Effexor XR

Venlafaxine should be taken with food at doses specifically directed by a physician. Individual doses vary greatly among individuals. The anti-depressant effects are not maximal for 1-2 weeks. If discontinued, the dose of venlafaxine should gradually be reduced under the direction of a physician. For patients with difficulty swallowing tablets or capsules, capsules of Effexor XR can be opened and the contents sprinkled on a spoonful of applesauce but removal from the capsule allows immediate release of the drug so it is no longer an extended release drug.

The dose for treatment of depression using the immediate release formulation is 75 to 375 mg daily divided in 2 or 3 doses and given every 8 or 12 hours. The extended release dose is 37.5 mg to 225 mg once daily. Dosing is usually begun with low initial concentrations and adjusted as needed by the treating doctor.

Generalized anxiety and panic disorder are treated with 37.5 mg to 225 mg once daily using the extended release formulation. Social anxiety is treated with 75 mg daily using the extended release formulation.

>10%

Headache (25-38%)

Nausea (21-58%)

Insomnia (15-24%)

Asthenia (16-20%)

Dizziness (11-24%)

Ejaculation disorder (2-19%)

Somnolence (12-26%)

Dry mouth (12-22%)

Diaphoresis (7-19%)

Anorexia (15-17%)

Nervousness (17-26%)

Anorgasmia (5-13%)

1-10%

Weight loss (1-6%)

Abnormal vision (4-6%)

Hypertension (2-5%)

Impotence (4-6%)

Paresthesia (2-3%)

Tremor (1-10%)

Vasodilation (2-6%)

Vomiting (3-8%)

Weight gain (2%)

Flatulence (3-4%)

Pruritus (1%)

Yawning (3-8%)

Dyspepsia (5-7%)

Twitching (1-3%)

Mydriasis (2%)

<1%

Angioedema

Agranulocytosis

Anemia

Anuria

Aneurism

Bacteremia

Myasthenia

Syncope

Suicide ideation/attempt

Postmarketing Reports

Chills

Dyspnea

Interstitial lung disease

Black Box Warnings

In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses

This increase was not seen in patients aged >24 years; slight decrease in suicidal thinking was seen in adults >65 years

Not FDA approved for children; in children and young adults; benefits of taking antidepressants must be weighed against risks

Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments

Patient’s family should communicate any abrupt behavioral changes to healthcare provider

Worsening behavior and suicidal tendencies that are not part of presenting symptoms may necessitate discontinuance of therapy

Not FDA approved for treatment of bipolar depression

Contraindications

Hypersensitivity

Coadministration with serotonergic drugs

• Coadministration with monoamine oxidase inhibitors (MAOIs)
• Concomitant MAOIs administration within 14 days before initiating venlafaxine or within 7 days after discontinuing venlafaxine
• Initiation of venlafaxine in patient being treated with linezolid or IV methylene blue

Cautions

Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy

Use caution in bipolar mania, history of seizures, and cardiovascular disease

May precipitate mania or hypomania episodes in patients with bipolar disorder; avoid monotherapy in bipolar disorder; screen patients presenting with depressive symptoms for bipolar disorder

Use caution in hepatic or renal impairment

Neonates exposed to serotonin-norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding

Clinical worsening and suicidal ideation may occur despite medication in adolescents and young adults (18-24 years)

When discontinuing, taper dosage to avoid flulike symptoms

May cause increase in nervousness, anxiety, or insomnia

May impair ability to operate heavy machinery; depresses CNS

Bone fractures reported with antidepressant therapy; consider possibility if patient experiences bone pain

May cause significant increase in serum cholesterol

Dose-dependent anorectic effects and weight loss reported in children and adult patients

Dose-related increase in systolic and diastolic pressure reported

Eosinophilic pneumonia and interstitial lung disease reported

SAIDH and hyponatremia reported SSRIs

Potentially life-threatening serotonin syndrome with SSRIs and SNRIs when used in combination with other serotonergic agents including TCAs, buspirone tryptophan, fentanyl, tramadol, lithium, tryptophan, buspirone, amphetamines, St. John’s Wort, and triptans; symptoms include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma

