` HIGHLIGHTS OF PRESCRIBING INFORMATION
` These highlights do not include all the information needed to use
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`VIIBRYD safely and effectively. See full prescribing information for
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`VIIBRYD.
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`VIIBRYD (vilazodone hydrochloride) tablets, for oral use
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`Initial U.S. Approval: 2011
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` WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
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` See full prescribing information for complete boxed warning.
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` • Antidepressants increase the risk of suicidal thoughts and behaviors in
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` patients aged 24 years and younger (5.1).
` • Monitor for clinical worsening and emergence of suicidal thoughts and
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` behaviors (5.1).
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`• Safety and effectiveness of VIIBRYD have not been established in
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` pediatric patients (8.4).
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`RECENT MAJOR CHANGES
`03/2015
`Dosage and Administration (2)
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`04/2014
`Warnings and Precautions (5.2)
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`07/2014
`Warnings and Precautions (5.7)
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`INDICATIONS AND USAGE
`VIIBRYD is indicated for the treatment of major depressive disorder (MDD)
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`(1).
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`DOSAGE AND ADMINISTRATION
`• Recommended target dosage: 20 mg to 40 mg once daily with food (2.1,
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`12.3)
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`• To titrate: start with initial dosage of 10 mg once daily for 7 days, followed
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`by 20 mg once daily. The dose may be increased up to 40 mg once daily
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`after a minimum of 7 days between dosage increases (2.1)
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`• Prior to initiating VIIBRYD, screen for bipolar disorder (2.2, 5.4)
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`• When discontinuing VIIBRYD, reduce dosage gradually (2.4, 5.5)
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`DOSAGE FORMS AND STRENGTHS
`Tablets: 10 mg, 20 mg, and 40 mg (3)
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`CONTRAINDICATIONS
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`• Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within
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`14 days of stopping MAOIs (4)
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`WARNINGS AND PRECAUTIONS
`• Serotonin Syndrome: Increased risk when co-administered with other
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`serotonergic agents (e.g., SSRI, SNRI, triptans), but also when taken alone.
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`If it occurs, discontinue VIIBRYD and initiate supportive treatment (5.2)
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`• Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-
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`inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other
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`anticoagulants may increase this risk (5.3)
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`• Activation of Mania/Hypomania: Screen patients for bipolar disorder (5.4).
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`• Seizures: Can occur with treatment. Use with caution in patients with a
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`seizure disorder (5.6).
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`• Angle Closure Glaucoma: Avoid use of antidepressants, including
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`VIIBRYD, in patients with untreated anatomically narrow angles. (5.7)
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`ADVERSE REACTIONS
`Most common adverse reactions (incidence ≥ 5% and at least twice the rate of
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`placebo): diarrhea, nausea, vomiting, and insomnia (6).
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`To report SUSPECTED ADVERSE REACTIONS, contact Forest
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`Laboratories, LLC. at 1-800-678-1605 or FDA at 1-800-FDA-1088 or
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`www.fda.gov/medwatch.
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`DRUG INTERACTIONS
`• CYP3A4 Inhibitors: The VIIBRYD dose should not exceed 20 mg once
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`daily when co-administered with strong CYP3A4 inhibitors (2.4, 7).
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`• CYP3A4 Inducers: Consider increasing VIIBRYD dosage by 2-fold, up to
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`80 mg once-daily over 1 to 2 weeks when used concomitantly with strong
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`CYP3A4 inducers for greater than 14 days (2.4, 7).
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`USE IN SPECIFIC POPULATIONS
`• Pregnancy: Third trimester use may increase risk for persistent pulmonary
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`hypertension and withdrawal in the newborn (8.1).
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`See 17 for PATIENT COUNSELING INFORMATION and Medication
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`Guide.
