Venlafaxine Hydrochloride (Page 2 of 15)

2.8 Discontinuing Venlafaxine Hydrochloride Extended-Release Capsules

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)] .

2.9 Switching Patients to or from a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

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), and 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 (5.2)].

3 DOSAGE FORMS AND STRENGTHS

Venlafaxine hydrochloride extended-release capsules USP are available in the following strengths:

  • 37.5 mg capsules are white to off white spherical to oval pellets filled in empty hard gelatin capsule shell (size ‘3’) of opaque grey color cap and opaque peach color body imprinted with “E” on cap and “73” on the body with edible black ink.
  • 75 mg capsules are white to off white spherical to oval pellets filled in empty hard gelatin capsule shell (size ‘1’) of opaque peach color cap and opaque peach color body imprinted with “E” on cap and “74” on the body with edible black ink.
  • 150 m g capsule s are white to off white spherical to oval pellets filled in empty hard gelatin capsule shell (size ‘0’) of opaque dark orange color cap and opaque dark orange color body imprinted with “E” on cap and “89” on the body with edible black ink.

4 CONTRAINDICATIONS

4.1 Hypersensitivity

Hypersensitivity to venlafaxine hydrochloride, desvenlafaxine succinate or to any excipients in the formulation

4.2 Concomitant 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)] .

5 WARNINGS AND PRECAUTIONS

5.1 Suicidal 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
Age Range Increases Compared to Placebo
< 18 14 additional cases
18 to 24 5 additional cases
Decreases 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, 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 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.

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