INDICATIONS
Venlafaxine hydrochloride is indicated for the treatment
of depression. Venlafaxine HCl extended-release is indicated
for depression and Generalized Anxiety Disorder.
Depression
The efficacy of venlafaxine HCl in the treatment of depression
was established in 6-week controlled trials of outpatients
whose diagnoses corresponded most closely to the DSM-III
or DSM-III-R category of major depressive disorder and
in a 4-week controlled trial of inpatients meeting diagnostic
criteria for major depressive disorder with melancholia
(see CLINICAL PHARMACOLOGY).
A major depressive episode implies a prominent and relatively
persistent depressed or dysphoric mood that usually interferes
with daily functioning (nearly every day for at least
2 weeks); it should include at least 4 of the following
8 symptoms: change in appetite, change in sleep, psychomotor
agitation or retardation, loss of interest in usual activities
or decrease in sexual drive, increased fatigue, feelings
of guilt or worthlessness, slowed thinking or impaired
concentration, and a suicide attempt or suicidal ideation.
The efficacy of venlafaxine HCl (extended release) in
the treatment of depression was established in 8- and
12-week controlled trials of outpatients whose diagnoses
corresponded most closely to the DSM-III-R or DSM-IV category
of major depressive disorder (see CLINICAL STUDIES).
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, markedly diminished 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 venlafaxine HCl (the immediate release
form of venlafaxine) in the treatment of depression in
inpatients meeting diagnostic criteria for major depressive
disorder with melancholia was established in a 4-week
controlled trial (see CLINICAL STUDIES).
The safety and efficacy of venlafaxine HCl (extended
release) in hospitalized depressed patients has not been
adequately studied.
The effectiveness of venlafaxine HCl (extended release)
in long-term use, that is, for more than 12 weeks, has
not been systematically evaluated in controlled trials.
The physician who elects to use venlafaxine HCl (extended
release) for extended periods should periodically re-evaluate
the long-term usefulness of the drug for the individual
patient (see
DOSAGE AND ADMINISTRATION
).
Generalized Anxiety Disorder
Venlafaxine HCl extended-release 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 venlafaxine HCl extended-release
in the treatment of GAD was established in 8-week placebo-controlled
trials in outpatients diagnosed with GAD according to
DSM-IV criteria (see CLINICAL STUDIES). 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. The effectiveness of venlafaxine HCl extended-release
in the long-term treatment of GAD, that is, for more than
8 weeks, has not been systematically evaluated in controlled
trials. The physician who elects to use venlafaxine HCl
extended-release for extended periods should periodically
re-evaluate the long-term usefulness of the drug for the
individual patient (see
DOSAGE AND ADMINISTRATION
.
DOSAGE AND ADMINISTRATION
Initial Treatment
Immediate-Release Tablets
The recommended starting dose for venlafaxine HCl is
75 mg/day, administered in two or three divided doses,
taken with food. Depending on tolerability and the need
for further clinical effect, the dose may be increased
to 150 mg/day. If needed, the dose should be further increased
up to 225 mg/day. When increasing the dose, increments
of up to 75 mg/day should be made at intervals of no less
than 4 days. In outpatient settings there was no evidence
of usefulness of doses greater than 225 mg/day for moderately
depressed patients, but more severely depressed inpatients
responded to a mean dose of 350 mg/day. Certain patients,
including more severely depressed patients, may therefore
respond more to higher doses, up to a maximum of 375 mg/day,
generally in three divided doses.
Extended-Release Capsules
Venlafaxine HCl (extended release) should be administered
in a single daily 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.
Depression
For most patients, the recommended starting dose for
venlafaxine HCl (extended release) is 75 mg/day, administered
in a single dose. In the clinical trials establishing
the efficacy of venlafaxine HCl (extended release) 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 venlafaxine HCl (extended
release) has not been adequately explored, 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, since steady state plasma levels of venlafaxine
and its major metabolite are achieved in most patients
by 4 days. In the clinical trials establishing efficacy,
upward titration was permitted at intervals of 2 weeks
or more; the average doses were about 140-180 mg/day (see
CLINICAL STUDIES).
It should be noted that, while the maximum recommended
dose for moderately depressed outpatients is also 225
mg/day for venlafaxine HCl (the immediate release form
of venlafaxine), 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 venlafaxine
HCl (extended release) are needed for more severely depressed
patients is unknown; however, the experience with venlafaxine
HCl (extended release) doses higher than 225 mg/day is
very limited.
Generalized Anxiety Disorder
For most patients, the recommended starting dose for
venlafaxine HCl extended-release is 75 mg/day, administered
in a single dose. In clinical trials establishing the
efficacy of venlafaxine HCl extended-release 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.
Switching Patients From Immediate Release
Venlafaxine Tablets to Extended Release Capsules
Depressed patients who are currently being treated at
a therapeutic dose with venlafaxine HCl immediate release
may be switched to venlafaxine HCl (extended release)
at the nearest equivalent dose (mg/day), e.g., 37.5 mg
venlafaxine two-times-a-day to 75 mg venlafaxine HCl (extended
release) once daily. However, individual dosage adjustments
may be necessary.
Dosage for 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 compared to normal
subjects (see CLINICAL PHARMACOLOGY), it is recommended
that the total daily dose be reduced by 50% in patients
with moderate hepatic impairment. Since there was much
individual variability in clearance between patients with
cirrhosis, it may be necessary to reduce the dose even
more than 50%, and individualization of dosing may be
desirable in some patients.
