WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
`
`See full prescribing information for complete boxed warning.
`
`
`
` Antidepressants increase the risk of suicidal thoughts and behaviors in
`patients aged 24 years and younger (5.1).
`
`
` Monitor for clinical worsening and emergence of suicidal thoughts and
`behaviors (5.1).
`
`
` Safety and effectiveness of VIIBRYD have not been established in
`pediatric patients (8.4).
`
`
`
`
`
`
`
`
`
`INDICATIONS AND USAGE
`VIIBRYD is indicated for the treatment of major depressive disorder (MDD)
`
`(1).
`
`
`
`
`
`
`
`
`DOSAGE AND ADMINISTRATION
`
`
` Recommended target dosage: 20 mg to 40 mg once daily with food (2.1,
`
`
`12.3)
`
`
` To titrate: start with initial dosage of 10 mg once daily for 7 days, followed
`
`by 20 mg once daily. The dose may be increased up to 40 mg once daily
`
`
`after a minimum of 7 days between dosage increases (2.1)
`
` Prior to initiating VIIBRYD, screen for bipolar disorder (2.2, 5.4)
`
`
` When discontinuing VIIBRYD, reduce dosage gradually (2.4, 5.5)
`
`
`
`
`
`
`
`DOSAGE FORMS AND STRENGTHS
`Tablets: 10 mg, 20 mg, and 40 mg (3)
`
`
`
`
`
`
`
`
`
`
`
`
`CONTRAINDICATIONS
`
` Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within
`
`
`14 days of stopping MAOIs (4)
`
`
`
`
`
`
`
`
`WARNINGS AND PRECAUTIONS
`
` Serotonin Syndrome: Increased risk when co-administered with other
`
`serotonergic agents (e.g., SSRI, SNRI, triptans), but also when taken alone.
`If it occurs, discontinue VIIBRYD and initiate supportive treatment (5.2)
`
`
` Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-
`inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other
`
`anticoagulants may increase this risk (5.3)
`
` Activation of Mania/Hypomania: Screen patients for bipolar disorder (5.4).
`
`
` Seizures: Can occur with treatment. Use with caution in patients with a
`seizure disorder (5.6).
`
`
` Angle Closure Glaucoma: Avoid use of antidepressants, including
`VIIBRYD, in patients with untreated anatomically narrow angles. (5.7)
`
`
`
`
`
`
`
`
`
`
`
`ADVERSE REACTIONS
`Most common adverse reactions (incidence ≥ 5% and at least twice the rate of
`placebo): diarrhea, nausea, vomiting, and insomnia (6).
`
`
`To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-
`
`800-433-8871 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
`
`
`
`
`
`
`
`
`
`DRUG INTERACTIONS
`
` CYP3A4 Inhibitors: The VIIBRYD dose should not exceed 20 mg once
`
`
`daily when co-administered with strong CYP3A4 inhibitors (2.4, 7).
`
` CYP3A4 Inducers: Consider increasing VIIBRYD dosage by 2-fold, up to
`80 mg once-daily over 1 to 2 weeks when used concomitantly with strong
`
`CYP3A4 inducers for greater than 14 days (2.4, 7).
`
`
`
`
`
`
`
`
`
`USE IN SPECIFIC POPULATIONS
`
` Pregnancy: Third trimester use may increase risk for persistent pulmonary
`
`hypertension and withdrawal in the newborn (8.1).
`
`
`
`
`
`
`
`
`
`
`
`
`
`See 17 for PATIENT COUNSELING INFORMATION and Medication
`Guide.
`
`
`Revised: 09/2016
`
`
`HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`These highlights do not include all the information needed to use
`VIIBRYD safely and effectively. See full prescribing information for
`
`
`
`VIIBRYD.
`
`VIIBRYD (vilazodone hydrochloride) tablets, for oral use
`
`Initial U.S. Approval: 2011
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` 
`9
`
` 
`8
`
` 
` Drugs Having Clinically Important Interactions With
`7.1
`
` 
`VIIBRYD
` 
`7.2 Drugs Having No Clinically Important Interactions With
`
` 
`VIIBRYD
` 
`USE IN SPECIFIC POPULATIONS
` 
` 
`8.1 Pregnancy
` 
`8.2 Lactation
`
` 
` 
`8.4 Pediatric Use
` 
` 
`8.5 Geriatric Use
` 
` 
`8.6 Use in Other Patient Populations
` 
`DRUG ABUSE AND DEPENDENCE
` 
` 
`9.1 Controlled Substance
` 
` 
`9.2 Abuse and Dependence
` 
` 
`10 OVERDOSAGE
` 
` 
`DESCRIPTION
`11
` 
` 
`12
`CLINICAL PHARMACOLOGY
` 
` 
`12.1 Mechanism of action
` 
` 
`12.2 Pharmacodynamics
` 
` 
`12.3 Pharmacokinetics
` 
` 
`13
`NONCLINICAL TOXICOLOGY
` 
` 
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`
` 
` 
`14
`CLINICAL STUDIES
` 
` 
`16 HOW SUPPLIED/STORAGE AND HANDLING
` 
` 
`17
`PATIENT COUNSELING INFORMATION
`
`*Sections or subsections omitted from the full prescribing information are
`not listed
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
` 
`WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
` 
` 
`1
`INDICATIONS AND USAGE
` 
` 
`2
`DOSAGE AND ADMINISTRATION
`
` 
` 
`2.1 Dosage for Treatment of Major Depressive Disorder
` 
`2.2 Screen for Bipolar Disorder Prior to Starting VIIBRYD
`
` 
`2.3
`Switching to or from a Monoamine Oxidase Inhibitor
`
`
` 
`Antidepressant
`2.4 Dosage Adjustments with CYP3A4 Inhibitors or
`Inducers
`
`2.5 Discontinuing Treatment with VIIBRYD
`
` 
` 
`DOSAGE FORMS AND STRENGTHS
`3
` 
` 
`CONTRAINDICATIONS
`4
` 
` 
`5 WARNINGS AND PRECAUTIONS
` 
`Suicidal Thoughts and Behavior in Children,
`5.1
`
` 
`Adolescents and Young Adults
` 
` 
`5.2
`Serotonin Syndrome
` 
` 
`5.3
`Increased Risk of Bleeding
` 
` 
`5.4 Activation of Mania or Hypomania
` 
` 
`5.5 Discontinuation Syndrome
`5.6
` Seizures
`
` 
` 
`5.7 Angle-Closure Glaucoma
` 
` 
`5.8 Hyponatremia
` 
`ADVERSE REACTIONS
` 
` 
`6.1 Clinical Trials Experience
` 
` 
` Post-marketing Experience
`6.2
` 
`DRUG INTERACTIONS
`
` 
`6
`
` 
`7
`
`
`
`Reference ID: 3982141
`
`