Venlafaxine in patient being treated with linezolid or IV methylene blue increases risk of serotonin syndrome; if linezolid or IV methylene blue must be administered, discontinue venlafaxine immediately and monitor for central nervous system (CNS) toxicity; therapy may be resumed 24 hours after last linezolid or methylene blue dose or after 2 weeks of monitoring, whichever comes first

SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage; concomitant use of aspirin, NSAIDs, warfarin, other anticoagulants, or other drugs known to affect platelet function may add to this risk

Control hypertension before initiating treatment; monitor blood pressure regularly during treatment

Risks of sustained hypertension, hyponatremia, and impeded height and weight in children

Drug-laboratory test interactions: False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been observed during venlafaxine therapy because of lack of specificity of the screening tests

May cause or exacerbate sexual dysfunction

Effexor XR is a prescription medication used to treat adults with major depressive disorder, panic disorder, and anxiety. It belongs to a class of drugs called serotonin norepinephrine reuptake inhibitors (SNRIs). These work by increasing serotonin and norepinephrine levels, which are natural substances in the brain that help maintain mental balance.

Effexor XR is available as an extended-release capsule and is usually taken once a day, with food. Capsules should be taken whole; do not divide, crush, chew, or dissolve capsules.

Common side effects of Effexor XR include dry mouth, insomnia, loss of appetite, and dizziness. Do not drive or operate heavy machinery until you know how Effexor XR will affect you.

Before receiving this medication, tell your doctor about all your medical conditions especially:

• have heart problems
• have diabetes
• have liver problems
• have kidney problems
• have thyroid problems
• have or had seizures or convulsions
• have bipolar disorder or mania
• have low sodium levels in your blood
• have high blood pressure
• have high cholesterol
• have or had bleeding problems
• are pregnant or plan to become pregnant. It is not known if Effexor XR will harm your unborn baby. Talk to your healthcare provider about the benefits and risks of treating depression during pregnancy
• are breast-feeding or plan to breast-feed. Some Effexor XR may pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking Effexor XR.

Tell your doctor about all the medicines you take or are planning to take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant, planning to become pregnant or breastfeeding.

• Store at controlled room temperature.
• Keep all medications out of the reach of children.

The following adverse reactions are discussed in greater detail in other sections of the label:

• Hypersensitivity [see Contraindications (4.1)]
• Suicidal Thoughts and Behaviors in Children, Adolescents, and Adults [see Warnings and Precautions (5.1)]
• Serotonin Syndrome [see Warnings and Precautions (5.2)]
• Elevations in Blood Pressure [see Warnings and Precautions (5.3)]
• Abnormal 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)]

Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in 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 of placebo) 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%) and decreased 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 treated patients in the short-term studies (up to 12 weeks) across indications are shown in Table 7.

Common Adverse Reactions in Placebo-controlled Studies

The number of patients receiving multiple doses of Effexor XR during the premarketing assessment 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 (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient (Effexor only) and outpatient studies, fixed-dose, and titration studies.

The incidences of common adverse reactions (those that occurred in ≥ 2% of Effexor XR treated patients [357 MDD patients, 1,381 GAD patients, 819 SAD patients, and 1,001 PD patients] and more 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.

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)]

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 (see Table 10). Across most indications, a dose-related increase in mean supine systolic and diastolic blood pressure was evident in patients treated with Effexor XRs. 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 in the 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 the placebo groups.

Effexor XR treatment was associated with sustained hypertension (defined as treatment-emergent Supine Diastolic Blood Pressure [SDBP] ≥ 90 mm Hg and ≥ 10 mm Hg above baseline for three consecutive on-therapy 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.

Effexor XR was associated with mean increases in pulse rate compared with placebo in premarketing placebo-controlled studies (see Table 12) [see Warnings and Precautions (5.3, 5.4)].

Laboratory 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).

