Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1282
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Effexor XR (Capsule, Extended Release)
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dailymed-instance:dosage |
Effexor XR should be
administered in a single dose with food either in the morning or in
the evening at approximately the same time each day. Each capsule
should be swallowed whole with fluid and not divided, crushed, chewed,
or placed in water, or it may be administered by carefully opening
the capsule and sprinkling the entire contents on a spoonful of applesauce.
This drug/food mixture should be swallowed immediately without chewing
and followed with a glass of water to ensure complete swallowing of
the pellets.<br/>Initial Treatment:<br/>Major Depressive Disorder: For most
patients, the recommended starting dose for Effexor XR is 75 mg/day,
administered in a single dose. In the clinical trials establishing
the efficacy of Effexor XR in moderately depressed outpatients,the initial dose of venlafaxine was 75 mg/day. For some patients,
it may be desirable to start at 37.5 mg/day for 4 to 7
days, to allow new patients to adjust to the medication before increasing
to 75 mg/day. While the relationship between dose and antidepressant
response for Effexor XR has not been adequately explored, patients
not responding to the initial 75 mg/day dose may benefit fromdose increases to a maximum of approximately 225 mg/day. Dose
increases should be in increments of up to 75 mg/day, as needed,
and should be made at intervals of not less than 4 days, since steady
state plasma levels of venlafaxine and its major metabolites are achieved
in most patients by day 4. In the clinical trials establishing efficacy,
upward titration was permitted at intervals of 2 weeks or more; the
average doses were about 140 to 180 mg/day . It should be noted that, while the maximum recommended dose for moderately
depressed outpatients is also 225 mg/day for Effexor (immediate
release), more severely depressed inpatients in one study of the development
program for that product responded to a mean dose of 350 mg/day
(range of 150 to 375 mg/day). Whether or not higher
doses of Effexor XR are needed for more severely depressed patients
is unknown; however, the experience with Effexor XR doses higher
than 225 mg/day is very limited. (See PRECAUTIONS-General-Use in Patients withConcomitant
Illness.)<br/>Generalized Anxiety Disorder: For most
patients, the recommended starting dose for Effexor XR is 75 mg/day,
administered in a single dose. In clinical trials establishing the
efficacy of Effexor XR in outpatients with Generalized Anxiety
Disorder (GAD), the initial dose of venlafaxine was 75 mg/day.
For some patients, it may be desirable to start at 37.5 mg/day
for 4 to 7 days, to allow new patients to adjust to the medication
before increasing to 75 mg/day. Although a dose-response relationship
for effectiveness in GAD was not clearly established in fixed-dose
studies, certain patients not responding to the initial 75 mg/day
dose may benefit from dose increases to a maximum of approximately
225 mg/day. Dose increases should be in increments of up to 75 mg/day,
as needed, and should be made at intervals of not less than 4 days.<br/>Social Anxiety Disorder (Social Phobia): The recommended
dose is 75 mg/day, administered in a single dose. There was no evidence
that higher doses confer any additional benefit. (See the Use in Patients with Concomitant Illness section
of PRECAUTIONS.)<br/>Panic Disorder: It is recommended
that initial single doses of 37.5 mg/day of Effexor XR be
used for 7 days. In clinical trials establishing the efficacy of Effexor XR
in outpatients with panic disorder, initial doses of 37.5 mg/day
for 7 days were followed by doses of 75 mg/day and subsequent
weekly dose increases of 75 mg/day to a maximum dose of 225 mg/day.
Although a dose-response relationship for effectiveness in patients
with panic disorder was not clearly established in fixed���dose
studies, certain patients not responding to 75 mg/day may benefit
from dose increases to a maximum of approximately 225 mg/day.
Dose increases should be in increments of up to 75 mg/day, as
needed, and should be made at intervals of not less than 7 days. (See
the Use in Patients with Concomitant Illness section of PRECAUTIONS.)<br/>Switching Patients from Effexor Tablets: Depressed patients
who are currently being treated at a therapeutic dose with Effexor
(immediate release) may be switched to Effexor XR at the nearest
equivalent dose (mg/day), eg, 37.5 mg venlafaxine two���times-a-day
to 75 mg Effexor XR once daily. However, individual dosage
adjustments may be necessary.<br/>Special Populations:<br/>Treatment of Pregnant Women During the Third Trimester: Neonates
exposed to Effexor XR, other SNRIs, or SSRIs, late in the third
trimester have developed complications requiring prolonged hospitalization,
respiratory support, and tube feeding . When treating
pregnant women with Effexor XR during the third trimester, the
physician should carefully consider the potential risks and benefits
of treatment. The physician may consider tapering Effexor XR
in the third trimester.<br/>Patients with Hepatic Impairment: Given the
decrease in clearance and increase in elimination half-life for both
venlafaxine and ODV that is observed in patients with hepatic cirrhosis
and mild and moderate hepatic impairment compared with normal subjects
, it is recommended that the total daily dose be reduced
by 50% in patients with mild to moderate hepatic impairment.
Since there was much individual variability in clearance between subjects
with cirrhosis, it may be necessary to reduce the dose even more than
50%, and individualization of dosing may be desirable in some patients.<br/>Patients with Renal Impairment: Given the
decrease in clearance for venlafaxine and the increase in elimination
half-life for both venlafaxine and ODV that is observed in patients
with renal impairment (GFR = 10 to 70 mL/min)
compared with normal subjects , it is recommended
that the total daily dose be reduced by 25% to 50%. In patients
undergoing hemodialysis, it is recommended that the total daily dose
be reduced by 50%. Because there was much individual variability in
clearance between patients with renal impairment, individualization
of dosage may be desirable in some patients.<br/>Elderly Patients: No dose
adjustment is recommended for elderly patients solely on the basis
of age. As with any drug for the treatment of major depressive disorder,
Generalized Anxiety Disorder, Social Anxiety Disorder, or panic disorder,
however, caution should be exercised in treating the elderly. When
individualizing the dosage, extra care should be taken when increasing
the dose.<br/>Maintenance Treatment: There is no body
of evidence available from controlled trials to indicate how long
patients with major depressive disorder, Generalized Anxiety Disorder,
Social Anxiety Disorder, or panic disorder, should be treated with
Effexor XR. It is generally agreed that acute episodes of major depressive disorder
require several months or longer of sustained pharmacological therapy
beyond response to the acute episode. In one study, in which patients
responding during 8 weeks of acute treatment with Effexor XR
were assigned randomly to placebo or to the same dose of Effexor XR
(75, 150, or 225 mg/day, qAM) during 26 weeks of maintenance
treatment as they had received during the acute stabilization phase,longer-term efficacy was demonstrated. A second longer-term study
has demonstrated the efficacy of Effexor in maintaining a response
in patients with recurrent major depressive disorder who had responded
and continued to be improved during an initial 26 weeks of treatment
and were then randomly assigned to placebo or Effexor for periods
of up to 52 weeks on the same dose (100 to 200 mg/day, on a b.i.d.
schedule) (see Clinical
Trials under CLINICAL PHARMACOLOGY). Based on
these limited data, it is not known whether or not the dose of Effexor/Effexor XR
needed for maintenance treatment is identical to the dose needed to
achieve an initial response. Patients should be periodically reassessed
to determine the need for maintenance treatment and the appropriate
dose for such treatment. In patients with Generalized Anxiety Disorder, Effexor XR has
been shown to be effective in 6���month clinical trials. The
need for continuing medication in patients with GAD who improve with
Effexor XR treatment should be periodically reassessed. In patients with Social
Anxiety Disorder, Effexor XR has been shown to be effective in a 6���month
clinical trial. The need for continuing medication in patients with
Social Anxiety Disorder who improve with Effexor XR treatment
should be periodically reassessed. In a study
of panic disorder in which patients responding during 12 weeks of
acute treatment with Effexor XR were assigned randomly to placebo
or to the same dose of Effexor XR (75, 150, or 225 mg/day), patients
continuing Effexor XR experienced a significantly longer time to relapse
than patients randomized to placebo. The need for continuing medication
in patients with panic disorder who improve with Effexor XR treatment
should be periodically reassessed.<br/>Discontinuing Effexor XR: Symptoms associated
with discontinuation of Effexor XR, other SNRIs, and SSRIs, have
been reported . Patients should be monitored for
these symptoms when discontinuing treatment. A gradual reduction in
the dose rather than abrupt cessation is recommended whenever possible.
If intolerable symptoms occur following a decrease in the dose or
upon discontinuation of treatment, then resuming the previously prescribed
dose may be considered. Subsequently, the physician may continue decreasing
the dose but at a more gradual rate. In clinical trials with Effexor XR,
tapering was achieved by reducing the daily dose by 75 mg at
1 week intervals. Individualization of tapering may be necessary.<br/>Switching Patients To or From a Monoamine Oxidase Inhibitor: At least 14 days
should elapse between discontinuation of an MAOI and initiation of
therapy with Effexor XR. In addition, at least 7 days should
be allowed after stopping Effexor XR before starting an MAOI
.
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dailymed-instance:descripti... |
Effexor XR is an extended-release
capsule for oral administration that contains venlafaxine hydrochloride,
a structurally novel antidepressant. It is designated (R/S)-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]
cyclohexanol hydrochloride or (��)-1-[��- [(dimethylamino)methyl]-p-methoxybenzyl]
cyclohexanol hydrochloride and has the empirical formula of CHNOHCl. Its molecular weight is
313.87. The structural formula is shown below. Venlafaxine hydrochloride is a white to off-white crystalline solid
with a solubility of 572 mg/mL in water (adjusted to ionic strength
of 0.2 M with sodium chloride). Its octanol:water (0.2 M sodium chloride)
partition coefficient is 0.43. Effexor XR is formulated as an extended-release capsule for
once-a-day oral administration. Drug release is controlled by diffusion
through the coating membrane on the spheroids and is not pH dependent.
Capsules contain venlafaxine hydrochloride equivalent to 37.5 mg,
75 mg, or 150 mg venlafaxine. Inactive ingredients consist
of cellulose, ethylcellulose, gelatin, hypromellose, iron oxide, and
titanium dioxide.
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dailymed-instance:clinicalP... |
Pharmacodynamics: The mechanism of
the antidepressant action of venlafaxine in humans is believed to
be associated with its potentiation of neurotransmitter activity in
the CNS. Preclinical studies have shown that venlafaxine and its active
metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of
neuronal serotonin and norepinephrine reuptake and weak inhibitors
of dopamine reuptake. Venlafaxine and ODV have no significant affinity
for muscarinic cholinergic, H���histaminergic, or��-adrenergic receptors in vitro. Pharmacologic activity
at these receptors is hypothesized to be associated with the various
anticholinergic, sedative, and cardiovascular effects seen with other
psychotropic drugs. Venlafaxine and ODV do not possess monoamine oxidase
(MAO) inhibitory activity.<br/>Pharmacokinetics: Steady-state concentrations
of venlafaxine and ODV in plasma are attained within 3 days of oral
multiple dose therapy. Venlafaxine and ODV exhibited linear kinetics
over the dose range of 75 to 450 mg/day. Mean��SD
steady-state plasma clearance of venlafaxine and ODV is 1.3��0.6 and
0.4��0.2 L/h/kg, respectively; apparent elimination half-life
is 5��2 and 11��2 hours, respectively; and apparent (steady-state)
volume of distribution is 7.5��3.7 and 5.7��1.8 L/kg,
respectively. Venlafaxine and ODV are minimally bound at therapeutic
concentrations to plasma proteins (27% and 30%, respectively).<br/>Absorption: Venlafaxine
is well absorbed and extensively metabolized in the liver. O-desmethylvenlafaxine
(ODV) is the only major active metabolite. On the basis of mass balance
studies, at least 92% of a single oral dose of venlafaxine is absorbed.
