This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
EFFEXOR XR safely and effectively. See full prescribing information for
EFFEXOR XR.
EFFEXOR XR® (venlafaxine extended-release) capsules, for oral use
Initial U.S. Approval: 1997••

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
See full prescribing information for complete boxed warning.
Increased risk of suicidal thoughts and behavior in pediatricpatients and young adults taking antidepressants. Closely monitor
all antidepressant-treated patients for clinical worsening andemergence of suicidal thoughts and behaviors (5.1).
Effexor XR is not approved for use in pediatric patients (8.4).

--------------------------- RECENT MAJOR CHANGES -------------------------Warnings and Precautions (5.2, 5.4)
8/2023--------------------------- INDICATIONS AND USAGE --------------------------Effexor XR is a serotonin and norepinephrine reuptake inhibitor (SNRI)
indicated for the treatment of adults with:•Major Depressive Disorder (MDD) (1)•Generalized Anxiety Disorder (GAD) (1)•Social Anxiety Disorder (SAD) (1)•Panic Disorder (PD) (1)---------------------- DOSAGE AND ADMINISTRATION ----------------------Indication
Starting Dose
Target DoseMaximum DoseMDD (2.2)
37.5-75 mg/day
75 mg/day
225 mg/day
GAD (2.3)
37.5-75 mg/day
75 mg/day
225 mg/day
SAD (2.4)75 mg/day
75 mg/day
75 mg/day
PD (2.5)
37.5 mg/day
75 mg/day
225 mg/day•
Take once daily with food. Capsules should be taken whole; do notdivide, crush, chew, or dissolve (2.1).
•
When discontinuing treatment, reduce the dose gradually (2.10, 5.7).
•
Renal impairment: reduce the total daily dose by 25% to 50% in patientswith renal impairment. Reduce the total daily dose by 50% or more inpatients undergoing dialysis or with severe renal impairment (2.9).
•
Hepatic impairment: reduce the daily dose by 50% in patients with mild
to moderate hepatic impairment. In patients with severe hepatic
impairment or hepatic cirrhosis, it may be necessary to reduce the doseby more than 50% (2.8).
--------------------- DOSAGE FORMS AND STRENGTHS --------------------•
Extended-release capsules: 37.5 mg, 75 mg, and 150 mg (3).

------------------------------ CONTRAINDICATIONS ----------------------------•
Hypersensitivity to venlafaxine hydrochloride, desvenlafaxine succinate,or any excipients in the Effexor XR formulation (4).
•Concomitant use of monoaminoxidase inhibitors (MAOIs) or within 14
days of discontinuing an MAOI (4, 5.2, 7.1).
----------------------- WARNINGS AND PRECAUTIONS ----------------------•
Serotonin Syndrome: Increased risk when co-administered with otherserotonergic agents, but also when taken alone. If it occurs, discontinue
Effexor XR and serotonergic agents and initiate supportive treatment (4,5.2, 7.1).
•
Elevated Blood Pressure: Control hypertension before initiating
treatment. Monitor blood pressure regularly during treatment (5.3).
•
Increased Risk of Bleeding: Concomitant use of aspirin, NSAIDs, otherantiplatelet drugs, warfarin, and other anticoagulants may increase risk
(5.4).
•
Angle-Closure Glaucoma: Angle-closure glaucoma has occurred inpatients with untreated anatomically narrow angles, treated withantidepressants (5.5).
•
Activation of Mania or Hypomania: Screen patients for bipolar disorder(5.6).
•
Discontinuation Syndrome: Taper dose and monitor for discontinuation
symptoms (5.7).
•
Seizures: Can occur. Use cautiously in patients with seizure disorder(5.8).
•
Hyponatremia: Can occur in association with SIADH (5.9).
•
Interstitial Lung Disease and Eosinophilic Pneumonia: Can occur(5.12).
•
Sexual Dysfunction: Effexor XR may cause symptoms of sexual
dysfunction (5.13).
------------------------------ ADVERSE REACTIONS -----------------------------Most common adverse reactions (incidence ≥ 5% and at least twice the rate ofplacebo): nausea, somnolence, dry mouth, sweating, abnormal ejaculation,
anorexia, constipation, impotence (men), and libido decreased (6.1).
To report SUSPECTED ADVERSE REACTIONS, contact Viatris at 1877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
----------------------- USE IN SPECIFIC POPULATIONS----------------------Pregnancy: Third trimester use may increase risk for symptoms of poor
neonatal adaptation (respiratory distress, temperature instability, feeding
difficulty, hypotonia, tremor, irritability) in the neonate (8.1).
See 17 for PATIENT COUNSELING INFORMATION and Medication
Guide.
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FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
1
INDICATIONS AND USAGE
2
DOSAGE AND ADMINISTRATION
2.1
General Administration Information
2.2
Major Depressive Disorder
2.3
Generalized Anxiety Disorder
2.4
Social Anxiety Disorder (Social Phobia)
2.5
Panic Disorder
2.6
Screen for Bipolar Disorder Prior to Starting Effexor
XR
2.7
Switching Patients from Effexor Tablets
2.8
Dosage Recommendations for Patients with Hepatic
Impairment
2.9
Dosage Recommendations for Patients with Renal
Impairment
2.10
Discontinuing Treatment with Effexor XR
2.11
Switching Patients to or from a Monoamine Oxidase
Inhibitor (MAOI) Antidepressant
3
DOSAGE FORMS AND STRENGTHS
4CONTRAINDICATIONS5WARNINGS AND PRECAUTIONS
5.1
Suicidal Thoughts and Behaviors in Adolescents andYoung Adults
5.2
Serotonin Syndrome
5.3
Elevated Blood Pressure
5.4
Increased Risk of Bleeding
5.5
Angle-Closure Glaucoma
5.6
Activation of Mania or Hypomania
5.7
Discontinuation Syndrome
5.8
Seizures5.9
Hyponatremia
5.10
Weight and Height Changes in Pediatric Patients
5.11
Appetite Changes in Pediatric Patients
5.12
Interstitial Lung Disease and Eosinophilic Pneumonia
5.13
Sexual Dysfunction

6

7

8

9

10
11
12

13
14

16
17

ADVERSE REACTIONS
6.1
Clinical Studies Experience
6.2
Postmarketing Experience
DRUG INTERACTIONS
7.1
Drugs Having Clinically Important Interactions with
Effexor XR
7.2
Other Drug Interactions with Effexor XR
USE IN SPECIFIC POPULATIONS
8.1
Pregnancy
8.2
Lactation
8.4
Pediatric Use
8.5
Geriatric Use
8.6
Hepatic Impairment
8.7
Renal Impairment
DRUG ABUSE AND DEPENDENCE
9.1
Controlled Substance
9.2
Abuse
9.3
Dependence
OVERDOSAGEDESCRIPTION
CLINICAL PHARMACOLOGY
12.1
Mechanism of Action
12.2
Pharmacodynamics
12.3
Pharmacokinetics
NONCLINICAL TOXICOLOGY
13.1
Carcinogenesis, Mutagenesis, Impairment of Fertility
CLINICAL STUDIES
14.1
Major Depressive Disorder
14.2
Generalized Anxiety Disorder
14.3
Social Anxiety Disorder (Also Known as Social
Phobia)14.4
Panic Disorder
HOW SUPPLIED/STORAGE AND HANDLINGPATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are notlisted.

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FULL PRESCRIBING INFORMATIONWARNING: SUICIDAL THOUGHTS AND BEHAVIORS
Antidepressants increased the risk of suicidal thoughts and behavior in pediatric andyoung adult patients in short-term studies. Closely monitor all antidepressant-treatedpatients for clinical worsening, and emergence of suicidal thoughts and behaviors [seeWarnings and Precautions (5.1)]. Effexor XR is not approved for use in pediatric patients[see Use in Specific Populations (8.4)].
1

INDICATIONS AND USAGE

Effexor XR is indicated in adults for the treatment of:• Major Depressive Disorder (MDD) [see Clinical Studies (14.1)]• Generalized Anxiety Disorder (GAD) [see Clinical Studies (14.2)]• Social Anxiety Disorder (SAD) [see Clinical Studies (14.3)]• Panic Disorder (PD) [see Clinical Studies (14.4)]
2

DOSAGE AND ADMINISTRATION

2.1

General Administration Information

Administer Effexor XR as a single dose with food, either in the morning or in the evening at
approximately the same time each day [see Clinical Pharmacology (12.3)]. Swallow capsules
whole with fluid. Do not divide, crush, chew, or place in water.
The capsule may also 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(spheroids).
2.2

Major Depressive Disorder

For most patients, the recommended starting dose for Effexor XR is 75 mg per day, administeredin a single dose. For some patients, it may be desirable to start at 37.5 mg per day for 4 to 7 days
to allow new patients to adjust to the medication before increasing to 75 mg per day. Patients not
responding to the initial 75 mg per day dose may benefit from dose increases to a maximum of
225 mg per day. Dose increases should be in increments of up to 75 mg per day, as needed, andshould be made at intervals of not less than 4 days. In the clinical studies establishing efficacy,
upward titration was permitted at intervals of 2 weeks or more.
2.3

Generalized Anxiety Disorder

For most patients, the recommended starting dose for Effexor XR is 75 mg per day, administeredin a single dose. For some patients, it may be desirable to start at 37.5 mg per day for 4 to 7 days

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to allow new patients to adjust to the medication before increasing to 75 mg per day. Patients not
responding to the initial 75 mg per day dose may benefit from dose increases to a maximum of
225 mg per day. Dose increases should be in increments of up to 75 mg per day, as needed, andshould be made at intervals of not less than 4 days.
2.4

Social Anxiety Disorder (Social Phobia)

The recommended dose is 75 mg per day, administered in a single dose. There was no evidence
that higher doses confer any additional benefit.
2.5

Panic Disorder

The recommended starting dose is 37.5 mg per day of Effexor XR for 7 days. Patients not
responding to 75 mg per day may benefit from dose increases to a maximum of approximately
225 mg per day. Dose increases should be in increments of up to 75 mg per day, as needed, andshould be made at intervals of not less than 7 days.
2.6

Screen for Bipolar Disorder Prior to Starting Effexor XR

Prior to initiating treatment with Effexor XR, screen patients for a personal or family history of
bipolar disorder, mania, or hypomania [see Warnings and Precautions (5.6)].
2.7

Switching Patients from Effexor Tablets

Patients with depression who are currently being treated with Effexor may be switched toEffexor XR at the nearest equivalent dose (mg per day), e.g., 37.5 mg venlafaxine twice a day to
75 mg Effexor XR once daily. However, individual dosage adjustments may be necessary.
2.8

Dosage Recommendations for Patients with Hepatic Impairment

Reduce the Effexor XR total daily dose by 50% in patients with mild (Child-Pugh Class A) tomoderate (Child-Pugh Class B) hepatic impairment. Reduce the total daily dose by 50% or morein patients with severe hepatic impairment (Child-Pugh Class C) or hepatic cirrhosis [see Use inSpecific Populations (8.6)].
2.9

