VENLAFAXINE HYDROCHLORIDE- venlafaxine hydrochloride_capsule, extended release

The exact mechanism of the antidepressant action of venlafaxine in humans is unknown, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of their reuptake. Non- clinical studies have demonstrated that venlafaxine and its active metabolite, ODV, are potent and selective inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Venlafaxine and ODV have no significant affinity for muscarinic-cholinergic, H 1 1 in vitro 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 adult subjects. No significant QT prolongation effect of venlafaxine 450 mg was detected. Steady-state concentrations of venlafaxine and ODV in plasma are attained within 3 days of oral multiple-dose therapy. Venlafaxine and ODV exhibited linear kinetics over the dose range of 75 to 450 mg per day. Mean+/-SD steady-state plasma clearance of venlafaxine and ODV is 1. 2 L/h/kg, respectively; apparent elimination half-life is 5+/-2 and 11+/-2 hours, respectively; and apparent (steady-state) volume of distribution is 7. 8 L/kg, respectively. Venlafaxine and ODV are minimally bound at therapeutic concentrations to plasma proteins (27% and 30%, respectively). max max Table 16: Comparison of C max max Venlafaxine ODV C max (ng/mL) T max (h) C max (ng/mL) T max (h) Venlafaxine Hydrochloride Extended-Release Capsules (150 mg once daily) 150 5. 5 260 9 Venlafaxine Hydrochloride (75 mg twice daily) 225 2 290 3 Food did not affect the bioavailability of venlafaxine or its active metabolite, ODV. Time of administration (AM versus PM) did not affect the pharmacokinetics of venlafaxine and ODV from the 75 mg venlafaxine hydrochloride extended-release capsules. In vitro [see Use in Specific Populations (8.

Venlafaxine hydrochloride extended-release capsules are a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of: Major Depressive Disorder ( MDD Social Anxiety Disorder ( SAD Generalized Anxiety Disorder ( GAD Panic Disorder ( PD Venlafaxine hydrochloride extended-release capsules are indicated for the treatment of major depressive disorder (MDD). Efficacy was established in three short-term (4, 8, and 12 weeks) and two long-term, maintenance trials. Venlafaxine hydrochloride extended-release capsules are indicated for the treatment of Generalized Anxiety Disorder (GAD). Efficacy was established in two 8-week and two 26-week placebo-controlled trials. Venlafaxine hydrochloride extended-release capsules are indicated for the treatment of Social Anxiety Disorder (SAD), also known as social phobia. Efficacy was established in four 12-week and one 26-week, placebo-controlled trials. Venlafaxine hydrochloride extended-release capsules are indicated for the treatment of Panic Disorder (PD), with or without agoraphobia. Efficacy was established in two 12-week placebo-controlled trials.

Venlafaxine hydrochloride extended-release capsules should be administered in 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) Indication Starting Dose Target Dose Maximum Dose MDD (2. 5 to 75 mg/day 75 mg/day 225 mg/day GAD (2. 5 to 75 mg/day 75 mg/day 225 mg/day SAD (2. 3) 75 mg/day 75 mg/day 75 mg/day PD (2. 5 mg/day 75 mg/day 225 mg/day Take once daily with food (2). Capsules should be taken whole; do not divide, crush, chew, or dissolve ( 2 When discontinuing treatment, reduce the dose gradually ( 2. 7 Renal impairment: reduce the total daily dose by 25% to 50% in patients with renal impairment. Reduce the total daily dose by 50% or more in patients undergoing dialysis or with severe renal impairment ( 2. 6 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 dose by more than 50% ( 2. 6 For most patients, the recommended starting dose for venlafaxine hydrochloride extended-release capsules are 75 mg per day, administered in 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, and should be made at intervals of not less than 4 days, since steady-state plasma levels of venlafaxine and its major metabolites are achieved in most patients by day 4 [see Clinical Pharmacology (12. 3) For most patients, the recommended starting dose for venlafaxine hydrochloride extended-release capsules is 75 mg per day, administered in a single dose. Dose increases should be in increments of up to 75 mg per day, as needed, and should be made at intervals of not less than 4 days, since steady-state plasma levels of venlafaxine and its major metabolites are achieved in most patients by day 4 [ see Clinical Pharmacology (12. The recommended dose is 75 mg per day, administered in a single dose. There was no evidence that higher doses confer any additional benefit. The recommended starting dose is 37. 5 mg per day of venlafaxine hydrochloride extended-release capsules 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, and should be made at intervals of not less than 7 days. Depressed patients who are currently being treated at a therapeutic dose with venlafaxine hydrochloride (immediate release) may be switched to venlafaxine hydrochloride extended-release capsules at the nearest equivalent dose (mg per day), e. 5 mg venlafaxine twice a day to 75 mg venlafaxine hydrochloride extended-release capsules once daily. However, individual dosage adjustments may be necessary. Patients with Hepatic Impairment The total daily dose should be reduced by 50% in patients with mild (Child-Pugh=5 to 6) to moderate (Child-Pugh=7 to 9) hepatic impairment. In patients with severe hepatic impairment (Child-Pugh=10 to 15) or hepatic cirrhosis, it may be necessary to reduce the dose by 50% or more [see Use in Specific Populations (8. 