`

`
`
`FULL PRESCRIBING INFORMATION
`
`
`
`DOSAGE AND ADMINISTRATION
`
`
`
`
`WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
`
`
`
`
`
`Antidepressants increased the risk of suicidal thoughts and behaviors in patients aged 24 years and younger in short-term
`
`
`
`
`studies. Monitor closely for clinical worsening and for emergence of suicidal thoughts and behaviors. The safety and efficacy of
`
`VIIBRYD have not been established in pediatric patients [see Warnings and Precautions (5.1), and Use in Specific Populations
`(8.4)].
`
`
`INDICATIONS AND USAGE
`1
`VIIBRYD® is indicated for the treatment of major depressive disorder (MDD) [see Clinical Studies (14)].
`
`
`
`2
`
`Dosage for Treatment of Major Depressive Disorder
`2.1
`
`
`
`The recommended target dosage for VIIBRYD is 20 mg to 40 mg orally once daily with food [see Clinical Pharmacology (12.3),
`
`
`
`
`
`Clinical Studies (14)]. To achieve the target dosage, titrate VIIBRYD as follows:
`
`
`
`
`
` Start with an initial dosage of 10 mg once daily with food for 7 days,
`
`
`
`
` Then increase to 20 mg once daily with food.
`
`
`
`
`
` The dose may be increased up to 40 mg once daily with food after a minimum of 7 days between dosage increases.
`
`
`
`
`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
`
`
`
`
`
`
`the missed dose and take the next dose at the regular time. Two doses should not be taken at the same time.
`
`
`
`
`
`2.2
` Screen for Bipolar Disorder Prior to Starting VIIBRYD
`
`
`
`Prior to initiating treatment with VIIBRYD or another antidepressant, screen patients for a personal or family history of bipolar
`
`
`
`
`disorder, mania, or hypomania [see Warnings and Precautions (5.4)].
`
`
`
`2.3
`Switching to or from a Monoamine Oxidase Inhibitor Antidepressant
`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
`
`
`
`Contraindications (4), Warnings and Precautions (5.2)].
`
`
`
`Dosage Adjustments with CYP3A4 Inhibitors or Inducers
`2.4
`
`Patients receiving concomitant CYP3A4 inhibitors:
`
`
`During concomitant use of a strong CYP3A4 inhibitor (e.g., itraconazole, clarithromycin, voriconazole), the VIIBRYD dose should
`
`not exceed 20 mg once daily. The original VIIBRYD dose level, can be resumed when the CYP3A4 inhibitor is discontinued [see
`
`
`
`
`
`
`Drug Interactions (7)].
`
`
`
`Patients receiving concomitant CYP3A4 inducers:
`
`
`
`
`
`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
`
`
`weeks in patients taking strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) for greater than 14 days. If CYP3A4
`
`
`inducers are discontinued, gradually reduce the VIIBRYD dosage to its original level over 1 to 2 weeks [see Drug Interactions (7)].
`
`
`2.5
`Discontinuing Treatment with VIIBRYD
`Adverse reactions may occur upon discontinuation of VIIBRYD [see Warnings and Precautions (5.5)]. A gradual reduction in dosage
`
`
`
`
`
`
`
`
`
`rather than abrupt cessation is recommended whenever possible. VIIBRYD should be down tapered from the 40 mg once daily dose to
`
`
`
`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
`to 10 mg once daily for 7 days.
`
`
`
`
`DOSAGE FORMS AND STRENGTHS
`3
`
`VIIBRYD Tablets are available as 10 mg, 20 mg and 40 mg film-coated tablets.
`
`
`
`
`
`
`
`
`10 mg pink, oval tablet, debossed with 10 on one side
`
`
`
`
`
`
`20 mg orange, oval tablet, debossed with 20 on one side
`
`
`
`
`
`40 mg blue, oval tablet, debossed with 40 on one side
`
`
`
`
`Reference ID: 3982141
`
`

