Venlafaxine: uses, appearance and warnings

Venlafaxine Hydrochloride Extended-Release Tablets are a selective serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for: Major Depressive Disorder (MDD) ( 1.1 ) Social Anxiety Disorder (SAD) ( 1.2 ) 1.1 Major Depressive Disorder Venlafaxine Hydrochloride Extended-Release Tablets are indicated for the treatment of major depressive disorder (MDD). Efficacy of venlafaxine in MDD was shown in both short-term trials and a longer-term trial in MDD [see Clinical Studies ( 14.1 )] . A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed mood or the loss of interest or pleasure in nearly all activities, representing a change from previous functioning, and includes the presence of at least five of the following nine symptoms during the same two-week period: depressed mood, markedly diminished interest or pleasure in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation. 1.2 Social Anxiety Disorder Venlafaxine Hydrochloride Extended-Release Tablets are indicated for the treatment of Social Anxiety Disorder (SAD), also known as Social Phobia, as defined in DSM-IV. Social Anxiety Disorder (DSM-IV) is characterized by a marked and persistent fear of 1 or more social or performance situations in which the person is exposed to unfamiliar people or to possible scrutiny by others. Exposure to the feared situation almost invariably provokes anxiety, which may approach the intensity of a panic attack. The feared situations are avoided or endured with intense anxiety or distress. The avoidance, anxious anticipation, or distress in the feared situation(s) interferes significantly with the person's normal routine, occupational or academic functioning, or social activities or relationships, or there is a marked distress about having the phobias. Lesser degrees of performance anxiety or shyness generally do not require psychopharmacological treatment. Efficacy of venlafaxine extended release in the treatment of SAD was established in short-term SAD trials [ see Clinical Studies ( 14.2 )] .

Venlafaxine Hydrochloride Extended-Release Tablets are available as: 150 mg tablets (white to off-white mottled round coated tablets imprinted in blue with "150mg" on one side) 225 mg tablets (white to off-white mottled round coated tablets imprinted in blue with "225mg" on one side) 150 mg and 225 mg tablets (3)

Venlafaxine Hydrochloride Extended-Release Tablets 150 mg are white to off-white mottled round coated tablets imprinted in blue with "150mg" on one side. They are supplied as follows: Bottles of 30 Tablets NDC 42799-962-01 Bottles of 90 Tablets NDC 42799-962-02 Venlafaxine Hydrochloride Extended-Release Tablets 225 mg are white to off-white mottled round coated tablets imprinted in blue with "225mg" on one side. They are supplied as follows: Bottles of 30 Tablets NDC 42799-963-01 Bottles of 90 Tablets NDC 42799-963-02 Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature]. Protect from moisture and humidity. Dispense in tight containers [USP].

Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with venlafaxine hydrochloride extended-release tablets or within 7 days of stopping treatment with Venlafaxine Hydrochloride Extended-Release Tablets. Do not use venlafaxine hydrochloride extended-release tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start venlafaxine hydrochloride extended-release tablets in a patient who is being treated with linezolid or intravenous methylene blue ( 4.1 ). 4.1 Monoamine Oxidase Inhibitors (MAOIs) The use of MAOIs intended to treat psychiatric disorders with Venlafaxine Hydrochloride Extended-Release Tablets or within 7 days of stopping treatment with Venlafaxine Hydrochloride Extended-Release Tablets is contraindicated because of an increased risk of serotonin syndrome. The use of Venlafaxine Hydrochloride Extended-Release Tablets within 14 days of stopping, an MAOI intended to treat psychiatric disorders is also contraindicated [ see Dosage and Administration ( 2.6 ), and Warnings and Precautions ( 5.2 )] . Starting Venlafaxine Hydrochloride Extended-Release Tablets in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [ see Dosage and Administration ( 2.7 ) and Warnings and Precautions ( 5.2 )] .

Serotonin Syndrome : Serotonin syndrome has been reported with SSRIs and SNRIs, including venlafaxine hydrochloride extended-release tablets, both when taken alone, but especially when co-administered with other serotonergic agents. If such symptoms occur, discontinue venlafaxine hydrochloride extended-release tablets and serotonergic agents and initiate supportive treatment. If concomitant use of Venlafaxine Hydrochloride Extended-Release Tablets with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases ( 5.2 ). Suicidality: Monitor for clinical worsening and suicide risk. ( 5.1 ) Sustained hypertension may occur. Blood pressure monitoring recommended. ( 5.3 ) Angle Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants. ( 5.4 ) Abrupt discontinuation or dose reduction: Discontinuation symptoms may occur (generally self-limiting; serious symptoms possible). Dose reduction recommended to be gradual. ( 5.5 ) Activation of Mania/Hypomania has occurred. ( 5.10 ) Symptomatic hyponatremia may occur. ( 5.11 ) Seizures have been reported. Use with caution in patients with seizure history. ( 5.12 ) Abnormal bleeding (most commonly ecchymosis) has been reported. ( 5.13 ) Serum cholesterol: Clinically relevant cholesterol increases may occur. Cholesterol measurements should be considered during long-term therapy. ( 5.14 ) Interstitial lung disease and eosinophilic pneumonia have been reported. ( 5.15 ) Sexual Dysfunction: Venlafaxine Hydrochloride Extended-Release Tablets may cause symptoms of sexual dysfunction. ( 5.18 ) 5.1 Clinical Worsening and Suicide Risk 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 trials 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 18-24) with major depressive disorder (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 trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4,400 patients. The pooled analyses of placebo- controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (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 vs 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 Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1,000 Patients Treated Increases Compared to Placebo <18 14 additional cases 18-24 5 additional cases Decreases Compared to Placebo 25-64 1 fewer case ≥65 6 fewer cases No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, 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 trials 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, especially during 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 major depressive disorder 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. …

Major Depressive Disorder - Adverse events in short-term studies that occurred in at least 5% of the patients receiving venlafaxine extended-release capsules and at a rate at least twice that of the placebo group were abnormal ejaculation, gastrointestinal complaints (nausea, dry mouth, and anorexia), CNS complaints (dizziness, somnolence, and abnormal dreams), and sweating. ( 6 ) Social Anxiety Disorder -Adverse events in short-term studies that occurred in at least 5% of the patients receiving venlafaxine extended-release capsules and at a rate at least twice that of the placebo group were asthenia, gastrointestinal complaints (anorexia, dry mouth, nausea), CNS complaints (anxiety, insomnia, libido decreased, nervousness, somnolence, dizziness), abnormalities of sexual function (abnormal ejaculation, orgasmic dysfunction, impotence), yawn, sweating, and abnormal vision. …

MAOIs: concomitant use contraindicated. ( 4 ) Avoid MAOIs 14 days before starting venlafaxine and 7 days after stopping venlafaxine. ( 5.2 ) Cimetidine: Caution in patients with pre-existing hypertension, in elderly patients and patients with hepatic dysfunction. ( 7.2 ) Haloperidol: Increase in haloperidol AUC and C max . ( 7.4 ) Ketoconazole: Increase in venlafaxine and O-desmethylvenlafaxine AUC and C max . Caution when using venlafaxine with substances that inhibit both CYP2D6 and CYP3A4. ( 7.7 ) Metoprolol: Possibly reduced blood pressure lowering effect despite increased metoprolol plasma levels. Caution should be exercised with co-administration of venlafaxine and metoprolol. ( 7.8 ) CNS-active drugs: Caution when using venlafaxine with such drugs. ( 7.10 ) Serotonergic drugs (e.g., triptans, SSRIs, other SNRIs, linezolid, lithium, tramadol, or St. …