Effexor XR (venlafaxine hydrochloride) extended-release capsules treatment for up to 12 weeks in premarketing placebo-controlled trials for major depressive disorder was associated with a mean final on-therapy increase in serum cholesterol concentration of approximately 1.5 mg/dL compared with a mean final decrease of 7.4 mg/dL for placebo. Effexor XR treatment for up to 8 weeks and up to 6 months in premarketing placebo-controlled GAD trials was associated with mean final on-therapy increases in serum cholesterol concentration of approximately 1.0 mg/dL and 2.3 mg/dL, respectively while placebo subjects experienced mean final decreases of 4.9 mg/dL and 7.7 mg/dL, respectively. Effexor XR treatment for up to 12 weeks and up to 6 months in premarketing placebo-controlled Social Anxiety Disorder trials was associated with mean final on-therapy increases in serum cholesterol concentration of approximately 7.9 mg/dL and 5.6 mg/dL, respectively, compared with mean final decreases of 2.9 and 4.2 mg/dL, respectively, for placebo. Effexor XR treatment for up to 12 weeks in premarketing placebo-controlled panic disorder trials was associated with mean final on-therapy increases in serum cholesterol concentration of approximately 5.8 mg/dL compared with a mean final decrease of 3.7 mg/dL for placebo.

Patients treated with Effexor (immediate release) for at least 3 months in placebo-controlled 12-month extension trials had a mean final on-therapy increase in total cholesterol of 9.1 mg/dL compared with a decrease of 7.1 mg/dL among placebo-treated patients. This increase was duration dependent over the study period and tended to be greater with higher doses. Clinically relevant increases in serum cholesterol, defined as 1) a final on-therapy increase in serum cholesterol ≥50 mg/dL from baseline and to a value ≥261 mg/dL, or 2) an average on-therapy increase in serum cholesterol ≥50 mg/dL from baseline and to a value ≥261 mg/dL, were recorded in 5.3% of venlafaxine-treated patients and 0.0% of placebo-treated patients.

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 (pooled data) and 6 months duration (Table 14).

Pediatric Patients

In general, the adverse reaction profile of venlafaxine (in placebo-controlled clinical studies) in children and adolescents (ages 6 to 17) was similar to that seen for adults. As with adults, decreased appetite, weight loss, increased blood pressure, and increased serum cholesterol were observed [see Warnings and Precautions (5.3, 5.10, 5.11) and Use in Specific Populations (8.4)].

In pediatric clinical studies, the adverse reaction, suicidal ideation, was observed.

Particularly, the following adverse reactions were observed in pediatric patients: abdominal pain, agitation, dyspepsia, ecchymosis, epistaxis, and myalgia.

Adverse Reactions Identified During Postapproval Use

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

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 system – Dyspnea, interstitial lung disease, pulmonary eosinophilia [see Warnings and Precautions (5.12)]

Skin and appendages – Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme

Special senses – Angle-closure glaucoma [see Warnings and Precautions (5.5)]

Central Nervous System (CNS)-Active Drugs

The risk of using venlafaxine in combination with other CNS-active drugs has not been systematically evaluated. Consequently, caution is advised when Effexor XR is taken in combination with other CNS-active drugs.

Monoamine Oxidase Inhibitors

Adverse reactions, some of which were serious, have been reported in patients who have recently been discontinued from an MAOI and started on antidepressants with pharmacological properties similar to Effexor XR (SNRIs or SSRIs), or who have recently had SNRI or SSRI therapy discontinued prior to initiation of an MAOI [see Dosage and Administration (2.9), Contraindications (4.2) and Warnings and Precautions (5.2)].

Serotonergic Drugs

Based on the mechanism of action of Effexor XR and the potential for serotonin syndrome, caution is advised when Effexor XR is coadministered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, SSRIs, other SNRIs, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, tramadol, or St. John's wort. If concomitant treatment with Effexor XR and these drugs is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. The concomitant use of Effexor XR with tryptophan supplements is not recommended [see Dosage and Administration (2.9), Contraindications (4.2), and Warnings and Precautions (5.2)].

Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, and Warfarin)

Serotonin release by platelets plays an important role in hemostasis. The use of psychotropic drugs that interfere with serotonin reuptake is associated with the occurrence of upper gastrointestinal bleeding and concurrent use of an NSAID or aspirin may potentiate this risk of bleeding [see Warnings and Precautions (5.4)]. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs and SNRIs are coadministered with warfarin. Patients receiving warfarin therapy should be carefully monitored when Effexor XR is initiated or discontinued.

Weight Loss Agents

The safety and efficacy of venlafaxine therapy in combination with weight loss agents, including phentermine, have not been established. Coadministration of Effexor XR and weight loss agents is not recommended. Effexor XR is not indicated for weight loss alone or in combination with other products.