7) Patients with Renal Impairment The total daily dose should be reduced by 25% to 50% in patients with mild (CLcr= 60 to 89 mL/min) or moderate (CLcr= 30 to 59 mL/min) renal impairment. In patients undergoing hemodialysis or with severe renal impairment (CLcr < 30 mL/min), the total daily dose should be reduced by 50% or more. Because there was much individual variability in clearance between patients with renal impairment, individualization of dosage may be desirable in some patients [see Use in Specific Populations (8. 7) There is no body of evidence available from controlled studies to indicate how long patients with MDD, GAD, SAD, or PD should be treated with venlafaxine hydrochloride extended-release capsules. It is generally agreed that acute episodes of MDD require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Venlafaxine hydrochloride extended-release capsules/venlafaxine hydrochloride have demonstrated continuation of response in clinical studies up to 52 weeks, at the same dose at which patients responded during the initial treatment [see Clinical Studies (14. 1) In patients with GAD and SAD, venlafaxine hydrochloride extended-release capsules have been shown to be effective in 6-month clinical studies. The need for continuing medication in patients with GAD and SAD who improve with venlafaxine hydrochloride extended-release capsules treatment should be periodically reassessed. In a clinical study for PD, patients continuing venlafaxine hydrochloride extended-release capsules at the same dose at which they responded during the initial 12 weeks of treatment experienced a statistically significantly longer time to relapse than patients randomized to placebo [see Clinical Studies (14. 4) A gradual reduction in the dose, rather than abrupt cessation, is recommended whenever possible. In clinical studies with venlafaxine hydrochloride extended-release capsules, tapering was achieved by reducing the daily dose by 75 mg at one-week intervals. Individualization of tapering may be necessary [see Warnings and Precautions (5. 7) At least 14 days should elapse between discontinuation of an MAOI (intended to treat psychiatric disorders) and initiation of therapy with venlafaxine hydrochloride extended-release capsules. In addition, at least 7 days should be allowed after stopping venlafaxine hydrochloride extended-release capsules before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4. 2) Warnings and Precautions (5. 2) Drug Interactions (7. 2) Use of Venlafaxine Hydrochloride Extended-Release Capsules with other MAOIs such as Linezolid or Intravenous Methylene Blue Do not start venlafaxine hydrochloride extended-release capsules in a patient who is being treated with linezolid or intravenous methylene blue, because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization should be considered [see Contraindications (4. 2) In some cases, a patient already receiving venlafaxine hydrochloride extended-release capsules therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, venlafaxine hydrochloride extended-release capsules should be stopped promptly, and linezolid or intravenous methylene blue can be administered. Monitor the patient for symptoms of serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with venlafaxine hydrochloride extended-release capsules can be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5. 2) The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg concomitantly with venlafaxine hydrochloride extended-release capsules are unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.

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) Most common adverse reactions (incidence >= 5% and at least twice the rate of placebo): nausea, somnolence, dry mouth, sweating, abnormal ejaculation, anorexia, constipation, erectile dysfunction, and libido decreased ( 6. 1 To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www. gov/medwatch. 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 venlafaxine hydrochloride extended-release capsules treated patients in MDD, GAD, SAD, and PD (incidence >= 5% and at least twice the rate of placebo) were: nausea (30%), 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. 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 venlafaxine hydrochloride extended-release capsules (37. 5 to 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 venlafaxine hydrochloride extended-release capsules treated patients in the short-term studies (up to 12 weeks) across indications are shown in Table 7. Table 7: Incidence (%) of Patients Reporting Adverse Reactions Leading to Discontinuation in Placebo-controlled Clinical Studies (up to 12 Weeks Duration) Body System Adverse Reaction Venlafaxine Hydrochloride Extended-Release Capsules n = 3,558 Placebo n = 2,197 Body as a whole Asthenia 1. 5 Headache 1. 8 Digestive system Nausea 4. 4 Nervous system Dizziness 2. 8 Insomnia 2. 6 Somnolence 1. 3 Skin and appendages 1. 6 Sweating 1 0. 