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Vilazodone

Class: Serotonin Modulators
VA Class: CN609
Chemical Name: (1) 2-Benzofurancarboxamide, 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-1-piperazinyl]-, hydrochloride (1:1); (2) 5-{4-[4-(5-Cyano-1H-indol-3-yl)butyl]piperazin-1-yl}benzofuran-2-carboxamide monohydrochloride
Molecular Formula: C26H27N5O2•HClC26H27N5O2
CAS Number: 163521-08-2
Brands: Viibryd

Medically reviewed by Drugs.com on Sep 23, 2021. Written by ASHP.

Warning

    Suicidality
  • Antidepressants increased risk of suicidal thinking and behavior (suicidality) compared with placebo in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders; balance this risk with clinical need. Vilazodone is not approved for use in pediatric patients. (See Pediatric Use under Cautions.)

  • In pooled data analyses, risk of suicidality was not increased in adults >24 years of age and apparently was reduced in adults ≥65 years of age with antidepressant therapy compared with placebo.

  • Depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.

  • Appropriately monitor and closely observe all patients who are started on vilazodone therapy for clinical worsening, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process. (See Worsening of Depression and Suicidality Risk under Cautions.)

Introduction

Antidepressant; combined SSRI and 5-HT1A receptor partial agonist.

Uses for Vilazodone

Major Depressive Disorder

Treatment of major depressive disorder in adults.

Vilazodone Dosage and Administration

General

  • Allow at least 2 weeks to elapse between discontinuance of an MAO inhibitor and initiation of vilazodone and vice versa. (See Contraindications and Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Cautionsand also see Specific Drugs under Interactions.)

  • Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments. (See Worsening of Depression and Suicidality Risk under Cautions.)

  • Avoid abrupt discontinuance. Taper dosage gradually and monitor for withdrawal symptoms. If intolerable symptoms occur following dosage reduction or discontinuance, consider reinstituting previously prescribed dosage, then resume more gradual dosage reductions. (See Withdrawal of Therapy under Cautions.)

Administration

Oral Administration

Administer immediate-release tablets orally once daily with food. Taking the drug without food may result in inadequate drug concentrations and reduced efficacy. (See Food under Pharmacokinetics.)

Dosage

Available as vilazodone hydrochloride; dosage expressed in terms of the salt.

Adults

Major Depressive Disorder
Oral

Titrate up to recommended target dosage of 40 mg once daily to reduce risk of adverse effects (particularly GI effects). Manufacturer recommends 10 mg once daily initially for 7 days, followed by 20 mg once daily for an additional 7 days, and 40 mg once daily thereafter. May use the Viibryd patient starter kit for initial 1-month titration period.

If used with a potent CYP3A4 inhibitor, dosage adjustment required; dosage adjustment also may be required if used with a moderate CYP3A4 inhibitor. (See Interactions.)

Optimum duration not established; may require several months or longer of sustained antidepressant therapy. Although manufacturer states that long-term efficacy (i.e., >8 weeks) not studied, long-term therapy at a dosage of 40 mg once daily was effective and well tolerated in a 52-week, open-label trial. Periodically reassess need for continued therapy and appropriateness of dosage.

Special Populations

Hepatic Impairment

No dosage adjustment required in patients with mild or moderate hepatic impairment; not studied in patients with severe hepatic impairment.

Renal Impairment

No dosage adjustment required in patients with mild, moderate, or severe renal impairment. (See Renal Impairment under Cautions.)

Geriatric Patients

Dosage adjustment not necessary.

Gender

Dosage adjustment based on gender not necessary.

Cautions for Vilazodone

Contraindications

  • Concurrent or recent (i.e., within 2 weeks) therapy with an MAO inhibitor. Allow at least 2 weeks to elapse between discontinuance of vilazodone and initiation of MAO inhibitor therapy and vice versa. (See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Cautions and also see Specific Drugs under Interactions.)

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs. (See Boxed Warning and also see Pediatric Use under Cautions.) However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.

