Venlafaxine hydrochloride extended-release capsules are serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of:
Major Depressive Disorder (MDD)
Generalized Anxiety Disorder (GAD)
Social Anxiety Disorder (SAD)
Panic Disorder (PD)
1.1Major Depressive Disorder
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.
1.2Generalized Anxiety Disorder
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.
1.3Social Anxiety Disorder
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.
1.4Panic Disorder
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.
Contraindications
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 ( 4.2 , 5.2 , 7.3 ).
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4.1 H ypersensitivity Hypersensitivity to venlafaxine hydrochloride, desvenlafaxine succinate or to any excipients in the formulation
4.2Concomitant Use with Monoamine Oxidase Inhibitors (MAOIs)
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 ), and 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 ( 2.9 ), Warnings and Precautions ( 5.2 ), and Drug Interactions ( 7.3 )].
Warnings and precautions
Clinical Worsening/Suicide Risk: Monitor for clinical worsening and suicide risk ( 5.1 ). Serotonin Syndrome: Risk increases with concomitant use of other serotonergic drugs. Discontinue venlafaxine hydrochloride extended-release capsules and initiate supportive treatment if serotonin syndrome occurs ( 4.2 , 5.2 , 7.3 ). Elevations in Blood Pressure: Control hypertension before initiating treatment. Monitor blood pressure regularly during treatment ( 5.3).
Abnormal Bleeding: Venlafaxine hydrochloride extended-release capsules may increase risk of bleeding events. Caution patients about the risk of bleeding associated with the concomitant use of venlafaxine hydrochloride extended-release and NSAIDs, aspirin, or other drugs that affect coagulation ( 5.4 ). Angle Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants.
( 5.5 ). Activation of Mania/Hypomania: Use cautiously in patients with bipolar disorder. Caution patients about the risk of activation of mania/hypomania ( 5.6 ).
5.1 Su i c i d a l Thoughts and Behaviors in Children, Adolescents, and Young Adults Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs.
Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short- term placebo-controlled studies of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with MDD and other psychiatric disorders.
Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled studies in children and adolescents with MDD, Obsessive Compulsive Disorder (OCD), or other psychiatric disorders included a total of 24 short-term studies of 9 antidepressant drugs in over 4,400 patients.
The pooled analyses of placebo-controlled studies in adults with MDD or other psychiatric disorders included a total of 295 short-term studies (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD.
The risk differences (drug versus placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1,000 patients treated) are provided in Table 1. Table 1: Difference in the Number of Cases of Suicidality per 1,000 Patients Treated versus Placebo A ge Range Increases Compared to Placebo < 18 14 additional cases 18 to 24 5 additional cases D ecreases Compared to Placebo 25 to 64 1 fewer case ≥ 65 6 fewer cases No suicides occurred in any of the pediatric studies.
There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance studies in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especiallyduring the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for MDD, as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms [see Warnings and Precautions ( 5.7) and Dosage and Administration ( 2.8 ) ].
Families and caregivers of patients being treated with antidepressants for MDD or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers .
Prescriptions for venlafaxine hydrochloride extended-release capsules should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose. Screening Patients for Bipolar Disorder A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled studies) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder.
Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that venlafaxine hydrochloride extended-release capsules are not approved for use in treating bipolar depression.
5.2Serotonin Syndrome
The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including venlafaxine hydrochloride extended-release capsules alone, but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s wort) and with drugs that impair metabolism of serotonin in particular, MAOIs, both those intended to treat psychiatric disorders and others, such as linezolid or intravenous methylene blue).
Serotonin syndrome symptoms may include mental status cha
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Interactions
· Serotonergic Drugs (e.g., MAOIs, triptans, SSRIs, other SNRIs, linezolid, lithium, tramadol, or St. John’s wort): Potential for serotonin syndrome. Careful patient observation is advised ( 4.2 , 5.2 , 7.3 ).