2 Common Adverse Reactions in Placebo-controlled Studies The number of patients receiving multiple doses of venlafaxine hydrochloride extended-release capsules 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 (venlafaxine hydrochloride only) and outpatient studies, fixed-dose, and titration studies. Table 8: Patients Receiving Venlafaxine Hydrochloride Extended-Release Capsules in Premarketing Clinical Studies a Indication Venlafaxine Hydrochloride Extended-Release Capsules MDD 705 a GAD 1,381 SAD 819 PD 1,314 The incidences of common adverse reactions (those that occurred in >= 2% of venlafaxine hydrochloride extended-release capsules treated patients [357 MDD patients, 1,381 GAD patients, 819 SAD patients, and 1,001 PD patients] and more frequently than placebo) in venlafaxine hydrochloride extended-release capsules 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 a b Body System Adverse Reaction Venlafaxine Hydrochloride Extended-Release Capsules n = 3,558 Placebo n = 2,197 Body as a whole Asthenia 12. 8 Cardiovascular system Hypertension 3. 6 Palpitation 2. 2 2 Vasodilatation 3. 9 Digestive system Anorexia 9. 6 Constipation 9. 4 Diarrhea 7. 2 Dry mouth 14. 3 Nausea 30 11. 8 Vomiting 4. 7 Nervous system Abnormal dreams 2. 4 Dizziness 15. 5 Insomnia 17. 5 Libido decreased 5. 6 Nervousness 7. 1 5 Paresthesia 2. 4 Somnolence 15. 6 Respiratory system Yawn 3. 2 Skin and appendages Sweating (including night sweats) 11. 9 Special senses Abnormal vision 4. 6 Urogenital system Abnormal ejaculation/orgasm (men) a 9. 5 Anorgasmia (men) a 3. 1 Anorgasmia (women) b 2 0. 2 Impotence (men) a 5. 3 1 Other Adverse Reactions Observed in Clinical Studies Body as a whole Cardiovascular system Digestive system [see Warnings and Precautions (5. 4) Hemic/Lymphatic system [see Warnings and Precautions (5. 4) Metabolic/Nutritional [see Warnings and Precautions (5. 10) [see Warnings and Precautions (5. 10) Nervous system [see Warnings and Precautions (5. 8) [see Warnings and Precautions (5. 6) Skin and appendages Special senses Urogenital system 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 venlafaxine hydrochloride extended-release capsules. Across all clinical studies in MDD, GAD, SAD and PD, 1. 4% of patients in the venlafaxine hydrochloride extended-release capsules 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 venlafaxine hydrochloride extended-release capsules 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. Table 10: Final On-therapy Mean Changes From Baseline in Supine Systolic (SSBP) and Diastolic (SDBP) Blood Pressure (mm Hg) in Placebo-controlled Studies Indication (Duration) Venlafaxine Hydrochloride Extended-Release Capsules Placebo <= 75 mg per day 75 mg per day SSBP SDBP SSBP SDBP SSBP SDBP MDD (8 to 12 weeks) -0. 1 GAD (8 weeks) -0. 92 (6 months) 1. 74 (12 weeks) -0. 22 (6 months) -0. 65 PD (10 to 12 weeks) -1. 99 Venlafaxine hydrochloride extended-release capsules treatment were 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 venlafaxine hydrochloride extended-release capsules 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 Venlafaxine Hydrochloride Extended-Release Capsules Premarketing Studies Indication Dose Range (mg per day) Incidence (%) MDD 75 to 375 19/705 (3) GAD 37. 5 to 225 5/1011 (0. 5) SAD 75 to 225 5/771 (0. 6) PD 75 to 225 9/973 (0. 9) Venlafaxine hydrochloride extended-release capsules were associated with mean increases in pulse rate compared with placebo in premarketing placebo-controlled studies (see Table 12) [see Warnings and Precautions (5. 4) Table 12: Approximate Mean Final On-therapy Increase in Pulse Rate (beats/min) in Venlafaxine Hydrochloride Extended-Release Capsules Premarketing Placebo-controlled Studies (up to 12 Weeks Duration) Indication (Duration) Venlafaxine Hydrochloride Extended-Release Capsules Placebo MDD (12 weeks) 2 1 GAD (8 weeks) 2 <1 SAD (12 weeks) 3 1 PD (12 weeks) 1 <1 Serum Cholesterol Venlafaxine hydrochloride extended-release capsule 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 Venlafaxine Hydrochloride Extended-Release Capsules Premarketing Studies Indication (Duration) Venlafaxine Hydrochloride Extended-Release Capsules Placebo MDD +1. 4 GAD SAD +7. 7 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. Venlafaxine hydrochloride extended-release capsules 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 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. Venlafaxine hydrochloride extended-release capsules 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. 2 mg/dL, respectively, for placebo. Venlafaxine hydrochloride extended-release capsules 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 venlafaxine hydrochloride (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% of placebo-treated patients. Serum Triglycerides Venlafaxine hydrochloride extended-release capsule 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). Table 14: Mean Final On-therapy Increases in Triglyceride Concentrations (mg/dL) in Venlafaxine Hydrochloride Extended-Release Capsules Premarketing Studies Indication (Duration) Venlafaxine Hydrochloride Extended-Release Capsules Placebo SAD 8. 3 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. 11 Use in Specific Populations (8. 4) In pediatric clinical studies, the adverse reaction, suicidal ideation, was observed. The following adverse reactions have been identified during postapproval use of venlafaxine hydrochloride extended-release capsules. 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 Cardiovascular system Digestive system Hemic/Lymphatic system [see Warnings and Precautions (5. 4 ) Metabolic/Nutritional [see Warnings and Precautions (5. 9) [see Warnings and Precautions (5. 9) Musculoskeletal Nervous system [see Warnings and Precautions (5. 2) [see Warnings and Precautions (5. 2) Respiratory system [see Warnings and Precautions (5. 12) Skin and appendages Special senses [see Warnings and Precautions (5.

