Vilazodone Hydrochloride

[Section Outline]

Administration
Dosage
Special Populations

Administration

Vilazodone hydrochloride is commercially available as immediate-release tablets, which are administered orally once daily and should be taken with food.1 The manufacturer cautions that taking the drug without food may result in inadequate drug concentrations and reduced efficacy.1 (See Description.)

Patients receiving vilazodone should be monitored for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustment.1,12,14,15 (See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)

The manufacturer states that at least 2 weeks must elapse between discontinuance of a monoamine oxidase (MAO) inhibitor and initiation of vilazodone therapy and vice versa.1 (See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions and also see Drug Interactions: Monoamine Oxidase Inhibitors.)

Dosage

Major Depressive Disorder

For the management of major depressive disorder in adults, the recommended target dosage of vilazodone hydrochloride is 40 mg orally once daily.1,29,30 To reduce the risk of adverse effects (particularly GI effects) early in therapy, the dosage should be titrated beginning with 10 mg once daily for the first 7 days, followed by 20 mg once daily for an additional 7 days, and then 40 mg once daily thereafter.1,29,30 A patient starter kit is commercially available for this initial 1-month dosage titration period.1

Although the manufacturer states that the efficacy of vilazodone for long-term therapy (i.e., longer than 8 weeks) has not been systematically demonstrated to date,1 long-term therapy with the drug in a dosage of 40 mg once daily was shown to be effective and well tolerated in adults with major depressive disorder in a 52-week, open-label trial.4 It is generally agreed that acute depressive episodes require several months or longer of sustained antidepressant therapy in responding patients.1,5 In addition, some clinicians recommend that long-term antidepressant therapy be considered in certain patients at risk for recurrence of depressive episodes (such as those with chronic and recurrent major depressive disorder).5 If vilazodone is used for extended periods, the need for continued maintenance therapy and the appropriate dosage of the drug should be reassessed periodically.1

Discontinuance of Therapy

Because withdrawal effects may occur with discontinuance of serotonergic drugs such as vilazodone, abrupt discontinuance should be avoided whenever possible.1,5 When vilazodone therapy is discontinued, the dosage should be reduced gradually and the patient monitored for possible withdrawal symptoms.1,5 If intolerable symptoms occur following dosage reduction or upon discontinuance of therapy, therapy may be reinstituted at the previously prescribed dosage.1 Subsequently, the clinician may continue decreasing the dosage, but at a more gradual rate.1 (See Withdrawal of Therapy under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Special Populations

Dosage adjustment is not necessary in patients with renal impairment.1 (See Renal Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

In patients with mild or moderate hepatic impairment, dosage adjustment is not necessary.1,8 Vilazodone has not been studied in patients with severe hepatic impairment.1 (See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

No dosage adjustment is necessary in geriatric patients.1 In addition, dosage adjustment is not recommended based on gender.1

The recommended target dosage of vilazodone hydrochloride should be decreased to 20 mg once daily when used concurrently with potent inhibitors of the cytochrome P-450 (CYP) isoenzyme 3A4 (e.g., clarithromycin, ketoconazole).1,19,30 During concurrent use with moderate inhibitors of CYP3A4 (e.g., erythromycin), the vilazodone dosage should be decreased to 20 mg once daily in patients who are experiencing intolerable adverse effects.1,30 No dosage adjustment is necessary when vilazodone is used with mild inhibitors of CYP3A4 (e.g., cimetidine).1,30 (See Drug Interactions.)

Cautions ⬆ ⬇

[Section Outline]

Contraindications
Warnings/Precautions
Common Adverse Effects

Contraindications

Concurrent or recent (i.e., within 2 weeks) therapy with a monoamine oxidase (MAO) inhibitor.1 At least 14 days should elapse between discontinuance of vilazodone and initiation of MAO inhibitor therapy and vice versa.1 (See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions and also see Drug Interactions: Monoamine Oxidase Inhibitors.)