The absolute bioavailability of venlafaxine is about 45%. Administration of
Effexor XR (150 mg q24 hours) generally resulted
in lower C(150 ng/mL for venlafaxine and 260 ng/mL
for ODV) and later T(5.5 hours for venlafaxine
and 9 hours for ODV) than for Effexor (immediate release) [C's for immediate release 75 mg q12 hours
were 225 ng/mL for venlafaxine and 290 ng/mL for ODV; T's were 2 hours for venlafaxine and 3 hours
for ODV]. When equal daily doses of venlafaxine were administered
as either an immediate release tablet or the extended-release capsule,
the exposure to both venlafaxine and ODV was similar for the two treatments,
and the fluctuation in plasma concentrations was slightly lower with
the Effexor XR capsule. Effexor XR, therefore, provides
a slower rate of absorption, but the same extent of absorption compared
with the immediate release tablet. Food did not affect the bioavailability of venlafaxine or its active
metabolite, ODV. Time of administration (AM vs PM) did not affect
the pharmacokinetics of venlafaxine and ODV from the 75 mg Effexor XR
capsule.<br/>Metabolism and Excretion: Following
absorption, venlafaxine undergoes extensive presystemic metabolism
in the liver, primarily to ODV, but also to N-desmethylvenlafaxine,
N,O-didesmethylvenlafaxine, and other minor metabolites. In vitro
studies indicate that the formation of ODV is catalyzed by CYP2D6;
this has been confirmed in a clinicalstudy showing that patients
with low CYP2D6 levels (���poor metabolizers���) had increased
levels of venlafaxine and reduced levels of ODV compared to people
with normal CYP2D6 (���extensive metabolizers���). The differences
between the CYP2D6 poor and extensive metabolizers, however, are not
expected to be clinically important because the sum of venlafaxine
and ODV is similar in the two groups and venlafaxine and ODV are pharmacologically
approximately equiactive and equipotent. Approximately 87% of a venlafaxine dose is recovered in the urine
within 48 hours as unchanged venlafaxine (5%), unconjugated ODV (29%),
conjugated ODV (26%), or other minor inactive metabolites (27%). Renal
elimination of venlafaxine and its metabolites is thus the primary
route of excretion.<br/>Special Populations: Age and
Gender: A population pharmacokinetic analysis of 404 venlafaxine-treated
patients from two studies involving both b.i.d. and t.i.d. regimens
showed that dose-normalized trough plasma levels of either venlafaxine
or ODV were unaltered by age or gender differences. Dosage adjustment
based on the age or gender of a patient is generally not necessary
. Extensive/Poor Metabolizers: Plasma concentrations of venlafaxine
were higher in CYP2D6 poor metabolizers than extensive metabolizers.
Because the total exposure (AUC) of venlafaxine and ODV was similar
in poor and extensive metabolizer groups, however, there is no need
for different venlafaxine dosing regimens for these two groups. Liver Disease: In
9 subjects with hepatic cirrhosis, the pharmacokinetic disposition
of both venlafaxine and ODV was significantly altered after oral administration
of venlafaxine. Venlafaxine elimination half-life was prolonged by
about 30%, and clearance decreased by about 50% in cirrhotic subjects
compared to normal subjects. ODV elimination half-life was prolonged
by about 60%, and clearance decreased by about 30% in cirrhotic subjects
compared to normal subjects. A large degree of intersubject variability
was noted. Three patients with more severe cirrhosis had a more substantial
decrease in venlafaxine clearance (about 90%) compared to normal subjects. In a second study, venlafaxine was administered orally
and intravenously in normal (n = 21) subjects, and in Child-Pugh A
(n = 8) and Child-Pugh B (n = 11) subjects (mildly and moderately
impaired, respectively). Venlafaxine oral bioavailability was increased
2-3 fold, oral elimination half-life was approximately twice as long
and oral clearance was reduced by more than half, compared to normal
subjects. In hepatically impaired subjects, ODV oral elimination half-life
was prolonged by about 40%, while oral clearance for ODV was similar
to that for normal subjects. A large degree of intersubject variability
was noted. Dosage adjustment is necessary in
these hepatically impaired patients . Renal
Disease: In a renal impairment study, venlafaxine elimination half-life
after oral administration was prolonged by about 50% and clearance
was reduced by about 24% in renally impaired patients (GFR=10 to 70 mL/min),
compared to normal subjects. In dialysis patients, venlafaxine elimination
half-life was prolonged by about 180% and clearance was reduced by
about 57% compared to normal subjects. Similarly, ODV elimination
half-life was prolonged by about 40% although clearance was unchanged
in patients with renal impairment (GFR=10 to 70 mL/min)
compared to normal subjects. In dialysis patients, ODV elimination
half-life was prolonged by about 142% and clearance was reduced by
about 56% compared to normal subjects. A large degree of intersubject
variability was noted. Dosage adjustment is necessary in these patients
.<br/>Clinical Trials:<br/>Major Depressive Disorder: The efficacy
of Effexor XR (venlafaxine hydrochloride) extended-release capsules
as a treatment for major depressive disorder was established in two
placebo-controlled, short-term, flexible-dose studies in adult outpatients
meeting DSM-III-R or DSM-IV criteria for major depressive disorder. A 12-week study
utilizing Effexor XR doses in a range 75 to 150 mg/day
(mean dose for completers was 136 mg/day) and an 8-week study
utilizing Effexor XR doses in a range 75 to 225 mg/day
(mean dose for completers was 177 mg/day) both demonstrated superiority
of Effexor XR over placebo on the HAM-D total score, HAM-D Depressed
Mood Item, the MADRS total score, the Clinical Global Impressions
(CGI) Severity of Illness item, and the CGI Global Improvement
item. In both studies, Effexor XR was also significantly better
than placebo for certain factors of the HAM-D, including the anxiety/somatization
factor, the cognitive disturbance factor, and the retardation factor,
as well as for the psychic anxiety score. A 4-week study of inpatients meeting DSM-III-R criteria for major
depressive disorder with melancholia utilizing Effexor (immediate
release) in a range of 150 to 375 mg/day (t.i.d. schedule)
demonstrated superiority of Effexor over placebo. The mean dose in
completers was 350 mg/day. Examination of gender subsets of the population studied did not reveal
any differential responsiveness on the basis of gender. In one longer-term
study, adult outpatients meeting DSM-IV criteria for major depressive
disorder who had responded during an 8-week open trial on Effexor XR
(75, 150, or 225 mg, qAM) were randomized to continuation of
their same Effexor XR dose or to placebo, for up to 26 weeks
of observation for relapse. Response during the open phase was defined
as a CGI Severity of Illness item score of���3 and a HAM-D-21
total score of���10 at the day 56 evaluation. Relapse during
the double-blind phase was defined as follows: (1) a reappearance
of major depressive disorder as defined by DSM-IV criteria and a CGI
Severity of Illness item score of���4 (moderately ill), (2) 2 consecutive
CGI Severity of Illness item scores of���4, or (3) a final CGI
Severity of Illness item score of���4 for any patient who withdrew
from the study for any reason. Patients receiving continued Effexor XR
treatment experienced significantly lower relapse rates over the subsequent
26 weeks compared with those receiving placebo. In a second longer-term trial, adult outpatients meeting DSM-III-R
criteria for major depressive disorder, recurrent type, who had responded
(HAM-D-21 total score���12 at the day 56 evaluation) and continued
to be improved [defined as the following criteria being met for days
56 through 180: (1) no HAM-D-21 total score���20; (2) no more
than 2 HAM-D-21 total scores>10, and (3) no single CGI Severity of
Illness item score���4 (moderately ill)] during an initial 26 weeks
of treatment on Effexor (immediate release) [100 to 200 mg/day,
on a b.i.d. schedule] were randomized to continuation of their same
Effexor dose or to placebo. The follow-up period to observe patients
for relapse, defined as a CGI Severity of Illness item score���4,
was for up to 52 weeks. Patients receiving continued Effexor treatment
experienced significantly lower relapse rates over the subsequent
52 weeks compared with those receiving placebo.<br/>Generalized Anxiety Disorder: The efficacy
of Effexor XR capsules as a treatment for Generalized Anxiety
Disorder (GAD) was established in two 8-week, placebo���controlled,
fixed-dose studies, one 6-month, placebo-controlled, fixed-dose study,
and one 6-month, placebo-controlled, flexible-dose study in adult
outpatients meeting DSM���IV criteria for GAD. One 8-week study evaluating
Effexor XR doses of 75, 150, and 225 mg/day, and placebo
showed that the 225 mg/day dose was more effective than placebo
on the Hamilton Rating Scale for Anxiety (HAM-A) total score, both
the HAM-A anxiety and tension items, and the Clinical Global Impressions
(CGI) scale. While there was also evidence for superiority over placebo
for the 75 and 150 mg/day doses, these doses were not as consistently
effective as the highest dose. A second 8-week study evaluating Effexor XR
doses of 75 and 150 mg/day and placebo showed that both doses
were more effective than placebo on some of these same outcomes; however,
the 75 mg/day dose was more consistently effective than the 150 mg/day
dose. A dose-response relationship for effectiveness in GAD was not
clearly established in the 75 to 225 mg/day dose range
utilized in these two studies. Two 6-month studies, one evaluating Effexor XR doses of 37.5,
75, and 150 mg/day and the other evaluating Effexor XR doses
of 75 to 225 mg/day, showed that daily doses of 75 mg
or higher were more effective than placebo on the HAM-A total, both
the HAM-A anxiety and tension items, and the CGI scale during 6 months
of treatment. While there was also evidence for superiority over placebo
for the 37.5 mg/day dose, this dose was not as consistently effective
as the higher doses. Examination of gender subsets of the population studied did not reveal
any differential responsiveness on the basis of gender.<br/>Social Anxiety Disorder (Social Phobia): The efficacy
of Effexor XR capsules as a treatment for Social Anxiety Disorder
(also known as Social Phobia) was established in four double-blind,
parallel���group, 12-week, multicenter, placebo-controlled, flexible-dose
studies and one double-blind, parallel-group, 6-month, placebo���controlled,
fixed/flexible-dose study in adult outpatients meeting DSM-IV criteria
for Social Anxiety Disorder. Patients received doses in a range
of 75 to 225 mg/day. Efficacy was assessed with the Liebowitz Social
Anxiety Scale (LSAS). In these five trials, Effexor XR was significantly
more effective than placebo on change from baseline to endpoint on
the LSAS totalscore. There was no evidence for any greater effectiveness
of the 150 to 225 mg/day group compared to the 75 mg/day group in
the 6-month study. Examination of subsets of the population studied did not reveal any
differential responsiveness on the basis of gender. There was insufficient
information to determine the effect of age or race on outcome in these
studies.<br/>Panic Disorder: The efficacy
of Effexor XR capsules as a treatment for panic disorder was
established in two double-blind, 12-week, multicenter, placebo-controlled
studies in adult outpatients meeting DSM-IV criteria for panic disorder,
with or without agoraphobia. Patients received fixed doses of 75 or 150
mg/day in one study and 75 or 225 mg/day in the other study. Efficacy was
assessed on the basis of outcomes in three variables: (1) percentage
of patients free of full-symptom panic attacks on the Panic and Anticipatory
Anxiety Scale (PAAS); (2) mean change from baseline to endpoint
on the Panic Disorder Severity Scale (PDSS) total score; and (3) percentage
of patients rated as responders (much improved or very much improved)
on the Clinical Global Impressions (CGI) Improvement scale. In these
two trials, Effexor XR was significantly more effective than
placebo in all three variables. In the two 12-week studies described above, one evaluating
Effexor XR doses of 75 and 150 mg/day and the other evaluating
Effexor XR doses of 75 and 225 mg/day, efficacy was established
for each dose. A dose-response relationship for effectiveness in patients
with panic disorder was not clearly established in fixed-dose studies. Examination of
subsets of the population studied did not reveal any differential
responsiveness on the basis of gender. There was insufficient information
to determine the effect of age or race on outcome in these studies. In a longer-term
study, adult outpatients meeting DSM-IV criteria for panic disorder
who had responded during a 12-week open phase with Effexor XR
(75 to 225 mg/day) were randomly assigned to continue
the same Effexor XR dose (75, 150, or 225 mg)
or switch to placebo for observation for relapse under double-blind
conditions. Response during the open phase was defined as���1 full-symptom panic attack per week during the last 2 weeks of the
open phase and a CGI Improvement score of 1 (very much improved) or
2 (much improved). Relapse during the double-blind phase was defined
as having 2 or more full-symptom panic attacks per week for 2 consecutive
weeks or having discontinued due to loss of effectiveness as determined
by the investigators during the study. Randomized patients were in
response status for a mean time of 34 days prior to being randomized.
In the randomized phase following the 12-week open-label period, patients
receiving continued Effexor XR experienced a significantly longer
time to relapse.
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dailymed-instance:activeIng... | |
dailymed-instance:contraind... |
Hypersensitivity to venlafaxine
hydrochloride or to any excipients in the formulation. Concomitant use in patients taking
monoamine oxidase inhibitors (MAOIs) is contraindicated .
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dailymed-instance:supply |
Effexor XR (venlafaxine hydrochloride) extended-release capsules are available
as follows: 37.5 mg,
grey cap/peach body withand���Effexor XR���on the cap and���37.5���on the body. 75 mg, peach cap and body withand���Effexor XR���on the cap and���75���on the body. 150 mg, dark orange cap and body withand���Effexor XR���on the cap and���150���on the body. Store at controlled room
temperature, 20��to 25��C (68��to 77��F). The unit of use package
is intended to be dispensed as a unit. The appearance of these capsules is a trademark of Wyeth Pharmaceuticals. U.S. Patent Nos. 4,535,186; 5,916,923;
6,274,171; 6,403,120; 6,419,958; and 6,444,708.