Appropriately monitor and closely observe patients receiving vilazodone for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality. Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of the patient’s presenting symptoms. If decision is made to discontinue drug therapy, taper vilazodone dosage as rapidly as is feasible but consider risks of abrupt discontinuance. (See Withdrawal of Therapy under Cautions.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.

Other Warnings and Precautions

Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions

Potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions reported during concurrent therapy with SSRIs or SNRIs and other serotonergic drugs (e.g., 5-HT1 receptor agonists [triptans]), drugs that impair serotonin metabolism (e.g., MAO inhibitors), or antipsychotics or other dopamine antagonists. (See Contraindications under Cautions and also see Interactions.)

Symptoms of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).

Severe serotonin syndrome may resemble NMS, which is characterized by hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes.

Monitor patients receiving vilazodone for the development of serotonin syndrome or NMS-like signs and symptoms. If serotonin syndrome or NMS signs and symptoms occur, discontinue vilazodone and any concurrently administered serotonergic or antidopaminergic agents, including antipsychotic agents, and initiate supportive and symptomatic treatment.

Seizures

Vilazodone has not been studied in patients with seizure disorders; use with caution in patients with a history of seizure disorder.

Abnormal Bleeding

Possible increased risk of bleeding with drugs that interfere with serotonin reuptake, including vilazodone; events ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages. Concurrent use of aspirin, NSAIAs, warfarin, and other anticoagulants may increase risk. (See Drugs Affecting Hemostasis and Specific Drugs under Interactions and also see Advice to Patients.)

Activation of Mania/Hypomania

Possible activation of mania and hypomania; use with caution in patients with personal or family history of bipolar disorder, mania, or hypomania.

Withdrawal of Therapy

Withdrawal effects (e.g., dysphoric mood, irritability, agitation, dizziness, sensory disturbances [e.g., paresthesias, such as electric shock sensations], anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, seizures) reported following discontinuance of serotonergic antidepressants, particularly when discontinuance was abrupt. Events generally self-limiting, but serious cases reported.

Taper dosage gradually; monitor patients for withdrawal symptoms when discontinuing therapy. If intolerable symptoms occur following dosage reduction or discontinuance, consider reinstituting previously prescribed dosage then resume more gradual dosage reductions.

Hyponatremia/SIADH

Although not reported with vilazodone therapy, treatment with SSRIs and SNRIs may cause hyponatremia; in many cases, SIADH is apparent cause. Increased risk in patients who are volume-depleted, elderly, or taking diuretics. Initiate appropriate medical intervention and consider drug discontinuance in patients with symptomatic hyponatremia.

Specific Populations

Pregnancy

Category C.

Possible complications, sometimes severe and requiring prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care in neonates exposed to serotonergic antidepressants (e.g., SSRIs, SNRIs) late in the third trimester; may arise immediately upon delivery.

Conflicting findings from available studies evaluating possible risk of persistent pulmonary hypertension of the newborn (PPHN) following in utero exposure to SSRIs; currently unclear whether SSRI use during pregnancy can cause PPHN.

Consult joint APA and ACOG guidelines (at [Web]) for additional information on management of depression in women prior to conception and during pregnancy, including treatment algorithms.

Effect on labor and delivery unknown.

Lactation

Distributed into milk in animals; not known whether distributed into human milk. Consider breastfeeding only if potential benefit outweighs potential risk to child.

Pediatric Use

Safety and efficacy not established in pediatric patients; not recommended for use in such patients.

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others). However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation. No suicides occurred in these pediatric trials.

Carefully consider these findings when assessing potential benefits and risks of vilazodone in a child or adolescent for any clinical use. (See Suicidality in the Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Geriatric Use

No substantial differences in pharmacokinetics relative to younger adults, but increased sensitivity in some geriatric individuals cannot be ruled out. (See Geriatric Patients under Dosage and Administration.)