Hypersensitivity to venlafaxine hydrochloride, desvenlafaxine succinate, or any excipients in the venlafaxine hydrochloride extended-release capsules formulation ( 4. 1 Do not use with an MAOI or within 14 days of stopping an MAOI. Allow 7 days after stopping venlafaxine hydrochloride extended-release capsules before starting an MAOI, because of the risk of serotonin syndrome ( 4. 3 Hypersensitivity to venlafaxine hydrochloride, desvenlafaxine succinate or to any excipients in the formulation The use of MAOIs (intended to treat psychiatric disorders) concomitantly with venlafaxine hydrochloride extended-release capsules or within 7 days of discontinuing treatment with venlafaxine hydrochloride extended-release capsules are contraindicated because of an increased risk of serotonin syndrome. The use of venlafaxine hydrochloride extended-release capsules within 14 days of discontinuing treatment with an MAOI (intended to treat psychiatric disorders) is also contraindicated [see Dosage and Administration (2. 9) Warnings and Precautions (5. 2) Drug Interactions (7. 2) Starting venlafaxine hydrochloride extended-release capsules in a patient who is being treated with an MAOI such as linezolid or intravenous methylene blue is also contraindicated, because of an increased risk of serotonin syndrome [see Dosage and Administration (2.

Pregnancy: Based on animal data, may cause fetal harm ( 8. 1 Nursing Mothers: Discontinue drug or nursing, taking into consideration importance of drug to mother ( 8. 3 Teratogenic Effects en dash Pregnancy Category C Venlafaxine did not cause malformations in offspring of rats or rabbits given doses up to 2. 5 times (rat) or 4 times (rabbit) the maximum recommended human daily dose on a mg/m 2 2 2 [see Warnings and Precautions (5. 2) Drug Interactions (7. 3) The effect of venlafaxine on labor and delivery in humans is unknown. Venlafaxine and ODV have been reported to be excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from venlafaxine hydrochloride extended-release capsules, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. 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 venlafaxine hydrochloride extended-release capsules, and the data were not sufficient to support a claim for use in pediatric patients. [see Boxed Warning Warnings and Precautions (5. 11 Adverse Reactions (6. 4 ) [see Warnings and Precautions (5. [see Warnings and Precautions (5. 11) [see Warnings and Precautions (5. 3) The percentage of patients in clinical studies for venlafaxine hydrochloride extended-release capsules for MDD, GAD, SAD, and PD who were 65 years of age or older are shown in Table 15. Table 15: Percentage (and Number of Patients Studied) of Patients 65 Years of Age and Older by Indication a a Indication Venlafaxine Hydrochloride Extended-Release Capsules MDD 4 (14/357) GAD 6 (77/1,381) SAD 1 (10/819) PD 2 (16/1,001) No overall differences in effectiveness or safety were observed between geriatric patients and younger patients, and other reported clinical experience generally has not identified differences in response between the elderly and younger patients. However, greater sensitivity of some older individuals cannot be ruled out. SSRIs and SNRIs, including venlafaxine hydrochloride extended-release capsules, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [see Warnings and Precautions (5. 9) The pharmacokinetics of venlafaxine and ODV are not substantially altered in the elderly [see Clinical Pharmacology (12. 3) [see Dosage and Administration (2. 6) A population pharmacokinetic analysis of 404 venlafaxine hydrochloride-treated patients from two studies involving both twice daily and three times daily regimens showed that dose-normalized trough plasma levels of either venlafaxine or ODV were unaltered by age or gender differences. Dosage adjustment based on the age or gender of a patient is generally not necessary [see Dosage and Administration (2. 6) Figure 3: Pharmacokinetics of venlafaxine and its metabolite O-desmethylvenlafaxine (ODV) in special populations. Abbreviations: ODV, O-desmethylvenlafaxine; AUC, area under the curve; C max Figure 3: Pharmacokinetics of venlafaxine and its metabolite O-desmethylvenlafaxine (ODV) in special populations.