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dailymed-instance:boxedWarn... |
Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal
thinking and behavior (suicidality) in children, adolescents, and
young adults in short-term studies of Major Depressive Disorder (MDD)
and other psychiatric disorders. Anyone considering the use of Effexor XR
or any other antidepressant in a child, adolescent, or young adult
must balance this risk with the clinical need. Short-term studies
did not show an increase in the risk of suicidality with antidepressants
compared to placebo in adults beyond age 24; there was a reduction
in risk with antidepressants compared to placebo in adults aged 65
and older. Depression and certain other psychiatric disorders are
themselves associated with increases in the risk of suicide. Patients
of all ages who are started on antidepressant therapy should be monitored
appropriately and observed closely for clinical worsening, suicidality,
or unusual changes in behavior. Families and caregivers should be
advised of the need for close observation and communication with the
prescriber. Effexor XR is not approved for use in pediatric patients.
(See WARNINGS: Clinical Worsening and Suicide
Risk, PRECAUTIONS: Information for
Patients, and PRECAUTIONS: Pediatric
Use)
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dailymed-instance:activeMoi... | |
dailymed-instance:inactiveI... | |
dailymed-instance:precautio... |
General:<br/>Discontinuation of Treatment with Effexor XR: Discontinuation
symptoms have been systematically evaluated in patients taking venlafaxine,
to include prospective analyses of clinical trials in Generalized
Anxiety Disorder and retrospective surveys of trials in major depressive
disorder, and Social Anxiety Disorder. Abrupt discontinuation or dose
reduction of venlafaxine at various doses has been found to be associated
with the appearance of new symptoms, the frequency of which increased
with increased dose level and with longer duration of treatment. Reported
symptoms include agitation, anorexia, anxiety, confusion, impaired
coordination and balance, diarrhea, dizziness, dry mouth, dysphoric
mood, fasciculation, fatigue, flu-like symptoms, headaches, hypomania,
insomnia, nausea, nervousness, nightmares, sensory disturbances (including
shock���like electrical sensations), somnolence, sweating, tremor,
vertigo, and vomiting. During marketing of Effexor XR, other SNRIs (Serotonin and Norepinephrine
Reuptake Inhibitors), and SSRIs (Selective Serotonin Reuptake Inhibitors),
there have been spontaneous reports of adverse events occurring upon
discontinuation of these drugs, particularly when abrupt, including
the following: dysphoric mood, irritability, agitation, dizziness,
sensory disturbances (e.g. paresthesiassuch as electric shock sensations),
anxiety, confusion, headache, lethargy, emotional lability, insomnia,
hypomania, tinnitus, and seizures. While these events are generally
self-limiting, there have been reports of serious discontinuation
symptoms. Patients should be monitored for these symptoms when discontinuing
treatment with Effexor XR. A gradual reduction in the dose rather
than abrupt cessation is recommended whenever possible. If intolerable
symptoms occur following a decrease in the dose or upon discontinuation
of treatment, then resuming the previously prescribed dose may be
considered. Subsequently, the physician may continue decreasing the
dose but at a more gradual rate .<br/>Insomnia and Nervousness: Treatment-emergent
insomnia and nervousness were more commonly reported for patients
treated with Effexor XR (venlafaxine hydrochloride) extended-release
capsules than with placebo in pooled analyses of short-term major
depressive disorder, GAD, Social Anxiety Disorder, and panic disorder
studies, as shown in Table 5. Insomnia and nervousness each led to drug discontinuation
in 0.9% of the patients treated with Effexor XR in major depressive
disorder studies. In GAD trials, insomnia and nervousness led to drug discontinuation
in 3% and 2%, respectively, of the patients treated with Effexor XR
up to 8 weeks and 2% and 0.7%, respectively, of the patients treated
with Effexor XR up to 6 months. In Social Anxiety Disorder trials, insomnia and nervousness led to
drug discontinuation in 2% and 1%, respectively, of the patients
treated with Effexor XR up to 12 weeks and 2% and 3% respectively,
of the patients treated with Effexor XR up to 6 months. In panic disorder
trials, insomnia and nervousness led to drug discontinuation in 1% and 0.1%,
respectively, of the patients treated with Effexor XR up to 12
weeks.<br/>Changes in Weight: Adult Patients:
A loss of 5% or more of body weight occurred in 7% of Effexor XR-treated
and 2% of placebo-treated patients in the short-term placebo-controlled
major depressive disorder trials. The discontinuation rate for weight
loss associated with Effexor XR was 0.1% in major depressive
disorder studies. In placebo-controlled GAD studies, a loss of 7%
or more of body weight occurred in 3% of Effexor XR patients
and 1% of placebo patients who received treatment for up to 6 months.
The discontinuation rate for weight loss was 0.3% for patients receiving
Effexor XR in GAD studies for up to eight weeks. In placebo-controlled
Social Anxiety Disorder trials, 4% of the Effexor XR-treated
and 1% of the placebo-treated patients sustained a loss of 7% or more
of body weight during up to 6 months of treatment. None of the patients
receiving Effexor XR in Social Anxiety Disorder studies discontinued
for weight loss. In placebo-controlled panic disorder trials, 3% of
the Effexor XR-treated and 2% of the placebo���treated patients
sustained a loss of 7% or more of body weight during up to 12 weeks
of treatment. None of the patients receiving Effexor XR in panic
disorder studies discontinued for weight loss. The safety and efficacy of venlafaxine therapy
in combination with weight loss agents, including phentermine, have
not been established. Co-administration of Effexor XR and weight
loss agents is not recommended. Effexor XR is not indicated for
weight loss alone or in combination with other products. Pediatric Patients:
Weight loss has been observed in pediatric patients (ages 6-17) receiving
Effexor XR. In a pooled analysis of four eight-week, double-blind,
placebo-controlled, flexible dose outpatient trials for major depressive
disorder (MDD) and generalized anxiety disorder (GAD), Effexor XR-treated
patients lost an average of 0.45 kg (n = 333), while placebo-treated
patients gained an average of 0.77 kg (n = 333). More patients treated
with Effexor XR than with placebo experienced a weight loss of at
least 3.5% in both the MDD and the GAD studies (18% of Effexor XR-treated
patients vs. 3.6% of placebo-treated patients; p<0.001). In a 16-week,
double-blind, placebo-controlled, flexible dose outpatient trial for
Social Anxiety Disorder, Effexor XR-treated patients lost an average
of 0.75 kg (n = 137), while placebo-treated patients gained an average
of 0.76 kg (n = 148). More patients treated with Effexor XR than with
placebo experienced a weight loss of at least 3.5% in the Social Anxiety
Disorder study (47% of Effexor XR-treated patients vs. 14% of placebo-treated
patients; p<0.001). Weight loss was not limited to patients with
treatment-emergent anorexia . The risks associated with longer-term Effexor XR use were assessed
in an open-label MDD study of children and adolescents who received
Effexor XR for up to six months. The children and adolescents
in the study had increases in weight that were less than expected
based on data from age- and sex-matched peers. The difference between
observed weight gain and expected weight gain was larger for children
(<12 years old) than for adolescents (���12 years old).<br/>Changes in Height: Pediatric
Patients: During the eight-week, placebo-controlled GAD studies, Effexor XR-treated
patients (ages 6-17) grew an average of 0.3 cm (n = 122), while placebo-treated
patients grew an average of 1.0 cm (n = 132); p=0.041. This difference
in height increase was most notable in patients younger than twelve.
During the eight-week placebo-controlled MDD studies, Effexor XR-treated
patients grew an average of 0.8 cm (n = 146), while placebo-treated
patients grew an average of 0.7 cm (n = 147). During the 16-week,
placebo-controlled Social Anxiety Disorder study, both the Effexor
XR-treated (n = 109) and the placebo-treated (n = 112) patients each
grew an average of 1.0 cm. In the six-month, open-label MDD study,
children and adolescents had height increases that were less than
expected based on data from age- and sex���matched peers. The
difference between observed growth rates and expected growth rates
was larger for children (<12 years old) than for adolescents (���12
years old).<br/>Changes in Appetite: Adult Patients:
Treatment-emergent anorexia was more commonly reported for Effexor XR���treated
(8%) than placebo-treated patients (4%) in the pool of short-term,
double���blind, placebo���controlled major depressive disorder
studies. The discontinuation rate for anorexia associated with Effexor XR
was 1.0% in major depressive disorder studies. Treatment-emergent
anorexia was more commonly reported for Effexor XR-treated (8%) than
placebo���treated patients (2%) in the pool of short-term, double-blind,
placebo���controlled GAD studies. The discontinuation rate for
anorexia was 0.9% for patients receiving Effexor XR for up to
8 weeks in GAD studies. Treatment-emergent anorexia was more commonly
reported for Effexor XR���treated (17%) than placebo���treated
patients (2%) in the pool of short-term, double-blind, placebo-controlled
Social Anxiety Disorder studies. The discontinuation rate for anorexia
was 0.6% for patients receiving Effexor XR for up to 12 weeks
in Social Anxiety Disorder studies; no patients discontinued for anorexia
between week 12 and month 6. Treatment-emergent anorexia was more
commonly reported for Effexor XR���treated (8%) than placebo-treated
patients (3%) in the pool of short-term, double-blind, placebo-controlled
panic disorder studies. The discontinuation rate for anorexia was
0.4% for patients receiving Effexor XR for up to 12 weeks in
panic disorder studies. Pediatric Patients: Decreased appetite has been observed in pediatric
patients receiving Effexor XR. In the placebo-controlled trials
for GAD and MDD, 10% of patients aged 6-17 treated with Effexor XR
for up to eight weeks and 3% of patients treated with placebo reported
treatment-emergent anorexia (decreased appetite). None of the patients
receiving Effexor XR discontinued for anorexia or weight loss.
In the placebo-controlled trial for Social Anxiety Disorder, 22% and
3% of patients aged 8-17 treated for up to 16 weeks with Effexor XR
and placebo, respectively, reported treatment-emergent anorexia (decreased
appetite). The discontinuation rates for anorexia were 0.7% and 0.0%
for patients receiving Effexor XR and placebo, respectively; the discontinuation
rates for weight loss were 0.7% for patients receiving either Effexor
XR or placebo.<br/>Activation of Mania/Hypomania: During premarketing
major depressive disorder studies, mania or hypomania occurred in
0.3% of Effexor XR-treated patients and no placebo patients.
In premarketing GAD studies, no Effexor XR-treated patients and
0.2% of placebo-treated patients experienced mania or hypomania. In
premarketing Social Anxiety Disorder studies, 0.2% Effexor XR-treated
patients and no placebo-treated patients experienced mania or hypomania.
In premarketing panic disorder studies, 0.1% of Effexor XR-treated
patients and no placebo-treated patients experienced mania or hypomania.
In all premarketing major depressive disorder trials with Effexor
(immediate release), mania or hypomania occurred in 0.5% of venlafaxine-treated
patients compared with no placebo patients. Mania/hypomania has also
been reported in a small proportion of patients with mood disorders
who were treated with other marketed drugs to treat major depressive
disorder. As with all drugs effective in the treatment of major depressive
disorder, Effexor XR should be used cautiously in patients with
a history of mania.<br/>Hyponatremia: Hyponatremia
may occur as a result of treatment with SSRIs and SNRIs, including
Effexor XR. In many cases, this hyponatremia appears to be the result
of the syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Cases with serum sodium lower than 110 mmol/L have been reported.
Elderly patients may be at greater risk of developing hyponatremia
with SSRIs and SNRIs. Also, patients taking diuretics or who are otherwise
volume depleted may be at greater risk . Discontinuation of Effexor XR should be considered in patients
with symptomatic hyponatremia and appropriatemedical intervention
should be instituted. Signs and symptoms of
hyponatremia include headache, difficulty concentrating, memory impairment,
confusion, weakness, and unsteadiness, which may lead to falls. Signs
and symptoms associated with more severe and/or acute cases have included
hallucination, syncope, seizure, coma, respiratory arrest, and death.<br/>Seizures: During premarketing
experience, no seizures occurred among 705 Effexor XR-treated
patients in the major depressive disorder studies, among 1381 Effexor XR-treated
patients in GAD studies, or among 819 Effexor XR-treated patients
in Social Anxiety Disorder studies. In panic disorder studies, 1 seizure
occurred among 1,001 Effexor XR-treated patients. In all premarketing
major depressive disorder trials with Effexor (immediate release),
seizures were reported at various doses in 0.3% (8/3082) of venlafaxine-treated
patients. Effexor XR, like many antidepressants, should be used
cautiously in patients with a history of seizures and should be discontinued
in any patient who develops seizures.<br/>Abnormal Bleeding: SSRIs and
SNRIs, including Effexor XR, may increase the risk of bleeding events.
Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs,
warfarin, and other anti-coagulants may add to this risk. Case reports
and epidemiological studies (case-control and cohort design) have
demonstrated an association between use of drugs that interfere with
serotonin reuptake and the occurrence of gastrointestinal bleeding.
Bleeding events related to SSRIs and SNRIs use have ranged from ecchymoses,
hematomas, epistaxis, and petechiae to life-threatening hemorrhages. Patients should be cautioned about the risk of bleeding
associated with the concomitant use of Effexor XR and NSAIDs, aspirin,
or other drugs that affect coagulation.<br/>Serum Cholesterol Elevation: Clinically
relevant increases in serum cholesterol were recorded in 5.3% of venlafaxine-treated
patients and 0.0% of placebo-treated patients treated for at least
3 months in placebo-controlled trials . Measurement of serum cholesterol levels should be considered
during long-term treatment.<br/>Interstitial Lung Disease and Eosinophilic Pneumonia: Interstitial lung disease and eosinophilic pneumonia
associated with venlafaxine therapy have been rarely reported. The
possibility of these adverse events should be considered in venlafaxine-treated
patients who present with progressive dyspnea, cough or chest discomfort.
Such patients should undergo a prompt medical evaluation, and discontinuation
of venlafaxine therapy should be considered.<br/>Use in Patients With Concomitant Illness: Premarketing
experience with venlafaxine in patients with concomitant systemic
illness is limited. Caution is advised in administering Effexor XR
to patients with diseases or conditions that could affect hemodynamic
responses or metabolism. Venlafaxine has not been evaluated or used to any appreciable extent
in patients with a recent history of myocardial infarction or unstable
heart disease. Patients with these diagnoses were systematically excluded
from many clinical studies during venlafaxine's premarketing
testing. The electrocardiograms were analyzed for 275 patients who
received Effexor XR and 220 patients who received placebo
in 8- to 12-week double-blind, placebo-controlled trials
in major depressive disorder, for 610patients who received Effexor XR
and 298 patients who received placebo in 8-week double-blind, placebo-controlled
trials in GAD, for 593 patients who received Effexor XR and 534
patients who received placebo in 12-week double-blind, placebo-controlled
trials in Social Anxiety Disorder, and for 661 patients who received
Effexor XR and 395 patients who received placebo in three 10- to 12-week
double-blind, placebo���controlled trials in panic disorder.
The mean change from baseline in corrected QT interval (QTc) for Effexor XR-treated
patients in major depressive disorder studies was increased relative
to that for placebo-treated patients (increase of 4.7 msec for
Effexor XR and decrease of 1.9 msec for placebo). The mean
change from baseline in QTc interval for Effexor XR-treated patients
in the GAD studies did not differ significantly from that with placebo.
The mean change from baseline in QTc interval for Effexor XR���treated
patients in the Social Anxiety Disorder studies was increased relative
to that for placebo-treated patients (increase of 3.4 msec for Effexor XR
and decrease of 1.6 msec for placebo). The mean change from baseline
in QTc interval for Effexor XR-treated patients in the panic
disorder studies was increased relative to that for placebo-treated
patients (increase of 1.5 msec for Effexor XR and decrease
of 0.7 msec for placebo). In these same trials, the mean change from baseline in heart rate
for Effexor XR-treated patients in the major depressive disorder
studies was significantly higher than that for placebo (a mean increase
of 4 beats per minute for Effexor XR and 1 beat per minute
for placebo). The mean change from baseline in heart rate for Effexor XR-treated
patients in the GAD studies was significantly higher than that for
placebo (a mean increase of 3 beats per minute for Effexor XR
and no change for placebo). The mean change from baseline in heart
rate for Effexor XR-treated patients in the Social Anxiety Disorder
studies was significantly higher than that for placebo (a mean increase
of 5 beats per minute for Effexor XR and no change for placebo).
The mean change from baseline in heart rate for Effexor XR-treated
patients in the panic disorder studies was significantly higher than
that for placebo (a mean increase of 3 beats per minute for Effexor XR
and a mean decrease of less than 1 beat per minute for placebo). In a flexible-dose
study, with Effexor (immediate release) doses in the range of 200 to 375 mg/day
and mean dose greater than 300 mg/day, Effexor-treated patients
had a mean increase in heart rate of 8.5 beats per minute compared
with 1.7 beats per minute in the placebo group. As increases in heart
rate were observed, caution should be exercised in patients whose
underlying medical conditions might be compromised by increases in
heart rate (eg, patients with hyperthyroidism, heart failure, or recent
myocardial infarction). Evaluation of the electrocardiograms for 769 patients who received
Effexor (immediate release) in 4- to 6-week double-blind,
placebo-controlled trials showed that the incidence of trial-emergent
conduction abnormalities did not differ from that with placebo. In patients with
renal impairment (GFR = 10 to 70 mL/min) or cirrhosis of
the liver, the clearances of venlafaxine and its active metabolites
were decreased, thus prolonging the elimination half-lives of these
substances. A lower dose may be necessary . Effexor XR, like all drugs effective in the treatment of
major depressive disorder, should be used with caution in such patients.<br/>Information for Patients: Prescribers or other
health professionals should inform patients, their families, and their
caregivers about the benefits and risks associated with treatment
with Effexor XR and should counsel them in its appropriate use.
A patient Medication Guide about���Antidepressant Medicines,
Depression and Other Serious Mental Illness, and Suicidal Thoughts
or Actions���is available for Effexor XR. The prescriber
or health professional should instruct patients, their families, and
their caregivers to read the Medication Guide and should assist them
in understanding its contents. Patients should be given the opportunity
to discuss the contents of the Medication Guide and to obtain answers
to any questions they may have. The complete
text of the Medication Guide is reprinted at the end of
this document. Patients should be advised of the following issues and asked to alert
their prescriber if these occur while taking Effexor XR. Clinical Worsening and Suicide Risk: Patients,
their families, and their caregivers should be encouraged to be alert
to the emergence of anxiety, agitation, panic attacks, insomnia, irritability,
hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness),
hypomania, mania, other unusual changes in behavior, worsening of
depression, and suicidal ideation, especially early during antidepressant
treatment and when the dose is adjusted up or down. Families and caregivers
of patients should be advised to look for the emergence of such symptoms
on a day-to-day basis, since changes may be abrupt. Such symptoms
should be reported to the patient's prescriber or health professional,
especially if they are severe, abrupt in onset, or were not part of
the patient's presenting symptoms. Symptoms such as these may
be associated with an increased risk for suicidal thinking and behavior
and indicate a needfor very close monitoring and possibly changes
in the medication.<br/>Interference with Cognitive and Motor Performance: Clinical
studies were performed to examine the effects of venlafaxine on behavioral
performance of healthy individuals. The results revealed no clinically
significant impairment of psychomotor, cognitive, or complex behavior
performance. However, since any psychoactive drug may impair judgment,
thinking, or motor skills, patients should be cautioned about operating
hazardous machinery, including automobiles, until they are reasonably
certain that venlafaxine therapy does not adversely affect their ability
to engage in such activities.<br/>Concomitant Medication: Patients
should be advised to inform their physicians if they are taking, or
plan to take, any prescription or over-the-counter drugs, including
herbal preparations and nutritional supplements, since there is a
potential for interactions. Patients should
be cautioned about the risk of serotonin syndrome with the concomitant
use of Effexor XR and triptans, tramadol, tryptophan supplements or
other serotonergic agents (see WARNINGS, Serotonin Syndrome and PRECAUTIONS, Drug Interactions,
CNS-Active Drugs). Patients
should be cautioned about the concomitant use of Effexor XR and NSAIDs,
aspirin, warfarin, or other drugs that affect coagulation since combined
use of psychotropic drugs that interfere with serotonin reuptake and
these agents has been associated with an increased risk of bleeding
.<br/>Alcohol: Although
venlafaxine has not been shown to increase the impairment of mental
and motor skills caused by alcohol, patients should be advised to
avoid alcohol while taking venlafaxine.<br/>Allergic Reactions: Patients
should be advised to notify their physician if they develop a rash,
hives, or a related allergic phenomenon.<br/>Pregnancy: Patients
should be advised to notify their physician if they become pregnant
or intend to become pregnant during therapy.<br/>Nursing: Patients
should be advised to notify their physician if they are breast-feeding
an infant.<br/>Mydriasis: Mydriasis (prolonged dilation of the pupils of the
eye) has been reported with venlafaxine. Patients should be advised
to notify their physician if they have a history of glaucoma or a
history of increased intraocular pressure .<br/>Laboratory Tests: There are no specific
laboratory tests recommended.<br/>Drug Interactions: As with all drugs,
the potential for interaction by a variety of mechanisms is a possibility.<br/>Alcohol: A single
dose of ethanol (0.5 g/kg) had no effect on the pharmacokinetics
of venlafaxine or O���desmethylvenlafaxine (ODV) when venlafaxine
was administered at 150 mg/day in 15 healthy male subjects. Additionally,
administration of venlafaxine in a stable regimen did not exaggerate
the psychomotor and psychometric effects induced by ethanol in these
same subjects when they were not receiving venlafaxine.<br/>Cimetidine: Concomitant
administration of cimetidine and venlafaxine in a steady-state study
for both drugs resulted in inhibition of first-pass metabolism of
venlafaxine in 18 healthy subjects. The oral clearance of venlafaxine
was reduced by about 43%, and the exposure (AUC) and maximum concentration
(C) of the drug were increased by about 60%. However,
coadministration of cimetidine had no apparent effect on the pharmacokinetics
of ODV, which is present in much greater quantity in the circulation
than venlafaxine. The overall pharmacological activity of venlafaxine
plus ODV is expected to increase only slightly, and no dosage adjustment
should be necessary for most normal adults. However, for patients
with pre-existing hypertension, and for elderly patients or patients
with hepatic dysfunction, the interaction associated with the concomitant
use of venlafaxine and cimetidine is not known and potentially could
be more pronounced. Therefore, caution is advised with such patients.<br/>Diazepam: Under steady-state
conditions for venlafaxine administered at 150 mg/day, a single
10 mg dose of diazepam did not appear to affect the pharmacokinetics
of either venlafaxine or ODV in 18 healthy male subjects. Venlafaxine
also did not have any effect on the pharmacokinetics of diazepam or
its active metabolite, desmethyldiazepam, or affect the psychomotor
and psychometric effects induced by diazepam.<br/>Haloperidol: Venlafaxine
administered under steady-state conditions at 150 mg/day in 24
healthy subjects decreased total oral-dose clearance (Cl/F) of a single
2 mg dose of haloperidol by 42%, which resulted in a 70% increase
in haloperidol AUC. In addition, the haloperidol Cincreased
88% when coadministered with venlafaxine, but the haloperidol
elimination half-life (t) was unchanged. The mechanism
explaining this finding is unknown.<br/>Lithium: The steady-state
pharmacokinetics of venlafaxine administered at 150 mg/day were
not affected when a single 600 mg oral dose of lithium was administered
to 12 healthy male subjects. ODV also was unaffected. Venlafaxine
had no effect on the pharmacokinetics of lithium (see also CNS-Active Drugs, below).<br/>Drugs Highly Bound to Plasma Proteins: Venlafaxine
is not highly bound to plasma proteins; therefore, administration
of Effexor XR to a patient taking another drug that is highly
protein bound should not cause increased free concentrations of the
other drug.<br/>Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin,
and Warfarin): Serotonin release by platelets plays an important
role in hemostasis. Epidemiological studies of the case-control and
cohort design that have demonstrated an association between use of
psychotropic drugs that interfere with serotonin reuptake and the
occurrence of upper gastrointestinal bleeding have also shown that
concurrent use of an NSAID or aspirin may potentiate this risk of
bleeding. Altered anticoagulant effects, including increased bleeding,
have been reported when SSRIs and SNRIs are coadministered with warfarin.
Patients receiving warfarin therapy should be carefully monitored
when EffexorXR is initiated or discontinued.<br/>Drugs that Inhibit Cytochrome P450 Isoenzymes: CYP2D6 Inhibitors:
In vitro and in vivo studies indicate that venlafaxine is metabolized
to its active metabolite, ODV, by CYP2D6, the isoenzyme that is responsible
for the genetic polymorphism seen in the metabolism of many antidepressants.
Therefore, the potential exists for a drug interaction between drugs
that inhibit CYP2D6-mediated metabolism of venlafaxine, reducing the
metabolism of venlafaxine to ODV, resulting in increased plasma concentrations
of venlafaxine and decreased concentrations of the active metabolite.