Effects of Other Drugs on Effexor XR

Abbreviations: ODV, O-desmethylvenlafaxine; AUC, area under the curve; Cmax, peak plasma concentrations; EM's, extensive metabolizers; PM's, poor metabolizers

* No dose adjustment on co-administration with CYP2D6 inhibitors (Fig 3 and Metabolism Section 12.3)

Effects of Effexor XR on Other Drugs

Abbreviations: 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 not receiving venlafaxine.

Drug-Laboratory Test Interactions

False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking venlafaxine. This is due to lack of specificity of the screening tests. False positive test results may be expected for several days following discontinuation of venlafaxine therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish venlafaxine from PCP and amphetamine.

Controlled Substance

Effexor XR is not a controlled substance.

Abuse

While venlafaxine has not been systematically studied in clinical studies for its potential for abuse, there was no indication of drug-seeking behavior in the clinical studies. However, it is not possible 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, physicians should carefully 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, incrementation of dose, drug-seeking behavior).

Dependence

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 abuse liability.

Discontinuation effects have been reported in patients receiving venlafaxine [see Dosage and Administration (2.8)].

See FDA-approved patient labeling (Medication Guide).

Prescribers or other healthcare professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Effexor XR and should counsel them in its appropriate use. A patient Medication Guide about "Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions" is available for Effexor XR. The prescriber or healthcare professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.

Patients should be advised of the following issues and should be asked to alert their prescriber if these occur while taking Effexor XR.

Suicidal Thoughts and Behaviors

Advise patients, their families and caregivers to look for the emergence of suicidality, worsening of depression, and other psychiatric symptoms (anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, psychomotor restlessness, hypomania, mania, other unusual changes in behavior), especially early during treatment and when the dose is adjusted up or down. Such symptoms should be reported to the patient's prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring [see Boxed Warning and Warnings and Precautions (5.1)].

Concomitant Medication

Advise patients taking Effexor XR not to use concomitantly other products containing venlafaxine or desvenlafaxine. Healthcare professionals should instruct patients not to take Effexor XR with an MAOI or within 14 days of stopping an MAOI and to allow 7 days after stopping Effexor XR before starting an MAOI [see Contraindications (4.2)].

Serotonin Syndrome

Patients should be cautioned about the risk of serotonin syndrome, with the concomitant use of Effexor XR and triptans, tramadol, amphetamines, tryptophan supplements, with antipsychotics or other dopamine antagonists, or other serotonergic agents [see Warnings and Precautions (5.2) and Drug Interactions (7.3)].

Elevated Blood Pressure

Advise patients that they should have regular monitoring of blood pressure when taking Effexor XR [see Warnings and Precautions (5.3)].

Abnormal Bleeding

Patients should be cautioned about the concomitant use of Effexor XR and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation since combined use of psychotropic drugs that interfere with serotonin reuptake and these agents has been associated with an increased risk of bleeding [see Warnings and Precautions (5.4)].

Angle Closure Glaucoma

Patients should be advised that taking Effexor XR can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible [see Warnings and Precautions (5.5)].

Activation of Mania/Hypomania

Advise patients, their families and caregivers to observe for signs of activation of mania/hypomania [see Warnings 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 that measurement of serum lipids may be considered [see Warnings and Precautions (6.3)].

Discontinuation [Symptoms]

Advise patients not to stop taking Effexor XR without talking first with their healthcare professional. Patients should be aware that discontinuation effects may occur when stopping Effexor XR [see Warnings and Precautions (5.7) and Adverse Reactions (6.1)].

Interference with Cognitive and Motor Performance

Caution patients about operating hazardous machinery, including automobiles, until they are reasonably certain that Effexor XR therapy does not adversely affect their ability to engage in such activities.

Alcohol

Advise patients to avoid alcohol while taking Effexor XR [see Drug Interactions (7.6)].

Allergic Reactions

Advise patients to notify their physician if they develop allergic phenomena such as rash, hives, swelling, or difficulty breathing.

Pregnancy

Advise patients to notify their physician if they become pregnant or intend to become pregnant during therapy [see Use in Specific Populations (8.1)].

Nursing

Advise patients to notify their physician if they are breast-feeding an infant [see Use in Specific Populations (8.3)].

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 in the stool or via colostomy. Patients should be informed that the active medication has already been absorbed by the time the patient sees the spheroids.