`

`
`
`4
`CONTRAINDICATIONS
`
`VIIBRYD is contraindicated in:
`
`
`
` Patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (MAOIs), including MAOIs such as linezolid or
`
`
`
`
`
`intravenous methylene blue, because of an increased risk of serotonin syndrome [see Warnings and Precautions (5.2), Drug
`
`
`Interactions (7)].
`
`WARNINGS AND PRECAUTIONS
`
`
`5
`
`
`Suicidal Thoughts and Behavior in Children, Adolescents and Young Adults
`5.1
`
`
`
`In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included
`
`
`approximately 77,000 adult patients, and over 4,400 pediatric patients, the incidence of suicidal thoughts and behaviors in patients age
`
`
`24 years and younger was greater in antidepressant-treated patients than in placebo-treated patients. The drug-placebo differences in
`
`
`
`the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 1.
`
`
`
`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 antidepressant drug effect on suicide.
`
`Table 1: Risk Differences of the Number of Patients with Suicidal Thoughts or Behaviors
`
`
`
`in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients
`
`
`
`
`Drug-Placebo Difference in Number of Patients with
`Suicidal Thoughts or Behaviors per 1000 Patients Treated
`Increases Compared to Placebo
`
`14 additional patients
`
`5 additional patients
`
`Decreases Compared to Placebo
`
`1 fewer patient
`6 fewer patients
`
`Age Range
`
`(years)
`
`<18
`18-24
`
`
`25-64
`
`≥65
`
`
`
`
`
`It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term
`use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance studies in adults with
`
`MDD that antidepressants delay the recurrence of depression.
`
`Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during
`
`the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor
`
`
`
`for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly
`
`
`
`
`discontinuing VIIBRYD, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or
`
`behaviors.
`
`
`5.2
`Serotonin Syndrome
`
`
`
`
`SNRIs and SSRIs, including VIIBRYD, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is
`
`increased 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, i.e., MAOIs [see Contraindications
`
`
`(4) and Drug Interactions (7)]. Serotonin syndrome can also occur when these drugs are used alone. Symptoms of serotonin syndrome
`
`
`
`
`were noted in 0.1% of MDD patients treated with VIIBRYD in premarketing clinical trials.
`
`
`
`Serotonin syndrome signs and 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 gastrointestinal symptoms (e.g., nausea,
`
`vomiting, diarrhea).
`
`The concomitant use of VIIBRYD with MAOIs is contraindicated. In addition, do not initiate VIIBRYD in a patient being treated with
`
`
`
`
`
`MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes
`
`
`
`(such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous
`
`
`
`
`
`Reference ID: 3982141
`
`