CYP2D6 inhibitors such as quinidine would be expected to do this,
but the effect would be similar to what is seen in patientswho are
genetically CYP2D6 poor metabolizers (see Metabolism
and Excretion under CLINICAL PHARMACOLOGY). Therefore,
no dosage adjustment is required when venlafaxine is coadministered
with a CYP2D6 inhibitor. Ketoconazole: A pharmacokinetic study with ketoconazole 100 mg b.i.d.
with a single dose of venlafaxine 50 mg in extensive metabolizers
(EM; n = 14) and 25 mg in poor metabolizers (PM; n = 6) of CYP2D6
resulted in higher plasma concentrations of both venlafaxine and O���desmethylvenlafaxine
(ODV) in most subjects following administration of ketoconazole. Venlafaxine
Cincreased by 26% in EM subjects and 48% in PM subjects.
Cvalues for ODV increased by 14% and 29% in EM and
PM subjects, respectively. Venlafaxine AUC
increased by 21% in EM subjects and 70% in PM subjects (range in PMs
- 2% to 206%), and AUC values for ODV increased by 23% and 33% in
EM and PM (range in PMs - 38% to 105%) subjects, respectively. Combined
AUCs of venlafaxine and ODV increased on average by approximately
23% in EMs and 53% in PMs (range in PMs - 4% to 134%). Concomitant use
of CYP3A4 inhibitors and venlafaxine may increase levels of venlafaxine
and ODV. Therefore, caution is advised if a patient's therapy includes
a CYP3A4 inhibitor and venlafaxine concomitantly.<br/>Drugs Metabolized by Cytochrome P450 Isoenzymes: CYP2D6:
In vitro studies indicate that venlafaxine is a relatively weak inhibitor
of CYP2D6. These findings have been confirmed in a clinical drug interaction
study comparing the effect of venlafaxine with that of fluoxetine
on the CYP2D6-mediated metabolism of dextromethorphan to dextrorphan. Imipramine - Venlafaxine
did not affect the pharmacokinetics of imipramine and 2���OH���imipramine.
However, desipramine AUC, C, and Cincreased
by about 35% in the presence of venlafaxine. The 2-OH-desipramine
AUC's increased by at least 2.5 fold (with venlafaxine 37.5 mg q12h)
and by 4.5 fold (with venlafaxine 75 mg q12h). Imipramine
did not affect the pharmacokinetics of venlafaxine and ODV. The clinical
significance of elevated 2���OH���desipramine levels is
unknown. Metoprolol - Concomitant administration
of venlafaxine (50 mg every 8 hours for 5 days) and metoprolol (100
mg every 24 hours for 5 days) to 18 healthy male subjects in a pharmacokinetic
interaction study for both drugs resulted in an increase of plasma
concentrations of metoprolol by approximately 30-40% without altering
the plasma concentrations of its active metabolite,�����hydroxymetoprolol.
Metoprolol did not alter the pharmacokinetic profile of venlafaxine
or its active metabolite, O-desmethylvenlafaxine. Venlafaxine appeared to
reduce the blood pressure lowering effect of metoprolol in this study.
The clinical relevance of this finding for hypertensive patients is
unknown. Caution should be exercised with co-administration of venlafaxine
and metoprolol. Venlafaxine treatment has been
associated with dose-related increases in blood pressure in some patients.
It is recommended that patients receiving Effexor XR have regular
monitoring of blood pressure . Risperidone - Venlafaxine administered under steady-state conditions
at 150 mg/day slightly inhibited the CYP2D6-mediated metabolism
of risperidone (administered as a single 1 mg oral dose) to its
active metabolite, 9-hydroxyrisperidone, resulting in an approximate
32% increase in risperidone AUC. However, venlafaxine coadministration
did not significantly alter the pharmacokinetic profile of the total
active moiety (risperidone plus 9-hydroxyrisperidone). CYP3A4: Venlafaxine
did not inhibit CYP3A4 in vitro. This finding was confirmed in vivo
by clinical drug interaction studies in which venlafaxine did not
inhibit the metabolism of several CYP3A4 substrates, including alprazolam,
diazepam, and terfenadine. Indinavir - In a study of 9 healthy volunteers, venlafaxine administered
under steady-state conditions at 150 mg/day resulted in a 28%
decrease in the AUC of a single 800 mg oral dose of indinavir
and a 36% decrease in indinavir C. Indinavir did not
affect the pharmacokinetics of venlafaxine and ODV. The clinical significance
of this finding is unknown. CYP1A2: Venlafaxine did not inhibit CYP1A2 in vitro. This finding
was confirmed in vivo by a clinical drug interaction study in which
venlafaxine did not inhibit the metabolism of caffeine, a CYP1A2 substrate. CYP2C9: Venlafaxine
did not inhibit CYP2C9 in vitro. In vivo, venlafaxine 75 mg by mouth
every 12 hours did not alter the pharmacokinetics of a single 500
mg dose of tolbutamide or the CYP2C9 mediated formation of 4-hydroxy-tolbutamide. CYP2C19: Venlafaxine
did not inhibit the metabolism of diazepam, which is partially metabolized
by CYP2C19 (see Diazepam above).<br/>Monoamine Oxidase Inhibitors: See CONTRAINDICATIONS and WARNINGS.<br/>CNS-Active Drugs: The risk
of using venlafaxine in combination with other CNS-active drugs has
not been systematically evaluated (except in the case of those CNS-active
drugs noted above). Consequently, caution is advised if the concomitant
administration of venlafaxine and such drugs is required. Serotonergic Drugs: Based on the mechanism of action of
Effexor XR and the potential for serotonin syndrome, caution is advised
when Effexor XR is co-administered with other drugs that may affect
the serotonergic neurotransmitter systems, such as triptans, SSRIs,
other SNRIs, linezolid (an antibiotic which is a reversible non-selective
MAOI), lithium, tramadol, or St. John's Wort . If concomitant treatment of Effexor XR with these drugs
is clinically warranted, careful observation of the patient is advised,
particularly during treatment initiation and dose increases . The concomitant use of Effexor XR with tryptophan supplements
is not recommended . Triptans: There have been rare postmarketing reports of serotonin
syndrome with use of an SSRI and a triptan. If concomitant treatment
of Effexor XR with a triptan is clinically warranted, careful observation
of the patient is advised, particularly during treatment initiation
and dose increases .<br/>Electroconvulsive Therapy: There are
no clinical data establishing the benefit of electroconvulsive therapy
combined with Effexor XR (venlafaxine hydrochloride) extended-release
capsules treatment.<br/>Postmarketing Spontaneous Drug Interaction Reports: See ADVERSE REACTIONS, Postmarketing
Reports.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility:<br/>Carcinogenesis: Venlafaxine
was given by oral gavage to mice for 18 months at doses up to 120 mg/kg
per day, which was 1.7 times the maximum recommended human dose on
a mg/mbasis. Venlafaxine was also given to rats
by oral gavage for 24 months at doses up to 120 mg/kg per day.
In rats receiving the 120 mg/kg dose, plasma concentrations of
venlafaxine at necropsy were 1 times (male rats) and 6 times (female
rats) the plasma concentrations of patients receiving the maximum
recommended human dose. Plasma levels of the O-desmethyl metabolitewere lower in rats than in patients receiving the maximum recommended
dose. Tumors were not increased by venlafaxine treatment in mice or
rats.<br/>Mutagenesis: Venlafaxine
and the major human metabolite, O-desmethylvenlafaxine (ODV), were
not mutagenic in the Ames reverse mutation assay in Salmonella bacteria
or the Chinese hamster ovary/HGPRT mammalian cell forward gene mutation
assay. Venlafaxine was also not mutagenic or clastogenic in the in
vitro BALB/c-3T3 mouse cell transformation assay, the sister chromatid
exchange assay in cultured Chinese hamster ovary cells, or in the
in vivo chromosomal aberration assay in rat bone marrow. ODV was not
clastogenic in the in vitro Chinese hamster ovary cell chromosomal
aberration assay, but elicited a clastogenic response in the in vivo
chromosomal aberration assay in rat bone marrow.<br/>Impairment of Fertility: Reproduction
and fertility studies in rats showed no effects on male or female
fertility at oral doses of up to 2 times the maximum recommended human
dose on a mg/mbasis.<br/>Pregnancy:<br/>Teratogenic Effects - Pregnancy Category C: Venlafaxine
did not cause malformations in offspring of rats or rabbits given
doses up to 2.5 times (rat) or 4 times (rabbit) the maximum recommended
human daily dose on a mg/mbasis. However, in
rats, there was a decrease in pup weight, an increase in stillborn
pups, and an increase in pup deaths during the first 5 days of lactation,
when dosing began during pregnancy and continued until weaning. The
cause of these deaths is not known. These effects occurred at 2.5
times (mg/m) the maximum human daily dose. The no effect
dose for rat pup mortality was 0.25 times the human dose on a mg/mbasis. There are no adequate and well���controlled studies
in pregnant women. Because animal reproduction studies are not always
predictive of human response, this drug should be used during pregnancy
only if clearly needed.<br/>Non-teratogenic Effects: Neonates
exposed to Effexor XR, other SNRIs (Serotonin and Norepinephrine
Reuptake Inhibitors), or SSRIs (Selective Serotonin Reuptake Inhibitors),
late in the third trimester have developed complications requiring
prolonged hospitalization, respiratory support, and tube feeding.
Such complications can arise immediately upon delivery. Reported clinical
findings have included respiratory distress, cyanosis, apnea, seizures,
temperature instability, feeding difficulty, vomiting, hypoglycemia,
hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability,
and constant crying. These features are consistent with either a direct
toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation
syndrome. It should be noted that, in some cases, the clinical picture
is consistent with serotonin syndrome . When treating a pregnant woman with Effexor XR
during the third trimester, the physician should carefully consider
the potential risks and benefits of treatment .<br/>Labor and Delivery: The effect of venlafaxine
on labor and delivery in humans is unknown.<br/>Nursing Mothers: Venlafaxine and
ODV have been reported to be excreted in human milk. Because of the
potential for serious adverse reactions in nursing infants from Effexor XR,
a decision should be made whether to discontinue nursing or to discontinue
the drug, taking into account the importance of the drug to the mother.<br/>Pediatric Use: Safety and effectiveness
in the pediatric population have not been established (see BOX WARNING and WARNINGS, Clinical
Worsening and Suicide Risk). Two placebo���controlled
trials in 766 pediatric patients with MDD and two placebo-controlled
trials in 793 pediatric patients with GAD have been conducted with
Effexor XR, and the data were not sufficient to support a claim for
use in pediatric patients. Anyone considering the use of Effexor XR in a child or adolescent
must balance the potential risks with the clinical need. Although no studies have
been designed to primarily assess Effexor XR's impact on
the growth, development, and maturation of children and adolescents,
the studies that have been done suggest that Effexor XR may adverselyaffect weight and height . Should
the decision be made to treat a pediatric patient with Effexor XR,
regular monitoring of weight and height is recommended during treatment,
particularly if it is to be continued long term. The safety of Effexor XR
treatment for pediatric patients has not been systematically assessed
for chronic treatment longer than six months in duration. In the studies conducted
in pediatric patients (ages 6-17), the occurrence of blood pressure
and cholesterol increases considered to be clinically relevant in
pediatric patients was similar to that observed in adult patients.
Consequently, the precautions for adults apply to pediatric patients
(see WARNINGS, Sustained
Hypertension, and PRECAUTIONS, General, Serum Cholesterol Elevation).<br/>Geriatric Use: Approximately 4%
(14/357), 6% (77/1381), 1% (10/819), and 2% (16/1001) of Effexor XR���treated
patients in placebo-controlled premarketing major depressive disorder,
GAD, Social Anxiety Disorder trials, and panic disorder trials, respectively,
were 65 years of age or over. Of 2,897 Effexor-treated (immediate
release) patients in premarketing phase major depressive disorder
studies, 12% (357) were 65 years of age or over. No overall differences
in effectiveness or safety were observed between geriatric patients
and younger patients, and other reported clinical experience generally
has not identified differences in response between the elderly and
younger patients. However, greater sensitivity of some older individuals
cannot be ruled out. SSRIs and SNRIs, including Effexor XR have been
associated with cases of clinically significant hyponatremia in elderly
patients, who may be at greater riskfor this adverse event . The pharmacokinetics of venlafaxine and ODV are not substantially
altered in the elderly . No dose adjustment
is recommended for the elderly on the basis of age alone, although
other clinical circumstances, some of which may be more common in
the elderly, such as renal or hepatic impairment, may warrant a dose
reduction (see DOSAGE
AND ADMINISTRATION).