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`Revised: 03/2015
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`8
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`9
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`7.1 Drugs Having Clinically Important Interactions With
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`VIIBRYD
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`7.2 Drugs Having No Clinically Important Interactions With
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`VIIBRYD
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`USE IN SPECIFIC POPULATIONS
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`8.1 Pregnancy
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`8.2 Lactation
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`8.4 Pediatric Use
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`8.5 Geriatric Use
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`8.6 Use in Other Patient Populations
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`DRUG ABUSE AND DEPENDENCE
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`9.1 Controlled Substance
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`9.2 Abuse and Dependence
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`10 OVERDOSAGE
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`11 DESCRIPTION
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`12 CLINICAL PHARMACOLOGY
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`12.1 Mechanism of action
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`12.2 Pharmacodynamics
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`12.3 Pharmacokinetics
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`13 NONCLINICAL TOXICOLOGY
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`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
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`14 CLINICAL STUDIES
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`16 HOW SUPPLIED/STORAGE AND HANDLING
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`17
`PATIENT COUNSELING INFORMATION
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`*Sections or subsections omitted from the full prescribing information are
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`not listed
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`FULL PRESCRIBING INFORMATION: CONTENTS*
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`WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
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`1
`INDICATIONS AND USAGE
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`2
`DOSAGE AND ADMINISTRATION
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`2.1 Dosage for Treatment of Major Depressive Disorder
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`Screen for Bipolar Disorder Prior to Starting VIIBRYD
`2.2
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`2.3
`Switching to or from a Monoamine Oxidase Inhibitor
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`Antidepressant
`2.4 Dosage Adjustments with CYP3A4 Inhibitors or
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`Inducers
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`2.5 Discontinuing Treatment with VIIBRYD
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`3
`DOSAGE FORMS AND STRENGTHS
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`CONTRAINDICATIONS
`4
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`5 WARNINGS AND PRECAUTIONS
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`Suicidal Thoughts and Behavior in Children,
`5.1
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`Adolescents and Young Adults
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`5.2
`Serotonin Syndrome
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`5.3
`Increased Risk of Bleeding
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`5.4 Activation of Mania or Hypomania
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`5.5 Discontinuation Syndrome
`5.6
`Seizures
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`5.7 Angle-Closure Glaucoma
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`5.8 Hyponatremia
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`ADVERSE REACTIONS
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`6.1 Clinical Trials Experience
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`Post-marketing Experience
`6.2
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`DRUG INTERACTIONS
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`6
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`7
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`Reference ID: 3716274
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`FULL PRESCRIBING INFORMATION
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` WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
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`Antidepressants increased the risk of suicidal thoughts and behaviors in patients aged 24 years and younger in short-term
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`studies. Monitor closely for clinical worsening and for emergence of suicidal thoughts and behaviors. The safety and efficacy of
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`VIIBRYD have not been established in pediatric patients [see Warnings and Precautions (5.1), and Use in Specific Populations
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` (8.4)].
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`INDICATIONS AND USAGE
`1
`VIIBRYD® is indicated for the treatment of major depressive disorder (MDD) [see Clinical Studies (14)].
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`2
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`Dosage for Treatment of Major Depressive Disorder
`2.1
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`The recommended target dosage for VIIBRYD is 20 mg to 40 mg orally once daily with food [see Clinical Pharmacology (12.3),
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`Clinical Studies (14)]. To achieve the target dosage, titrate VIIBRYD as follows:
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`• Start with an initial dosage of 10 mg once daily with food for 7 days,
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`• Then increase to 20 mg once daily with food.
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`• The dose may be increased up to 40 mg once daily with food after a minimum of 7 days between dosage increases.
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`If a dose is missed, it should be taken as soon as the patient remembers. If it is almost time for the next dose, the patient should skip
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`the missed dose and take the next dose at the regular time. Two doses should not be taken at the same time.
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`2.2
`Screen for Bipolar Disorder Prior to Starting VIIBRYD
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`Prior to initiating treatment with VIIBRYD or another antidepressant, screen patients for a personal or family history of bipolar
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`disorder, mania, or hypomania [see Warnings and Precautions (5.4)].
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`Switching to or from a Monoamine Oxidase Inhibitor Antidepressant
`2.3
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`At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of
`VIIBRYD. In addition, at least 14 days must elapse after stopping VIIBRYD before starting an MAOI antidepressant [see
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`Contraindications (4), Warnings and Precautions (5.2)].
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`Dosage Adjustments with CYP3A4 Inhibitors or Inducers
`2.4
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`Patients receiving concomitant CYP3A4 inhibitors:
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`During concomitant use of a strong CYP3A4 inhibitor (e.g., itraconazole, clarithromycin, voriconazole), the VIIBRYD dose should
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`not exceed 20 mg once daily. The original VIIBRYD dose level, can be resumed when the CYP3A4 inhibitor is discontinued [see
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`Drug Interactions (7)].