Clinically important hyponatremia reported with serotonergic antidepressants (e.g., SSRIs, SNRIs) in geriatric patients. (See Hyponatremia/SIADH under Cautions.)

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo. (See Suicidality in the Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Hepatic Impairment

No dosage adjustment required in patients with mild or moderate hepatic impairment; not studied in patients with severe hepatic impairment.

Renal Impairment

No dosage adjustment required in patients with mild, moderate, or severe renal impairment.

Removal by dialysis not studied; however, vilazodone's large volume of distribution suggests that dialysis will not substantially reduce plasma concentrations of the drug.

Common Adverse Effects

Diarrhea, nausea, vomiting, insomnia.

Interactions for Vilazodone

Metabolized by CYP isoenzymes, principally by 3A4 with minor contributions from CYP2C19 and CYP2D6 and non-CYP (possibly by carboxylesterase) pathways.

Did not induce CYP1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4, or 3A5 in an in vitro study.

Moderate inhibitor of CYP2C19 and CYP2D6.

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased plasma vilazodone concentrations). Reduce vilazodone dosage to 20 mg once daily if used concomitantly with a potent CYP3A4 inhibitor. Reduce vilazodone dosage to 20 mg once daily if used concomitantly with a moderate CYP3A4 inhibitor and patient experiences intolerable adverse effects. Vilazodone dosage adjustment not necessary when used concurrently with a mild CYP3A4 inhibitor.

CYP3A4 inducers: Potential pharmacokinetic interaction (decreased vilazodone AUC).

CYP2C19 or CYP2D6 inhibitors: Clinically important pharmacokinetic interaction unlikely.

Drugs Metabolized by Hepatic Microsomal Enzymes

Drugs metabolized by CYP1A2, 2C9, 2D6, or 3A4: Clinically important pharmacokinetic interaction unlikely.

Drugs metabolized by CYP2C19: Potential pharmacokinetic interaction (possible increased plasma concentrations of CYP2C19 substrate).

Drugs metabolized by CYP2C8: Potential pharmacokinetic interaction (possible increased plasma concentrations of CYP2C8 substrate).

Drugs Associated with Serotonin Syndrome

Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions) with serotonergic drugs. Avoid concomitant use or exercise caution. If serotonin syndrome or NMS occurs, immediately discontinue vilazodone and any concurrently administered antidopaminergic or serotonergic agents and initiate supportive and symptomatic treatment. (See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Cautions.)

Drugs Affecting Hemostasis

Potential pharmacologic interaction (increased risk of bleeding) if used concurrently with drugs that affect coagulation or bleeding; use with caution. (See Abnormal Bleeding under Cautions.)

Drugs Highly Bound to Plasma Protein

Potential pharmacokinetic interaction (possible increased free concentrations of other highly protein bound drugs if used concurrently with vilazodone).

Specific Drugs

Drug

Interaction

Comments

Alcohol

Does not substantially alter pharmacokinetics of vilazodone; possible risk of additive CNS effects

Avoiding concomitant alcohol use recommended

Anticoagulants (e.g., warfarin)

Potential increased risk of bleeding

Carefully monitor patients receiving warfarin during initiation and discontinuance of vilazodone

Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) or SNRIs (e.g., desvenlafaxine, duloxetine, milnacipran, venlafaxine)

Potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions

Use concomitantly with caution

If serotonin syndrome or NMS occurs, immediately discontinue vilazodone and any concurrently administered antidopaminergic or serotonergic agents; initiate supportive and symptomatic treatment

Antipsychotic agents

Potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions

Use concomitantly with caution

If serotonin syndrome or NMS occurs, immediately discontinue vilazodone and any concurrently administered antidopaminergic or serotonergic agents; initiate supportive and symptomatic treatment

Buspirone

Potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions

Use concomitantly with caution

If serotonin syndrome or NMS occurs, immediately discontinue vilazodone and any concurrently administered antidopaminergic or serotonergic agents; initiate supportive and symptomatic treatment