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dailymed-instance:overdosag... |
Human Experience: Among the patients
included in the premarketing evaluation of Effexor XR, there
were 2 reports of acute overdosage with Effexor XR in major depressive
disorder trials, either alone or in combination with other drugs.
One patient took a combination of 6 g of Effexor XR and
2.5 mg of lorazepam. This patient was hospitalized, treated symptomatically,
and recovered without any untoward effects. Theother patient took
2.85 g of Effexor XR. This patient reported paresthesia
of all four limbs but recovered without sequelae. There were 2 reports of acute overdose with
Effexor XR in GAD trials. One patient took a combination of 0.75 g
of Effexor XR and 200 mg of paroxetine and 50 mg of
zolpidem. This patient was described as being alert, able to communicate,
and a little sleepy. This patient was hospitalized, treated with activatedcharcoal, and recovered without any untoward effects. The other patient
took 1.2 g of Effexor XR. This patient recovered and no
other specific problems were found. The patient had moderate dizziness,
nausea, numb hands and feet, and hot-cold spells 5 days after the
overdose. These symptoms resolved over the next week. There were no reports of
acute overdose with Effexor XR in Social Anxiety Disorder trials. There were 2 reports of acute overdose with Effexor XR
in panic disorder trials. One patient took 0.675 g of Effexor XR
once, and the other patient took 0.45 g of Effexor XR for
2 days. No signs or symptoms were associated with either overdose,
and no actions were taken to treat them. Among the patients included in the premarketing evaluation with Effexor
(immediate release), there were 14 reports of acute overdose with
venlafaxine, either alone or in combination with other drugs and/or
alcohol. The majority of the reports involved ingestion in which the
total dose of venlafaxine taken wasestimated to be no more than several-fold
higher than the usual therapeutic dose. The 3 patients who took the
highest doses were estimated to have ingested approximately 6.75 g,
2.75 g, and 2.5 g. The resultant peak plasma levels of venlafaxine
for the latter 2 patients were 6.24 and 2.35��g/mL, respectively,
and the peak plasma levels of O���desmethylvenlafaxine were 3.37
and 1.30��g/mL, respectively. Plasma venlafaxine levels
were not obtained for the patient who ingested 6.75 g of venlafaxine.
All 14 patients recovered without sequelae. Most patients reported
no symptoms. Among the remaining patients, somnolence was the most
commonly reported symptom. The patient who ingested 2.75 g of
venlafaxine was observed to have 2 generalized convulsions and
a prolongation of QTc to 500 msec, compared with 405 msec
at baseline. Mild sinus tachycardia was reported in 2 of the other
patients. In
postmarketing experience, overdose with venlafaxine has occurred predominantly
in combination with alcohol and/or other drugs. The most commonly
reported events in overdosage include tachycardia, changes in level
of consciousness (ranging from somnolence to coma), mydriasis, seizures,
and vomiting. Electrocardiogram changes (eg, prolongation of QT interval,
bundle branch block, QRS prolongation), ventricular tachycardia, bradycardia,
hypotension, rhabdomyolysis, vertigo, liver necrosis, serotonin syndrome,
and death have been reported. Published retrospective
studies report that venlafaxine overdosage may be associated with
an increased risk of fatal outcomes compared to that observed with
SSRI antidepressant products, but lower than that for tricyclic antidepressants.
Epidemiological studies have shown that venlafaxine-treated patients
have a higher pre-existing burden of suicide risk factors than SSRI���treated
patients. The extent to which the finding of an increased risk of
fatal outcomes can be attributed to the toxicity of venlafaxine in
overdosage as opposed to some characteristic(s) of venlafaxine-treated
patients is not clear. Prescriptions for Effexor XR should be written
for the smallest quantity of capsules consistent with good patient
management, in order to reduce the risk of overdose.<br/>Management of Overdosage: Treatment should
consist of those general measures employed in the management of overdosage
with any antidepressant. Ensure an adequate airway, oxygenation, and ventilation. Monitor
cardiac rhythm and vital signs. General supportive and symptomatic
measures are also recommended. Induction of emesis is not recommended.
Gastric lavage with a large bore orogastric tube with appropriate
airway protection, if needed, may be indicated if performed soon after
ingestion or in symptomatic patients. Activated charcoal should be administered. Due to the large volume
of distribution of this drug, forced diuresis, dialysis, hemoperfusion,
and exchange transfusion are unlikely to be of benefit. No specific
antidotes for venlafaxine are known. In managing overdosage, consider the possibility of multiple drug
involvement. The physician should consider contacting a poison control
center for additional information on the treatment of any overdose.
Telephone numbers for certified poison control centers are listed
in the Physicians' Desk Reference (PDR).
|
dailymed-instance:genericMe... |
venlafaxine hydrochloride
|
dailymed-instance:fullName |
Effexor XR (Capsule, Extended Release)
|
dailymed-instance:adverseRe... |
The information included
in the Adverse Findings
Observed in Short-Term, Placebo���Controlled Studies with Effexor XR subsection is based on data from a pool of three 8- and 12���week
controlled clinical trials in major depressive disorder (includes
two U.S. trials and one European trial), on data up to 8 weeks from
a pool of five controlled clinical trials in GAD with Effexor XR, on data up to 12 weeks from a pool of five controlled
clinical trials in Social Anxiety Disorder, and on data up to 12 weeks
from a pool of four controlled clinical trials in panic disorder.
Information on additional adverse events associated with Effexor XR
in the entire development program for the formulation and with Effexor
(immediate release) is included in the Other Adverse Events Observed During the Premarketing
Evaluation of Effexor and Effexor XR subsection
.<br/>Adverse Findings Observed in Short-Term, Placebo-Controlled
Studies with Effexor XR:<br/>Adverse Events Associated with Discontinuation of Treatment: Approximately
11% of the 357 patients who received Effexor XR (venlafaxine
hydrochloride) extended-release capsules in placebo-controlled clinical
trials for major depressive disorder discontinued treatment due to
an adverse experience, compared with 6% of the 285 placebo���treated
patients in those studies. Approximately 18% of the 1381 patients
who received Effexor XR capsules in placebo-controlled clinical
trials for GAD discontinued treatment due to an adverse experience,
compared with 12% of the 555 placebo-treated patients in those studies.
Approximately 15% of the 819 patients who received Effexor XR
capsules in placebo-controlled clinical trials for Social Anxiety
Disorder discontinued treatment due to an adverse experience, compared
with 5% of the 695 placebo-treated patients in those studies. Approximately
7% of the 1,001 patients who received Effexor XR capsules in
placebo-controlled clinical trials for panic disorder discontinued
treatment due to an adverse experience, compared with 6% of the 662
placebo-treated patients in those studies. The most common events
leading to discontinuation and considered to be drug-related (ie,
leading to discontinuation in at least 1% of the Effexor XR-treated
patients at a rate at least twice that of placebo for any indication)
are shown in Table 6.<br/>Adverse Events Occurring at an Incidence of 2% or More Among
Effexor XR-Treated Patients: Tables 7, 8, 9, and 10 enumerate the incidence, rounded to the
nearest percent, of treatment-emergent adverse events that occurred
during acute therapy of major depressive disorder (up to 12 weeks;
dose range of 75 to 225 mg/day), of GAD (up to 8 weeks;
dose range of 37.5 to 225 mg/day), of Social Anxiety
Disorder (up to 12 weeks; dose range of 75 to 225 mg/day),
and of panic disorder (upto 12 weeks; dose range of 37.5 to 225 mg/day),
respectively, in 2% or more of patients treated with Effexor XR
(venlafaxine hydrochloride) where the incidence in patients treated
with Effexor XR was greater than the incidence for the respective
placebo-treated patients. The table 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 basisfor estimating the relative contribution of drug and nondrug
factors to the side effect incidence rate in the population studied. Commonly Observed
Adverse Events from Tables 7, 8, 9, and 10:<br/>Vital Sign Changes: Effexor XR
(venlafaxine hydrochloride) extended-release capsules treatment for
up to 12 weeks in premarketing placebo-controlled major depressive
disorder 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. Effexor XR treatment for up to 8
weeks in premarketing placebo-controlled GAD trials was associated
with a mean final on-therapy increase in pulse rate of approximately
2 beats per minute, compared with less than 1 beat per minute for
placebo. Effexor XR treatment for up to 12 weeks in premarketing
placebo���controlled Social Anxiety Disorder trials was associated
with a mean final on-therapy increase in pulse rate of approximately
3 beats per minute, compared with an increase of 1 beat per minute
for placebo. Effexor XR treatment for up to 12 weeks in premarketing
placebo-controlled panic disorder trials was associated with a mean
final on-therapy increase in pulse rate of approximately 1 beat per
minute, compared with a decrease of less than 1 beat per minute for
placebo. (See the Sustained Hypertension and Elevations in Systolic and
Diastolic Blood Pressure sections of WARNINGS for effects on blood pressure.) In a flexible-dose study, with Effexor (immediate release) doses
in the range of 200 to 375 mg/day and mean dose greater
than 300 mg/day, the mean pulse was increased by about 2 beats
per minute compared with a decrease of about 1 beat per minute for
placebo.<br/>Laboratory Changes:<br/>Serum Cholesterol: Effexor XR (venlafaxine hydrochloride) extended-release
capsules treatment for up to 12 weeks in premarketing placebo-controlled
trials for major depressive disorder was associated with a mean final
on-therapy increase in serum cholesterol concentration of approximately
1.5 mg/dL compared with a mean final decrease of 7.4 mg/dL
for placebo. Effexor XR treatment for up to 8 weeks and
up to 6 months in premarketing placebo-controlled GAD trials was associated
with mean final on-therapy increases in serum cholesterol concentration
of approximately 1.0 mg/dL and 2.3 mg/dL, respectively while
placebo subjects experienced mean final decreases of 4.9 mg/dL
and 7.7 mg/dL, respectively. Effexor XR treatment for up
to 12 weeks and up to 6 months in premarketing placebo-controlled
Social Anxiety Disorder trials was associated with mean final on-therapy
increases in serum cholesterol concentration of approximately 7.9
mg/dL and 5.6 mg/dL, respectively, compared with mean final decreases
of 2.9 and 4.2 mg/dL, respectively, for placebo. Effexor XR treatment
for up to 12 weeks in premarketing placebo-controlled panic disorder
trials was associated with mean final on-therapy increases in serum
cholesterol concentration of approximately 5.8 mg/dL compared
with a mean final decrease of 3.7 mg/dL for placebo. Patients treated with Effexor (immediate release) for
at least 3 months in placebo-controlled 12-month extension trials
had a mean final on-therapy increase in total cholesterol of 9.1 mg/dL
compared with a decrease of 7.1 mg/dL among placebo-treated patients.