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`Patients receiving concomitant CYP3A4 inducers:
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`Based on clinical response, consider increasing the dosage of VIIBRYD by 2-fold, up to a maximum 80 mg once daily, over 1 to 2
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`weeks in patients taking strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) for greater than 14 days. If CYP3A4
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`inducers are discontinued, gradually reduce the VIIBRYD dosage to its original level over 1 to 2 weeks [see Drug Interactions (7)].
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`Discontinuing Treatment with VIIBRYD
`2.5
`Adverse reactions may occur upon discontinuation of VIIBRYD [see Warnings and Precautions (5.5)]. A gradual reduction in dosage
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`rather than abrupt cessation is recommended whenever possible. VIIBRYD should be down tapered from the 40 mg once daily dose to
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`20 mg once daily for 4 days, followed by 10 mg once daily for 3 days. Patients taking VIIBRYD 20 mg once daily should be tapered
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`to 10 mg once daily for 7 days.
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`3
`DOSAGE FORMS AND STRENGTHS
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`VIIBRYD Tablets are available as 10 mg, 20 mg and 40 mg film-coated tablets.
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`DOSAGE AND ADMINISTRATION
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`10 mg pink, oval tablet, debossed with 10 on one side
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`20 mg orange, oval tablet, debossed with 20 on one side
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`40 mg blue, oval tablet, debossed with 40 on one side
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`Reference ID: 3716274
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`CONTRAINDICATIONS
`4
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`VIIBRYD is contraindicated in:
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`• Patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (MAOIs), including MAOIs such as linezolid or
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`intravenous methylene blue, because of an increased risk of serotonin syndrome [see Warnings and Precautions (5.2), Drug
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`Interactions (7)].
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`WARNINGS AND PRECAUTIONS
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`5
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`Suicidal Thoughts and Behavior in Children, Adolescents and Young Adults
`5.1
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`In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included
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`approximately 77,000 adult patients, and over 4,400 pediatric patients, the incidence of suicidal thoughts and behaviors in patients age
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`24 years and younger was greater in antidepressant-treated patients than in placebo-treated patients. The drug-placebo differences in
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`the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 1.
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`No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to
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`reach any conclusion about antidepressant drug effect on suicide.
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`Table 1: Risk Differences of the Number of Patients with Suicidal Thoughts or Behaviors
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`in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients
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` Drug-Placebo Difference in Number of Patients with
` Suicidal Thoughts or Behaviors per 1000 Patients Treated
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` Increases Compared to Placebo
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`14 additional patients
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`5 additional patients
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`Decreases Compared to Placebo
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`1 fewer patient
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`6 fewer patients
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` Age Range
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` (years)
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`<18
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`18-24
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`25-64
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`≥65
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`It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term
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`use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance studies in adults with
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`MDD that antidepressants delay the recurrence of depression.
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`Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during
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`the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor
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`for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly
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`discontinuing VIIBRYD, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or
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`behaviors.
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`Serotonin Syndrome
`5.2
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`SNRIs and SSRIs, including VIIBRYD, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is
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`increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol,
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`tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications
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`(4) and Drug Interactions (7)]. Serotonin syndrome can also occur when these drugs are used alone. Symptoms of serotonin syndrome
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`were noted in 0.1% of MDD patients treated with VIIBRYD in premarketing clinical trials.
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`Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma),
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`autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular
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`symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea,
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`vomiting, diarrhea).
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`The concomitant use of VIIBRYD with MAOIs is contraindicated. In addition, do not initiate VIIBRYD in a patient being treated with
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`MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes
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`(such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous
`methylene blue in a patient taking VIIBRYD, discontinue VIIBRYD before initiating treatment with the MAOI [see
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`Contraindications (4), Drug Interactions (7.1)].
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`Reference ID: 3716274
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` Monitor all patients taking VIIBRYD for the emergence of serotonin syndrome. Discontinue treatment with VIIBRYD and any
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`concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If
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`concomitant use of VIIBRYD with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin
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`syndrome and monitor for symptoms.
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`Increased Risk of Bleeding
`5.3
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`Drugs that interfere with serotonin reuptake inhibition, including VIIBRYD, increase the risk of bleeding events. Concomitant use of
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`aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), other antiplatelet drugs, warfarin, and other anticoagulants may add to this
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`risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs
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`that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to drugs that interfere
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`with serotonin reuptake have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages.
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`Inform patients about the risk of bleeding associated with the concomitant use of VIIBRYD and antiplatelet agents or anticoagulants.
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`For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing VIIBRYD.
