital
System |
| Abnormal
ejaculation/orgasm |
0.0% |
4.5% |
2.2% |
12.5% |
| Impotence |
0.0% |
5.8% |
2.1% |
3.6% |
| (Number
of men) |
(n=63) |
(n=52) |
(n=48) |
(n=56) |
Adaptation to Certain Adverse Events
Over a 6 week period, there was evidence of adaptation
to some adverse events with continued therapy (e.g., dizziness
and nausea), but less to other effects (e.g., abnormal
ejaculation and dry mouth).
Postmarketing Reports
Voluntary reports of other adverse events temporally
associated with the use of venlafaxine HCl that have been
received since market introduction and that may have no
causal relationship with the use of venlafaxine HCl include
the following: abnormal gait, agranulocytosis, anaphylaxis,
aplastic anemia, bruxism, catatonia, congenital anomalies,
congestive heart failure, CPK increased, deep vein thrombophlebitis,
dehydration, delirium, EKG abnormalities (such as atrial
fibrillation, bigeminy, supraventricular tachycardia,
ventricular extrasystole, ventricular tachycardia), epidermal
necrosis/Stevens-Johnson Syndrome, extrapyramidal symptoms
(including tardive dyskinesia), heart arrest, hemorrhage
(including eye and gastrointestinal bleeding), hepatic
events (including GGT elevation; abnormalities of unspecified
liver function tests; liver damage, necrosis, or failure;
and fatty liver), involuntary movements, LDH increased,
myocardial infarction, neuroleptic malignant syndrome-like
events (including a case of a 10-year-old who may have
been taking methylphenidate, was treated and recovered),
pancreatitis, panic, prolactin increased, renal failure,
serotonin syndrome, shock-like electrical sensations (in
some cases, subsequent to the discontinuation of venlafaxine
HCl or tapering of dose), and syndrome of inappropriate
antidiuretic hormone secretion.
Extended Release Capsules
The information included in the Adverse Findings Observed
in Short-Term, Placebo-Controlled Studies with venlafaxine
HCl Extended-Release subsection is based on data from
a pool of three 8- and 12-week controlled clinical trials
(includes two U.S. trials and one European trial) with
venlafaxine HCl (extended release). Information on additional
adverse events associated with venlafaxine HCl (extended
release) in the entire development program for the formulation
and with venlafaxine HCl (the immediate release formulation
of venlafaxine) is included in Other Adverse Events Observed
During the Premarketing Evaluation of Venlafaxine HCl
Immediate Release and Extended-Release Capsules. (See
also WARNINGS and PRECAUTIONS).
Adverse Findings Observed in Short-Term,
Placebo-Controlled Studies With Extended-Release Venlafaxine
HCl
Adverse Events Associated with Discontinuation
of Treatment
Approximately 11% of the 357 patients who received venlafaxine
hydrochloride extended release capsules in placebo-controlled
clinical trials discontinued treatment due to an adverse
experience, compared to 6% of the 285 placebo-treated patients
in those studies. The most common events leading to discontinuation
and considered drug related (i.e., leading to discontinuation
in at least 1% of the extended release venlafaxine HCl-treated
patients at a rate at least twice that of placebo) are shown
in TABLE 7.