7.1Central 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 venlafaxine hydrochloride extended-release capsules are taken in combination with other CNS-active drugs.
7.2Monoamine 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 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) and Warnings and Precautions ( 5.2) ].
7.3 Serotonergic Drugs 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 (2.9 ), Contraindications ( 4.2 ),and Warnings and Precautions ( 5.2 )].
7.4 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 venlafaxine hydrochloride extended-release capsules are initiated or discontinued.
7.5Weight Loss Agents
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 extended-release capsules are not indicated for weight loss alone or in combination with other products.
7.6Effects of Other Drugs
on venlafaxine extended-release F i gure 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 )
7.7 Effects of Venlafaxine extended-release on Other Drugs F i gure 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 * 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.
N o te: *: 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.
7.8Drug-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.
Adverse reactions
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 Dr. Reddy’s Laboratories Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical 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 venlafaxine extended-release capsules 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 venlafaxine hydrochloride extended-release capsules (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 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 1.7
0.5 Headache 1.5
0.8 Digestive system Nausea 4.3
0.4 Nervous system Dizziness 2.2
0.8 Insomnia 2.1
0.6 Somnolence 1.7
0.3Skin
and appendages 1.5
0.6 Sweating 1
0.2Common Adverse Reactions in Placebo-controlled Studies
The number of patients receiving multiple doses of venlafaxine hydrochloride extended-release capsuels 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.
T able 8: Patients Receiving Venlafaxine Hydrochloride Extended-Release Capsules in Premarketing Clinical Studies Indication Venlafaxine Hydrochloride Extended-Release Capsules MDD 705 a GAD 1,381 SAD 819 PD 1,314 a In addition, in the premarketing assessment of venlafaxine hydrochloride, multiple doses were administered to 2,897 patients in studies for MDD. 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 B ody System Adverse Reaction Venlafaxine Hydrochloride Extended-Release Capsules n = 3,558 P l acebo n = 2,197 Body as a whole Asthenia 12.6
7.8 Cardiovascular system Hypertension 3.4
2.6 Palpitation 2.2 2 Vasodilatation 3.7
1.9 Digestive system Anorexia 9.8
2.6 Constipation 9.3
3.4 Diarrhea 7.7
7.2 Dry mouth 14.8
5.3 Nausea 30
11.8 Vomiting 4.3
2.7 Nervous system Abnormal dreams 2.9
1.4 Dizziness 15.8
9.5 Insomnia 17.8
9.5 Libido decreased 5.1
1.6 Nervousness 7.1 5 Paresthesia 2.4
1.4 Somnolence 15.3
7.5 Tremor 4.7
1.6 Respiratory system Yawn 3.7
0.2Skin
and appendages Sweating (including night sweats) 11.4
2.9 Special senses Abnormal vision 4.2
1.6 Urogenital system Abnormal ejaculation/orgasm (men) a 9.9
0.5 Anorgasmia (men) a 3.6
0.1Anorgasmia
(women) b 2
0.2 Impotence (men) a 5.3 1 a Percentages based on the number of men (venlafaxine hydrochloride extended release capsules, n = 1,440; placebo, n = 923) b Percentages based on the number of women (venlafaxine hydrochloride extended release capsules, n = 2,118; placebo, n = 1,274) Other Adverse Reactions Observed in Clinical Studies B ody as a whole – Photosensitivity reaction, chills C ardiovascular system – Postural hypotension, syncope, hypotension, tachycardia D i gestive 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 S kin and appendages – Urticaria, pruritus, rash, alopecia S pecial senses – Mydriasis, abnormality of accommodation, tinnitus, taste perversion U rogenital system – Urinary retention, urination impaired, urinary incontinence, urinary frequency increased, menstrual disorders associated with increased bleeding or increased irregular bleeding (e.g., menorrhagia, metrorrhagia)
6.2Vital 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 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-contro
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Composition
Active ingredients
VENLAFAXINE HYDROCHLORIDE EQ 75MG BASE
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
