Venlafaxine Hydrochloride (Page 4 of 16)

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 trials) 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.

Serotonin 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, and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome.

The concomitant use of venlafaxine hydrochloride extended-release capsules with MAOIs intended to treat psychiatric disorders is contraindicated. Venlafaxine hydrochloride extended-release capsules should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. There may be circumstances when it is necessary to initiate treatment with a MAOI such as linezolid or intravenous methylene blue in a patient taking venlafaxine hydrochloride extended-release capsules. Venlafaxine hydrochloride extended-release capsules should be discontinued before initiating treatment with the MAOI (see CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION).

If concomitant use of venlafaxine hydrochloride extended-release capsules with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John’s Wort is clinically warranted, patients should be made aware of a potential increased risk of serotonin syndrome, particularly during treatment initiation and dose increases.

Treatment with venlafaxine hydrochloride extended-release capsules and any concomitant serotonergic agents should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.

Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant drugs including Venlafaxine hydrochloride extended-release capsules may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

Sustained Hypertension

Venlafaxine hydrochloride extended-release capsule treatment is associated with sustained hypertension (defined as treatment-emergent supine diastolic blood pressure (SDBP) ≥ 90 mm Hg and ≥ 10 mm Hg above baseline for 3 consecutive on-therapy visits) (see Table 2).

An analysis for patients in venlafaxine hydrochloride tablet (immediate release) studies meeting criteria for sustained hypertension revealed a dose-dependent increase in the incidence of sustained hypertension for venlafaxine hydrochloride tablets (immediate release) (see Table 3).

An insufficient number of patients received mean doses of venlafaxine hydrochloride extended-release capsules over 300 mg/day to fully evaluate the incidence of sustained increases in blood pressure at these higher doses.

Table 2: Number (%) of Sustained Elevations in SDBP in Venlafaxine Hydrochloride Extended-Release Capsules Premarketing Studies by Indication

MDD

(75 to 375 mg/day)

Panic Disorder

(75 to 225 mg/day)

19/705 (3)

9/973 (0.9)

MDD = major depressive disorder

Table 3: Incidence (%) of Sustained Elevations in SDBP in Venlafaxine Hydrochloride Tablet Immediate Release Studies

Venlafaxine Hydrochloride Tablets mg/day

Incidence

< 100

3%

> 100 to ≤ 200

5%

> 200 to ≤ 300

7%

> 300

13%

In premarketing major depressive disorder studies, 0.7% (5/705) of the venlafaxine hydrochloride extended-release capsule-treated patients discontinued treatment because of elevated blood pressure. Among these patients, most of the blood pressure increases were in a modest range (12 to 16 mm Hg, SDBP). In premarketing panic disorder studies up to 12 weeks, 0.5% (5/1001) of the venlafaxine hydrochloride extended-release capsule-treated patients discontinued treatment because of elevated blood pressure. In these patients, the blood pressure increases were in a modest range (7 to 19 mm Hg, SDBP).

Sustained increases of SDBP could have adverse consequences. Cases of elevated blood pressure requiring immediate treatment have been reported in postmarketing experience. Preexisting hypertension should be controlled before treatment with venlafaxine. It is recommended that patients receiving venlafaxine hydrochloride extended-release capsules have regular monitoring of blood pressure. For patients who experience a sustained increase in blood pressure while receiving venlafaxine, either dose reduction or discontinuation should be considered.

Elevations in Systolic and Diastolic Blood Pressure

In placebo-controlled premarketing studies, there were changes in mean blood pressure (see Table 4 for mean changes in supine systolic and supine diastolic blood pressure). Across most indications, a dose-related increase in supine systolic and diastolic blood pressure was evident in venlafaxine hydrochloride extended-release capsule-treated patients.

Table 4: Final On-Therapy Mean Changes From Baseline in Supine Systolic and Diastolic Blood Pressure (mm Hg) Results by Indication, Study Duration, and Dose in Placebo-Controlled Trials
*
Supine Systolic Blood Pressure
Supine Diastolic Blood Pressure

Venlafaxine Hydrochloride Extended-Release Capsules mg/day

Placebo

≤ 75

> 75

SSBP *

SDBP

SSBP

SDBP

SSBP

SDBP

Major Depressive Disorder

8 to 12 weeks

-0.28

0.37

2.93

3.56

-1.08

-0.10

Panic Disorder

10 to 12 weeks

-1.15

0.97

-0.36

0.16

-1.29

-0.99

Across all clinical trials in MDD, 1.4% of patients in the venlafaxine hydrochloride extended-release capsule-treated groups experienced a ≥ 15 mm Hg increase in supine diastolic blood pressure with 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 capsule-treated groups experienced a ≥ 20 mm Hg increase in supine systolic blood pressure with blood pressure ≥ 180 mm Hg compared to 0.3% of patients in the placebo groups.

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