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior may occur in both adult and pediatric (see Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions) patients with major depressive disorder or other psychiatric disorders, whether or not they are taking antidepressants.1,12,14,15,28 This risk may persist until clinically important remission occurs.1,14 Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.1,12,14,15 However, there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.1,14 Pooled analyses of short-term, placebo-controlled studies of antidepressants (i.e., selective serotonin-reuptake inhibitors [SSRIs] and other antidepressants) have shown an increased risk of suicidality in children, adolescents, and young adults (18-24 years of age) with major depressive disorder and other psychiatric disorders.1,12,14 An increased suicidality risk was not demonstrated with antidepressants compared with placebo in adults older than 24 years of age, and a reduced risk was observed in adults 65 years of age or older.1,12,14

The US Food and Drug Administration (FDA) recommends that all patients being treated with antidepressants for any indication be appropriately monitored and closely observed for clinical worsening, suicidality, and unusual changes in behavior, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.12,14,15 Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, also should be advised to monitor patients on a daily basis for the emergence of agitation, irritability, or unusual changes in behavior as well as the emergence of suicidality, and to report such symptoms immediately to a health-care provider.1,14,15

Although a causal relationship between the emergence of symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.1,14,15 Consequently, consideration should be given to changing the therapeutic regimen or discontinuing therapy in patients whose depression is persistently worse or in patients experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if such manifestations are severe, abrupt in onset, or were not part of the patient's presenting symptoms.1,14 If a decision is made to discontinue therapy, vilazodone dosage should be tapered as rapidly as is feasible but consideration should be given to the risks of abrupt discontinuance.1,14 FDA also recommends that the drugs be prescribed in the smallest quantity consistent with good patient management, in order to reduce the risk of overdosage.1,14

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 have been reported with antidepressants alone, but particularly with concurrent use of other serotonergic drugs (including serotonin [5-hydroxytryptamine; 5-HT] type 1 receptor agonists [“triptans”]), drugs that impair the metabolism of serotonin (e.g., MAO inhibitors), or antipsychotics or other dopamine antagonists.1,18,31 Manifestations of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).1,18,31 In its most severe form, serotonin syndrome may resemble NMS, which is characterized by hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation in vital signs, and mental status changes.1,31 Patients receiving vilazodone should be monitored for the development of serotonin syndrome or NMS-like signs and symptoms.1 (See Contraindications and also see Drug Interactions.)

Concurrent or recent (i.e., within 2 weeks) therapy with MAO inhibitors intended to treat depression is contraindicated.1 (See Contraindications and also see Drug Interactions: Monoamine Oxidase Inhibitors.)

If concurrent therapy with vilazodone and a 5-HT₁ receptor agonist (triptan) is clinically warranted, the patient should be observed carefully, particularly during initiation of therapy, when dosage is increased, or when another serotonergic agent is initiated.18

Concomitant use of vilazodone and serotonin precursors (e.g., tryptophan) is not recommended.1

If signs and symptoms of serotonin syndrome or NMS occur, treatment with vilazodone and any concurrently administered serotonergic or antidopaminergic agents, including antipsychotic agents, should be immediately discontinued and supportive and symptomatic treatment initiated.1

Seizures

Vilazodone has not been systematically evaluated in patients with seizure disorders; such patients were excluded from clinical studies.1 As with other antidepressants, vilazodone should be used with caution in patients with a history of seizure disorder.1

Abnormal Bleeding

Drugs that interfere with serotonin reuptake, including vilazodone, may increase the risk of bleeding events.1,21 Concurrent use of aspirin, nonsteroidal anti-inflammatory agents (NSAIAs), warfarin, and other anticoagulants may add to this risk.1 Case reports and epidemiologic studies have demonstrated an association between the use of drugs that interfere with serotonin reuptake and the occurrence of GI bleeding.1,21 Bleeding events related to SSRI use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.1,21 The manufacturer recommends that patients be advised of the risk of bleeding associated with the concomitant use of vilazodone and aspirin or other NSAIAs, warfarin, or other drugs that affect coagulation or bleeding.1 (See Drug Interactions: Drugs Affecting Hemostasis.)

Activation of Mania/Hypomania

Symptoms of mania and hypomania have been reported in 0.1% of vilazodone-treated patients in clinical studies.1 Activation of mania and hypomania has also been reported in a small proportion of patients with major affective disorder who were treated with other antidepressants.1 Vilazodone should therefore be used with caution in patients with a personal or family history of bipolar disorder, mania, or hypomania.1

Withdrawal of Therapy

Withdrawal symptoms, including dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures, have been reported upon discontinuance of serotonergic antidepressants, particularly when discontinuance of these drugs is abrupt.1,5,6,7 While these reactions are generally self-limiting, there have been reports of serious discontinuance symptoms.1,5,6,7 Therefore, patients should be monitored for such symptoms when discontinuing vilazodone therapy.1 A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible.1 (See Discontinuance of Therapy under Dosage and Administration: Dosage.)