Dosage Recommendations for Patients with Renal Impairment

Reduce the Effexor XR total daily dose by 25% to 50% in patients with mild (CLcr 60-89
mL/min) or moderate (CLcr 30-59 mL/min) renal impairment. Reduce the total daily dose by
50% or more in patients undergoing hemodialysis or with severe renal impairment (CLcr < 30
mL/min). Because there was much individual variability in clearance between patients with renal
impairment, individualization of dosage is recommended in some patients [see Use in Specific
Populations (8.7)].
2.10

Discontinuing Treatment with Effexor XR

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A gradual reduction in the dose, rather than abrupt cessation, is recommended when
discontinuing therapy with Effexor XR. In clinical studies with Effexor XR, tapering wasachieved by reducing the daily dose by 75 mg at one-week intervals. Individualization oftapering may be necessary. In some patients, discontinuation may need to occur over a period ofseveral months [see Warnings and Precautions (5.7)].
2.11 Switching Patients to or from a Monoamine Oxidase Inhibitor (MAOI)
AntidepressantAt least 14 days must elapse between discontinuation of an MAOI antidepressant and initiationof Effexor XR. In addition, at least 7 days must elapse after stopping Effexor XR before startingan MAOI antidepressant [see Contraindications (4), Warnings and Precautions (5.2), and Drug
Interactions (7.1)].
3

DOSAGE FORMS AND STRENGTHS

Effexor XR® is available in the following strengths:• 37.5 mg extended-release capsule: grey cap and peach body with “W” and “Effexor XR” on
the cap and “37.5” on the body• 75 mg extended-release capsule: peach cap and body with “W” and “Effexor XR” on the cap
and “75” on the body• 150 mg extended-release capsule: dark orange cap and body with “W” and “Effexor XR” on
the cap and “150” on the body
4

CONTRAINDICATIONS

Effexor XR is contraindicated in patients:• with known hypersensitivity to venlafaxine hydrochloride, desvenlafaxine succinate or to any
excipients in the formulation [see Adverse Reactions (6.2)].
• taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid andintravenous methylene blue) because of the risk of serotonin syndrome [see Dosage andAdministration (2.11), Warnings and Precautions (5.2), and Drug Interactions (7.1)].
5

WARNINGS AND PRECAUTIONS

5.1

Suicidal Thoughts and Behaviors in Adolescents and Young Adults

In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and otherantidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatricpatients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age
24 years and younger was greater than in placebo-treated patients. There was considerable
variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk
identified in young patients for most drugs studied. There were differences in absolute risk ofsuicidal thoughts and behaviors across the different indications, with the highest incidence inpatients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts
and behaviors per 1,000 patients treated are provided in Table 1.

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Table 1:Risk Differences of the Number of Patients of Suicidal Thoughts and Behaviors
in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric* and Adult
Patients
Drug-Placebo Difference in Number of Patients of
Suicidal Thoughts and Behaviors per 1,000 Patients
Age Range
TreatedIncreases Compared to Placebo<18 years old
14 additional patients
18-24 years old
5 additional patients
Decreases Compared to Placebo
25-64 years old
1 fewer patient≥65 years old
6 fewer patients*
Effexor XR is not approved in pediatric patients.
It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, andyoung adults extends to longer-term use, i.e., beyond four months. However, there is substantial
evidence from placebo-controlled maintenance trials in adults with MDD that antidepressantsdelay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts
and behaviors.
Monitor all antidepressant-treated patients for any indication for clinical worsening andemergence of suicidal thoughts and behaviors, especially during the initial few months of drug
therapy, and at times of dosage changes. Counsel family members or caregivers of patients tomonitor for changes in behavior and to alert the healthcare provider. Consider changing thetherapeutic regimen, including possibly discontinuing Effexor XR, in patients whose depression
is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.
5.2

Serotonin Syndrome

Serotonin-norepinephrine reuptake inhibitors (SNRIs), including Effexor XR, can precipitate
serotonin syndrome, a potentially life-threatening condition. The risk is increased withconcomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants,
fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and
St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [seeContraindications (4), Drug Interactions (7.1)]. Serotonin syndrome can also occur when thesedrugs are used alone.
Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation,
hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile blood pressure,dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity,
myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea,
vomiting, diarrhea).
The concomitant use of Effexor XR with MAOIs is contraindicated. In addition, do not initiate
Effexor XR in a patient being treated with MAOIs such as linezolid or intravenous methylene

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blue. No reports involved the administration of methylene blue by other routes (such as oral
tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as
linezolid or intravenous methylene blue in a patient taking Effexor XR, discontinue Effexor XR
before initiating treatment with the MAOI [see Contraindications (4), Drug Interactions (7.1)].
Monitor all patients taking Effexor XR for the emergence of serotonin syndrome. Discontinue
treatment with Effexor XR and any concomitant serotonergic agents immediately if the above
symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Effexor
XR with other serotonergic drugs is clinically warranted, inform patients of the increased risk forserotonin syndrome and monitor for symptoms.
5.3

Elevated Blood Pressure

In controlled trials, there were dose-related increases in systolic and diastolic blood pressure, as
well as cases of sustained hypertension [see Adverse Reactions (6.1)].
Monitor blood pressure before initiating treatment with Effexor XR and regularly during
treatment. Control pre-existing hypertension before initiating treatment with Effexor XR. Usecaution in treating patients with pre-existing hypertension or cardiovascular or cerebrovascularconditions that might be compromised by increases in blood pressure. Sustained blood pressure
elevation can lead to adverse outcomes. Cases of elevated blood pressure requiring immediate
treatment have been reported with Effexor XR. Consider dose reduction or discontinuation oftreatment for patients who experience a sustained increase in blood pressure.
Across all clinical studies with Effexor, 1.4% of patients in the Effexor XR treated groups
experienced a ≥15 mm Hg increase in supine diastolic blood pressure (SDBP) ≥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 (SSBP) withblood pressure ≥180 mm Hg, compared to 0.3% of patients in the placebo groups [see Adverse
Reactions (6.1)]. Treatment with Effexor XR was associated with sustained hypertension definedas SDBP ≥90 mm Hg and ≥10 mm Hg above baseline for three consecutive on-therapy visits[see Adverse Reactions (6.1)]. An insufficient number of patients received mean doses ofEffexor XR over 300 mg per day in clinical studies to fully evaluate the incidence of sustained
increases in blood pressure at these higher doses.
5.4

Increased Risk of Bleeding

Drugs that interfere with serotonin reuptake inhibition, including Effexor XR, may increase therisk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, andgastrointestinal hemorrhage to life-threatening hemorrhage. Concomitant use of aspirin,
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), warfarin, and other anti-coagulants or otherdrugs known to affect platelet function may add to this risk. Case reports and epidemiologicalstudies (case-control and cohort design) have demonstrated an association between use of drugs
that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Based ondata from the published observational studies, exposure to SNRIs, particularly in the month7
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before delivery, has been associated with a less than 2-fold increase in the risk of postpartum
hemorrhage [see Use in Specific Populations (8.1)].
Inform patients about the increased risk of bleeding associated with the concomitant use of
Effexor XR and nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, or other drugs that
affect coagulation. For patients taking warfarin, carefully monitor coagulation indices when
initiating, titrating, or discontinuing Effexor XR.
5.5

Angle-Closure Glaucoma

The pupillary dilation that occurs following use of many antidepressant drugs including Effexor
XR may trigger an angle closure attack in a patient with anatomically narrow angles who does
not have a patent iridectomy. Avoid use of antidepressants, including Effexor XR, in patientswith untreated anatomically narrow angles.
5.6

Activation of Mania or Hypomania

In patients with bipolar disorder, treating a depressive episode with Effexor XR or anotherantidepressant may precipitate a mixed/manic episode. Mania or hypomania was reported in
Effexor XR treated patients in the premarketing studies in MDD, SAD, and PD (see Table 2).
Prior to initiating treatment with Effexor XR, screen for any personal or family history of bipolar
disorder, mania, or hypomania.
Table 2: Incidence (%) of Mania or Hypomania Reported in Effexor XR Treated
Patients in the Premarketing Studies
Indication
Effexor XR
Placebo
MDD
0.3
0.0
GAD
0.0
0.2
SAD
0.2
0.0
PD
0.1
0.0
5.7

Discontinuation Syndrome

Discontinuation symptoms have been systematically evaluated in patients taking venlafaxine,
including prospective analyses of clinical studies in GAD and retrospective surveys of studies in
MDD and SAD. 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 shocklike electrical sensations), somnolence, sweating, tremor, vertigo, and vomiting.
There have been postmarketing reports of serious discontinuation symptoms which can be
protracted and severe. Completed suicide, suicidal thoughts, aggression and violent behavior
have been observed in patients during reduction in Effexor XR dosage, including during

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discontinuation. Other postmarketing reports describe visual changes (such as blurred vision or
trouble focusing) and increased blood pressure after stopping or reducing the dose of Effexor
XR.
During marketing of Effexor XR, other SNRIs, and SSRIs, there have been reports of adverse
events occurring upon discontinuation of these drugs, particularly when abrupt, including thefollowing: irritability, lethargy, emotional lability, tinnitus, and seizures.
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. If intolerable
symptoms occur following a decrease in the dose or upon discontinuation of treatment, thenresuming the previously prescribed dose may be considered. Subsequently, the healthcare
provider may continue decreasing the dose, but at a more gradual rate. In some patients,
discontinuation may need to occur over a period of several months [see Dosage andAdministration (2.10)].
5.8

Seizures

Cases of seizure have been reported with venlafaxine therapy. Effexor XR has not beensystematically evaluated in patients with seizure disorder. Effexor XR should be prescribed withcaution in patients with a seizure disorder.
5.9

Hyponatremia

Hyponatremia can occur as a result of treatment with SNRIs, including Effexor XR. In manycases, the hyponatremia appears to be the result of the Syndrome of Inappropriate Antidiuretic
Hormone (SIADH) secretion. Cases with serum sodium lower than 110 mmol/L have beenreported. Elderly patients may be at greater risk of developing hyponatremia with SNRIs. Also,patients taking diuretics, or those who are otherwise volume-depleted, may be at greater risk [seeUse in Specific Populations (8.5) and Clinical Pharmacology (12.3)]. Consider discontinuationof Effexor XR in patients with symptomatic hyponatremia, and institute appropriate medical
intervention.
Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory
impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs andsymptoms associated with more severe and/or acute cases have included hallucination, syncope,
seizure, coma, respiratory arrest, and death.
5.10

Weight and Height Changes in Pediatric Patients

Weight Changes
The average change in body weight and incidence of weight loss (percentage of patients who lost
3.5% or more) in the placebo-controlled pediatric studies in MDD, GAD, and SAD are shown in
Tables 3 and 4.