|
TABLE
7 Common Adverse Events Leading to Discontinuation
of Treatment in Placebo-Controlled Trials* |
|
Adverse Event |
Percentage
of Patients Discontinuing Due to Adverse Event |
| Depression
Indication† |
GAD
Indication |
| Venlafaxine
HCl Extended-Release (n=357) |
Placebo
(n=285) |
Venlafaxine
HCl Extended-Release (n=476) |
Placebo
(n=201) |
| Body
as a Whole |
|
|
|
| Headache |
— |
— |
4% |
<1% |
| Asthenia |
— |
— |
3% |
<1% |
| Cardiovascular
System |
| Vasoldilation |
— |
— |
1% |
0% |
| Digestive
System |
| Nausea |
4% |
<1% |
10% |
<1% |
| Anorexia |
1% |
<1% |
2% |
<1% |
| Dry Mouth |
1% |
0% |
2% |
<1% |
| Nervous
System |
| Dizziness |
2% |
1% |
4% |
1% |
| Insomnia |
1% |
<1% |
5% |
2% |
| Nervousness |
— |
— |
3% |
<1% |
| Somnolence |
2% |
<1% |
4% |
<1% |
| Thinking Abnormal |
— |
— |
1% |
0% |
| Tremor |
— |
— |
1% |
0% |
| Special
Senses |
| Abnormal vision |
— |
— |
1% |
0% |
| *
Two of the depression studies were flexible dose and
one was fixed dose. The two GAD studies were fixed
dose. |
| †
In U.S. placebo-controlled trials, the following were
also common events leading to discontinuation and
were considered to be drug-related for extended-release
venlafaxine HCl-treated patients (% venlafaxine HCl
extended-release [n=192], % Placebo [n=202]): hypertension
(1%, <1%); diarrhea (1%, 0%); paresthesia (1%,
0%); tremor (1%, 0%); abnormal vision, mostly blurred
vision (1%, 0%); and abnormal, mostly delayed, ejaculation
(1%, 0%)). |
Adverse Events Occurring at an Incidence of 2% or
More Among Extended Release Venlafaxine HCl-Treated Patients
TABLE 8 enumerates the incidence, rounded to the nearest
percent, of treatment-emergent adverse events that occurred
during acute therapy (up to 12 weeks) of depression in
2% or more of patients treated with venlafaxine HCl (extended
release) (dose range of 75 to 225 mg/day) where the incidence
in patients treated with venlafaxine HCl (extended release)
was greater than the incidence in placebo-treated patients.
TABLE 8 shows the percentage of patients in each group
who had at least one episode of an event at some time
during their treatment. Reported adverse events were classified
using a standard COSTART-based Dictionary terminology.
The prescriber should be aware that these figures cannot
be used to predict the incidence of side effects in the
course of usual medical practice where patient characteristics
and other factors differ from those which prevailed in
the clinical trials. Similarly, the cited frequencies
cannot be compared with figures obtained from other clinical
investigations involving different treatments, uses and
investigators. The cited figures, however, do provide
the prescribing physician with some basis for estimating
the relative contribution of drug and nondrug factors
to side effect incidence in the population studied.
Commonly Observed Adverse Events from TABLE
8
Depression: Note in particular the following adverse
events that occurred in at least 5% of venlafaxine HCl
(extended release) patients and at a rate at least twice
that of the placebo group for all placebo-controlled trials:
Abnormal ejaculation, gastrointestinal complaints (nausea,
dry mouth, and anorexia), CNS complaints (dizziness, somnolence,
and abnormal dreams), and sweating. In the two U.S. placebo-controlled
trials, the following additional events occurred in at
least 5% of extended release venlafaxine HCl-treated patients
(n=192) and at a rate at least twice that of the placebo
group: Abnormalities of sexual function (impotence in
men, anorgasmia in women, and libido decreased), gastrointestinal
complaints (constipation and flatulence), CNS complaints
(insomnia, nervousness, and tremor), problems of special
senses (abnormal vision), cardiovascular effects (hypertension
and vasodilatation), and yawning.
Generalized Anxiety Disorder:
Note in particular the following adverse events that occurred
in at least 5% of the venlafaxine HCl extended-release
patients and at a rate at least twice that of the placebo
group for all placebo-controlled trials for the GAD indication
(see TABLE 8): Abnormalities of sexual function (abnormal
ejaculation and impotence in men, and libido decreased),
gastrointestinal complaints (nausea, dry mouth, anorexia,
constipation, and vomiting), CNS complaints (insomnia
and nervousness), problems of special senses (abnormal
vision), cardiovascular complaints (vasodilatation), yawning,
and sweating.