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`Activation of Mania or Hypomania
`5.4
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`In patients with bipolar disorder, treating a depressive episode with VIIBRYD or another antidepressant may precipitate a
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`mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were excluded; however, symptoms of mania or
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`hypomania were reported in 0.1% of undiagnosed patients treated with VIIBRYD. Prior to initiating treatment with VIIBRYD, screen
`patients for any personal or family history of bipolar disorder, mania, or hypomania [see Dosage and Administration (2.2)].
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`Discontinuation Syndrome
`5.5
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`Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea,
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`sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations),
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`tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in
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`dosage rather than abrupt cessation is recommended whenever possible [see Dosage and Administration (2.5)].
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`Seizures
`5.6
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`VIIBRYD has not been systematically evaluated in patients with a seizure disorder. Patients with a history of seizures were excluded
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`from clinical studies. VIIBRYD should be prescribed with caution in patients with a seizure disorder.
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`Angle-Closure Glaucoma
`5.7
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`The pupillary dilation that occurs following use of many antidepressant drugs including VIIBRYD may trigger an angle closure attack
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`in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of antidepressants, including
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`VIIBRYD, in patients with untreated anatomically narrow angles.
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`Hyponatremia
`5.8
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`
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`Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including VIIBRYD. Cases of serum sodium lower than 110
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`mmol/L have been reported. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment,
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`confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases
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`have included hallucination, syncope, seizure, coma, respiratory arrest, and death. In many cases, this hyponatremia appears to be the
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`result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH).
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`In patients with symptomatic hyponatremia, discontinue VIIBRYD and institute appropriate medical intervention. Elderly patients,
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`patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SSRIs and
`SNRIs [see Use in Specific Populations (8.5)].
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`
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`ADVERSE REACTIONS
`6
`
`The following adverse reactions are discussed in greater detail in other sections of the labeling:
`
`
`
`
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`• Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults [see Warnings and Precautions (5.1)].
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`
`
`
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`• Serotonin Syndrome [see Warnings and Precautions (5.2)].
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`Increased Risk of Bleeding [see Warnings and Precautions (5.3)].
`
`•
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`• Activation of Mania or Hypomania [see Warnings and Precautions (5.4)].
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`• Discontinuation Syndrome [see Warnings and Precautions (5.5)].
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`• Seizures [see Warnings and Precautions (5.6)]
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`• Angle-Closure Glaucoma [see Warnings and Precautions (5.7)].
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`
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`• Hyponatremia [see Warnings and Precautions (5.8)].
`
`
`
`
`
`Reference ID: 3716274
`
`
`
` Clinical Trials Experience
` 6.1
`
`
`
` Because clinical trials are conducted under widely varying conditions and varying lengths of time, adverse reaction rates observed in
`
`
`
`
`
`
`
` the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect rates
`
` observed in practice.
`
`
`
`
`
`
` The most commonly observed adverse reactions in VIIBRYD-treated patients with major depressive disorder (MDD) in placebo-
`
` controlled studies (incidence ≥ 5% and at least twice the rate of placebo) were diarrhea, nausea, vomiting, and insomnia.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Patient Exposure
`
`
`
`
`
`The safety of VIIBRYD was evaluated in 3,007 patients (18-70 years of age) diagnosed with MDD who participated in clinical
`
`
`
`studies, representing 676 patient-years of exposure. In an open-label 52 week study at 40 mg daily, 599 patients were exposed to
`
`
`VIIBRYD for a total of 348 patient-years.
`
`
`
`
`
`
`
`
`
`The adverse reaction information presented below was derived from studies of VIIBRYD 20 mg and 40 mg daily in patients with
`
`
`MDD including:
`
`
`
`
`
`
`
`
`
`
`• Four placebo-controlled 8 to 10-week studies in 2,233 patients, including 1,266 VIIBRYD-treated patients; and
`
`
`
`
`• An open-label 52-week study of 599 VIIBRYD-treated patients.
`
`
`
`
`
`
`
`
`These studies included a titration period of 10 mg daily for 7 days, followed by 20 mg daily for 7 days or to 40 mg daily over 2 weeks.
`
`
`
`
`In these clinical trials, VIIBRYD was administered with food.