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Table 3: Average Change in Body Weight (kg) From Beginning of Treatment in
Pediatric Patientsa in Double-blind, Placebo-controlled Studies of Effexor XR
Indication
Effexor XR
Placebo(Duration)
MDD and GAD-0.45 (n = 333)
+0.77 (n = 333)
(4 pooled studies, 8 weeks)
SAD-0.75 (n = 137)
+0.76 (n = 148)
(16 weeks)aEffexor XR is not approved for use in pediatric patients.
Table 4: Incidence (%) of Pediatric Patientsa Experiencing Weight Loss (3.5% or more)in Double-blind, Placebo-controlled Studies of Effexor XR
Indication
Effexor XR
Placebo(Duration)
MDD and GAD
18b (n = 333)
3.6 (n = 333)
(4 pooled studies, 8 weeks)SAD
47b (n = 137)
14 (n = 148)
(16 weeks)aEffexor XR is not approved for use in pediatric patients.
bp <0.001 versus placebo
Weight loss was not limited to patients with anorexia [see Warnings and Precautions (5.11)].
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 datafrom 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).
Effexor XR is not approved for use in pediatric patients [Use in Specific Populations (8.4)].
Height Changes
Table 5 shows the average height increase in pediatric patients in the short-term, placebocontrolled MDD, GAD, and SAD studies. The differences in height increases in GAD and MDD
studies were most notable in patients younger than 12 years old.
Table 5: Average Height Increases (cm) in Pediatric Patientsa in Placebo-controlled
Studies of Effexor XR
Indication(Duration)
Effexor XR
PlaceboMDD
0.8 (n = 146)
0.7 (n = 147)
(8 weeks)
GAD
0.3b (n = 122)
1.0 (n = 132)
(8 weeks)SAD
1.0 (n = 109)
1.0 (n = 112)

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Effexor XR is not approved for use in pediatric patients.
b
p = 0.041
a

In the six-month, open-label MDD study, children and adolescents had height increases that wereless than expected, based on data from age- and sex-matched peers. The difference between
observed and expected growth rates was larger for children (<12 years old) than for adolescents(≥12 years old) [see Use in Specific Populations (8.4)].
5.11

Appetite Changes in Pediatric Patients

Decreased appetite (reported as anorexia) was more commonly observed in Effexor XR treatedpatients versus placebo-treated patients in the premarketing evaluation of Effexor XR for MDD,
GAD, and SAD (see Table 6).
Effexor XR is not approved for use in pediatric patients [see Use in Specific Populations (8.4)].
Table 6: Incidence (%) of Decreased Appetite and Associated Discontinuation Ratesa (%)
in Pediatric Patientsb in Placebo-controlled Studies of Effexor XR
Indication
Effexor XR
Placebo(Duration)
Incidence
Discontinuation Incidence
Discontinuation
MDD and GAD
10
0.0
3
–
(pooled, 8 weeks)
SAD
22
0.7
3
0.0
(16 weeks)a
The discontinuation rates for weight loss were 0.7% for patients receiving either Effexor XR orplacebo.
b
Effexor XR is not approved for use in pediatric patients.
5.12

Interstitial Lung Disease and Eosinophilic Pneumonia

Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine therapy havebeen rarely reported. The possibility of these events should be considered in Effexor XR-treatedpatients who present with progressive dyspnea, cough or chest discomfort. Such patients should
undergo a prompt medical evaluation, and discontinuation of Effexor XR should be considered.
5.13

Sexual Dysfunction

Use of SNRIs, including Effexor XR, may cause symptoms of sexual dysfunction [see Adverse
Reactions (6.1)]. In male patients, SNRI use may result in ejaculatory delay or failure, decreased
libido, and erectile dysfunction. In female patients, SNRI use may result in decreased libido anddelayed or absent orgasm. It is important for prescribers to inquire about sexual function prior toinitiation of Effexor XR and to inquire specifically about changes in sexual function during
treatment, because sexual function may not be spontaneously reported. When evaluating changes
in sexual function, obtaining a detailed history (including timing of symptom onset) is importantbecause sexual symptoms may have other causes, including the underlying psychiatric disorder.

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Discuss potential management strategies to support patients in making informed decisions about
treatment.
6

ADVERSE REACTIONS

The following adverse reactions are discussed in more detail in other sections of the labeling:• Hypersensitivity [see Contraindications (4)]• Suicidal Thoughts and Behaviors in Adolescents and Young Adults [see Warnings andPrecautions (5.1)]• Serotonin Syndrome [see Warnings and Precautions (5.2)]• Elevated Blood Pressure [see Warnings and Precautions (5.3)]• Increased Risk of Bleeding [see Warnings and Precautions (5.4)]• Angle-Closure Glaucoma [see Warnings and Precautions (5.5)]• Activation of Mania/Hypomania [see Warnings and Precautions (5.6)]• Discontinuation Syndrome [see Warnings and Precautions (5.7)]• Seizure [see Warnings and Precautions (5.8)]• Hyponatremia [see Warnings and Precautions (5.9)]• Weight and Height Changes in Pediatric Patients [see Warnings and Precautions (5.10)]• Appetite Changes in Pediatric Patients [see Warnings and Precautions (5.11)]• Interstitial Lung Disease and Eosinophilic Pneumonia [see Warnings and Precautions(5.12)]• Sexual Dysfunction [see Warnings and Precautions (5.13)]
6.1

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studiesof another drug and may not reflect the rates observed in clinical practice.
Most Common Adverse Reactions
The most commonly observed adverse reactions in the clinical study database in Effexor XR
treated patients in MDD, GAD, SAD, and PD (incidence ≥5% and at least twice the rate ofplacebo) were: nausea (30.0%), somnolence (15.3%), dry mouth (14.8%), sweating (11.4%),
abnormal ejaculation (9.9%), anorexia (9.8%), constipation (9.3%), impotence (5.3%), anddecreased libido (5.1%).
Adverse Reactions Reported as Reasons for Discontinuation of Treatment
Combined across short-term, placebo-controlled premarketing studies for all indications, 12% of
the 3,558 patients who received Effexor XR (37.5-225 mg) discontinued treatment due to an
adverse experience, compared with 4% of the 2,197 placebo-treated patients in those studies.
The most common adverse reactions leading to discontinuation in ≥1% of the Effexor XR treatedpatients in the short-term studies (up to 12 weeks) across indications are shown in Table 7.

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Table 7: Incidence (%) of Patients Reporting Adverse Reactions Leading to
Discontinuation in Placebo-controlled Clinical Studies (up to 12 Weeks Duration)
Body System
Effexor XR
Placebo
Adverse Reactionn = 3,558
n = 2,197
Body as a whole
Asthenia
1.7
0.5
Headache
1.5
0.8
Digestive system
Nausea4.3
0.4
Nervous system
Dizziness
2.2
0.8
Insomnia
2.1
0.6
Somnolence
1.7
0.3
Skin and appendages
1.5
0.6
Sweating
1.0
0.2
Common Adverse Reactions in Placebo-controlled Studies
The number of patients receiving multiple doses of Effexor XR during the premarketingassessment for each approved indication is shown in Table 8. The conditions and duration of
exposure to venlafaxine in all development programs varied greatly, and included (inoverlapping categories) open and double-blind studies, uncontrolled and controlled studies,inpatient (Effexor only) and outpatient studies, fixed-dose, and titration studies.
Table 8: Patients Receiving Effexor XR in Premarketing Clinical Studies
Indication
Effexor XR
MDD
705a
GAD
1,381
SAD
819
PD
1,314
a
In addition, in the premarketing assessment of Effexor, multiple doses were administered to2,897 patients in studies for MDD.
The incidences of common adverse reactions (those that occurred in ≥2% of Effexor XR treatedpatients [357 MDD patients, 1,381 GAD patients, 819 SAD patients, and 1,001 PD patients] andmore frequently than placebo) in Effexor XR treated patients in short-term, placebo-controlled,
fixed- and flexible-dose clinical studies (doses 37.5 to 225 mg per day) are shown in Table 9.
The adverse reaction profile did not differ substantially between the different patient populations.
Table 9: Common Adverse Reactions: Percentage of Patients Reporting Adverse
Reactions (≥2% and > placebo) in Placebo-controlled Studies (up to 12 Weeks Duration)across All Indications
Body System
Effexor XR
Placebo
Adverse Reactionn = 3,558
n = 2,197
Body as a whole
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Asthenia
12.6
7.8
Cardiovascular system
Hypertension
3.4
2.6
Palpitation
2.2
2.0
Vasodilatation
3.7
1.9
Digestive system
Anorexia
9.8
2.6
Constipation
9.3
3.4
Diarrhea
7.7
7.2
Dry mouth
14.8
5.3
Nausea30.0
11.8
Vomiting
4.3
2.7
Nervous system
Abnormal dreams
2.9
1.4
Dizziness
15.8
9.5
Insomnia
17.8
9.5
Libido decreased
5.1
1.6
Nervousness
7.1
5.0
Paresthesia
2.4
1.4
Somnolence
15.3
7.5
Tremor
4.7
1.6
Respiratory system
Yawn
3.7
0.2
Skin and appendages
Sweating (including night sweats)
11.4
2.9
Special senses
Abnormal vision
4.2
1.6
Urogenital system
Abnormal ejaculation/orgasm (men)a9.9
0.5
Anorgasmia (men)a
3.6
0.1
b
Anorgasmia (women)
2.0
0.2
a
Impotence (men)
5.3
1.0
a
Percentages based on the number of men (Effexor XR, n = 1,440; placebo, n = 923)b
Percentages based on the number of women (Effexor XR, n = 2,118; placebo, n = 1,274)
Other Adverse Reactions Observed in Clinical Studies
Body as a Whole – Photosensitivity reaction, chills
Cardiovascular System – Postural hypotension, syncope, hypotension, tachycardia
Digestive System – Gastrointestinal hemorrhage [see Warnings and Precautions (5.4)], bruxism
Hemic/Lymphatic System – Ecchymosis [see Warnings and Precautions (5.4)]
Metabolic/Nutritional – Hypercholesterolemia, weight gain [see Warnings and Precautions(5.10)], weight loss [see Warnings and Precautions (5.10)]