| TABLE 8 Treatment-Emergent
Adverse Event Incidence in Short-Term Placebo-Controlled
Extended-Release Venlafaxine HCl Clinical Trials |
| |
|
%
Reporting Event |
| |
|
Depression
Trials*,‡ |
GAD
Trials†,‡ |
| Body
System/Preferred Term |
Venlafaxine
HCl Extended-Release (n=357) |
Placebo (n=285) |
Venlafaxine
HCl Extended-Release (n=357) |
Placebo (n=285) |
| Body
as a Whole |
|
|
| |
Asthenia |
8%
|
7%
|
16%
|
9%
|
| |
Infection§ |
—
|
—
|
10%
|
9%
|
| |
Abdominal pain |
—
|
—
|
6%
|
5%
|
| |
Fever |
—
|
—
|
3%
|
<1%
|
| |
Neck pain |
—
|
—
|
3%
|
2%
|
| |
Chills |
—
|
—
|
3%
|
<1%
|
| Cardiovascular
System |
| |
Vasodilatation¤ |
4%
|
2%
|
6%
|
2%
|
| |
Hypertension |
4%
|
1%
|
—
|
—
|
| |
Tachycardia |
—
|
—
|
3%
|
2%
|
| Digestive
System |
| |
Nausea |
31%
|
12%
|
43%
|
11%
|
| |
Diarrhea |
|
|
|
|
| |
Constipation |
8%
|
5%
|
12%
|
5%
|
| |
Anorexia |
8%
|
4%
|
13%
|
2%
|
| |
Vomiting |
4%
|
2%
|
6%
|
2%
|
| |
Flatulence |
4%
|
3%
|
3%
|
1%
|
| Metabolic/Nutritional |
| |
Weight Loss |
3%
|
0%
|
—
|
—
|
| Musculoskeletal
System |
|
|
| |
Myalgia |
—
|
—
|
4%
|
3%
|
| Nervous
System |
| |
Dizziness |
20%
|
9%
|
20%
|
11%
|
| |
Somnolence |
17%
|
8%
|
20%
|
11%
|
| |
Insomnia |
17%
|
11%
|
22%
|
11%
|
| |
Dry Mouth |
12%
|
6%
|
23%
|
5%
|
| |
Nervousness |
10%
|
5%
|
12%
|
5%
|
| |
Abnormal Dreams¶ |
7%
|
2%
|
4%
|
2%
|
| |
Tremor |
5%
|
2%
|
4%
|
<1%
|
| |
Depression |
3%
|
<1%
|
|
|
| |
Paresthesia |
3%
|
1%
|
3%
|
<1%
|
| |
Libido Decreased |
3%
|
<1%
|
6%
|
2%
|
| |
Agitation |
3%
|
1%
|
—
|
—
|
| |
Thinking abnormal** |
—
|
—
|
2%
|
1%
|
| |
Trismus |
—
|
—
|
2%
|
0%
|
| |
Twitching |
—
|
—
|
2%
|
<1%
|
| Respiratory
System |
| |
Pharyngitis |
7%
|
6%
|
—
|
—
|
| |
Rhinits |
—
|
—
|
8%
|
6%
|
| |
Yawn |
3%
|
0%
|
6%
|
<1%
|
| |
Cough increased |
—
|
—
|
3%
|
2%
|
| Skin |
| |
Sweating |
14%
|
3%
|
11%
|
<1%
|
| Special
Senses |
| |
Abnormal Vision†† |
4%
|
<1%
|
8%
|
0%
|
| Urogenital
System |
| |
Abnormal Ejaculation‡‡,§§ |
16%
|
<1%
|
17%
|
0%
|
| |
Impotence§§ |
4%
|
<1%
|
6%
|
1%
|
| |
Orgasmic dysfunction
(female)¤¤,¶¶ |
3%
|
<1%
|
4%
|
0%
|
| |
Dysmenorrhea¤¤ |
—
|
—
|
6%
|
5%
|
| |
Urinary frequency |
—
|
—
|
3%
|
2%
|
| *
Incidence, rounded to the nearest %, for events reported
by at least 2% of patients treated with venlafaxine
HCl (extended release), except the following events
which had an incidence equal to or less than placebo:
abdominal pain, accidental injury, anxiety, back pain,
bronchitis, diarrhea, dysmenorrhea, dyspepsia, flu
syndrome, headache, infection, pain, palpitation,
rhinitis, and sinusitis. |
| †
Incidence, rounded to the nearest %, for events reported
by at least 2% of patients treated with venlafaxine
HCl extended-release, except the following events
which had an incidence equal to or less than placebo:
accidental injury, agitation, back pain, depression,
dyspepsia, flu syndrome, headache, hypertonia, pain,
palpitation, pharyngitis, sinusitis, and tinnitus. |
| ‡
<1% indicates an incidence greater than zero but
less than 1%. |
| §
Mostly upper respiratory infections.Mostly “hot
flashes.” |
| ¤
Mostly “hot flashes.” |
| ¶
Mostly “vivid dreams,” “nightmares,”
and “increased dreaming.” |
| **
Mostly "difficulty concentrating." |
| ††
Mostly “blurred vision” and “difficulty
focusing eyes.” |
| ‡‡
Mostly “delayed ejaculation.” |
| §§