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 = 10-70 ml/min) compared with normal subjects (see
CLINICAL PHARMACOLOGY), it is recommended that the total
daily dose be reduced by 25-50% in patients with mild
to moderate renal impairment. in patients undergoing hemodialysis,
it is recommended that the total daily dose be reduced
by 50% and that the dose be withheld until the dialysis
treatment is completed (4 hrs). Since there was much individual
variability in clearance between patients with renal impairment,
individualization of dosing may be desirable in some patients.
Dosage for Elderly Patients
No dose adjustment is recommended for elderly patients
on the basis of age. As with any antidepressant, however,
caution should be exercised in treating the elderly. When
individualizing the dosage, extra care should be taken
when increasing the dose.
Maintenance/Extended Treatment
There is no body of evidence available to answer the
question of how long a patient should continue to be treated
with venlafaxine HCl.
It is generally agreed, however, that pharmacological
treatment for acute episodes of depression should continue
for up to six months or longer. Whether the dose of antidepressant
needed to induce remission is identical to the dose needed
to maintain euthymia is unknown. In patients with Generalized
Anxiety Disorder, there are no efficacy data beyond eight
weeks of treatment with venlafaxine HCl extended-release.
The need for continuing medication in patients with GAD
who improve with venlafaxine HCl extended-release treatment
should be periodically reassessed.
Discontinuing Venlafaxine Hydrochloride
Immediate Release Tablets: When discontinuing venlafaxine
HCl after more than 1 week of therapy, it is generally
recommended that the dose be tapered to minimize the risk
of discontinuation symptoms. Patients who have received
venlafaxine HCl for 6 weeks or more should have their
dose tapered gradually over a 2-week period.
Extended Release Capsules: When
discontinuing venlafaxine HCl (extended release) after
more than 1 week of therapy, it is generally recommended
that the dose be tapered to minimize the risk of discontinuation
symptoms. In clinical trials with venlafaxine HCl (extended
release), tapering was achieved by reducing the daily
dose by 75 mg at 1 week intervals. Individualization of
tapering may be necessary. While the discontinuation effects
of venlafaxine HCl (extended release) have not been systematically
evaluated in controlled clinical trials, a retrospective
survey of new events occurring during taper or following
discontinuation revealed the following six events that
occurred at an incidence of at least 3% and for which
the incidence for venlafaxine HCl (extended release) was
at least twice the placebo incidence: dizziness, dry mouth,
insomnia, nausea, nervousness, and sweating.
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 venlafaxine
HCl. In addition, at least 7 days should be allowed after
stopping venlafaxine HCl before starting an MAOI (see
CONTRA
INDICATIONS
and WARNINGS).
HOW SUPPLIED
Effexor: 25 mg: peach, shield-shaped
tablet with “25” and a "W"
on one side and “701” on scored reverse side.
37.5 mg: peach, shield-shaped tablet with “37.5”
and a "W" on one side and “781”
on scored reverse side. 50 mg: peach, shield-shaped tablet
with “50” and a "W" on one side
and “703” on scored reverse side. 75 mg: peach,
shield-shaped tablet with “75” and a "W"
on one side and “704” on scored reverse side.
100 mg: peach, shield-shaped tablet with “100”
and a "W" on one side and “705”
on scored reverse side.
Effexor XR: 37.5 mg: gray cap/peach
body with “"W" and Effexor XR” on
the cap and “37.5” on the body. 75 mg: peach
cap and body with “"W" and Effexor XR”
on the cap and “75” on the body. 150 mg: dark
orange cap and body with “"W" and Effexor
XR” on the cap and “150” on the body.
Store at controlled room temperature, 20°C
to 25°C (68°F to 77°F), in a dry place.
Dispense in a well-closed container.
PRODUCT LISTING
| Capsule,
Extended Release - Oral - 37.5 mg |
| 100's |
Effexor
Xr, Wyeth Labs |
00008-0837-01 |
| Capsule,
Extended Release - Oral - 75 mg |
| 100's |
Effexor
Xr, Wyeth Labs |
00008-0833-01 |
| Capsule,
Extended Release - Oral - 150 mg |
| 100's |
Effexor
Xr, Wyeth Labs |
00008-0836-01 |
| Tablet
- Oral - 25 mg |
| 100's |
Effexor,
Wyeth Labs |
00008-0701-01 |
| 100's |
Effexor,
Wyeth Labs |
00008-0701-02 |
| Tablet
- Oral - 37.5 mg |
| 100's |
Effexor,
Wyeth Labs |
00008-0781-01 |
| 100's |
Effexor,
Wyeth Labs |
00008-0781-02 |
| Tablet
- Oral - 50 mg |
| 100's |
Effexor,
Wyeth Labs |
00008-0703-01 |
| 100's |
Effexor,
Wyeth Labs |
00008-0703-02 |
| Tablet
- Oral - 75 mg |
| 100's |
Effexor,
Wyeth Labs |
00008-0704-01 |
| 100's |
Effexor,
Wyeth Labs |
00008-0704-02 |
| Tablet
- Oral - 100 mg |
| 100's |
Effexor,
Wyeth Labs |
00008-0705-01 |
| 100's |
Effexor,
Wyeth Labs |
00008-0705-02 |
|
|