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Nervous System – Seizures [see Warnings and Precautions (5.8)], manic reaction [see Warnings
and Precautions (5.6)], agitation, confusion, akathisia, hallucinations, hypertonia, myoclonus,
depersonalization, apathy
Skin and Appendages – Urticaria, pruritus, rash, alopecia
Special Senses – Mydriasis, abnormality of accommodation, tinnitus, taste perversion
Urogenital System – Urinary retention, urination impaired, urinary incontinence, urinary
frequency increased, menstrual disorders associated with increased bleeding or increased
irregular bleeding (e.g., menorrhagia, metrorrhagia)
Vital Sign Changes
In placebo-controlled premarketing studies, there were increases in mean blood pressure (seeTable 10). Across most indications, a dose-related increase in mean supine systolic and diastolicblood pressure was evident in patients treated with Effexor XR. Across all clinical studies in
MDD, GAD, SAD and PD, 1.4% of patients in the Effexor XR groups experienced an increase in
SDBP of ≥15 mm Hg along with a blood pressure ≥105 mm Hg, compared to 0.9% of patients inthe placebo groups. Similarly, 1% of patients in the Effexor XR groups experienced an increase
in SSBP of ≥20 mm Hg with a blood pressure ≥180 mm Hg, compared to 0.3% of patients in theplacebo groups.
Table 10: Final On-therapy Mean Changes from Baseline in Supine Systolic (SSBP) andDiastolic (SDBP) Blood Pressure (mm Hg) in Placebo-controlled Studies
Effexor XR
Placebo
Indication≤75 mg per day>75 mg per day(Duration)
SSBP
SDBP
SSBP
SDBP
SSBP
SDBP
MDD
(8-12 weeks)
-0.28
0.37
2.93
3.56
-1.08
-0.10
GAD
(8 weeks)
-0.28
0.02
2.40
1.68
-1.26
-0.92
(6 months)
1.27
-0.69
2.06
1.28
-1.29
-0.74
SAD
(12 weeks)
-0.29
-1.26
1.18
1.34
-1.96
-1.22
(6 months)
-0.98
-0.49
2.51
1.96
-1.84
-0.65
PD
(10-12 weeks)
-1.15
0.97
-0.36
0.16
-1.29
-0.99
Effexor XR treatment was associated with sustained hypertension (defined as Supine Diastolic
Blood Pressure [SDBP] ≥90 mm Hg and ≥10 mm Hg above baseline for three consecutive ontherapy visits (see Table 11). An insufficient number of patients received mean doses of Effexor
XR over 300 mg per day in clinical studies to fully evaluate the incidence of sustained increases
in blood pressure at these higher doses.
Table 11: Sustained Elevations in SDBP in Effexor XR Premarketing Studies
Indication
Dose Range (mg per day)
Incidence (%)
a
MDD
75-37519/705 (3)GAD
37.5-225
5/1011 (0.5)
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SAD
75-2255/771 (0.6)
PD75-225
9/973 (0.9)
aMaximum recommended dosage for Effexor XR is 225 mg once daily.
Effexor XR was associated with mean increases in pulse rate compared with placebo inpremarketing placebo-controlled studies (see Table 12) [see Warnings and Precautions (5.3,5.4)].
Table 12: Approximate Mean Final On-therapy Increase in Pulse Rate (beats/min) in
Effexor XR Premarketing Placebo-controlled Studies (up to 12 Weeks Duration)
Indication
Effexor XR
Placebo(Duration)
MDD(12 weeks)
2
1GAD(8 weeks)
2<1
SAD(12 weeks)
31PD(12 weeks)
1<1Laboratory Changes
Serum Cholesterol
Effexor XR was associated with mean final increases in serum cholesterol concentrations
compared with mean final decreases for placebo in premarketing MDD, GAD, SAD and PD
clinical studies (Table 13).
Table 13: Mean Final On-therapy Changes in Cholesterol Concentrations (mg/dL) in
Effexor XR Premarketing Studies
Indication
Effexor XR
Placebo(Duration)
MDD(12 weeks)
+1.5
-7.4
GAD
(8 weeks)+1.0-4.9(6 months)
+2.3
-7.7
SAD
(12 weeks)
+7.9
-2.9
(6 months)
+5.6
-4.2
PD
(12 weeks)
+5.8
-3.7
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 a16
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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 withmean 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 and5.6 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 12month 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 wasduration 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, wererecorded in 5.3% of venlafaxine-treated patients and 0.0% of placebo-treated patients.
Serum Triglycerides
Effexor XR was associated with mean final on-therapy increases in fasting serum triglycerides
compared with placebo in premarketing clinical studies of SAD and PD up to 12 weeks (pooleddata) and 6 months duration (Table 14).
Table 14: Mean Final On-therapy Increases in Triglyceride Concentrations (mg/dL) in
Effexor XR Premarketing Studies
Indication
Effexor XR
Placebo(Duration)
SAD(12 weeks)
8.2
0.4
SAD
(6 months)
11.8
1.8
PD
(12 weeks)
5.9
0.9
PD
(6 months)
9.3
0.3
6.2

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Effexor XR.
Because these reactions are reported voluntarily from a population of uncertain size, it is not

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always possible to reliably estimate their frequency or establish a causal relationship to drug
exposure.
Body as a Whole – Anaphylaxis, angioedema
Cardiovascular System – QT prolongation, ventricular fibrillation, ventricular tachycardia(including torsade de pointes), takotsubo cardiomyopathy
Digestive System – Pancreatitis
Hemic/Lymphatic System – Mucous membrane bleeding [see Warnings and Precautions (5.4)],
blood dyscrasias (including agranulocytosis, aplastic anemia, neutropenia and pancytopenia),
prolonged bleeding time, thrombocytopenia
Metabolic/Nutritional – Hyponatremia [see Warnings and Precautions (5.9)], Syndrome of
Inappropriate Antidiuretic Hormone (SIADH) secretion [see Warnings and Precautions (5.9)],
abnormal liver function tests, hepatitis, prolactin increased
Musculoskeletal – Rhabdomyolysis
Nervous System – Neuroleptic Malignant Syndrome (NMS) [see Warnings and Precautions(5.2)], serotonergic syndrome [see Warnings and Precautions (5.2)], delirium, extrapyramidal
reactions (including dystonia and dyskinesia), impaired coordination and balance, tardive
dyskinesia
Respiratory, Thoracic and Mediastinal Disorders – Anosmia, dyspnea, hyposmia, interstitiallung disease, pulmonary eosinophilia [see Warnings and Precautions (5.12)]
Skin and Appendages – Stevens-Johnson syndrome, toxic epidermal necrolysis, erythemamultiforme
Special Senses – Angle-closure glaucoma [see Warnings and Precautions (5.5)]
7

DRUG INTERACTIONS

7.1

Drugs Having Clinically Important Interactions with Effexor XR

Table 15: Clinically Important Drug Interactions with Effexor XR
Monoamine Oxidase Inhibitors (MAOI)
Clinical Impact
The concomitant use of SNRIs, including Effexor XR, with
MAOIs increases the risk of serotonin syndrome.
Intervention
Concomitant use of Effexor XR is contraindicated in patientstaking MAOIs, including MAOIs such as linezolid or intravenous
methylene blue[see Dosage and Administration (2.11), Contraindications (4) andWarnings and Precautions (5.2)].
Other Serotonergic Drugs
Clinical Impact
Concomitant use of Effexor XR with other serotonergic drugs(including other SNRIs, SSRIs, triptans, tricyclic antidepressants,
opioids, lithium, buspirone, amphetamines, tryptophan, and St.
John's Wort) increases the risk of serotonin syndrome.
Intervention
Monitor for symptoms of serotonin syndrome when Effexor XR isused concomitantly with other drugs that may affect theserotonergic neurotransmitter systems. If serotonin syndrome
occurs, consider discontinuation of Effexor XR and/or

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concomitant serotonergic drugs [see Dosage and Administration(2.11) and Warnings and Precautions (5.2)].
Drugs that Interfere with Hemostasis
Clinical Impact
Concomitant use of Effexor XR with an antiplatelet or
anticoagulant drug may potentiate the risk of bleeding. This may
be due to the effect of Effexor XR on the release of serotonin byplatelets.
Intervention
Closely monitor for bleeding for patients receiving an antiplatelet
or anticoagulant drug when Effexor XR is initiated or discontinued[see Warnings and Precautions (5.4)].
Effect of CYP3A Inhibitors
Clinical Impact
Concomitant use of a CYP3A inhibitor increases the Cmax and
AUC of venlafaxine and O-desmethylvenlafaxine (ODV) [seeClinical Pharmacology (12.3)], which may increase the risk of
toxicity of Effexor XR.
Intervention
Consider reducing the dose of Effexor XR.
CYP2D6 Substrates
Clinical Impact
Concomitant use of Effexor XR increases Cmax and AUC of a
CYP2D6 substrate, which may increase the risk of toxicity of the
CYP2D6 substrate [see Clinical Pharmacology (12.3)].
Intervention
Consider reduction in dose of concomitant CYP2D6 substrates.
7.2

Other Drug Interactions with Effexor XR

Central Nervous System (CNS)-Active Drugs
The risk of using venlafaxine concomitantly with other CNS-active drugs (including alcohol) has
not been systematically evaluated. Consequently, caution is advised when Effexor XR is taken
concomitantly in combination with other CNS-active drugs.
Weight Loss Agents
Concomitant use of Effexor XR and weight loss agents is not recommended. The safety andefficacy of venlafaxine therapy in combination with weight loss agents, including phentermine,
have not been established. Effexor XR is not indicated for weight loss alone or in combination
with other products.
Laboratory Test Interference
False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine
have been reported in patients taking venlafaxine due to lack of specificity of the screening tests.
False-positive test results may be expected for several days following discontinuation ofvenlafaxine therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will
distinguish venlafaxine from PCP and amphetamine.
8

USE IN SPECIFIC POPULATIONS

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8.1

Pregnancy

Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to
antidepressants, including Effexor XR, during pregnancy. Healthcare providers are encouraged
to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-4056185 or visiting online at https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/.
Risk Summary
Based on data from published observational studies, exposure to SNRIs, particularly in themonth before delivery, has been associated with a less than 2-fold increase in the risk of
postpartum hemorrhage [see Warnings and Precautions (5.4) and Clinical Considerations].
Available data from published epidemiologic studies on venlafaxine use in pregnant women havenot identified a drug-associated risk of major birth defects, miscarriage or adverse fetal outcomes(see Data). Available data from observational studies with venlafaxine have identified a potential
increased risk for preeclampsia when used during mid to late pregnancy; exposure to SNRIs neardelivery may increase the risk for postpartum hemorrhage (see Clinical Considerations). There
are risks associated with untreated depression in pregnancy and poor neonatal adaptation in
newborns with exposure to SNRIs, including Effexor XR, during pregnancy (see Clinical
Considerations).
In animal studies, there was no evidence of malformations or fetotoxicity following
administration of venlafaxine during organogenesis at doses up to 2.5 times (rat) or 4 times(rabbit) the maximum recommended human daily dose on a mg/m2 basis. Postnatal mortality anddecreased pup weights were observed following venlafaxine administration to pregnant rats
during gestation and lactation at 2.5 times (mg/m2) the maximum human daily dose.
The estimated background risk of major birth defects and miscarriage for the indicatedpopulations is unknown. All pregnancies have a background risk of birth defect, loss, or otheradverse outcomes. In the U.S. general population, the estimated background risk of major birthdefects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%,
respectively.
Clinical Considerations
Disease-Associated Maternal and/or Embryo/Fetal Risk
Women who discontinue antidepressants during pregnancy are more likely to experience a
relapse of major depression than women who continue antidepressants. This finding is from aprospective, longitudinal study that followed 201 pregnant women with a history of major
depression who were euthymic and taking antidepressants at the beginning of pregnancy.