Incidence is based on the number of male patients. |
| ¤¤
Mostly “delayed orgasm” or “anorgasmia.” |
| ¶¶
Incidence is based on the number of female patients. |
Vital Sign Changes
Immediate Release Tablets: Venlafaxine
hydrochloride treatment (averaged over all dose groups)
in clinical trials was associated with a mean increase
in pulse rate of approximately 3 beats per minute, compared
to no change for placebo. It was associated with mean
increases in diastolic blood pressure ranging from 0.7
to 2.5 mm Hg averaged over all dose groups, compared to
mean decreases ranging from 0.9 to 3.8 mm Hg for placebo.
However, there is a dose dependency for blood pressure
increase (see WARNINGS).
Extended Release Tablets: Venlafaxine
hydrochloride extended release capsules treatment for
up to 12 weeks in premarketing placebo-controlled depression
trials was associated with a mean final on-therapy increase
in pulse rate of approximately 2 beats per minute, compared
with 1 beat per minute for placebo. (See WARNINGS, Sustained
Hypertension for effects on blood pressure.)
Laboratory Changes
Immediate Release Tablets:
Of the serum chemistry and hematology parameters monitored
during clinical trials with venlafaxine HCl, a statistically
significant difference with placebo was seen only for
serum cholesterol, i.e., patients treated with venlafaxine
HCl had mean increases from baseline of 3 mg/dl, a change
of unknown clinical significance.
Extended Release Tablets: Venlafaxine
hydrochloride extended release capsules treatment for
up to 12 weeks in premarketing placebo-controlled depression
trials was associated with a mean final on-therapy increase
in serum cholesterol concentration of approximately 1.5
mg/dl. This change is of unknown clinical significance.
ECG Changes
Immediate Release Tablets:
In an analysis of ECGs obtained in 769 patients treated
with venlafaxine HCl and 450 patients treated with placebo
in controlled clinical trials, the only statistically
significant difference observed was for heart rate (i.e.,
a mean increase from baseline of 4 beats per minute for
venlafaxine HCl).
Extended Release Tablets: (See
PRECAUTIONS, Use in Patients with Concomitant Illnesses).
Other Adverse Events Observed During the Premarketing
Evaluation of Venlafaxine HCl Immediate Release and Extended-Release
Capsules
During its premarketing assessment, multiple doses of
venlafaxine HCl (extended release) were administered to
705 patients in phase 3 depression studies and venlafaxine
HCl was administered to 96 patients. In addition, in the
premarketing assessment of venlafaxine HCl, multiple doses
were administered to 2897 patients in phase 2-3 depression
studies. The conditions and duration of exposure to venlafaxine
in both development programs varied greatly, and included
(in overlapping categories) open and double-blind studies,
uncontrolled and controlled studies, inpatient (immediate
release only) and outpatient studies, fixed-dose, and
titration studies. Untoward events associated with this
exposure were recorded by clinical investigators using
terminology of their own choosing. Consequently, it is
not possible to provide a meaningful estimate of the proportion
of individuals experiencing adverse events without first
grouping similar types of untoward events into a smaller
number of standardized event categories.