`

`
`methylene blue in a patient taking VIIBRYD, discontinue VIIBRYD before initiating treatment with the MAOI [see
`
`
`Contraindications (4), Drug Interactions (7.1)].
`
`
`
`
`
`
`Monitor all patients taking VIIBRYD for the emergence of serotonin syndrome. Discontinue treatment with VIIBRYD and any
`concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If
`
`
`
`
`
`
`concomitant use of VIIBRYD with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin
`
`
`syndrome and monitor for symptoms.
`
`
`5.3
`Increased Risk of Bleeding
`
`Drugs that interfere with serotonin reuptake inhibition, including VIIBRYD, increase the risk of bleeding events. Concomitant use of
`
`
`aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), other antiplatelet drugs, warfarin, and other anticoagulants may add to this
`
`
`
`risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs
`
`
`that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to drugs that interfere
`
`with serotonin reuptake have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages.
`
`
`
`Inform patients about the risk of bleeding associated with the concomitant use of VIIBRYD and antiplatelet agents or anticoagulants.
`
`
`For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing VIIBRYD.
`
`
`
`
`Activation of Mania or Hypomania
`5.4
`
`
`
`In patients with bipolar disorder, treating a depressive episode with VIIBRYD or another antidepressant may precipitate a
`
`
`mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were excluded; however, symptoms of mania or
`
`
`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)].
`
`
`
`
`
`
`5.5
`Discontinuation Syndrome
`
`
`
`
`
`Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea,
`
`
`sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations),
`tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in
`dosage rather than abrupt cessation is recommended whenever possible [see Dosage and Administration (2.5)].
`
`
`5.6
`Seizures
`
`
`
`VIIBRYD has not been systematically evaluated in patients with a seizure disorder. Patients with a history of seizures were excluded
`
`
`
`from clinical studies. VIIBRYD should be prescribed with caution in patients with a seizure disorder.
`
`
`5.7
`Angle-Closure Glaucoma
`
`
`
`The pupillary dilation that occurs following use of many antidepressant drugs including VIIBRYD may trigger an angle closure attack
`
`
`in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of antidepressants, including
`VIIBRYD, in patients with untreated anatomically narrow angles.
`
`Hyponatremia
`5.8
`
`
`
`Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including VIIBRYD. Cases of serum sodium lower than 110
`
`
`
`
`
`mmol/L have been reported. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment,
`
`
`confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases
`
`
`have included hallucination, syncope, seizure, coma, respiratory arrest, and death. In many cases, this hyponatremia appears to be the
`
`
`
`result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH).
`
`
`
`In patients with symptomatic hyponatremia, discontinue VIIBRYD and institute appropriate medical intervention. Elderly patients,
`
`
`
`
`
`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)].
`
`
`
`6
`ADVERSE REACTIONS
`
`
`The following adverse reactions are discussed in greater detail in other sections of the labeling:
`
`
`
` Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults [see Warnings and Precautions (5.1)].
`
`
`
` Serotonin Syndrome [see Warnings and Precautions (5.2)].
`
`
`Increased Risk of Bleeding [see Warnings and Precautions (5.3)].
`
`
` Activation of Mania or Hypomania [see Warnings and Precautions (5.4)].
`
` Discontinuation Syndrome [see Warnings and Precautions (5.5)].
`
` Seizures [see Warnings and Precautions (5.6)]
`
`
`
`
`Reference ID: 3982141
`
`

`

`
`
`
` Angle-Closure Glaucoma [see Warnings and Precautions (5.7)].
`
`
`
`  Hyponatremia [see Warnings and Precautions (5.8)].
`
`
`
`
`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
`
`
`
`
`Reference ID: 3982141
`
`
`
`
`
`
`Placebo
`N=967
`
`
`10%
`
`7%
`
`5%
`
`2%
`
` 3%
`
`2%
`
`1%
`
`1%
`
`1%
`
`14%
`5%
`
`
`
`
`
`
`VIIBRYD
`20 mg/day
`N=288
`
`
`26%
`
`22%
`
`8%
`
`4%
`
` 7%
`
`2%
`
`3%
`
`1%
`
`2%
`
`
`15%
`6%
`
`
`
`
`
`
`VIIBRYD
`40 mg/day
`N=978
`
`
`29%
`
`24%
`
`7%
`
`5%
`
` 4%
`
`3%
`
`3%
`
`2%
`
`1%
`
`
`14%
`8%
`
`
`