If intolerable symptoms occur following dosage reduction or discontinuance of vilazodone, the previously prescribed dosage should be reinstituted until symptoms abate; dosage reductions may then be resumed at a more gradual rate.1

Hyponatremia/Syndrome of Inappropriate Antidiuretic Hormone Secretion

Although no cases of hyponatremia associated with vilazodone therapy were reported in clinical trials, treatment with SSRIs and selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs) may result in hyponatremia.1 In many cases, hyponatremia appears to be due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH).1 Cases with serum sodium concentrations lower than 110 mEq/L have been reported.1 Geriatric individuals and patients receiving diuretics or who are otherwise volume depleted may be at greater risk of developing hyponatremia.1 Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls; more severe and/or acute cases have been associated with hallucinations, syncope, seizures, coma, respiratory arrest, and death.1 Vilazodone should be discontinued and appropriate medical intervention should be initiated in patients with symptomatic hyponatremia.1

Specific Populations

Pregnancy

Category C.1 (See Users Guide.)

Some neonates exposed to serotonergic antidepressants (e.g., SSRIs, SNRIs) late in the third trimester of pregnancy have developed complications that have sometimes been severe and required prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care in special-care nurseries.1,22,23,24,25,26,27 Such complications may arise immediately upon delivery and usually last several days or up to 2-4 weeks.1,22,23,24,25,26,27 Clinical findings reported to date in the neonates have included respiratory distress, cyanosis, apnea, seizures, temperature instability or fever, feeding difficulty, dehydration, excessive weight loss, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying.1,22,23,24,25,26,27 These features appear to be consistent with either a direct toxic effect of serotonergic antidepressants or, possibly, a drug withdrawal syndrome.1,22,23,24,25,26,27 In some cases, the clinical picture was consistent with serotonin syndrome.1,23

Infants exposed to SSRIs in late pregnancy may have an increased risk of persistent pulmonary hypertension of the newborn (PPHN), a rare heart and lung condition associated with substantial neonatal morbidity and mortality.32,34,37,42 Although several epidemiologic studies have suggested an increased risk of PPHN with SSRI use during pregnancy,32,34,37,42 other studies did not demonstrate a statistically significant association.32,38,39,40 The FDA states that it is currently unclear whether the use of SSRIs, including vilazodone, during pregnancy can cause PPHN and recommends that clinicians not alter their current clinical practice of treating depression during pregnancy.32

For additional information on the management of depression in women prior to conception and during pregnancy, including treatment algorithms, clinicians may consult the joint American Psychiatric Association and American College of Obstetricians and Gynecologists guidelines (at [Web]).32,35

The effect of vilazodone on labor and delivery is unknown.1 The manufacturer states that the drug should be used during labor and delivery only if the potential benefit to the mother outweighs the potential risk to the infant.1

Lactation

Vilazodone is distributed into milk in rats.1 It is not known whether the drug is distributed into human milk.1 The manufacturer states that breast-feeding in vilazodone-treated patients should only be considered if the potential benefit to the mother outweighs the potential risk to the infant.1

Pediatric Use

Safety and effectiveness of vilazodone in pediatric patients have not been established.1

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 other antidepressants).1,14 However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and other antidepressants) in patients younger than 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 ideation.28 No suicides occurred in these pediatric trials.1,14,28 These findings should be carefully considered when assessing potential benefits and risks of vilazodone in a child or adolescent for any clinical use.1,14,15,28 (See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)

The manufacturer states that vilazodone is not approved for use in pediatric patients.1

Geriatric Use

In clinical trials with vilazodone, 1.7% of patients were 65 years of age or older and 12.5% were 55-64 years of age.1 Results from a single-dose pharmacokinetic study have shown that the pharmacokinetics of vilazodone are generally similar between geriatric and younger adults.1 The manufacturer states that dosage adjustment is not necessary based on age.1 However, increased sensitivity to the drug in some older individuals cannot be ruled out.1

Serotonergic antidepressants (e.g., SSRIs, SNRIs) have been associated with clinically important hyponatremia in geriatric patients, who may be at greater risk for this adverse effect.1 (See Hyponatremia/Syndrome of Inappropriate Antidiuretic Hormone Secretion under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

In pooled data analyses, a reduced risk of suicidality was observed in adults 65 years of age or older with antidepressant therapy compared with placebo.1,12,14 (See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)

Hepatic Impairment

Dosage modification of vilazodone is not necessary in patients with mild or moderate hepatic impairment.1,8 However, safety and efficacy of the drug have not been established in patients with severe hepatic impairment.1

Renal Impairment

Dosage adjustment of vilazodone is not necessary in patients with renal impairment.1

The removal of vilazodone by dialysis has not been studied; however, the drug's large volume of distribution suggests that dialysis will not substantially reduce plasma concentrations of the drug.1