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Consider the risk of untreated depression when discontinuing or changing treatment withantidepressant medication during pregnancy and postpartum.
Maternal Adverse Reactions
Exposure to Effexor XR in mid to late pregnancy may increase the risk for preeclampsia, andexposure to Effexor XR in the month before delivery may be associated with an increased risk of
postpartum hemorrhage [see Warnings and Precautions (5.4)].
Fetal/Neonatal Adverse Reactions
Neonates exposed to SNRIs 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, tremors, jitteriness, irritability, and constant crying. Thesefindings are consistent with either a direct toxic effect of SNRIs or possibly a drug
discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent
with serotonin syndrome [see Warnings and Precautions (5.2)]. Monitor neonates who were
exposed to Effexor XR in the third trimester of pregnancy for drug discontinuation syndrome(see Data).
Data
Human Data
Published epidemiological studies of pregnant women exposed to venlafaxine have notestablished an increased risk of major birth defects, miscarriage or other adverse developmental
outcomes. Methodological limitations may both fail to identify true findings and also identify
findings that are not true.
Retrospective cohort studies based on claims data have shown an association between
venlafaxine use and preeclampsia, compared to depressed women who did not take anantidepressant during pregnancy. One study that assessed venlafaxine exposure in the second
trimester or first half of the third trimester and preeclampsia showed an increased risk compared
to unexposed depressed women (adjusted [adj] RR 1.57, 95% confidence interval [CI] 1.291.91). Preeclampsia was observed at venlafaxine doses equal to or greater than 75 mg per day
and a duration of treatment >30 days. Another study that assessed venlafaxine exposure ingestational weeks 10-20 and preeclampsia showed an increased risk at doses equal to or greaterthan 150 mg per day. Available data are limited by possible outcome misclassification andpossible confounding due to depression severity and other confounders.
Retrospective cohort studies based on claims data have suggested an association between
venlafaxine use near the time of delivery or through delivery and postpartum hemorrhage. One
study showed an increased risk for postpartum hemorrhage when venlafaxine exposure occurred
through delivery, compared to unexposed depressed women (adj RR 2.24 [95% CI 1.69-2.97]).

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There was no increased risk in women who were exposed to venlafaxine earlier in pregnancy.
Limitations of this study include possible confounding due to depression severity and otherconfounders. Another study showed an increased risk for postpartum hemorrhage when SNRI
exposure occurred for at least 15 days in the last month of pregnancy or through delivery,
compared to unexposed women (adj RR 1.64-1.76). The results of this study may be confoundedby the effects of depression.
Animal Data
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/m2 basis.
However, in rats, there was a decrease in pup weight, an increase in stillborn pups, and anincrease 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/m2) the maximum human daily dose. The no effect dose for rat pup mortality was
0.25 times the human dose on a mg/m2 basis.
When desvenlafaxine succinate, the major metabolite of venlafaxine, was administered orally topregnant rats and rabbits during the period of organogenesis at doses up to 300 mg/kg/day and 75
mg/kg/day, respectively, no fetal malformations were observed. These doses were associatedwith a plasma exposure (AUC) 19 times (rats) and 0.5 times (rabbits) the AUC exposure at an
adult human dose of 100 mg per day. However, fetal weights were decreased and skeletal
ossification was delayed in rats in association with maternal toxicity at the highest dose, with an
AUC exposure at the no-effect dose that is 4.5-times the AUC exposure at an adult human doseof 100 mg per day.
8.2

Lactation

Risk Summary
Data from published literature report the presence of venlafaxine and its active metabolite inhuman milk and have not shown adverse reactions in breastfed infants (see Data). There are nodata on the effects of venlafaxine on milk production.
The developmental and health benefits of breastfeeding should be considered along with themother’s clinical need for Effexor XR and any potential adverse effects on the breastfed childfrom Effexor XR or from the underlying maternal condition.
Data
In a lactation study conducted in 11 breastfeeding women (at a mean of 20.1 months postpartum) who were taking a mean daily dose of 194.3 mg of venlafaxine and in a lactation study
conducted in 6 breastfeeding women who were taking a daily dose of 225 mg to 300 mg ofvenlafaxine (at a mean of 7 months post-partum), the estimated mean relative infant dose was
8.1% and 6.4% based on the sum of venlafaxine and its major metabolite, desvenlafaxine. No
adverse reactions were seen in the infants.

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8.4

Pediatric Use

Safety and effectiveness of Effexor XR in pediatric patients have not been established.
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 use in pediatric patients.
In the studies conducted in pediatric patients ages 6 to 17 years, the occurrence of blood pressure
and cholesterol increases was considered to be clinically relevant in pediatric patients and was
similar to that observed in adult patients [see Warnings and Precautions (5.3), Adverse
Reactions (6.1)]. The following adverse reactions were also observed in pediatric patients:
abdominal pain, agitation, dyspepsia, ecchymosis, epistaxis, and myalgia.
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 donesuggest that Effexor XR may adversely affect weight and height [see Warnings and Precautions(5.10, 5.11)]. Decreased appetite and weight loss were observed in placebo-controlled studies ofpediatric patients 6 to 17 years.
In pediatric clinical studies, the adverse reaction, suicidal ideation, was observed.
Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [seeBoxed Warning, Warnings and Precautions (5.1)].
8.5

Geriatric Use

The percentage of patients in clinical studies for Effexor XR for MDD, GAD, SAD, and PD whowere 65 years of age or older are shown in Table 16.
Table 16: Percentage (and Number of Patients Studied) of Patients
65 Years of Age and Older by Indicationa
Indication
Effexor XR
MDD
4 (14/357)
GAD
6 (77/1,381)
SAD
1 (10/819)
PD
2 (16/1,001)
a
In addition, in the premarketing assessment of Effexor (immediate-release), 12% (357/2,897) ofpatients were ≥ 65 years of age.
No overall differences in effectiveness or safety were observed between geriatric patients andyounger patients, and other reported clinical experience generally has not identified differencesin 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 associatedwith cases of clinically significant hyponatremia in elderly patients, who may be at greater risk
for this adverse event [see Warnings and Precautions (5.9)].

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The pharmacokinetics of venlafaxine and ODV are not substantially altered in the elderly [seeClinical Pharmacology (12.3)] (see Figure 1). No dose adjustment is recommended for theelderly 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 (2.8, 2.9)].
8.6

Hepatic Impairment

Dosage adjustment is recommended in patients with mild (Child-Pugh Class A), moderate(Child-Pugh Class B), or severe (Child-Pugh Class C) hepatic impairment or hepatic cirrhosis[see Dosage and Administration (2.8) and Clinical Pharmacology (12.3)].
8.7

Renal Impairment

Dosage adjustment is recommended in patients with mild (CLcr = 60-89 mL/min), moderate(CLcr = 30-59 mL/min), or severe (CLcr <30 mL/min) renal impairment, and in patients
undergoing hemodialysis [see Dosage and Administration (2.9) and Clinical Pharmacology(12.3)].
9

DRUG ABUSE AND DEPENDENCE

9.1

Controlled SubstanceEffexor XR contains venlafaxine which is not a controlled substance.
9.2

Abuse

Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychologicalor physiological effects.
While venlafaxine has not been systematically studied in clinical studies for its potential forabuse, there was no indication of drug-seeking behavior in the clinical studies. However, it is notpossible to predict on the basis of premarketing experience the extent to which a CNS-active
drug will be misused, diverted, and/or abused once marketed. Consequently, providers shouldcarefully evaluate patients for history of drug abuse and follow such patients closely, observing
them for signs of misuse or abuse of venlafaxine (e.g., development of tolerance, incrementationof dose, drug-seeking behavior).
9.3

Dependence

Physical dependence is a state that develops as a result of physiological adaptation in response torepeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation ora significant dose reduction of a drug.

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In vitro studies revealed that venlafaxine has virtually no affinity for opiate, benzodiazepine,
phencyclidine (PCP), or N-methyl-D-aspartic acid (NMDA) receptors.
Venlafaxine was not found to have any significant CNS stimulant activity in rodents. In primate
drug discrimination studies, venlafaxine showed no significant stimulant or depressant abuseliability.
Discontinuation effects have been reported in patients receiving venlafaxine [see Dosage andAdministration (2.10) and Warnings and Precautions (5.7)].
10

OVERDOSAGE

Human Experience
During the premarketing evaluations of Effexor XR (for MDD, GAD, SAD, and PD) andEffexor (for MDD), there were twenty reports of acute overdosage with Effexor (6 and 14
reports in Effexor XR and Effexor patients, respectively), either alone or in combination withother drugs and/or alcohol.
Somnolence was the most commonly reported symptom. Among the other reported symptoms
were paresthesia of all four limbs, moderate dizziness, nausea, numb hands and feet, and hotcold spells 5 days after the overdose. In most cases, no signs or symptoms were associated withoverdose. The majority of the reports involved ingestion in which the total dose of venlafaxine
taken was estimated to be no more than several-fold higher than the usual therapeutic dose. One
patient who ingested 2.75 g of venlafaxine was observed to have two generalized convulsions
and a prolongation of QTc to 500 msec, compared with 405 msec at baseline. Mild sinus
tachycardia was reported in two of the other patients.
Actions taken to treat the overdose included no treatment, hospitalization and symptomatic
treatment, and hospitalization plus treatment with activated charcoal. All patients recovered.
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 (e.g., 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 anincreased risk of fatal outcomes compared to that observed with SSRI antidepressant products,
but lower than that for tricyclic antidepressants. Epidemiological studies have shown thatvenlafaxine-treated patients have a higher preexisting burden of suicide risk factors than SSRItreated 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 the25
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smallest quantity of capsules consistent with good patient management, in order to reduce therisk of overdose.
Management of Overdosage
No specific antidotes for Effexor XR are known. In managing overdosage, consider the
possibility of multiple drug involvement. Consider contacting a Poison Center (1-800-222-1222)
or a medical toxicologist for overdosage management recommendations for Effexor XR.
11

DESCRIPTION

Effexor XR is an extended-release capsule for once-a-day oral administration that contains
venlafaxine hydrochloride, a serotonin and norepinephrine reuptake inhibitor (SNRI).
Venlafaxine is designated (R/S)-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexanolhydrochloride or (±)-1-[α- [(dimethylamino)methyl]-p-methoxybenzyl] cyclohexanolhydrochloride and has the empirical formula of C17H27NO2 HCl. Its molecular weight is 313.86.
The structural formula is shown as follows:

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.
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.
12

CLINICAL PHARMACOLOGY

12.1

Mechanism of Action

The mechanism of action of venlafaxine in the treatment of MDD, GAD, SAD, and PD is
unclear, but is thought to be related to the potentiation of serotonin and norepinephrine in thecentral nervous system, through inhibition of their reuptake.
12.2

Pharmacodynamics

In vitro studies have demonstrated that venlafaxine and its active metabolite, Odesmethylvenlafaxine (ODV), are potent and selective inhibitors of neuronal serotonin and26
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norepinephrine reuptake and weak inhibitors of dopamine reuptake. Venlafaxine and ODV haveno significant affinity for muscarinic-cholinergic, H1-histaminergic, or α1-adrenergic receptors invitro. 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.
Cardiac Electrophysiology
The effect of venlafaxine on the QT interval was evaluated in a randomized, double-blind,placebo- and positive-controlled three-period crossover thorough QT study in 54 healthy adultsubjects. No significant QT prolongation effect of venlafaxine at 450 mg (2 times the maximum
recommended dosage) was detected.
12.3

Pharmacokinetics

Venlafaxine and ODV steady-state concentrations are reached within 3 days. Venlafaxine andODV exhibited linear kinetics over the dosage range of 75 to 450 mg per day (0.33 to 2 times the
maximum recommended dosage). Time of administration (AM versus PM) did not affect thepharmacokinetics of venlafaxine and ODV from the 75 mg Effexor XR capsule.
Absorption
Venlafaxine is well absorbed. 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 approximately
45%.
Administration of Effexor XR (150 mg once daily) generally resulted in lower Cmax and later
Tmax values than for Effexor administered twice daily (Table 17). When equal daily doses ofvenlafaxine were administered as either an immediate-release tablet or the extended-releasecapsule, the exposure to both venlafaxine and ODV was similar for the two treatments, and thefluctuation in plasma concentrations was slightly lower with the Effexor XR capsule. Therefore,
Effexor XR provides a slower rate of absorption, but the same extent of absorption comparedwith the immediate-release tablet.
Table 17: Comparison of Cmax and Tmax Values for Venlafaxine and ODV Following Oral
Administration of Effexor XR and Effexor (Immediate-Release)
Venlafaxine
ODV
Cmax
Tmax
Cmax
Tmax
(ng/mL)(h)(ng/mL)(h)Effexor XR (150 mg once daily)
150
5.5
260
9
Effexor (75 mg twice daily)
225
2
290
3
Effect of Food
Food did not affect the bioavailability of venlafaxine or its active metabolite, ODV.