LAB-0466-15.0

ALWAYS DISPENSE WITH MEDICATION GUIDE

NDC 0008-0833-20

Pfizer

Effexor XR®
(venlafaxine HCl)
Extended-Release Capsules

75 mg*

15 Capsules

Rx only

Effexor XR®
(venlafaxine HCl)
Extended-Release Capsules
75 mg

Wyeth® Phila. PA 19101

ALWAYS DISPENSE WITH MEDICATION GUIDE
NDC 0008-0833-03

Pfizer

Effexor XR®
(venlafaxine HCl)
Extended-Release Capsules

75 mg*

10 Redipak® Blister
Strips of 10 Capsules
100 Capsules

Rx only

In the U.S.

• Effexor
• Effexor-XR

Available Dosage Forms:

• Capsule, Extended Release
• Tablet, Extended Release
• Tablet

Therapeutic Class: Antidepressant

Pharmacologic Class: Serotonin/Norepinephrine Reuptake Inhibitor

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated any benefit to using venlafaxine in children. Studies have shown that some children, teenagers, and young adults think about suicide or attempt suicide when taking the medicine. Because of this toxicity, use in children is not recommended.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of venlafaxine in the elderly. However, elderly patients might be more sensitive to the effects of this medicine which may cause low levels of sodium in the blood. Elderly patients could also have age-related liver or kidney problems, which may require caution and an adjustment in the dose for patients taking venlafaxine.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Bepridil
• Bromopride
• Cisapride
• Dronedarone
• Furazolidone
• Iproniazid
• Isocarboxazid
• Linezolid
• Mesoridazine
• Methylene Blue
• Metoclopramide
• Moclobemide
• Nialamide
• Pargyline
• Phenelzine
• Pimozide
• Piperaquine
• Procarbazine
• Rasagiline
• Safinamide
• Saquinavir
• Selegiline
• Sparfloxacin
• Terfenadine
• Thioridazine
• Toloxatone
• Tranylcypromine
• Trifluoperazine
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Acenocoumarol
• Alfentanil
• Almotriptan
• Amiodarone
• Amitriptyline
• Amoxapine
• Amoxicillin
• Amphetamine
• Amtolmetin Guacil
• Anagrelide
• Ancrod
• Anisindione
• Antithrombin III Human
• Apixaban
• Argatroban
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Aspirin
• Atazanavir
• Bemiparin
• Benzphetamine
• Bivalirudin
• Bromfenac
• Bufexamac
• Buprenorphine
• Bupropion
• Buserelin
• Butorphanol
• Celecoxib
• Choline Salicylate
• Cilostazol
• Clarithromycin
• Clomipramine
• Clonixin
• Clopidogrel
• Clozapine
• Codeine
• Crizotinib
• Cyclobenzaprine
• Dabigatran Etexilate
• Dabrafenib
• Dalteparin
• Danaparoid
• Darunavir
• Defibrotide
• Degarelix
• Delamanid
• Dermatan Sulfate
• Desipramine
• Desirudin
• Deslorelin
• Desvenlafaxine
• Deutetrabenazine
• Dexfenfluramine
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Dextromethorphan
• Dibenzepin
• Diclofenac
• Dicumarol
• Diflunisal
• Dihydrocodeine
• Dipyridamole
• Dipyrone
• Dolasetron
• Domperidone
• Donepezil
• Dothiepin
• Doxepin
• Droxicam
• Duloxetine
• Edoxaban
• Efavirenz
• Eletriptan
• Enoxaparin
• Entacapone
• Epoprostenol
• Eptifibatide
• Escitalopram
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenfluramine
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Floctafenine
• Fluconazole
• Flufenamic Acid
• Fluoxetine
• Flurbiprofen
• Fondaparinux
• Foscarnet
• Frovatriptan
• Gonadorelin
• Goserelin
• Granisetron
• Haloperidol
• Heparin
• Histrelin
• Hydrocodone
• Hydromorphone
• Hydroxychloroquine
• Hydroxyzine
• Ibuprofen
• Iloprost
• Imipramine
• Indomethacin
• Iobenguane I 123
• Itraconazole
• Ivabradine
• Jujube
• Ketoconazole
• Ketoprofen
• Ketorolac
• Lamifiban
• Lepirudin
• Leuprolide
• Levofloxacin
• Levomilnacipran
• Levorphanol
• Lexipafant
• Lisdexamfetamine
• Lorcaserin
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Meperidine
• Methadone
• Methamphetamine
• Metronidazole
• Milnacipran
• Mirtazapine
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nabumetone
• Nafarelin
• Nalbuphine
• Naproxen
• Naratriptan
• Nefazodone
• Nelfinavir
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Nortriptyline
• Ondansetron
• Oxaprozin
• Oxycodone
• Oxymorphone
• Oxyphenbutazone
• Palonosetron
• Panobinostat
• Parecoxib
• Paroxetine
• Pasireotide
• Pazopanib
• Pentazocine
• Pentosan Polysulfate Sodium
• Phenindione
• Phenprocoumon
• Phenylbutazone
• Piketoprofen
• Pimavanserin
• Piroxicam
• Pitolisant
• Posaconazole
• Pranoprofen
• Proglumetacin
• Propyphenazone
• Proquazone
• Protein C
• Protriptyline
• Quetiapine
• Remifentanil
• Ribociclib
• Ritonavir
• Rivaroxaban
• Rizatriptan
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sertraline
• Sevoflurane
• Sibrafiban
• Sibutramine
• Sodium Salicylate
• Sotalol
• Sufentanil
• Sulfinpyrazone
• Sulindac
• Sulodexide
• Sulpiride
• Sumatriptan
• Tacrolimus
• Tapentadol
• Telithromycin
• Tenoxicam
• Tiaprofenic Acid
• Ticlopidine
• Tinzaparin
• Tirofiban
• Tolfenamic Acid
• Tolmetin
• Toremifene
• Tramadol
• Trazodone
• Trimipramine
• Triptorelin
• Valdecoxib
• Vandetanib
• Vasopressin
• Vemurafenib
• Vilazodone
• Vinflunine
• Vortioxetine
• Warfarin
• Xemilofiban
• Zolmitriptan
• Zuclopenthixol