Common Adverse Effects

Adverse effects reported in 5% or more of patients with major depressive disorder receiving vilazodone in clinical studies and at an incidence of at least twice that reported with placebo include diarrhea,1,2,3,4 nausea,1,2,3,4 vomiting,1 and insomnia.1

Drug Interactions ⬆ ⬇

[Section Outline]

Drugs Affecting Hepatic Microsomal Enzymes
Drugs Metabolized by Hepatic Microsomal Enzymes
Cimetidine and Other Mild CYP3A4 Inhibitors
Erythromycin and Other Moderate CYP3A4 Inhibitors
Ketoconazole and Other Potent CYP3A4 Inhibitors
Monoamine Oxidase Inhibitors
Linezolid
Selective Serotonin-reuptake Inhibitors and Selective Serotonin- and Norepinephrine-reuptake Inhibitors
5-HT1 Receptor Agonists (“Triptans”)
Tryptophan and Other Serotonin Precursors
Antipsychotic Agents and Other Dopamine Antagonists
Other Serotonergic Drugs
CNS-active Drugs
Drugs Affecting Hemostasis
Pantoprazole
Protein-bound Drugs
Alcohol

Drugs Affecting Hepatic Microsomal Enzymes

Metabolism by the cytochrome P-450 (CYP) 3A4 isoenzyme is a major metabolic pathway for vilazodone.1 Concomitant administration of vilazodone and CYP3A4 inhibitors (e.g., clarithromycin, erythromycin, ketoconazole) potentially may result in increased vilazodone plasma concentrations.1,19 (See Drug Interactions: Cimetidine and Other Mild CYP3A4 Inhibitors, see Drug Interactions: Erythromycin and Other Moderate CYP3A4 Inhibitors, and also see Drug Interactions: Ketoconazole and Other Potent CYP3A4 Inhibitors.)

The manufacturer states that concomitant use of vilazodone with CYP3A4 inducers (e.g., carbamazepine) potentially can reduce vilazodone systemic exposure.1,11 However, the effect of CYP3A4 inducers on plasma vilazodone concentrations has not been evaluated to date.1

Concomitant administration of vilazodone with inhibitors of CYP2C19 or CYP2D6 is not expected to substantially alter plasma concentrations of vilazodone, since these isoenzymes are minor elimination pathways in the metabolism of the drug.1 In vitro studies have shown that the CYP isoenzymes 1A2, 2A6, 2C9, and 2E1 minimally contribute to the metabolism of vilazodone.1

Drugs Metabolized by Hepatic Microsomal Enzymes

No clinically important pharmacokinetic interaction has been observed during concomitant administration of vilazodone and caffeine (a CYP1A2 substrate), flurbiprofen (a CYP2C9 substrate), nifedipine (a CYP3A4 substrate), or debrisoquine (a CYP2D6 substrate).1,30 Concurrent administration of vilazodone with substrates of the CYP isoenzymes 1A2, 2C9, 3A4, or 2D6 is unlikely to result in clinically relevant changes in plasma concentrations of these substrates.1 Concurrent administration of vilazodone with mephenytoin increased mephenytoin biotransformation by 11%, suggesting minor induction of CYP2C19.1,30 In vitro studies have shown that vilazodone is a moderate inhibitor of CYP2C19 and CYP2D6.1

Concurrent administration of vilazodone with a CYP2C8 substrate may inhibit biotransformation of the CYP2C8 substrate resulting in an increased substrate concentration.1

In an in vitro study, vilazodone did not induce CYP1A1, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4, or 3A5.1 Chronic administration of vilazodone appears unlikely to induce the metabolism of drugs metabolized by these isoenzymes.1

Cimetidine and Other Mild CYP3A4 Inhibitors

The manufacturer states that no dosage adjustment is necessary when vilazodone is given concomitantly with cimetidine or other mild CYP3A4 inhibitors.1,30 (See Drug Interactions: Drugs Affecting Hepatic Microsomal Enzymes.)

Erythromycin and Other Moderate CYP3A4 Inhibitors

Concomitant administration of vilazodone and moderate CYP3A4 inhibitors (e.g., erythromycin) can result in increased plasma vilazodone concentrations.1 During concurrent administration with moderate inhibitors of CYP3A4 (e.g., erythromycin), the dosage of vilazodone should be reduced to 20 mg once daily in patients experiencing intolerable adverse effects.1,30

Ketoconazole and Other Potent CYP3A4 Inhibitors

Concomitant administration of vilazodone and potent CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) can increase plasma vilazodone concentrations by approximately 50%.1,19 The manufacturer states that the dosage of vilazodone should be reduced to 20 mg once daily if administered concomitantly with a potent CYP3A4 inhibitor.1,30