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Distribution
Venlafaxine is 27% and ODV is 30% bound to plasma proteins. The apparent volume of
distribution at steady-state is 7.5 ± 3.7 L/kg for venlafaxine and 5.7 ± 1.8 L/kg for ODV.
Elimination
Mean ± SD plasma apparent clearance at steady-state is 1.3 ± 0.6 L/h/kg for venlafaxine and 0.4± 0.2 L/h/kg for ODV. The apparent elimination half-life is 5 ± 2 hours for venlafaxine and 11 ±2 hours for ODV.
Metabolism
Following absorption, venlafaxine undergoes extensive presystemic metabolism in the liver,primarily to ODV, but also to N-desmethylvenlafaxine, N,O-didesmethylvenlafaxine, and otherminor metabolites. In vitro studies indicate that the formation of ODV is catalyzed by CYP2D6;
this has been confirmed in a clinical study showing that patients with low CYP2D6 levels (poormetabolizers) had increased levels of venlafaxine and reduced levels of ODV compared topeople with normal CYP2D6 levels (extensive metabolizers) (see Figure 1).
Excretion
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%).
Specific Populations
The effect of intrinsic patient factors on the pharmacokinetics of venlafaxine and its active
metabolite ODV is presented in Figure 1.
Figure 1: Pharmacokinetics of Venlafaxine and Active Metabolite O-desmethylvenlafaxine(ODV) in Special Populations

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ODV=O-desmethylvenlafaxine; AUC=area under the curve; Cmax=peak plasma concentrations.
*
Similar effect is expected with strong CYP2D6 inhibitors.
Drug Interaction Studies
Clinical Studies
Effect of Other Drugs on Effexor XR and Active Metabolite ODVThe effects of other drugs on the exposure of venlafaxine and ODV are summarized in Figure 2.
Figure 2: Effect of Other Drugs on the Pharmacokinetics of Venlafaxine and Active
Metabolite O-desmethylvenlafaxine (ODV)

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ODV=O-desmethylvenlafaxine; AUC=area under the curve; Cmax=peak plasma concentrations;
EM’s=extensive metabolizers; PM’s=poor metabolizers.
Effect of Effexor XR on Other Drugs
The effects of Effexor XR on the exposure of other drugs are summarized in Figure 3.
Figure 3: Effect of Venlafaxine on the Pharmacokinetics of Interacting Drugs and their
Active Metabolites

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AUC=area under the curve; Cmax=peak plasma concentrations; OH=hydroxyl.
*
Data for 2-OH desipramine were not plotted to enhance clarity; the fold change and 90% CI for
Cmax and AUC of 2-OH desipramine were 6.6 (5.5, 7.9) and 4.4 (3.8, 5.0), respectively.
Note: *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 notreceiving venlafaxine.
13

NONCLINICAL TOXICOLOGY

13.1

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis
Tumors were not increased by venlafaxine treatment in mice or rats. Venlafaxine was given byoral 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/m2 basis. Venlafaxine was also given to rats byoral gavage for 24 months at doses up to 120 mg/kg per day. In rats receiving the 120 mg/kg
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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 humandose. Plasma levels of the ODV were lower in rats than in patients receiving the maximum
recommended dose. ODV, the major human metabolite of venlafaxine, administered by oral
gavage to mice and rats for 2 years did not increase the incidence of tumors in either study. Micereceived ODV at dosages up to 500/300 mg/kg/day (dosage lowered after 45 weeks of dosing).
The exposure at the 300 mg/kg/day dose is 9 times that of a human dose of 225 mg/day. Rats
received ODV at dosages up to 300 mg/kg/day (males) or 500 mg/kg/day (females). The
exposure at the highest dose is approximately 8 (males) or 11 (females) times that of a humandose of 225 mg/day.
Mutagenesis
Venlafaxine and the major human metabolite, ODV, were not mutagenic in the Ames reverse
mutation assay in Salmonella bacteria or the Chinese hamster ovary/HGPRT mammalian cellforward 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 or in the in vivo chromosomal aberration assay in rats.
Impairment of Fertility
Reproduction and fertility studies of venlafaxine in rats showed no adverse effects of venlafaxine
on male or female fertility at oral doses of up to 2 times the maximum recommended humandose of 225 mg/day on a mg/m2 basis. However, when desvenlafaxine succinate, the major
human metabolite of venlafaxine, was administered orally to male and female rats, fertility was
reduced at the high dose of 300 mg/kg/day, which is 10 (males) and 19 (females) times the AUC
exposure at an adult human dose of 100 mg per day. There was no effect on fertility at 100
mg/kg/day, which is 3 (males) or 5 (females) times the AUC exposure at an adult human dose of
100 mg per day. These studies did not address reversibility of the effect on fertility. The
relevance of these findings to humans is not known.
14

CLINICAL STUDIES

14.1

Major Depressive Disorder

The efficacy of Effexor XR (venlafaxine hydrochloride) extended-release capsules as a treatment
for Major Depressive Disorder (MDD) was established in two placebo-controlled, short-term (8weeks for study 1; 12 weeks for study 2), flexible-dose studies, with doses starting at 75 mg per
day and ranging to 225 mg per day in adult outpatients meeting DSM-III-R or DSM-IV criteriafor MDD. In moderately depressed outpatients, the initial dose of venlafaxine was 75 mg perday. In both studies, Effexor XR demonstrated superiority over placebo on the primary efficacy
measure defined as change from baseline in the HAM-D-21 total score to the endpoint visit,
Effexor XR also demonstrated superiority over placebo on the key secondary efficacy endpoint,32
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the Clinical Global Impressions (CGI) Severity of Illness scale. Examination of gender subsets ofthe population studied did not reveal any differential responsiveness on the basis of gender.
A 4-week study of inpatients meeting DSM-III-R criteria for MDD with melancholia utilizing
Effexor in a range of 150 to 375 mg per day (divided in a three-times-a-day schedule)
demonstrated superiority of Effexor over placebo based on the HAM-D-21 total score. The meandose in completers was 350 mg per day (study 3).
In a longer-term study, adult outpatients with MDD who had responded during an 8-week openlabel study on Effexor XR (75, 150, or 225 mg, once daily every morning) were randomized tocontinuation of their same Effexor XR dose or to placebo, for up to 26 weeks of observation forrelapse. Response during the open-label 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) 2consecutive 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 statistically significantly lower relapse rates overthe subsequent 26 weeks compared with those receiving placebo (study 4).
In a second longer term trial, adult outpatients with MDD, 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 [100 to 200 mg per day,on a twice daily schedule] were randomized to continuation of their same Effexor dose or toplacebo. 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 statistically significantly lower relapse rates over the subsequent 52 weeks
compared with those receiving placebo (study 5).
Table 18: Primary Efficacy Results for Studies in Major Depressive Disorder in Adults(Studies 1, 2, 3)
StudyPrimary Efficacy Measure: HAM-D
Treatment Group
Number
Score
Mean
Placebo Subtracted
LS Mean Change
Baseline
Differencea
from Baseline
Score (SD)(95%CI)
Effexor (XR 75-225 mg/day)* 24.5
-11.7
-4.45 (-6.66, -2.25)
Study 1
Placebo
23.6-7.24
Effexor (XR 75-225 mg/day)* 24.5
-15.11-6.40 (-8.45, -4.34)
Study 2
Placebo
24.9-8.71
Effexor (IR 150-375 mg/day)* 28.2 (0.5)-14.9-10.2 (-14.4, -6.0)
Study 3
Placebo28.6 (0.6)-4.7
SD=standard deviation; LS Mean=least-squares mean; CI=confidence interval.
aDifference (drug minus placebo) in least-squares mean change from baseline.

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Doses statistically significantly superior to placebo.

14.2

Generalized Anxiety Disorder

The efficacy of Effexor XR as a treatment for Generalized Anxiety Disorder (GAD) wasestablished in two 8-week, placebo-controlled, fixed-dose studies (75 to 225 mg per day), one 6month, placebo-controlled, flexible-dose study (75 to 225 mg per day), and one 6-month,placebo-controlled, fixed-dose study (37.5, 75, and 150 mg per day) in adult outpatients meeting
DSM-IV criteria for GAD.
In one 8-week study, Effexor XR demonstrated superiority over placebo for the 75, 150, and 225
mg per day doses as measured by 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.
However, the 75 and 150 mg per day doses were not as consistently effective as the highest dose(study 1). A second 8-week study evaluating doses of 75 and 150 mg per day and placebo
showed that both doses were more effective than placebo on some of these same outcomes;
however, the 75 mg per day dose was more consistently effective than the 150 mg per day dose(study 2). A dose-response relationship for effectiveness in GAD was not clearly established inthe 75 to 225 mg per day dose range studied.
Two 6-month studies, one evaluating Effexor XR doses of 37.5, 75, and 150 mg per day (study3) and the other evaluating Effexor XR doses of 75 to 225 mg per day (study 4), showed thatdaily 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 per 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.
Table 19: Primary Efficacy Results for Studies in Generalized Anxiety Disorder in Adults(Studies 1, 2, 3, 4)
Study
Treatment Group Primary Efficacy Measure: HAM-A Score
NumberLS MeanMean Baseline
Placebo Subtracted
Change from
Score (SD)
Differencea (95% CI)
Baseline (SE)*Ven XR 75 mg
24.7-11.1 (0.95)-1.5 (-3.8, 0.8)
Ven XR 150 mg
24.5-11.7 (0.87)-2.2 (-4.5, 0.1)
Study 1
Ven XR 225 mg
23.6-12.1 (0.81)-2.6 (-4.9, -0.3)
Placebo
24.1-9.5 (0.85)
Ven XR 75 mg
23.7-10.6 (0.82)-2.6 (-4.6, -0.5)
Study 2 Ven XR 150 mg
23.0-9.8 (0.86)-1.7 (-3.8, 0.3)
Placebo23.7-8.0 (0.73)
Ven XR 37.5 mg
26.6 (0.4)-13.8-2.8 (-5.1, -0.6)
Study 3
Ven XR 75 mg
26.3 (0.4)-15.5-4.6 (-6.9, -2.3)