`

`
`
`System Organ Class
` Preferred Term
`
`
`Placebo
`N=967
`
`2%
`
`1%
`
`VIIBRYD
`20 mg/day
`N=288
`
`4%
`
`1%
`
`VIIBRYD
`40 mg/day
`N=978
`
`5%
`
`2%
`
`
`
`
`
`
`
`
`
`
`
`
`2%
`
`2%
`
` 1%
`
`
`3%
`
`
`<1%
`
`
`1%
`
`
`1%
`
`
`
`
`
`
`
`
`
`
`
`
`7%
`
`2%
`
` 2%
`
`
`4%
`
`
`1%
`
`
`1%
`
`
`2%
`
`
`
`
`
`
`
`
`
`
`
`
`6%
`
`3%
`
` 3%
`
`
`3%
`
`
`2%
`
`
`3%
`
`
`1%
`
`
`2%
`
`
` Somnolence
`
` Paresthesia
`
`Psychiatric disorders
`
` Insomnia
`
` Abnormal dreams
` Restlessness3
`
`General disorders
`
` Fatigue
`
`Cardiac disorders
`
` Palpitations
`
`Metabolism and nutrition disorders
`
` Increased appetite
`
`Musculoskeletal and connective tissue disorders
`
` Arthralgia
`
`Investigations
`
`
`
`
`1%
`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
`
`
`Preferred Term
`
`
`VIIBRYD
`40 mg/day
`N=417
`
`2%
`
`3%
`
`4%
`
`2%
`
`
`Placebo
`N=551
`
`0%
`-
`
`<1%
`
`-
`
`Females
`VIIBRYD
`20 mg/day
`N=166
`
`1%
`-
`
`2%
`
`-
`
`VIIBRYD
`40 mg/day
`N=561
`
`1%
`-
`
`2%
`
`-
`
`Males
`VIIBRYD
`
`Placebo
`20 mg/day
`N=416
`N=122
`
`
`
`2%
`<1%
`Abnormal Orgasm*
`
`
`
`0%
`1%
`Erectile dysfunction
`
`
`
`
`3%
`<1%
`Libido decreased
`
`
`
`1%
`0%
`Ejaculation disorder
`− 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
`
`
`
`Reference ID: 3982141
`
`

`

`
`
`DRUG INTERACTIONS
`
`Drugs Having Clinically Important Interactions With VIIBRYD
`
`
`Clinical Rationale
`
`Clinical Recommendation
`
`
`Nervous System: frequent: sedation, tremor; infrequent: migraine
`
`
`
`
`Psychiatric disorders: infrequent: panic attack
`
`
`
`Skin and subcutaneous tissue disorders: infrequent: hyperhidrosis, night sweats
`
`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
`
`Nervous System Disorders: sleep paralysis
`
`Psychiatric Disorders: hallucinations, suicide attempt, suicidal ideation
`Skin and subcutaneous tissue disorders: rash, generalized rash, urticaria, drug eruption
`
`
`
`
`
`Gastrointestinal System: acute pancreatitis
`
`7
`
`7.1
`
`
`Table 4: Clinically Important Drug Interactions with VIIBRYD
`
`
`Concomitant
`
`Drug Name or
`
`Drug Class
`
`
`Monoamine
`Oxidase Inhibitors
`(MAOIs)
`
`
`The concomitant use of MAOIs and
`
`serotonergic drugs including VIIBRYD
`
`increases the risk of serotonin syndrome.
`
`
`Other Serotonergic
`
`Drugs
`
`Antiplatelet Agents
`
`and Anticoagulants
`
`Strong CYP3A4
`
`Inhibitors (e.g.,
`itraconazole,
`clarithromycin,
`voriconazole)
`Strong CYP3A4
`
`Inducers (e.g.,
`
`carbamazepine,
`phenytoin,
`rifampin)
`
`
`Digoxin
`
`
`The concomitant use of serotonergic
`
`drugs including VIIBRYD and other
`serotonergic drugs increases the risk of
`
`serotonin syndrome.
`
`
`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)].
`
`
`
`
`Reference ID: 3982141
`
`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.
`
`
`
`

`

`
`
`
`Drugs Having No Clinically Important Interactions With VIIBRYD
` 7.2
`
`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)].
`
`
`
`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 norepinephrine reuptake inhibitors (SNRIs) late in the third trimester, have developed
`
`
`
`
`
`complications requiring prolonged hospitalization, respiratory support, and tube feeding. These findings are based on post-marketing
`
`reports. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress,
`
`cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia,
`tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs
`or, possibly, a drug discontinuation syndrome. In some cases, the clinical picture was consistent with serotonin syndrome [see
`
`
`Warnings and Precautions (5.2)].
`
`
`
`
`Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN).
`
`
`
`
`
`PPHN occurs in 1-2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality.
`
`
`
`
`
`In a retrospective case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born
`
`
`
`
`healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20th week of gestation
`
`
`
`
`
`
`compared t