In the tabulations that follow, reported adverse events
were classified using a standard COSTART-based Dictionary
terminology. The frequencies presented, therefore, represent
the proportion of the 3698 patients exposed to multiple
doses of either formulation of venlafaxine who experienced
an event of the type cited on at least one occasion while
receiving venlafaxine. All reported events are included
except those already listed in TABLE 8 and those events
for which a drug cause was remote. If the COSTART term
for an event was so general as to be uninformative, it
was replaced with a more informative term. It is important
to emphasize that, although the events reported occurred
during treatment with venlafaxine, they were not necessarily
caused by it.
Events are further categorized by body system and listed
in order of decreasing frequency according to the following
definitions: Frequent adverse events are those occurring
on one or more occasions in at least 1/100 patients (only
those not already listed in the tabulated results from
placebo-controlled trials appear in this listing); Infrequent
adverse events are those occurring in 1/100 to 1/1000
patients; Rare events are those occurring in fewer than
1/1000 patients.
Body as a Whole: Frequent:
chest pain substernal, chills, fever; Infrequent: face
edema, intentional injury, malaise, moniliasis, neck rigidity,
pelvic pain, photosensitivity reaction, suicide attempt;
Rare: appendicitis, carcinoma, cellulitis, withdrawal
syndrome.
Cardiovascular System: Frequent:
migraine, postural hypotension, tachycardia; Infrequent:
angina pectoris, arrhythmia, bundle branch block, congestive
heart failure, extrasystoles, hypotension, myocardial
infarct, peripheral vascular disorder (mainly cold feet
and/or cold hands), syncope, thrombophlebitis; Rare: arteritis,
first-degree atrioventricular block, bigeminy, bradycardia,
cerebral ischemia, coronary artery disease, heart arrest,
mitral valve disorder, mucocutaneous hemorrhage, pallor.
Digestive System: Frequent:
Vital Sign Changes
Immediate Release Tablets:
Venlafaxine hydrochloride treatment (averaged over all
dose groups) in clinical trials was associated with a
mean increase in pulse rate of approximately 3 beats per
minute, compared to no change for placebo. It was associated
with mean increases in diastolic blood pressure ranging
from 0.7 to 2.5 mm Hg averaged over all dose groups, compared
to mean decreases ranging from 0.9 to 3.8 mm Hg for placebo.
However, there is a dose dependency for blood pressure
increase (see WARNINGS).
Extended Release Tablets: Venlafaxine
hydrochloride extended release capsules treatment for
up to 12 weeks in premarketing placebo-controlled depression
trials was associated with a mean final on-therapy increase
in pulse rate of approximately 2 beats per minute, compared
with 1 beat per minute for placebo. (See WARNINGS, Sustained
Hypertension for effects on blood pressure.)
Laboratory Changes
Immediate Release Tablets:
Of the serum chemistry and hematology parameters monitored
during clinical trials with venlafaxine HCl, a statistically
significant difference with placebo was seen only for
serum cholesterol, i.e., patients treated with venlafaxine
HCl had mean increases from baseline of 3 mg/dl, a change
of unknown clinical significance.
Extended Release Tablets: Venlafaxine
hydrochloride extended release capsules treatment for
up to 12 weeks in premarketing placebo-controlled depression
trials was associated with a mean final on-therapy increase
in serum cholesterol concentration of approximately 1.5
mg/dl. This change is of unknown clinical significance.
ECG Changes
Immediate Release Tablets:
In an analysis of ECGs obtained in 769 patients treated
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