`
`
`
`
`Adverse reactions reported as reasons for discontinuation of treatment
`
`
`In these studies, 7.3% of the VIIBRYD-treated patients discontinued treatment due to an adverse reaction, compared with 3.5% of
`
`
`placebo-treated patients. The most common adverse reaction leading to discontinuation in at least 1% of the VIIBRYD-treated patients
`
`
`in the placebo-controlled studies was nausea (1.4%).
`
`
`
`Common adverse reactions in placebo-controlled MDD studies
`
`
`
`
`
`
`
`
`
`Table 2 shows the incidence of common adverse reactions occuring in ≥ 2% of VIIBRYD-treated patients and greater than the rate of
`
`
`
`
`
`placebo-treated patients in MDD Studies. There were no dose-related adverse reactions between 20 mg and 40 mg reported.
`
`
`
`
`
`
`
`
`
`
`
`Table 2: Common Adverse Reactions Occurring in ≥ 2% of VIIBRYD-treated Patients and Greater than the Rate of Placebo-
`
`Treated Patients
`
`
`System Organ Class
`
`
`Preferred Term
`
` Gastrointestinal disorders
`
`
`
`Diarrhea
`
`
`Nausea
`
`
`
`Dry mouth
`
`
`Vomiting
` Abdominal pain1
`
`
`
`
`Dyspepsia
`
`
`Flatulence
`
`
`Gastroenteritis
`
`
`Abdominal distension
`
`Nervous system disorders
`
` Headache2
`
`
`
` Dizziness
`
`
`Somnolence
`
`
`Paresthesia
`
`Psychiatric disorders
`
`
`Reference ID: 3716274
`
`
`
` Placebo
`
` N=967
`
`
`10%
`
`7%
`
`5%
`
`2%
`
` 3%
`
`2%
`
`1%
`
`1%
`
`1%
`
`
` 14%
` 5%
`
`
`2%
`
`1%
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` VIIBRYD
`
` 20 mg/day
`
` N=288
`
`
`26%
`
`22%
`
`8%
`
`4%
`
` 7%
`
`2%
`
`3%
`
`1%
`
`2%
`
`
` 15%
` 6%
`
`
`4%
`
`1%
`
`
` VIIBRYD
`
` 40 mg/day
`
` N=978
`
`
`29%
`
`24%
`
`7%
`
`5%
`
` 4%
`
`3%
`
`3%
`
`2%
`
`1%
`
`
` 14%
` 8%
`
`
`5%
`
`2%
`
`
`
`
`
`
`
`
`
`
` System Organ Class
`
`
` Preferred Term
`
`
`
` Placebo
`
` N=967
`
` 2%
`
`2%
`
` 1%
`
`
` VIIBRYD
`
` 20 mg/day
`
` N=288
`
` 7%
`
`2%
`
` 2%
`
`
` VIIBRYD
`
` 40 mg/day
`
` N=978
`
` 6%
`
`3%
`
` 3%
`
` Insomnia
`
`
`
`
`Abnormal dreams
`Restlessness3
`
`
`
`General disorders
`
`
`Fatigue
`
`Cardiac disorders
`
`
`Palpitations
`
`Metabolism and nutrition disorders
`
`
`Increased appetite
`
`Musculoskeletal and connective tissue disorders
`
`
`Arthralgia
`
`Investigations
`
`
`
`1%
`Increased weight
`
` 1 Includes abdominal discomfort, abdominal pain upper, and abdominal pain.
`
`2 Includes headache and tension headache
`
`
`
`
`3 Includes restlessness, akathisia, and restless legs syndrome
`
`
`
`Sexual adverse reactions are presented in Table 3
`
`
`
`Sexual adverse reactions
`
`
`
`Table 3 displays the most common sexual adverse reactions in the placebo-controlled MDD studies.