Serotonergic Drugs (e. , MAOIs, triptans, SSRIs, other SNRIs, linezolid, lithium, tramadol, or St. John’s wort): 4. 3 The risk of using venlafaxine in combination with other CNS-active drugs has not been systematically evaluated. Consequently, caution is advised when venlafaxine hydrochloride extended-release capsules are taken in combination with other CNS-active drugs. 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 venlafaxine hydrochloride extended-release capsules (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) Warnings and Precautions (5. 2) Based on the mechanism of action of venlafaxine hydrochloride extended-release capsules and the potential for serotonin syndrome, caution is advised when venlafaxine hydrochloride extended-release capsules are 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 venlafaxine hydrochloride extended-release capsules and these drugs is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. The concomitant use of venlafaxine hydrochloride extended-release capsules with tryptophan supplements are not recommended [see Dosage and Administration (2. 2) 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) ] The safety and efficacy of venlafaxine therapy in combination with weight loss agents, including phentermine, have not been established. Coadministration of venlafaxine hydrochloride extended-release capsules and weight loss agents are not recommended. Venlafaxine hydrochloride extended-release capsules are not indicated for weight loss alone or in combination with other products. Figure 1: Effect of interacting drugs on the pharmacokinetics of venlafaxine and active metabolite O-desmethylvenlafaxine (ODV). 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) Figure 2: Effect of venlafaxine on the pharmacokinetics interacting drugs and their active metabolites. Abbreviations: AUC, area under the curve; Cmax, peak plasma concentrations; OH, hydroxyl 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. 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.

OVERDOSAGE
During the premarketing evaluations of venlafaxine hydrochloride extended-release capsules (for MDD, GAD, SAD, and PD) and venlafaxine hydrochloride (for MDD), there were twenty reports of acute overdosage with venlafaxine hydrochloride (6 and 14 reports in venlafaxine hydrochloride extended-release capsules and venlafaxine hydrochloride patients, respectively), either alone or in combination with other drugs and/or alcohol. Consult a Certified Poison Control Center for up-to-date guidance and advice (1-800-222-1222 or www. In case of an overdose, provide supportive care, including close medical supervision and monitoring. Treatment should consist of those general measures employed in the management of overdosage with any drug. Consider the possibility of multiple drug overdose. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Provide supportive and symptomatic measures.
NONCLINICAL TOXICOLOGY
Carcinogenesis 2 Salmonella in vitro in vivo in vitro in vivo 2
CLINICAL STUDIES
The efficacy of venlafaxine hydrochloride extended-release capsules as a treatment for Major Depressive Disorder (MDD) was established in two placebo-controlled, short-term (8 weeks 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 criteria for MDD. In moderately depressed outpatients, the initial dose of venlafaxine was 75 mg per day. In both studies, venlafaxine hydrochloride extended-release capsules 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, venlafaxine hydrochloride extended-release capsules also demonstrated superiority over placebo on the key secondary efficacy endpoint, the Clinical Global Impressions (CGI) Severity of Illness scale. Examination of gender subsets of the 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 venlafaxine hydrochloride in a range of 150 to 375 mg per day (divided in a three-times-a-day schedule) demonstrated superiority of venlafaxine hydrochloride over placebo based on the HAM-D-21 total score. The mean dose 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 open-label study on venlafaxine hydrochloride extended-release capsules (75, 150, or 225 mg, once daily every morning) were randomized to continuation of their same venlafaxine hydrochloride extended-release capsules dose or to placebo, for up to 26 weeks of observation for relapse. 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) 2 consecutive CGI Severity of Illness item scores of >=4, or (3) a final CGI Severity of Illness item score of >=4 for any patient who withdrew from the study for any reason. Patients receiving continued venlafaxine hydrochloride extended-release capsules treatment experienced statistically significantly lower relapse rates over the 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 venlafaxine hydrochloride [100 to 200 mg per day, on a twice daily schedule] were randomized to continuation of their same venlafaxine hydrochloride dose or to placebo. The follow-up period to observe patients for relapse, defined as a CGI Severity of Illness item score >= 4, was for up to 52 weeks. Patients receiving continued venlafaxine hydrochloride treatment experienced statistically significantly lower relapse rates over the subsequent 52 weeks compared with those receiving placebo (study 5). Table 17: Major Depressive Disorder Studies: SD: standard deviation; LS Mean: least-squares mean; CI: confidence interval. a Study number Treatment Group Primary Efficacy Measure: HAM-D Score Mean Baseline Score (SD) LS Mean Change from Baseline Placebo Subtracted Difference a Study 1 Venlafaxine Hydrochloride Extended-Release Capsules (75 to 225 mg/day)* 24. 