VIIBRYD tablets for oral administration contain polymorph Form IV vilazodone hydrochloride (HCl), a selective serotonin reuptake inhibitor and a 5HT 1A receptor partial agonist. Vilazodone HCl is 2-benzofurancarboxamide, 5-[4-[4-(5-cyano-1 H -indol-3-yl)butyl]-1-piprazinyl]-, hydrochloride (1:1). Its molecular weight is 477.99. The structural formula is: VIIBRYD tablets are available as 10 mg, 20 mg, and 40 mg film-coated tablets containing 10 mg, 20 mg, and 40 mg of vilazodone HCl, respectively. In addition to the active ingredient, VIIBRYD tablets contain the following inactive ingredients: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, FD&C Blue #1 (40 mg only), FD&C Red #40 (10 mg only), and FD&C Yellow #6 (20 mg only). The structural formula for Vilazodone HCl is 2-benzofurancarboxamide, 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-1-piperazinyl]-, hydrochloride (1:1). Its molecular weight is 477.99.

VIIBRYD ® is indicated for the treatment of major depressive disorder (MDD) in adults . VIIBRYD is indicated for the treatment of major depressive disorder (MDD) in adults.

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 Tablets: 10 mg, 20 mg, and 40 mg

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 Prior to initiating VIIBRYD, screen for bipolar disorder When discontinuing VIIBRYD, reduce dosage gradually 2.1 Dosage for Treatment of Major Depressive Disorder The recommended target dosage for VIIBRYD is 20 mg to 40 mg orally once daily with food [ see Clinical Pharmacology , 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

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 . 2. 3 Switching t o or f rom 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 . 2. 4 Dosage Adjustments with CYP3A4 Inhibitors or Inducers 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 . 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 . 2. 5 Discontinuing Treatment with VIIBRYD Adverse reactions may occur upon discontinuation of VIIBRYD . 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.

Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone. If it occurs, discontinue VIIBRYD and serotonergic agents and initiate supportive treatment Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk Activation of Mania/Hypomania: Screen patients for bipolar disorder Seizures: Can occur with treatment. Use with caution in patients with a seizure disorder Angle Closure Glaucoma: Avoid use of antidepressants, including VIIBRYD, in patients with untreated anatomically narrow angles Sexual Dysfunction: VIIBRYD may cause symptoms of sexual dysfunction 5.1 Suicidal Thoughts and Behavior in Adolescents and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients, and over 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater in antidepressant-treated patients than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 1. 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 Age Range (years) Drug-Placebo Difference in Number of Patient s with Suicidal Thoughts or Behaviors per 1000 Patients Treated Increases Compared to Placebo <18 14 additional patients 18-24 5 additional patients Decreases Compared to Placebo 25-64 1 fewer patient ≥65 6 fewer patients 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 and that depression itself is a risk factor for suicidal thoughts and behaviors. 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

Serotonin Syndrome Serotonin and norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitor (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, meperidine, methadone, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs . 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 methylene blue in a patient taking VIIBRYD, discontinue VIIBRYD before initiating treatment with the MAOI [ see Contraindications , Drug Interactions ]. 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. Based on data from the published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage . 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 increased 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. 5. 4 Activation of Mania or Hypomania 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 . 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

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. 5. 8 Hyponatremia 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

Sexual Dysfunction Use of SSRIs, including VIIBRYD, may cause symptoms of sexual dysfunction . In male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SSRI use may result in decreased libido and delayed or absent orgasm. It is important for prescribers to inquire about sexual function prior to initiation of VIIBRYD and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment.

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 )

Drugs Having Clinically Important Interactions With VIIBRYD Table 4: Clinically Important Drug Interactions with VIIBRYD Concomitant Drug Name or Drug Class Clinical Rationale Clinical Recommendation Monoamine Oxidase Inhibitors (MAOIs) The concomitant use of MAOIs and serotonergic drugs including VIIBRYD increases the risk of serotonin syndrome. VIIBRYD is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue . Other Serotonergic Drugs Concomitant use of VIIBRYD with other serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John's Wort) increases the risk of serotonin syndrome. 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 . Antiplatelet Agents and Anticoagulants 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. 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, titrating, or discontinuing VIIBRYD . Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin, voriconazole) The concomitant use of VIIBRYD and strong CYP3A4 inhibitors increased the exposure of vilazodone compared to the use of VIIBRYD alone . The VIIBRYD dose should not exceed 20 mg once daily with the concomitant use of a strong CYP3A4 inhibitor . Strong CYP3A4 Inducers (e.g., carbamazepine, phenytoin, rifampin) The concomitant use of VIIBRYD and strong CYP3A4 inducers decreased the exposure of vilazodone compared to the use of VIIBRYD alone . 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 . Digoxin Digoxin is a narrow therapeutic index drug. Concomitant use of VIIBRYD increased digoxin concentrations . 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 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 .