Cimetidine

Possible increased plasma vilazodone concentrations; unlikely to be clinically important

Vilazodone dosage adjustment not necessary

Clarithromycin

Increased plasma vilazodone concentrations by about 50%

Reduce vilazodone dosage to 20 mg once daily during concurrent administration

CNS drugs

Potential pharmacologic interaction

Use concomitantly with caution

Diuretics

Consider risk of hyponatremia

Dopamine antagonists

Potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions

If serotonin syndrome or NMS occurs, immediately discontinue vilazodone and any concurrently administered antidopaminergic or serotonergic agents; initiate supportive and symptomatic treatment

Erythromycin

Increased plasma vilazodone concentrations

Reduce vilazodone dosage to 20 mg once daily if patient experiences intolerable adverse effects during concurrent administration

5-HT1 receptor agonists (triptans; e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan)

Potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions

Use concomitantly with caution; observe carefully, particularly during treatment initiation, dosage increases, or when another serotonergic agent is initiated

If serotonin syndrome or NMS signs and symptoms occur, immediately discontinue vilazodone and any concurrently administered antidopaminergic or serotonergic agents; initiate supportive and symptomatic treatment

Ketoconazole

Increased plasma vilazodone concentrations by about 50%

Reduce vilazodone dosage to 20 mg once daily during concurrent administration

Linezolid

Increased risk of serotonin syndrome

Do not use concurrently; consider availability of alternative anti-infectives and weigh benefit of linezolid against risk of serotonin syndrome

If emergency use of linezolid is considered necessary, immediately discontinue vilazodone; monitor closely for symptoms of CNS toxicity for 2 weeks or until 24 hours after the last linezolid dose, whichever comes first

If nonemergency use of linezolid is planned, withhold vilazodone for at least 2 weeks prior to initiating linezolid; vilazodone may be resumed 24 hours after last linezolid dose

Do not initiate vilazodone in patients receiving linezolid; when necessary, initiate 24 hours after last linezolid dose

MAO inhibitors

Potentially life-threatening serotonin syndrome or NMS-like reactions

Concomitant use contraindicated

Allow at least 2 weeks to elapse between discontinuance of an MAO inhibitor and initiation of vilazodone, or vice versa

Mephenytoin

Increased mephenytoin biotransformation by 11%

Pantoprazole

Pharmacokinetics of vilazodone not substantially altered

Dosage adjustment not necessary

Tramadol

Potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions

Use concomitantly with caution

If serotonin syndrome or NMS occurs, immediately discontinue vilazodone and any concurrently administered antidopaminergic or serotonergic agents; initiate supportive and symptomatic treatment

Tryptophan and other serotonin precursors

Potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions

Concomitant use not recommended

If serotonin syndrome or NMS occurs, immediately discontinue vilazodone and any concurrently administered antidopaminergic or serotonergic agents; initiate supportive and symptomatic treatment

Vilazodone Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability is 72% when taken with food.

Peak plasma concentrations usually achieved within approximately 4–5 hours after oral administration. Steady-state concentrations are achieved within about 3 days.

Absorption is decreased by about 25% if vomiting occurs within 7 hours of ingestion.

Food

Administration with food (a high-fat or light meal) increases oral bioavailability (peak plasma concentrations increased by about 147–160%; AUC increased by about 64–85%).

Distribution

Extent

Widely distributed.

Distributed into milk in rats; not known whether distributed into human milk.

Plasma Protein Binding

Approximately 96–99%.

Elimination

Metabolism

Extensively metabolized by CYP isoenzymes (primarily by CYP3A4; minor contributions from CYP2C19 and CYP2D6) and non-CYP (possibly by carboxylesterase) pathways.

Elimination Route

Primarily by hepatic metabolism; only 1% recovered in urine and 2% recovered in feces as unchanged vilazodone.

Half-life

Approximately 25 hours.

Special Populations

Mild or moderate hepatic impairment does not affect apparent clearance.