25) Placebo 23. 24 - Study 2 Venlafaxine Hydrochloride Extended-Release Capsules (75 to 225 mg/day)* 24. 34) Placebo 24. 71 Study 3 Venlafaxine Hydrochloride (immediate release)(150 to 375 mg/day)* 28. 4,-6) Placebo 28. 7 - The efficacy of venlafaxine hydrochloride extended-release capsules as a treatment for Generalized Anxiety Disorder (GAD) was established in two 8-week, placebo-controlled, fixed-dose studies (75 to 225 mg per day), one 6-month, 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, venlafaxine hydrochloride extended-release capsules 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 in the 75 to 225 mg per day dose range studied. Two 6-month studies, one evaluating venlafaxine hydrochloride extended-release capsules doses of 37. 5, 75, and 150 mg per day (study 3) and the other evaluating venlafaxine hydrochloride extended-release capsules doses of 75 to 225 mg per day (study 4), showed that daily doses of 75 mg or higher were more effective than placebo on the HAM-A total, both the HAM-A anxiety and tension items, and the CGI scale during 6 months of treatment. While there was also evidence for superiority over placebo for the 37. 5 mg per day dose, this dose was not as consistently effective as the higher doses. Table 18: Generalized Anxiety Disorder Studies: SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: confidence interval. a Study Number Treatment Group Primary Efficacy Measure: HAM-A Score Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo Subtracted Difference a (95% CI) Study 1 Venlafaxine Hydrochloride Extended-Release Capsules 75 mg 24. 8) Venlafaxine Hydrochloride Extended-Release Capsules 150 mg Venlafaxine Hydrochloride Extended-Release Capsules 225 mg Placebo 24. 85) Study 2 Venlafaxine Hydrochloride Extended-Release Capsules 75 mg -10. 5) Venlafaxine Hydrochloride Extended-Release Capsules 150 mg 23 -9. 3) Placebo 23. 73) Study 3 Venlafaxine Hydrochloride Extended-Release Capsules 37. 6) Venlafaxine Hydrochloride Extended-Release Capsules 75 mg 26. 3) Venlafaxine Hydrochloride Extended-Release Capsules 150 mg 26. 1) Placebo 26. 5) -11 - Study 4 Venlafaxine Hydrochloride Extended-Release Capsules 75 to 225 mg 25 -13. 9) Placebo 24. 7) The efficacy of venlafaxine hydrochloride extended-release capsules as a treatment for Social Anxiety Disorder (SAD) was established in four double-blind, parallel-group, 12-week, multicenter, placebo-controlled, flexible-dose studies (studies 1 to 4) and one double-blind, parallel-group, 6-month, placebo-controlled, fixed/flexible-dose 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, venlafaxine hydrochloride extended-release capsules were 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 group compared to the 75 mg per day group in the 6-month study. Examination of subsets of the population studied did not reveal any differential responsiveness on the basis of gender. There was insufficient information to determine the effect of age or race on outcome in these studies. Table 19: Social Anxiety Disorder Studies SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: confidence interval. a Study Number Treatment Group Primary Efficacy Measure: LSAS Score Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo Subtracted Difference a Study 1 Venlafaxine Hydrochloride Extended-Release Capsules (75 to 225 mg) 91. 1) Placebo 86. 22) - Study 2 Venlafaxine Hydrochloride Extended-Release Capsules (75 to 225 MG) 90. 6) Placebo 87. 66) - Study 3 Venlafaxine Hydrochloride Extended-Release Capsules (75 to 225 MG) 83. 2) Placebo 83. 5, -19) Study 4 Venlafaxine Hydrochloride Extended-Release Capsules (75 to 225 mg) 86. 4) Placebo 86. 47) Study 5 Venlafaxine Hydrochloride Extended-Release Capsules 75 mg 91. 4) Venlafaxine Hydrochloride Extended-Release Capsules (150 to 225 mg) 86. 9) Placebo 89. 08) The efficacy of venlafaxine hydrochloride extended-release capsules 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 free of full-symptom panic attacks on the Panic and Anticipatory Anxiety Scale (PAAS); (2) mean change from baseline to endpoint on the Panic Disorder Severity Scale (PDSS) total score; and (3) percentage of patients rated as responders (much improved or very much improved) on the Clinical Global Impressions (CGI) Improvement scale. In these two studies, venlafaxine hydrochloride extended-release capsules were statistically significantly more effective than placebo (for each fixed dose) on all three endpoints, but a dose-response relationship was not clearly established. 