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Ven XR150 mg
26.3 (0.4)-16.4-5.5 (-7.8, -3.1)
Placebo26.7 (0.5)-11.0
Ven XR 75-225 mg 25.0
-13.4 (0.79)- 4.7 (-6.6, -2.9)
Study 4
Placebo
24.9-8.7 (0.70)
SD=standard deviation; SE=standard error; LS Mean=least-squares mean; CI=confidence
interval.
aDifference (drug minus placebo) in least-squares mean change from baseline.
*
Doses statistically significantly superior to placebo.
14.3

Social Anxiety Disorder (Also Known as Social Phobia)

The efficacy of Effexor XR as a treatment for Social Anxiety Disorder (SAD) was established infour double-blind, parallel-group, 12-week, multicenter, placebo-controlled, flexible-dose studies(studies 1-4) and one double-blind, parallel-group, 6-month, placebo-controlled, fixed/flexibledose study, which included doses in a range of 75 to 225 mg per day in adult outpatients meeting
DSM-IV criteria for SAD (study 5).
In these five studies, Effexor XR was statistically significantly more effective than placebo on
change from baseline to endpoint on the Liebowitz Social Anxiety Scale (LSAS) total score.
There was no evidence for any greater effectiveness of the 150 to 225 mg per day groupcompared to the 75 mg per day group in the 6-month study.
Examination of subsets of the population studied did not reveal any differential responsivenesson the basis of gender. There was insufficient information to determine the effect of age or raceon outcome in these studies.
Table 20: Primary Efficacy Results for Studies in Social Anxiety Disorder in Adults(Studies 1, 2, 3, 4, 5)
Study
Treatment Group
Primary Efficacy Measure: LSAS Score
NumberPlacebo Subtracted
Mean Baseline LS Mean Change
Differencea (95%
Score (SD)from Baseline (SE)CI)
Ven XR (75-225 mg)*
91.1
-31.0 (2.22)
11.2 (-5.3, -17.1)
Study 1
Placebo
86.7-19.9 (2.22)
Ven XR (75-225 mg)*90.8
-32.8 (2.69)-10.7 (-3.7, -17.6)
Study 2
Placebo
87.4-22.1 (2.66)
Ven XR (75-225 mg)*83.2
-36.0 (2.35)-16.9 (-22.6, -11.2)
Study 3
Placebo
83.6-19.1 (2.40)-12.7 (-6.5, -19.0)
Ven XR (75-225 mg)*86.2
-35.0 (2.64)-14.6 (-21.8, -7.4)
Study 4
Placebo
86.1-22.2 (2.47)
Ven XR 75 mg
91.8-38.1 (3.16)-14.6 (-21.8, -7.4)
Study 5
Ven XR (150-225 mg)* 86.2
-37.6 (3.05)-14.1 (-21.3, -6.9)
Placebo
89.3-23.5 (3.08)
SD=standard deviation; SE=standard error; LS Mean=least-squares mean; CI=confidence
interval.
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Doses statistically significantly superior to placebo.

14.4

Panic Disorder

The efficacy of Effexor XR as a treatment for Panic Disorder (PD) was established in two
double-blind, 12-week, multicenter, placebo-controlled studies in adult outpatients meeting
DSM-IV criteria for PD, with or without agoraphobia. Patients received fixed doses of 75 or 150
mg per day in one study (study 1) and 75 or 225 mg per day in the other study (study 2).
Efficacy was assessed on the basis of outcomes in three variables: (1) percentage of patients freeof full-symptom panic attacks on the Panic and Anticipatory Anxiety Scale (PAAS); (2) meanchange 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 theClinical Global Impressions (CGI) Improvement scale. In these two studies, Effexor XR was
statistically significantly more effective than placebo (for each fixed dose) on all three endpoints,
but a dose-response relationship was not clearly established.
Examination of subsets of the population studied did not reveal any differential responsivenesson the basis of gender. There was insufficient information to determine the effect of age or raceon outcome in these studies.
In a longer term study (study 3), adult outpatients meeting DSM-IV criteria for PD who had
responded during a 12-week open phase with Effexor XR (75 to 225 mg per day) were randomly
assigned to continue the same Effexor XR dose (75, 150, or 225 mg) or switch to placebo forobservation for relapse under double-blind conditions. Response during the open phase wasdefined as ≤ 1 full-symptom panic attack per week during the last 2 weeks of the open phase anda 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 theinvestigators 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 statistically significantly longer
time to relapse.
Table 21: Primary Efficacy Results for Studies in Panic Disorder in Adults (Studies 1 and 2)
Study Treatment Group
Primary Efficacy Measure: Whether Free of Full-symptom
NumberPanic Attacks
Adjusted Odds
Percent of Patients
Adjusted Odds
Ratioa 95%
Free of Full SymptomaRatio to Placebo
Confidence
Panic Attack
Interval
Ven XR 75 mg*
54.1% (85/157)
2.268(1.43, 3.59)
Study 1 Ven XR 150 mg* 61.4% (97/158)
3.035(1.91, 4.82)
Placebo34.4% (53/154)--Study 2 Ven XR 75 mg*
64.1% (100/156)
2.350(1.46, 3.78)

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Ven XR 225 mg* 70.0% (112/160)
2.890(1.80, 4.64)
Placebo46.5% (73/157)--a
Odds ratio (drug to placebo) in terms of probability of free of full-symptom panic attacks basedon logistic regression model.
95% CI: 95% confidence interval without adjusting for multiple dose arms.
*
Doses statistically significantly superior to placebo.
16

HOW SUPPLIED/STORAGE AND HANDLING

Effexor XR® is available as:• 37.5 mg, grey cap/peach body with “W” and “Effexor XR” on the cap and “37.5” on thebody.
NDC 58151-125-93, bottle of 30 capsules in unit-of-use package.
NDC 58151-125-77, bottle of 90 capsules in unit-of-use package.
• 75 mg, peach cap and body with “W” and “Effexor XR” on the cap and “75” on the body.
NDC 58151-126-93, bottle of 30 capsules in unit-of-use package.
NDC 58151-126-77, bottle of 90 capsules in unit-of-use package.
• 150 mg, dark orange cap and body with “W” and “Effexor XR” on the cap and “150” on thebody.
NDC 58151-127-93, bottle of 30 capsules in unit-of-use package.
NDC 58151-127-77, bottle of 90 capsules in unit-of-use package.
Store at controlled room temperature, 20° to 25°C (68° to 77°F).
17

PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Suicidal Thoughts and Behaviors
Advise patients and caregivers to look for the emergence of suicidality, especially early during
treatment and when the dose is adjusted up or down, and instruct them to report such symptoms
to the healthcare provider [see Boxed Warning and Warnings and Precautions (5.1)].
Concomitant Medication
Instruct patients not to take Effexor XR with an MAOI or within 14 days of stopping an MAOI
[see Contraindications (4)].
Serotonin Syndrome
Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of
Effexor XR with other serotonergic drugs including triptans, tricyclic antidepressants, opioids,
lithium, tryptophan, buspirone, amphetamines, St. John’s Wort, and with drugs that impair
metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders
and also others, such as linezolid). Instruct patients to contact their healthcare provider or report

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to the emergency room if they experience signs or symptoms of serotonin syndrome [seeWarnings and Precautions (5.2) and Drug Interactions (7.1)].
Elevated Blood Pressure
Advise patients that they should have regular monitoring of blood pressure when taking Effexor
XR [see Warnings and Precautions (5.3)].
Increased Risk of Bleeding
Inform patients about the concomitant use of Effexor XR with NSAIDs, aspirin, otherantiplatelet drugs, warfarin, or other drugs that affect coagulation because the combined use has
been associated with an increased risk of bleeding. Advise patients to inform their health careproviders if they are taking or planning to take any prescription or over-the-counter medications
that increase the risk of bleeding [see Warnings and Precautions (5.4)].
Activation of Mania/Hypomania
Advise patients, their families and caregivers to observe for signs of activation ofmania/hypomania and instruct them to report such symptoms to the healthcare provider [seeWarnings and Precautions (5.6)].
Cardiovascular/Cerebrovascular Disease
Caution is advised in administering Effexor XR to patients with cardiovascular, cerebrovascular,
or lipid metabolism disorders [see Adverse Reactions (6.1)].
Serum Cholesterol and Triglyceride Elevation
Advise patients that elevations in total cholesterol, LDL and triglycerides may occur and thatmeasurement of serum lipids may be considered [see Adverse Reactions (6.1)].
Discontinuation Syndrome
Advise patients not to abruptly stop taking Effexor XR without talking first with their healthcare
provider. Patients should be aware that discontinuation effects may occur when stopping Effexor
XR and they should monitor for discontinuation symptoms [see Warnings and Precautions (5.7)
and Adverse Reactions (6.1)].
Sexual Dysfunction
Advise patients that use of Effexor XR may cause symptoms of sexual dysfunction in both maleand female patients. Inform patients that they should discuss any changes in sexual function andpotential management strategies with their healthcare provider [see Warnings and Precautions(5.13)].

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Interference with Cognitive and Motor Performance
Caution patients about operating hazardous machinery, including automobiles, until they arereasonably certain that Effexor XR therapy does not adversely affect their ability to engage insuch activities.
Alcohol
Advise patients to avoid alcohol while taking Effexor XR [see Drug Interactions (7.2)].
Allergic Reactions
Advise patients to notify their healthcare provider if they develop allergic phenomena such asrash, hives, swelling, or difficulty breathing [see Contraindications (4) and Adverse Reactions(6.2)].
Pregnancy
Advise patients to notify their healthcare provider if they become pregnant or intend to become
pregnant during treatment with Effexor XR. Advise patients that Effexor XR use during mid tolate pregnancy may lead to an increased risk for preeclampsia and may increase the risk forneonatal complications requiring prolonged hospitalization, respiratory support, and tube
feeding. Advise patients that there is a pregnancy exposure registry that monitors pregnancy
outcomes in women exposed to Effexor XR during pregnancy [see Use in Specific Populations(8.1)].
Residual Spheroids
Effexor XR contains spheroids, which release the drug slowly into the digestive tract. The
insoluble portion of these spheroids is eliminated, and patients may notice spheroids passing inthe stool or via colostomy. Patients should be informed that the active medication has alreadybeen absorbed by the time the patient sees the spheroids.
Distributed by:Viatris Specialty LLC
Morgantown, WV 26505 U.S.A.
Made in Ireland© 2023 Viatris Inc.
EFFEXOR XR is a registered trademark of Viatris Specialty LLC, a Viatris Company.
UPJ:EFFXRXR:RX2