`
`
`
`
`
`
`
`
`
`
`
`Table 3: Common Sexual Adverse Reactions Occurring in ≥ 2% of VIIBRYD-treated Patients and Greater than the Rate of
`
`Placebo-Treated Patients
`
`
`
`
`
`
`
`
`
`
`3%
`
`
`<1%
`
`
`1%
`
`
`1%
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`4%
`
`
`1%
`
`
`1%
`
`
`2%
`
`
`1%
`
`
`
`
`
`
`
`
`
`
`
`3%
`
`
`2%
`
`
`3%
`
`
`1%
`
`
`2%
`
`
`
` Preferred Term
`
`
`
` VIIBRYD
`
` 40 mg/day
`
` N=417
`
` 2%
`
` 3%
`
` 4%
`
` 2%
`
`
`
`
`
` Placebo
`
` N=551
` 0%
`
`
`-
` <1%
`
`
`-
`
`
`
`
` VIIBRYD
`
` 40 mg/day
`
` N=561
`
` 1%
`
`-
`
` 2%
`
`-
`
` Females
`
`VIIBRYD
`
` 20 mg/day
`
` N=166
` 1%
`
`
`-
` 2%
`
`
`-
`
` Males
`
`VIIBRYD
`
`
` 20 mg/day
`
` Placebo
`
`
` N=416
` N=122
`
` 2%
`
` <1%
`
`
` Abnormal Orgasm*
`
` 0%
`
`
` Erectile dysfunction
` 1%
`
` 3%
`
` <1%
`
` Libido decreased
`
` 1%
`
`
` Ejaculation disorder
` 0%
`
` − Not applicable*Includes abnormal orgasm and anorgasmia
`
`
`
`Other adverse reactions observed in clinical studies
`
`
`
`
`The following list does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause
`
`
`
`
`
`
`
`was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications,
`
`
`or 5) which occurred at a rate equal to or less than placebo.
`
`
`
`Reactions are categorized by body system according to the following definitions: frequent adverse reactions are those occurring in at
`
`
`
`
`least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in
`
`
`
`
`
`fewer than 1/1000 patients:
`
`
`Cardiac disorders: infrequent: ventricular extrasystoles
`
`
`
`
`Eye disorders: infrequent: dry eye, vision blurred, rare: cataracts
`
`
`
`
`
`Nervous System: frequent: sedation, tremor; infrequent: migraine
`
`
`
`
`Psychiatric disorders: infrequent: panic attack
`
`
`
`
`
`Reference ID: 3716274
`
`
`
`
`
` Skin and subcutaneous tissue disorders: infrequent: hyperhidrosis, night sweats
`
`
`
`
`
`
`
` DRUG INTERACTIONS
`
`
`
`
`
`
`
` Drugs Having Clinically Important Interactions With VIIBRYD
`
`
`
` 6.2
`
`
` Post-marketing Experience
`
`
` The following adverse reactions have been identified during post-approval use of VIIBRYD. Because these reactions are reported
`
` voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to
`
`
`
` drug exposure. Reports of adverse reactions temporally associated with VIIBRYD that have been received since market introduction
`
`
`
`
`
` and that are not listed above include the following:
`
`
`
`
`
`
`
`
`
` General Disorders and Administration Site Conditions: irritability
`
`
` Psychiatric Disorders: hallucinations, suicide attempt, suicidal ideation
` Skin and subcutaneous tissue disorders: rash, generalized rash, urticaria, drug eruption
`
`
`
` 7
`
` 7.1
`
`
`
`
`Table 4: Clinically Important Drug Interactions with VIIBRYD
` Concomitant
`
`
` Drug Name or
` Drug Class
`
`
`
`
` Clinical Rationale
`
`
`
` Clinical Recommendation
`
`
` VIIBRYD is contraindicated in patients taking MAOIs,
`
`
` including MAOIs such as linezolid or intravenous
` methylene blue [see Contraindications (4), Dosage and
`
`
`
`
` Administration (2.3), and Warnings and Precautions
`
` (5.2)].
` Monitor patients for signs and symptoms of serotonin
`
`
`
` syndrome, particularly during VIIBRYD initiation. If
` serotonin syndrome occurs, consider discontinuation of
`
`
`
` VIIBRYD and/or concomitant serotonergic drugs [see
` Warnings and Precautions (5.2)].
`
` Inform patients of the increased risk of bleeding with
`
`
`
` the concomitant use of VIIBRYD and antiplatelet
` agents and anticoagulants. For patients taking
`
`
`
` warfarin, carefully monitor the international
`
` normalized ratio (INR) when initiating or discontinuing
`
` VIIBRYD [see Warnings and Precautions (5.3)].
`
`
` The VIIBRYD dose should not exceed 20 mg once
`
` daily with the concomitant use of a strong CYP3A4
`
`
`
`
` inhibitor [see Dosage and Administration (2.4),
`
` Clinical Pharmacology (12.3)].
`
`Based on clinical response, consider increasing the
`
` dosage of VIIBRYD, over 1 to 2 weeks in patients
` taking strong CYP3A4 inducers for greater than 14
`
`
` days [see Dosage and Administration (2.4), Clinical
` Pharmacology (12.3)].