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 venlafaxine hydrochloride extended-release capsules (75 to 225 mg per day) were randomly assigned to continue the same venlafaxine hydrochloride extended-release capsules dose (75, 150, or 225 mg) or switch to placebo for observation for relapse under double-blind conditions. Response during the open phase was defined as <= 1 full-symptom panic attack per week during the last 2 weeks of the open phase and a CGI Improvement score of 1 (very much improved) or 2 (much improved). Relapse during the double-blind phase was defined as having 2 or more full-symptom panic attacks per week for 2 consecutive weeks or having discontinued due to loss of effectiveness as determined by the investigators during the study. Randomized patients were in response status for a mean time of 34 days prior to being randomized. In the randomized phase following the 12-week open-label period, patients receiving continued venlafaxine hydrochloride extended-release capsules experienced a statistically significantly longer time to relapse. Table 20: Panic Disorder Studies: a * Study Number Treatment Group Primary Efficacy Measure: Whether Free of Full-symptom Panic Attacks Percent of patients Free of Full symptom panic attack Adjusted Odds Ratio a Adjusted Odds Ratio a Study 1 Venlafaxine Hydrochloride Extended-Release Capsules 75 mg * 54. 1% (85/157) 2. 59) Venlafaxine Hydrochloride Extended-Release Capsules 150 mg * 61. 4% (97/158) 3. 82) Placebo 34. 4% (53/154) -- -- Study 2 Venlafaxine Hydrochloride Extended-Release Capsules 75 mg * 64. 1% (100/156) 2. 78) Venlafaxine Hydrochloride Extended-Release Capsules 225 mg * 70% (112/160) 2. 64) Placebo 46. 5% (73/157) -- -- Two placebo-controlled studies in 766 pediatric patients with MDD and two placebo-controlled studies in 793 pediatric patients with GAD have been conducted with venlafaxine hydrochloride extended-release capsules, and the data were not sufficient to support a claim for use in pediatric patients.
Medication Guide
Venlafaxine Hydrochloride Extended-Release Capsules USP (ven'''' la fax'' een hye'''' droe klor'' ide) Read the Medication Guide that comes with venlafaxine hydrochloride extended-release capsules What is the most important information I should know about venlafaxine hydrochloride extended-release capsules ? Venlafaxine hydrochloride extended-release capsules 1. Suicidal thoughts or actions: Venlafaxine hydrochloride extended-release capsules and other antidepressant medicines may increase suicidal thoughts or actions within the first few months of treatment or when the dose is changed. Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. Watch for these changes and call your healthcare provider right away if you notice: New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe. Pay particular attention to such changes when venlafaxine hydrochloride extended-release capsules Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms. Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you: attempts to commit suicide acting on dangerous impulses acting aggressive or violent thoughts about suicide or dying new or worse depression new or worse anxiety or panic attacks feeling agitated, restless, angry or irritable trouble sleeping an increase in activity or talking more than what is normal for you other unusual changes in behavior or mood Visual problems eye pain changes in vision swelling or redness in or around the eye Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency. Venlafaxine hydrochloride extended-release capsule s may be associated with these serious side effects 2. Serotonin Syndrome This condition can be life-threatening and may include agitation, hallucinations, coma or other changes in mental status coordination problems or muscle twitching (overactive reflexes) racing heartbeat, high or low blood pressure sweating or fever nausea, vomiting, or diarrhea muscle rigidity 3. Changes in blood pressure. Venlafaxine hydrochloride extended-release capsules increase your blood pressure. Control high blood pressure before starting treatment and monitor blood pressure regularly 4. Enlarged pupils (mydriasis). 5. Anxiety and insomnia. 6. Changes in appetite or weight. 7. Manic/hypomanic episodes: greatly increased energy severe trouble sleeping racing thoughts reckless behavior unusually grand ideas excessive happiness or irritability talking more or faster than usual 8. Low salt (sodium) levels in the blood. Elderly people may be at greater risk for this. Symptoms may include: headache weakness or feeling unsteady confusion, problems concentrating or thinking or memory problems 9. Seizures or convulsions. 10. Abnormal bleeding Venlafaxine hydrochloride extended-release capsules registered registered 11. Elevated cholesterol. 12. Lung disease and pneumonia Venlafaxine hydrochloride extended-release capsules worsening shortness of breath cough chest discomfort 13. Severe allergic reactions: trouble breathing swelling of the face, tongue, eyes or mouth rash, itchy welts (hives) or blisters, alone or with fever or joint pain. Do not stop venlafaxine hydrochloride extended-release capsules without first talking to your healthcare provider venlafaxine hydrochloride extended-release capsules anxiety, irritability feeling tired, restless or problems sleeping headache, sweating, dizziness electric shock-like sensations, shaking, confusion, nightmares vomiting, nausea, diarrhea What are venlafaxine hydrochloride extended-release capsules? Venlafaxine hydrochloride extended-release capsules Venlafaxine hydrochloride extended-release capsules Generalized Anxiety Disorder (GAD) Social Anxiety Disorder (SAD) Panic Disorder (PD) Talk to your healthcare provider if you do not think that your condition is getting better with venlafaxine