This increase was duration dependent over the study period and tended
to be greater with higher doses. Clinically relevant increases in
serum cholesterol, defined as 1) a final on���therapy increase
in serum cholesterol���50 mg/dL from baseline and to a
value���261 mg/dL, or 2) an average on-therapy increase
in serum cholesterol���50 mg/dL from baseline and to a
value���261 mg/dL, were recorded in 5.3% of venlafaxine-treated
patients and 0.0% of placebo-treated patients (see PRECAUTIONS-General-Serum Cholesterol
Elevation).<br/>Serum Triglycerides: Effexor XR treatment for up to 12 weeks in pooled
premarketing Social Anxiety Disorder trials was associated with a
mean final on-therapy increase in fasting serum triglyceride concentration
of approximately 8.2 mg/dL, compared with a mean final increase of
0.4 mg/dL for placebo. Effexor XR treatment for up to 6 months in
a premarketing Social Anxiety Disorder trial was associated with a
mean final on-therapy increase in fasting serum triglyceride concentration
of approximately 11.8 mg/dL, compared with a mean final on-therapy
increase of 1.8 mg/dL for placebo. Effexor XR
treatment for up to 12 weeks in pooled premarketing Panic Disorder
trials was associated with a mean final on-therapy increase in fasting
serum triglyceride concentration of approximately 5.9 mg/dL, compared
with a mean final increase of 0.9 mg/dL for placebo. Effexor XR treatment
for up to 6 months in a premarketing Panic Disorder trial was associated
with a mean final on-therapy increase in fasting serum triglyceride
concentration of approximately 9.3 mg/dL, compared with a mean final
on-therapy decrease of 0.3 mg/dL for placebo.<br/>ECG Changes: In a flexible-dose
study, with Effexor (immediate release) doses in the range of 200 to 375 mg/day
and mean dose greater than 300 mg/day, the mean change in heart
rate was 8.5 beats per minute compared with 1.7 beats per minute for
placebo.<br/>Other Adverse Events Observed During the Premarketing Evaluation
of Effexor and Effexor XR: During its premarketing
assessment, multiple doses of Effexor XR were administered to
705 patients in Phase 3 major depressive disorder studies and
Effexor was administered to 96 patients. During its premarketing
assessment, multiple doses of Effexor XR were also administered
to 1381 patients in Phase 3 GAD studies, 819 patients in Phase 3 Social
Anxiety Disorder studies, and 1314 patients in Phase 3 panic disorder
studies. In addition, in premarketing assessment of Effexor, multiple
doses were administered to 2897 patients in Phase 2 to Phase 3 studies
for major depressive disorder. 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 (Effexor 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 7212 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 Tables 7, 8, 9, and 10 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 using the following definitions: frequent adverse events are defined as
those occurring on one or more occasions in at least 1/100 patients; 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, neck pain; Infrequent: face
edema, intentional injury, malaise, moniliasis, neck rigidity, pelvic
pain, photosensitivity reaction, suicide attempt, withdrawal syndrome; Rare: appendicitis, bacteremia, carcinoma,
cellulitis, granuloma. Cardiovascular system - Frequent: migraine, tachycardia; Infrequent: angina pectoris, arrhythmia, bradycardia, extrasystoles, hypotension,
peripheral vascular disorder (mainly cold feet and/or cold hands),
postural hypotension, syncope; Rare: aortic aneurysm, arteritis, first-degree atrioventricular block,
bigeminy, bundle branch block, capillary fragility, cerebral ischemia,
coronary artery disease, congestive heart failure, heart arrest, hematoma,
cardiovascular disorder (mitral valve and circulatory disturbance),
mucocutaneous hemorrhage, myocardial infarct, pallor, sinus arrhythmia,
thrombophlebitis. Digestive system - Frequent: increased
appetite; Infrequent: bruxism,
colitis, dysphagia, tongue edema, eructation, esophagitis, gastritis,
gastroenteritis, gastrointestinal ulcer, gingivitis, glossitis, rectal
hemorrhage, hemorrhoids, melena, oral moniliasis, stomatitis, mouth
ulceration; Rare: abdominal distension,
biliary pain, cheilitis, cholecystitis, cholelithiasis, esophageal
spasms, duodenitis, hematemesis, gastroesophageal reflux disease,
gastrointestinal hemorrhage, gum hemorrhage, hepatitis, ileitis, jaundice,
intestinal obstruction, liver tenderness, parotitis, periodontitis,
proctitis, rectal disorder, salivary gland enlargement, increased
salivation, soft stools, tongue discoloration. Endocrine system - Rare: galactorrhoea,
goiter, hyperthyroidism, hypothyroidism, thyroid nodule, thyroiditis. Hemic and lymphatic system
- Frequent: ecchymosis; Infrequent: anemia, leukocytosis, leukopenia,
lymphadenopathy, thrombocythemia; Rare: basophilia, bleeding time increased, cyanosis, eosinophilia, lymphocytosis,
multiple myeloma, purpura, thrombocytopenia. Metabolic and nutritional - Frequent: edema, weight gain; Infrequent: alkaline phosphatase increased, dehydration, hypercholesteremia,
hyperglycemia, hyperlipidemia, hypokalemia, SGOT (AST) increased,
SGPT (ALT) increased, thirst; Rare: alcohol intolerance, bilirubinemia, BUN increased, creatinine increased,
diabetes mellitus, glycosuria, gout, healing abnormal, hemochromatosis,
hypercalcinuria, hyperkalemia, hyperphosphatemia, hyperuricemia, hypocholesteremia,
hypoglycemia, hyponatremia, hypophosphatemia, hypoproteinemia, uremia. Musculoskeletal system - Infrequent: arthritis, arthrosis, bone
spurs, bursitis, leg cramps, myasthenia, tenosynovitis; Rare: bone pain, pathological fracture,
muscle cramp, muscle spasms, musculoskeletal stiffness, myopathy,
osteoporosis, osteosclerosis, plantar fasciitis, rheumatoid arthritis,
tendon rupture. Nervous system - Frequent: amnesia,
confusion, depersonalization, hypesthesia, thinking abnormal, trismus,
vertigo; Infrequent: akathisia,
apathy, ataxia, circumoral paresthesia, CNS stimulation, emotional
lability, euphoria, hallucinations, hostility, hyperesthesia, hyperkinesia,
hypotonia, incoordination, libido increased, manic reaction, myoclonus,neuralgia, neuropathy, psychosis, seizure, abnormal speech, stupor,
suicidal ideation; Rare: abnormal/changed
behavior, adjustment disorder, akinesia, alcohol abuse, aphasia, bradykinesia,
buccoglossal syndrome, cerebrovascular accident, feeling drunk, loss
of consciousness, delusions, dementia, dystonia, energy increased,
facial paralysis, abnormal gait, Guillain-Barre Syndrome, homicidal
ideation, hyperchlorhydria, hypokinesia, hysteria, impulse control
difficulties, motion sickness, neuritis, nystagmus,paranoid reaction,
paresis, psychotic depression, reflexes decreased, reflexes increased,
torticollis. Respiratory system - Frequent: cough increased, dyspnea; Infrequent: asthma, chest congestion, epistaxis, hyperventilation, laryngismus,
laryngitis, pneumonia, voice alteration; Rare: atelectasis, hemoptysis, hypoventilation, hypoxia,
larynx edema, pleurisy, pulmonary embolus, sleep apnea. Skin and appendages - Frequent: pruritus; Infrequent: acne, alopecia, contact dermatitis, dry skin,
eczema, maculopapular rash, psoriasis, urticaria; Rare: brittle nails, erythema nodosum,
exfoliative dermatitis, lichenoid dermatitis, hair discoloration,
skin discoloration, furunculosis, hirsutism, leukoderma, miliaria,
petechial rash, pruritic rash, pustular rash, vesiculobullous rash,
seborrhea, skin atrophy, skin hypertrophy, skin striae, sweating decreased. Special senses - Frequent: abnormality of accommodation,
mydriasis, taste perversion; Infrequent: conjunctivitis, diplopia, dry eyes, eye pain, otitis media, parosmia,
photophobia, taste loss; Rare: blepharitis, cataract, chromatopsia, conjunctival edema, corneal
lesion, deafness, exophthalmos, eye hemorrhage, glaucoma, retinal
hemorrhage, subconjunctival hemorrhage, hyperacusis, keratitis, labyrinthitis,
miosis, papilledema, decreased pupillary reflex, otitis externa, scleritis,
uveitis, visual field defect. Urogenital system - Frequent: albuminuria, urination impaired; Infrequent: amenorrhea,* cystitis, dysuria,
hematuria, kidney calculus, kidney pain, leukorrhea,* menorrhagia,* metrorrhagia,* nocturia,
breast pain, polyuria, pyuria, prostatic disorder (prostatitis, enlarged
prostate, and prostate irritability,* urinary incontinence, urinary retention, urinary urgency, vaginal
hemorrhage,* vaginitis*; Rare: abortion,* anuria, breast discharge,
breast engorgement, balanitis,* breast enlargement, endometriosis,* female lactation,* fibrocystic
breast, calcium crystalluria, cervicitis,* orchitis,* ovarian
cyst,* bladder pain, prolonged
erection,* gynecomastia (male),* hypomenorrhea,* kidney function abnormal, mastitis, menopause,* pyelonephritis, oliguria, salpingitis,* urolithiasis, uterine hemorrhage,* uterine spasm,* vaginal dryness.* * Based on
the number of men and women as appropriate.<br/>Postmarketing Reports:<br/>Adverse Events: Voluntary reports of other adverse events temporally
associated with the use of venlafaxine that have been received since
market introduction and that may have no causal relationship with
the use of venlafaxine include the following: agranulocytosis, anaphylaxis,
aplastic anemia, catatonia, congenital anomalies, impaired coordination
and balance, CPK increased, deep vein thrombophlebitis, delirium,
EKG abnormalities such as QT prolongation; cardiac arrhythmias including
atrial fibrillation, supraventricular tachycardia, ventricular extrasystoles,
and rare reports of ventricular fibrillation and ventricular tachycardia,
including torsade de pointes; toxic epidermal necrolysis/Stevens-Johnson
Syndrome, erythema multiforme, extrapyramidal symptoms (including
dyskinesia and tardive dyskinesia), angle-closure glaucoma, 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), interstitial
lung disease, involuntary movements, LDH increased, neuroleptic malignant
syndrome-like events (including a case ofa 10-year-old who may have
been taking methylphenidate, was treated and recovered), neutropenia,
night sweats, pancreatitis, pancytopenia, panic, prolactin increased,
renal failure, rhabdomyolysis, serotonin syndrome, shock-like electrical
sensations or tinnitus (in some cases, subsequent to the discontinuation
of venlafaxine or tapering of dose), and syndrome of inappropriate
antidiuretic hormone secretion (usually in the elderly).<br/>Drug Interactions: There have been reports of elevated clozapine levels
that were temporally associated with adverse events, including seizures,
following the addition of venlafaxine. There have been reports of
increases in prothrombin time, partial thromboplastin time, or INR
when venlafaxine was given to patients receiving warfarin therapy.
|
dailymed-instance:warning |
Clinical Worsening and Suicide Risk: Patients with major
depressive disorder (MDD), both adult and pediatric, may experience
worsening of their depression and/or the emergence of suicidal ideation
and behavior (suicidality) or unusual changes in behavior, whether
or not they are taking antidepressant medications, and this risk may
persist until significant remission occurs. Suicide is a known risk
of depression and certain other psychiatric disorders,and these disorders
themselves are the strongest predictors of suicide. There has been
a long standing concern, however, that antidepressants may have a
role in inducing worsening of depression and the emergence of suicidality
in certain patients during the early phases of treatment. Pooled analyses
of short-term placebo-controlled trials of antidepressant drugs (SSRIs
and others) showed that these drugs increase the risk of suicidal
thinking and behavior (suicidality) in children, adolescents, and
young adults (ages 18-24) with major depressive disorder (MDD) and
other psychiatric disorders. Short-term studies did not show an increase
in the risk of suicidality with antidepressants compared to placebo
in adults beyond age 24; there was a reduction with antidepressants
compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and
adolescents with MDD, obsessive compulsive disorder (OCD), or other
psychiatric disorders included a total of 24 short-term trials of
9 antidepressant drugs in over 4400 patients. The pooled analyses
of placebo-controlled trials in adults with MDD or other psychiatric
disorders included a total of 295 short-term trials (median duration
of 2 months) of 11 antidepressant drugs in over 77,000 patients. There
was considerable variation in risk of suicidality among drugs, but
a tendency toward an increase in the younger patients for almost all
drugs studied. There were differences in absolute risk of suicidality
across the different indications, with the highest incidence in MDD.