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Ginkgo
• Metoprolol
• St John's Wort
• Zolpidem

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bipolar disorder (mood disorder with mania and depression), or risk of or
• Bleeding problems or
• Glaucoma, angle-closure or
• Heart attack, recent or history of or
• Hypercholesterolemia (high cholesterol in the blood) or
• Hypertension (high blood pressure) or
• Hyponatremia (low sodium in the blood) or
• Interstitial lung disease, history of or
• Mania, history of or
• Seizures, history of or
• Stroke, history of or
• Tachycardia (fast heart rate)—Use with caution. May make these conditions worse.

• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Drinking alcohol with Effexor XR can cause side effects.

Ask your doctor before taking a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib (Celebrex), diclofenac, indomethacin, meloxicam, and others. Using an NSAID with Effexor XR may cause you to bruise or bleed easily.

Avoid driving or hazardous activity until you know how this medicine will affect you. Your reactions could be impaired.

Get emergency medical help if you have signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have:

• blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;

• easy bruising or bleeding (nosebleeds, bleeding gums), blood in your urine or stools, coughing up blood;

• cough, chest tightness, trouble breathing;

• a seizure (convulsions);

• low sodium level --headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady; or

• severe nervous system reaction--very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out.

Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea

Common side effects may include:

• dizziness, drowsiness,

• anxiety, feeling nervous;

• sleep problems (insomnia);

• vision changes;

• nausea, vomiting, diarrhea;

• changes in weight or appetite;

• dry mouth, yawning;

• increased sweating; or

• decreased sex drive, impotence, abnormal ejaculation, difficulty having an orgasm.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Using Effexor XR with other drugs that make you drowsy can worsen this effect. Ask your doctor before using opioid medication, a sleeping pill, a muscle relaxer, or medicine for anxiety or seizures.

Tell your doctor about all your current medicines. Many drugs can affect Effexor XR, especially:

• any other antidepressant;

• cimetidine;

• St. John's wort;

• tramadol;

• tryptophan (sometimes called L-tryptophan);

• a blood thinner--warfarin, Coumadin, Jantoven;

• medicine to treat mood disorders, thought disorders, or mental illness--buspirone, lithium, and many others; or

• migraine headache medicine--sumatriptan, zolmitriptan, and others.

This list is not complete and many other drugs may affect Effexor XR. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.