Mild or moderate renal impairment does not affect apparent clearance.

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).

Actions

  • Indolalkylamine antidepressant with dual mechanism of action; acts as a combined SSRI and 5-HT1A receptor partial agonist.

  • Precise mechanism of antidepressant action not fully elucidated, but appears to be associated with potentiation of serotonergic activity in the CNS. Net result of vilazodone's SSRI activity and partial agonist activity at 5-HT1A receptors on serotonergic transmission and its role in the drug's antidepressant effect are unknown.

  • Binds with high affinity to the serotonin reuptake site, but not to norepinephrine or dopamine reuptake sites.

  • Potently and selectively inhibits reuptake of serotonin and binds selectively with high affinity to 5-HT1A receptors.

Advice to Patients

  • Importance of providing copy of written patient information (medication guide) each time vilazodone is dispensed. Importance of advising patients to read the patient information before taking vilazodone and each time the prescription is refilled.

  • Risk of suicidality; importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment. (See Worsening of Depression and Suicidality Risk under Cautions.)

  • Importance of advising patients to take vilazodone with food since the drug may be less effective when taken on an empty stomach. Importance of also informing patients that dosage of vilazodone should be titrated when initiating therapy.

  • Importance of instructing patients not to take vilazodone with an MAO inhibitor or within 14 days of stopping the drug, and vice versa.

  • Importance of informing patients of potential risk of serotonin syndrome and neuroleptic malignant syndrome (NMS)-like reactions, particularly with concurrent use of vilazodone and 5-HT1 receptor agonists (also called triptans), tramadol, tryptophan, other serotonergic agents, or antipsychotic agents. Importance of immediately contacting clinician if signs and symptoms of these syndromes develop (e.g., restlessness, hallucinations, loss of coordination, fast heart beat, increased body temperature, muscle stiffness, labile BP, diarrhea, coma, nausea, vomiting, confusion).

  • Risk of seizures; caution patients about use of vilazodone if they have a history of a seizure disorder.

  • Importance of patients being aware that withdrawal effects may occur when stopping vilazodone, especially with abrupt discontinuance of the drug.

  • Importance of informing patients that if they receive diuretics, or are otherwise volume-depleted, or are elderly, that they may be at greater risk of developing hyponatremia during vilazodone therapy.

  • Risk of cognitive and motor impairment; importance of exercising caution while operating hazardous machinery, including automobile driving, until patients are reasonably certain that vilazodone therapy does not adversely affect their ability to engage in such activities.

  • Importance of avoiding alcohol during vilazodone therapy.

  • Importance of advising patients to notify their clinician if they develop any allergic signs or symptoms during therapy (e.g., rash, hives, swelling, difficulty breathing).

  • Importance of advising patients, their families, and caregivers to observe vilazodone-treated patients for signs of activation of mania/hypomania.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs or herbal supplements, as well as any concomitant illnesses (e.g., bipolar disorder, seizure disorder) or personal or family history of suicidality or bipolar disorder.

    Importance of advising patients about the risk of bleeding or bruising associated with concomitant use of vilazodone with aspirin or other NSAIAs, warfarin, or other drugs that affect coagulation.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of advising patients that it usually takes several weeks of antidepressant therapy before they will start to feel better. Advise patients not to stop taking the drug if they do not feel the results right away.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Vilazodone Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Kit

7 Tablets, film-coated, Vilazodone Hydrochloride 10 mg (Viibryd)

7 Tablets, film-coated, Vilazodone Hydrochloride 20 mg (Viibryd)

16 Tablets, film-coated, Vilazodone Hydrochloride 40 mg (Viibryd)

Viibryd Patient Starter Kit (available as blister card containing tablets for the first month of therapy)

Forest

Tablets, film-coated

10 mg

Viibryd

Forest

20 mg

Viibryd

Forest

40 mg

Viibryd

Forest

AHFS DI Essentials™. © Copyright 2022, Selected Revisions October 3, 2014. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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