The risk differences (drug vs placebo), however, were relatively stable
within age strata and across indications. These risk differences (drug-placebo
difference in the number of cases of suicidality per 1000 patients
treated) are provided in Table 1. No suicides occurred in any of the pediatric trials. There were suicides
in the adult trials, but the number was not sufficient to reach any
conclusion about drug effect on suicide. It
is unknown whether the suicidality risk extends to longer-term use,
i.e., beyond several months. However, there is substantial evidence
from placebo-controlled maintenance trials in adults with depression
that the use of antidepressants can delay the recurrence of depression. All patients being treated with
antidepressants for any indication should be monitored appropriately
and observed closely for clinical worsening, suicidality, and unusual
changes in behavior, especially during the initial few months of a
course of drug therapy, or at times of dose changes, either increases
or decreases. The following symptoms, anxiety,
agitation, panic attacks, insomnia, irritability, hostility, aggressiveness,
impulsivity, akathisia (psychomotor restlessness), hypomania, and
mania, have been reported in adult and pediatric patients being treated
with antidepressants for major depressive disorder as well as for
other indications, both psychiatric and nonpsychiatric. Although a
causal link between the emergence of such symptoms and either the
worsening of depression and/or the emergence of suicidal impulses
has not been established, there is concern that such symptoms may
represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen,
including possibly discontinuing the medication, in patients whose
depression is persistently worse, or who are experiencing emergent
suicidality or symptoms that might be precursors to worsening depression
or suicidality, especially if these symptoms are severe, abrupt in
onset, or were not part of the patient's presenting symptoms. If the decision has been
made to discontinue treatment, medication should be tapered, as rapidly
as is feasible, but with recognition that abrupt discontinuation can
be associated with certain symptoms (see PRECAUTIONS and DOSAGE AND ADMINISTRATION,
Discontinuation of Treatment with Effexor XR, for a description of the risks of discontinuation of Effexor XR). Families and caregivers of patients being treated with antidepressants
for major depressive disorder or other indications, both psychiatric
and nonpsychiatric, should be alerted about the need to monitor patients
for the emergence of agitation, irritability, unusual changes in behavior,
and the other symptoms described above, as well as the emergence of
suicidality, and to report such symptoms immediately to health care
providers. Such monitoring should include daily observation by families
and caregivers. Prescriptions for Effexor XR should
be written for the smallest quantity of capsules consistent with good
patient management, in order to reduce the risk of overdose.<br/>Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation
of bipolar disorder. It is generally believed (though not established
in controlled trials) that treating such an episode with an antidepressant
alone may increase the likelihood of precipitation of a mixed/manic
episode in patients at risk for bipolar disorder. Whether any of the
symptoms described above represent such a conversion is unknown. However,
prior to initiating treatment with an antidepressant, patients with
depressive symptoms should be adequately screened to determine if
they are at risk for bipolar disorder; such screening should include
a detailed psychiatric history, including a family history of suicide,
bipolar disorder, and depression. It should be noted that Effexor XR
is not approved for use in treating bipolar depression.<br/>Potential for Interaction with Monoamine Oxidase Inhibitors: Adverse reactions, some of which were serious, have
been reported in patients who have recently been discontinued from
a monoamine oxidase inhibitor (MAOI) and started on venlafaxine, or
who have recently had venlafaxine therapy discontinued prior to initiation
of an MAOI. These reactions have included tremor, myoclonus, diaphoresis,
nausea, vomiting, flushing, dizziness, hyperthermia with features
resembling neuroleptic malignant syndrome, seizures, and death. In
patients receiving antidepressants with pharmacological properties
similar to venlafaxine in combination with an MAOI, there have also
been reports of serious, sometimes fatal, reactions. For a selective
serotonin reuptake inhibitor, these reactions have included hyperthermia,
rigidity, myoclonus, autonomic instability with possible rapid fluctuations
of vital signs, and mental status changes that include extreme agitation
progressing to delirium and coma. Some cases presented with features
resembling neuroleptic malignant syndrome. Severe hyperthermia and
seizures, sometimes fatal, have been reported in association with
the combined use of tricyclic antidepressants and MAOIs. These reactions
have also been reported in patients who have recently discontinued
these drugs and have been started on an MAOI. The effects of combined
use of venlafaxine and MAOIs have not been evaluated in humans or
animals. Therefore, because venlafaxine is an inhibitor of both norepinephrine
and serotonin reuptake, it is recommended that Effexor XR (venlafaxine
hydrochloride) extended-release capsules not be used in combination
with an MAOI, or within at least 14 days ofdiscontinuing treatment
with an MAOI. Based on the half-life of venlafaxine, at least 7 days
should be allowed after stopping venlafaxine before starting an MAOI.<br/>Serotonin Syndrome: The development of a potentially life-threatening
serotonin syndrome may occur with Effexor XR treatment, particularly
with concomitant use of serotonergic drugs (including SSRIs, SNRIs
and triptans) and with drugs that impair metabolism of serotonin (including
MAOIs). Serotonin syndrome symptoms may include mental status changes
(e.g., agitation, hallucinations, coma), autonomic instability (e.g.,
tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations
(e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms
(e.g., nausea, vomiting, diarrhea). The concomitant use of Effexor XR with
MAOIs intended to treat depression is contraindicated (see CONTRAINDICATIONS and WARNINGS,
Potential for Interaction with Monoamine Oxidase Inhibitors). If concomitant treatment of Effexor
XR with an SSRI, an SNRI or a 5-hydroxytryptamine receptor agonist
(triptan) is clinically warranted, careful observation of the patient
is advised, particularly during treatment initiation and dose increases
(see PRECAUTIONS,
Drug Interactions). The
concomitant use of Effexor XR with serotonin precursors (such as tryptophan
supplements) is not recommended .<br/>Sustained Hypertension: Effexor XR treatment is associated with sustained hypertension (defined
as treatment-emergent supine diastolic blood pressure (SDBP)���90
mm Hg and���10 mm Hg above baseline for 3 consecutive on-therapy
visits (see Table 2). An analysis for patients in Effexor (immediate release) studies meeting
criteria for sustained hypertension revealed a dose-dependent increase
in the incidence of sustained hypertension for Effexor (immediate
release) (see Table 3). An insufficient number of patients received mean doses
of Effexor XR over 300 mg/day to fully evaluate the incidence of sustained
increases in blood pressure at these higher doses. In premarketing major
depressive disorder studies, 0.7% (5/705) of the Effexor XR-treated
patients discontinued treatment because of elevated blood pressure.
Among these patients, most of the blood pressure increases were in
a modest range (12 to 16 mm Hg, SDBP). In premarketing
GAD studies up to 8 weeks and up to 6 months, 0.7% (10/1381) and 1.3% (7/535) of
the Effexor XR-treated patients, respectively, discontinued treatment
because of elevated blood pressure. Among these patients, most of
the blood pressure increases were in a modest range (12 to 25 mm Hg,
SDBP up to 8 weeks; 8 to 28 mm Hg up to 6 months).
In premarketing Social Anxiety Disorder studies up to 6 months, 0.6%
(5/771) of the Effexor XR���treated patients discontinued
treatment because of elevated blood pressure. In these patients, the
blood pressure increases were modest (1-24 mm Hg, SDBP). In premarketing
panic disorder studies up to 12 weeks, 0.5% (5/1001) of the Effexor XR-treated
patients discontinued treatment because of elevated blood pressure.
In these patients, the blood pressure increases were in a modest range
(7 to 19 mm Hg, SDBP). Sustained increases of SDBP could have adverse consequences. Cases
of elevated blood pressure requiring immediate treatment have been
reported in post marketing experience. Pre-existing hypertension should
be controlled before treatment with venlafaxine. It is recommended
that patients receiving Effexor XR have regular monitoring of
blood pressure. For patients who experience a sustained increase in
blood pressure while receiving venlafaxine, either dose reduction
or discontinuation should be considered.<br/>Elevations in Systolic and Diastolic Blood Pressure: In placebo-controlled premarketing studies, there
were changes in mean blood pressure (see Table
4 for mean changes in supine systolic and supine diastolic
blood pressure). Across most indications, a dose-related increase
in supine systolic and diastolic blood pressure was evident in Effexor
XR-treated patients. Across all clinical trials in MDD, GAD, Social
Anxiety Disorder and panic disorder, 1.4% of patients in the Effexor
XR-treated groups experienced a���15 mm Hg increase in supine
diastolic blood pressure with blood pressure���105 mm Hg compared
to 0.9% of patients in the placebo groups. Similarly, 1% of patients
in the Effexor XR-treated groups experienced a���20 mm Hg increase
in supine systolic blood pressure with blood pressure���180
mm Hg compared to 0.3% of patients in the placebo groups.<br/>Mydriasis: Mydriasis has been reported in association with venlafaxine;
therefore patients with raised intraocular pressure or those at risk
of acute narrow-angle glaucoma (angle-closure glaucoma) should be
monitored (see PRECAUTIONS,
Information for Patients).
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Major Depressive Disorder: Effexor XR
(venlafaxine hydrochloride) extended-release capsules is indicated
for the treatment of major depressive disorder. The efficacy of Effexor XR in the treatment of major depressive
disorder was established in 8���and 12-week controlled
trials of adult outpatients whose diagnoses corresponded most closely
to the DSM-III-R or DSM-IV category of major depressive disorder (see Clinical Trials). A major depressive
episode (DSM-IV) implies a prominent and relatively persistent (nearly
every day for at least 2 weeks) depressed mood or the loss of interest
or pleasure in nearly all activities, representing a change from previous
functioning, and includes the presence of at least five of the following
nine symptoms during the same two-week period: depressed mood, markedlydiminished interest or pleasure in usual activities, significant change
in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation
or retardation, increased fatigue, feelings of guilt or worthlessness,
slowed thinking or impaired concentration, a suicide attempt or suicidal
ideation. The
efficacy of Effexor (immediate release) in the treatment of major
depressive disorder in adult inpatients meeting diagnostic criteria
for major depressive disorder with melancholia was established in
a 4-week controlled trial (see Clinical Trials). The safety and
efficacy of Effexor XR in hospitalized depressed patients have
not been adequately studied. The efficacy of Effexor XR in maintaining a response in major
depressive disorder for up to 26 weeks following 8 weeks of acute
treatment was demonstrated in a placebo-controlled trial. The efficacy
of Effexor (immediate release) in maintaining a response in patients
with recurrent major depressive disorder who hadresponded and continued
to be improved during an initial 26 weeks of treatment and were then
followed for a period of up to 52 weeks was demonstrated in a second
placebo-controlled trial (see Clinical Trials). Nevertheless, the
physician who elects to use Effexor/Effexor XR for extended periods
should periodically re-evaluate the long-term usefulness of the drug
for the individual patient .<br/>Generalized Anxiety Disorder: Effexor XR
is indicated for the treatment of Generalized Anxiety Disorder (GAD)
as defined in DSM-IV. Anxiety or tension associated with the stress
of everyday life usually does not require treatment with an anxiolytic. The efficacy of Effexor XR
in the treatment of GAD was established in 8-week and 6-month placebo-controlled
trials in adult outpatients diagnosed with GAD according to DSM-IV
criteria (see Clinical
Trials). Generalized Anxiety Disorder (DSM-IV) is characterized by excessive
anxiety and worry (apprehensive expectation) that is persistent for
at least 6 months and which the person finds difficult to control.
It must be associated with at least 3 of the following 6 symptoms:
restlessness or feeling keyed up or on edge, being easily fatigued,
difficulty concentrating or mind going blank,irritability, muscle
tension, sleep disturbance. Although the effectiveness of Effexor XR has been demonstrated
in 6-month clinical trials in patients with GAD, the physician who
elects to use Effexor XR for extended periods should periodically
re-evaluate the long-term usefulness of the drug for the individual
patient (see DOSAGE
AND ADMINISTRATION).<br/>Social Anxiety Disorder: Effexor XR
is indicated for the treatment of Social Anxiety Disorder, also known
as Social Phobia, as defined in DSM-IV (300.23). Social Anxiety Disorder (DSM-IV) is characterized by a marked and
persistent fear of 1 or more social or performance situations in which
the person is exposed to unfamiliar people or to possible scrutiny
by others. Exposure to the feared situation almost invariably provokes
anxiety, which may approach the intensity of a panic attack. The feared
situations are avoided or endured with intense anxiety or distress.
The avoidance, anxious anticipation, or distress in the feared situation(s)
interferes significantly with the person's normal routine, occupationalor academic functioning, or social activities or relationships, or
there is a marked distress about having the phobias. Lesser degrees
of performance anxiety or shyness generally do not require psychopharmacological
treatment. The
efficacy of Effexor XR in the treatment of Social Anxiety Disorder
was established in four 12-week and one 6-month placebo-controlled
trials in adult outpatients with Social Anxiety Disorder (DSM-IV)
(see Clinical Trials). Although the effectiveness of Effexor XR has been demonstrated
in a 6-month clinical trial in patients with Social Anxiety Disorder,
the physician who elects to use Effexor XR for extended periods
should periodically re-evaluate the long-term usefulness of the drug
for the individual patient .<br/>Panic Disorder: Effexor XR
is indicated for the treatment of panic disorder, with or without
agoraphobia, as defined in DSM���IV. Panic disorder is characterized
by the occurrence of unexpected panic attacks and associated concern
about having additional attacks, worry about the implications or consequences
of the attacks, and/or a significant change in behavior related to
the attacks. Panic disorder (DSM-IV) is characterized by recurrent, unexpected
panic attacks, ie, a discrete period of intense fear or discomfort,
in which four (or more) of the following symptoms develop abruptly
and reach a peak within 10 minutes: 1) palpitations, pounding heart,
or accelerated heart rate; 2) sweating; 3) trembling or shaking;
4) sensations of shortness of breath or smothering; 5) feeling
of choking; 6) chest pain or discomfort; 7) nausea or abdominal distress;
8) feeling dizzy, unsteady, lightheaded, or faint; 9) derealization
(feelings of unreality) or depersonalization (being detached from
oneself); 10) fear of losing control; 11) fear of dying; 12) paresthesias
(numbness or tingling sensations); 13) chills or hot flushes. The efficacy of Effexor XR
in the treatment of panic disorder was established in two 12-week
placebo-controlled trials in adult outpatients with panic disorder
(DSM-IV). The efficacy of Effexor XR in prolonging time to relapse
in panic disorder among responders following 12 weeks of open-label
acute treatment was demonstrated in a placebo-controlled study (see CLINICAL PHARMACOLOGY, Clinical
Trials). Nevertheless, the physician who elects
to use Effexor XR for extended periods should periodically re-evaluate
the long-term usefulness of the drug for the individual patient .
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Effexor XR
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