hydrochloride extended-release capsules Who should not take venlafaxine hydrochloride extended-release capsules? Do not take venlafaxine hydrochloride extended-release capsules are allergic to venlafaxine hydrochloride venlafaxine hydrochloride extended-release capsules venlafaxine hydrochloride extended-release capsules have uncontrolled angle-closure glaucoma take a Monoamine Oxidase Inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid. Do not take an MAOI within 7 days of stopping venlafaxine hydrochloride extended-release capsules Do not start venlafaxine hydrochloride extended-release capsules People who take venlafaxine hydrochloride extended-release capsules close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms: high fever uncontrolled muscle spasms stiff muscles rapid changes in heart rate or blood pressure confusion loss of consciousness (pass out) What should I tell my healthcare provider before taking venlafaxine hydrochloride extended-release capsules? Ask if you are not sure. Before starting venlafaxine hydrochloride extended-release capsules Are taking certain drugs such as: Amphetamines Medicines used to treat migraine headaches such as: triptans Medicines used to treat mood, anxiety, psychotic or thought disorders, such as: tricyclic antidepressants lithium SSRIs SNRIs antipsychotic drugs Medicines used to treat pain such as: tramadol Medicines used to thin your blood such as: warfarin Medicines used to treat heartburn such as: Cimetidine Over-the-counter medicines or supplements such as: Aspirin or other NSAIDs Tryptophan St. John’s Wort 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 venlafaxine hydrochloride extended-release capsules are breast-feeding or plan to breast-feed. Some venlafaxine hydrochloride venlafaxine hydrochloride extended-release capsules Tell your healthcare provider about all the medicines that you take, Venlafaxine hydrochloride extended-release capsules Your healthcare provider or pharmacist can tell you if it is safe to take venlafaxine hydrochloride extended-release capsules venlafaxine hydrochloride extended-release capsules If you take venlafaxine hydrochloride extended-release capsules How should I take venlafaxine hydrochloride extended-release capsules? Take venlafaxine hydrochloride extended-release capsules venlafaxine hydrochloride extended-release capsules Venlafaxine hydrochloride extended-release capsules If you miss a dose of venlafaxine hydrochloride extended-release capsules venlafaxine hydrochloride extended-release capsules If you take too much venlafaxine hydrochloride When switching from another antidepressant to venlafaxine hydrochloride extended-release capsules What should I avoid while taking venlafaxine hydrochloride extended-release capsules? Venlafaxine hydrochloride extended-release capsules venlafaxine hydrochloride extended-release capsules venlafaxine hydrochloride extended-release capsules What are the possible side effects of venlafaxine hydrochloride extended-release capsules ? Venlafaxine hydrochloride extended-release capsules See “What is the most important information I should know about venlafaxine hydrochloride extended-release capsules Increased cholesterol- have your cholesterol checked regularly Newborns whose mothers take venlafaxine hydrochloride extended-release capsules problems feeding and breathing seizures shaking, jitteriness or constant crying Angle-closure glaucoma Common possible side effects in people who take venlafaxine hydrochloride extended-release capsules : unusual dreams sexual problems loss of appetite, constipation, diarrhea, nausea or vomiting, or dry mouth feeling tired, fatigued or overly sleepy change in sleep habits, problems sleeping yawning tremor or shaking dizziness, blurred vision sweating feeling anxious, nervous or jittery headache increase in heart rate Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of venlafaxine hydrochloride extended-release capsules CALL YOUR DOCTOR FOR MEDICAL ADVICE ABOUT SIDE EFFECTS. YOU MAY REPORT SIDE EFFECTS TO THE FDA AT 1-800-FDA-1088. How should I store venlafaxine hydrochloride extended-release capsules? Store venlafaxine hydrochloride extended-release capsules Keep venlafaxine hydrochloride extended-release capsules Keep venlafaxine hydrochloride extended-release capsules and all medicines out of the reach of children. General information about venlafaxine hydrochloride extended-release capsules Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use venlafaxine hydrochloride extended-release capsules venlafaxine hydrochloride extended-release capsules This Medication Guide summarizes the most important information about venlafaxine hydrochloride extended-release capsules . venlafaxine hydrochloride extended-release capsules For more information about venlafaxine hydrochloride extended-release capsules 1-866-850-2876. What are the ingredients in venlafaxine hydrochloride extended-release capsules? Active ingredient: Venlafaxine hydrochloride Inactive ingredients: Extended-Release Capsules This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants. Coumadin registered Jantoven registered Dispense with Medication Guide available at: www.aurobindousa.com/product-medication-guides Aurobindo Pharma USA, Inc. Aurobindo Pharma Limited

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