`
`
` Measure serum digoxin concentrations before initiating
`
`
` concomitant use of VIIBRYD. Continue monitoring
` and reduce digoxin dose as necessary.
`
`
`
`
`
`Monoamine
`
`Oxidase Inhibitors
`
`(MAOIs)
`
`
`
`
`The concomitant use of MAOIs and
`
`serotonergic drugs including VIIBRYD
`
`
`increases the risk of serotonin syndrome.
`
`Other Serotonergic
`
`Drugs
`
`
`
`The concomitant use of serotonergic
`
`
`drugs including VIIBRYD and other
`
`serotonergic drugs increases the risk of
`
`serotonin syndrome.
`
`
` Antiplatelet Agents
`
` and Anticoagulants
`
`
`Strong CYP3A4
`
` Inhibitors (e.g.,
` itraconazole,
`
`clarithromycin,
`
` voriconazole)
`Strong CYP3A4
`
`
` Inducers (e.g.,
`
` carbamazepine,
`
` phenytoin,
`
` rifampin)
`
`
`
` Digoxin
`
`
`
`
`
`
` Serotonin release by platelets plays an
`
` important role in hemostasis. The
`
`
` concurrent use of an antiplatelet agent or
`
` anticoagulant with VIIBRYD may
`
` potentiate the risk of bleeding.
`
`
` The concomitant use of VIIBRYD and
`
`
`
` strong CYP3A4 inhibitors increased the
`
`
`
` exposure of vilazodone compared to the
`
`use of VIIBRYD alone [see Clinical
`
`Pharmacology (12.3)].
`
` The concomitant use of VIIBRYD and
`
` strong CYP3A4 inducers decreased the
`
` exposure of vilazodone compared to the
`
`use of VIIBRYD alone [see Clinical
`
` Pharmacology (12.3)].
`Digoxin is a narrow therapeutic index
`drug. Concomitant use of VIIBRYD
`
`
`increased digoxin concentrations [see
`
`
` Clinical Pharmacology (12.3)].
`
`
`
`
`
`
`
`
`
`
`7.2
`
`
`
` Drugs Having No Clinically Important Interactions With VIIBRYD
`
` Based on pharmacokinetic studies, no dosage adjustment is required for drugs that are substrates of CYP1A2, CYP2B6, CYP2C9,
`
` CYP2C19, CYP2D6, CYP3A4, and/or P-glycoprotein (except narrow therapeutic index drugs, e.g., digoxin), when VIIBRYD is
`
`
`
`
` administered concomitantly [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].
`
`
`
`
`
`
`
`
`
`Reference ID: 3716274
`
`
`
` USE IN SPECIFIC POPULATIONS
`
`
`
`
`
`
` 8
`
` 8.1
`
` Pregnancy
` Risk Summary
`
`
` There are no adequate and well-controlled studies of VIIBRYD in pregnant women. The background risk of major birth defects and
`
`
`
`
`
`
` miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth
` defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. In animal reproduction studies, oral
`
`
`
`
`
`
` administration of vilazodone during the period of organogenesis at doses up to 48 and 17 times the maximum recommended human
`
` dose (MRHD) in rats and rabbits, respectively, resulted in decreased fetal body weight gain and delayed skeletal ossification but no
`
`
`
` teratogenic effects were observed. Decreased fetal body weight and delayed skeletal ossification were not observed at doses up to 10
`
`
`
` and 4 times the MRHD in rats and rabbits, respectively [see Data].
`
`
`
`
` Clinical Considerations
`
`
` Disease-associated maternal and/or embryo/fetal risk
`
`
`
`
`
`
`
`
`
`A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and
`
`
`taking antidepressants at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more
`
`
`
`
`likely to experience a relapse of major depression than women who continued antidepressants. Consider the risks of untreated
`
`
`
`depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum.
`
`
`Fetal/Neonatal adverse reactions
`
`
`
`
`Exposure to SSRIs and SNRIs, including VIIBRYD, in late pregnancy may lead to an increased risk for neonatal complications
`
`
`requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn
`
`
`
`
`
`
`(PPHN). Monitor neonates who were exposed to VIIBRYD in the third trimester of pregnancy for PPHN and drug discontinuation
`
`
`syndrome [see Data)].
`
`
`
`Data
`
`Human Data
`
`Third Trimester Exposure
`
`
`
`Neonates exposed to SSRIs or serotonin and no