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MEDICATION GUIDEEFFEXOR XR (e-fex-or XR)(venlafaxine extended-release)capsulesWhat is the most important information I should know about EFFEXOR XR?
EFFEXOR XR may cause serious side effects, including:• Increased risk of suicidal thoughts and actions. EFFEXOR XR and other antidepressant medicines
may increase suicidal thoughts and actions in some children, adolescents, and young adults, especiallywithin the first few months of treatment or when the dose is changed. EFFEXOR XR is not for use
in children.
o Depression or other serious mental illnesses are the most important causes of suicidal thoughts or
actions.
How can I watch for and try to prevent suicidal thoughts and actions in myself or a family
member?
o Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or
feelings. This is very important when an antidepressant medicine is started or when the dose ischanged.
o Call your healthcare provider right away to report new or sudden changes in mood, behavior,thoughts, or feelings.
o Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider
between visits as needed, especially if you have concerns about symptoms.
Call your healthcare provider or get emergency help right away if you or a family member haveany of the following symptoms, especially if they are new, worse, or worry you:• attempts to commit suicide• thoughts about suicide or dying• acting aggressive, being angry, or violent• acting on dangerous impulses• new or worse depression• new or worse anxiety• panic attacks• feeling very agitated or restless• new or worse irritability• trouble sleeping• an extreme increase in activity or talking (mania)• other unusual changes in behavior or mood
What is EFFEXOR XR?
EFFEXOR XR is a prescription medicine used to treat adults with:• a certain type of depression called Major Depressive Disorder (MDD)• Generalized Anxiety Disorder (GAD)• Social Anxiety Disorder (SAD)• Panic Disorder (PD)It is not known if EFFEXOR XR is safe and effective for use in children.
Do not take EFFEXOR XR if you:••••are allergic to venlafaxine hydrochloride, desvenlafaxine succinate, or any of the ingredients in EFFEXOR
XR. See the end of this Medication Guide for a complete list of ingredients in EFFEXOR XR.
take a Monoamine Oxidase Inhibitor (MAOI)
have stopped taking an MAOI in the last 14 days
are being treated with the antibiotic linezolid or intravenous methylene blue

Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including MAOIs such as
linezolid or intravenous methylene blue.

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Do not start taking an MAOI for at least 7 days after you stop treatment with EFFEXOR XR.
Before taking EFFEXOR XR tell your healthcare provider about all your medical conditions, including
if you:• have, or have a family history of suicide, bipolar disorder, depression, mania or hypomania• have high blood pressure• have heart problems• have cerebrovascular problems or had a stroke• have or have had bleeding problems• have high pressure in the eye (glaucoma)• have high cholesterol or high triglycerides• have kidney or liver problems• have or had seizures or convulsions• have low sodium levels in your blood• have lung problems• drink alcohol• are pregnant or plan to become pregnant. EFFEXOR XR may harm your unborn baby. Talk to yourhealthcare provider about the risk to you and your unborn baby if you take EFFEXOR XR during
pregnancy.
o Tell your healthcare provider if you become pregnant or think you are pregnant during treatment with
EFFEXOR XR.
o Pregnancy Exposure Registry. There is a pregnancy registry for women who are exposed to
EFFEXOR XR during pregnancy. The purpose of the registry is to collect information about the healthof you and your baby. If you become pregnant during treatment with EFFEXOR XR, talk to yourhealthcare provider about registering with the National Pregnancy Registry for Antidepressants. You
can register by calling 1-844-405-6185 or by visiting online athttps://womensmentalhealth.org/research/pregnancyregistry/antidepressants.
• are breastfeeding or plan to breastfeed. EFFEXOR XR passes into your breast milk and may harm yourbaby. Talk to your healthcare provider about the best way to feed your baby during treatment with
EFFEXOR XR.
Tell your healthcare provider about all the medicines you take, including prescription and over-thecounter medicines, vitamins, and herbal supplements.
EFFEXOR XR and other medicines may affect each other causing possible serious side effects. EFFEXOR
XR may affect the way other medicines work and other medicines may affect the way EFFEXOR XR works.
Especially tell your healthcare provider if you take:• medicines to treat migraine headaches known as triptans• tricyclic antidepressants• lithium• tramadol, fentanyl, meperidine, methadone, or other opioids• tryptophan• buspirone• amphetamines• St. John’s Wort
• phentermine• other medicines containing desvenlafaxine or venlafaxine• medicines that can affect blood clotting such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs),
warfarin
Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare
provider can tell you if it is safe to take EFFEXOR XR with your other medicines.

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Do not start or stop any other medicines during treatment with EFFEXOR XR without first talking to yourhealthcare provider. Stopping EFFEXOR XR suddenly may cause you to have serious side effects. See“What are the possible side effects of EFFEXOR XR?”
Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when
you get a new medicine.
How should I take EFFEXOR XR?
•
•
•
•
•
•

•

Take EFFEXOR XR exactly as your healthcare provider tells you to. Do not change your dose or stoptaking EFFEXOR XR without first talking to your healthcare provider.
Your healthcare provider may need to change the dose of EFFEXOR XR until it is the right dose for you.
Take EFFEXOR XR 1 time each day with food.
EFFEXOR may be taken either in the morning or in the evening, but take it the same way each time.
Swallow EFFEXOR XR whole with fluid. Do not divide, crush, chew, or dissolve EFFEXOR XR.
If you cannot swallow EFFEXOR XR capsules whole, the EFFEXOR XR capsules may be opened andthe entire contents sprinkled on a spoonful of applesauce.
o Swallow the EFFEXOR XR and applesauce mixture right away without chewing.
o Follow with a glass of water to make sure you have swallowed all of the EFFEXOR XR pellets.
If you take too much EFFEXOR XR, call your healthcare provider or poison control center at 1-800-2221222 or go to the nearest hospital emergency room right away.

What should I avoid while taking EFFEXOR XR?
••

Do not drive, or operate heavy machinery, or do other dangerous activities until you know how EFFEXOR
XR affects you. EFFEXOR XR can make you drowsy.
You should not drink alcohol during treatment with EFFEXOR XR. Drinking alcohol during treatment with
EFFEXOR XR can increase your risk of having serious side effects.

What are the possible side effects of EFFEXOR XR?
EFFEXOR XR may cause serious side effects, including:• See “What is the most important information I should know about EFFEXOR XR?”
• Serotonin syndrome. Taking EFFEXOR XR can cause a potentially life-threatening problem called
serotonin syndrome. The risk of developing serotonin syndrome is increased when EFFEXOR XR istaken with certain other medicines. See “Do not take EFFEXOR XR if you:” Stop taking EFFEXOR XR
and call your healthcare provider or go to the nearest hospital emergency room right away if you haveany of the following signs and symptoms of serotonin syndrome:o agitationo seeing or hearing things that are not real
(hallucinations)o confusiono comao fast heartbeato changes in blood pressureo dizzinesso sweatingo flushingo high body temperature (hyperthermia)
o tremors, stiff muscles, or muscle
twitchingo loss of coordinationo seizures
o nausea, vomiting, diarrhea••

Increases in blood pressure. Your healthcare provider should check your blood pressure before starting
treatment and regularly during treatment with EFFEXOR XR. If you have high blood pressure, it should becontrolled before you start treatment with EFFEXOR XR.
Increased risk of bleeding. Taking EFFEXOR XR with aspirin, nonsteroidal anti-inflammatory drugs(NSAIDs), or blood thinners may add to this risk. Tell your healthcare provider right away about any
unusual bleeding or bruising.

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Eye problems (angle-closure glaucoma). EFFEXOR XR may cause a certain type of eye problem
called angle-closure glaucoma. You may want to undergo an eye examination to see if you are at risk andreceive preventative treatment if you are. Call your healthcare provider if you have eye pain, changes inyour vision, or swelling or redness in or around the eye.
Manic episodes. Manic episodes may happen in people with bipolar disorder who take EFFEXOR XR.
Symptoms may include:o greatly increased energy
o severe trouble sleepingo racing thoughts
o reckless behavior
o unusually grand ideas
o excessive happiness or irritability
o talking more or faster than usual•

Discontinuation syndrome. Suddenly stopping EFFEXOR XR may cause you to have serious side
effects. Your healthcare provider may want to decrease your dose slowly. Symptoms may include:o dizziness
o nauseao headacheo irritability and agitationo problems sleepingo diarrhea
o anxietyo tirednesso abnormal dreams
o sweatingo confusiono changes in your moodo seizureso electric shock sensation (paresthesia) o hypomania
o ringing in your ears (tinnitus)••

Seizures (convulsions).
Low sodium levels in your blood (hyponatremia). Low sodium levels can happen during treatment
with EFFEXOR XR. Low sodium levels in your blood may be serious and may cause death. Elderly
people may be at greater risk for this. Signs and symptoms of low sodium levels in your blood may
include:o headacheo difficulty concentratingo memory changeso confusiono weakness and unsteadiness on your feet which can lead to falls
In severe or more sudden cases, signs and symptoms include:o hallucinations (seeing or hearing things that are not real)o faintingo seizures
o comao respiratory arrest••

Lung problems. Some people who have taken the medicine venlafaxine, which is the same kind of
medicine as the medicine in EFFEXOR XR, have had lung problems. Symptoms of lung problems includedifficulty breathing, cough, or chest discomfort. Tell your healthcare provider right away if you have any ofthese symptoms.
Sexual problems (dysfunction). Taking selective serotonin reuptake inhibitors (SNRIs), including
EFFEXOR XR, may cause sexual problems.
Symptoms in males may include:
o delayed ejaculation or inability to have an ejaculationo decreased sex driveo problems getting or keeping an erection
Symptoms in females may include:o decreased sex driveo delayed orgasm or inability to have an orgasm

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Talk to your healthcare provider if you develop any changes in your sexual function or if you have any
questions or concerns about sexual problems during treatment with EFFEXOR XR. There may betreatments your healthcare provider can suggest.
Your healthcare provider may tell you to stop taking EFFEXOR XR if you develop serious side effects during
treatment with EFFEXOR XR.
The most common side effects of EFFEXOR XR include:• nausea• sleepiness• dry mouth• sweating• male and female sexual problems• constipation• loss of appetite (anorexia)
These are not all the possible side effects of EFFEXOR XR.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA1088.
How should I store EFFEXOR XR?
• Store EFFEXOR XR at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep EFFEXOR XR in a dry place.
Keep EFFEXOR XR and all medicines out of the reach of children.
General information about the safe and effective use of EFFEXOR XR.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use
EFFEXOR XR for a condition for which it was not prescribed. Do not give EFFEXOR XR to other people,
even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider
or pharmacist for information about EFFEXOR XR that is written for healthcare professionals.
What are the ingredients in EFFEXOR XR?
Active ingredient: venlafaxine
Inactive ingredients: cellulose, ethylcellulose, gelatin, hypromellose, iron oxide, and titanium dioxide.
Distributed by:Viatris Specialty LLC
Morgantown, WV 26505 U.S.A.
Made in Ireland© 2023 Viatris Inc.
EFFEXOR XR is a registered trademark of Viatris Specialty LLC, a Viatris Company.
UPJ:MG:EFFXRXR:RX2
For more information about EFFEXOR XR, call Viatris at 1-877-446-3679 (1-877-4-INFO-RX).
This Medication was approved by the U.S. Food and Drug Administration.

Revised: 8/2023

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