Monoamine Oxidase Inhibitors

Potentially serious, sometimes fatal adverse reactions may occur in patients who are receiving or have recently received a monoamine oxidase (MAO) inhibitor and then initiate therapy with antidepressant(s) that are pharmacologically similar to vilazodone (e.g., SSRIs), or in those who received SSRI therapy shortly before initiation of an MAO inhibitor. Concomitant use of MAO inhibitors with vilazodone is contraindicated.1 In addition, at least 2 weeks should elapse between discontinuance of an MAO inhibitor and initiation of vilazodone and vice versa.1 (See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Linezolid

Linezolid, an anti-infective agent that is also a reversible MAO inhibitor, has been associated with drug interactions resulting in serotonin syndrome, including some associated with SSRIs.16,17 Because of this potential risk, linezolid generally should not be used in patients receiving vilazodone.16 While the US Food and Drug Administration (FDA) has not received reports of serotonin syndrome with concomitant use of linezolid and vilazodone to date, the risk is considered comparable to that with SSRIs.17 However, the FDA states that certain life-threatening or urgent situations may necessitate immediate linezolid treatment in a patient receiving a serotonergic drug.16 In such emergency situations, the availability of alternative anti-infectives should be considered and the benefits of linezolid should be weighed against the risk of serotonin syndrome.16 If linezolid is indicated in such emergency situations, vilazodone must be immediately discontinued and the patient monitored for symptoms of CNS toxicity for 2 weeks or until 24 hours after the last linezolid dose, whichever comes first.16 Treatment with vilazodone may be resumed 24 hours after the last linezolid dose.16

If nonemergency use of linezolid is being planned for a patient receiving vilazodone, vilazodone should be withheld for at least 2 weeks prior to initiating linezolid.16

Treatment with vilazodone should not be initiated in a patient receiving linezolid; when necessary, vilazodone may be started 24 hours after the last linezolid dose.16 (See Drug Interactions: Serotonergic Drugs, in Linezolid 8:12.28.24.)

Selective Serotonin-reuptake Inhibitors and Selective Serotonin- and Norepinephrine-reuptake Inhibitors

Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions).1 (See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

5-HT1 Receptor Agonists (“Triptans”)

Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions) if used concurrently with serotonin type 1 (5-hydroxytryptamine [5-HT₁]) receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan).1,18 If concomitant therapy is clinically warranted, the patient should be observed carefully, particularly during treatment initiation, when dosage is increased, or when another serotonergic agent is initiated.1,18 (See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Tryptophan and Other Serotonin Precursors

Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions).1 Concomitant use is not recommended.1 (See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Antipsychotic Agents and Other Dopamine Antagonists

Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions) if used concurrently with antipsychotic agents or other dopamine antagonists.1 If serotonin syndrome or NMS signs and symptoms occur, treatment with vilazodone and any concurrently administered antidopaminergic or serotonergic agents should be discontinued immediately and supportive and symptomatic treatment should be initiated.1 (See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Other Serotonergic Drugs

Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions) with other drugs affecting serotonergic neurotransmission, including buspirone and tramadol; these agents should be used concomitantly with caution.1 If signs and symptoms of serotonin syndrome or NMS occur, treatment with vilazodone and any concurrently administered serotonergic or antidopaminergic agents should be discontinued immediately and supportive and symptomatic treatment should be initiated.1 (See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

CNS-active Drugs

The risk of concurrent administration of vilazodone and other CNS-active drugs has not been systematically evaluated to date.1 The manufacturer recommends using caution when vilazodone is given in combination with other centrally acting drugs.1

Drugs Affecting Hemostasis

Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs and SNRIs were concurrently administered with warfarin.1,21 Patients receiving warfarin therapy should be carefully monitored when vilazodone is initiated or discontinued.1

Potential pharmacologic interaction (increased risk of bleeding) if used concurrently with aspirin or other nonsteroidal anti-inflammatory agents (NSAIAs); vilazodone and drugs that affect hemostasis should be used concomitantly with caution.1,21

Pantoprazole

Administration of vilazodone with pantoprazole sodium, a proton-pump inhibitor, did not substantially alter the rate or extent of vilazodone absorption.1 In addition, neither the time to peak concentration nor the elimination rate of vilazodone was affected by concurrent pantoprazole administration.1 The manufacturer states that dosage adjustment is not necessary when these drugs are given in combination.1

Protein-bound Drugs

Potential drug interactions between vilazodone and other highly protein-bound drugs have not been evaluated to date.1 However, vilazodone is highly bound to plasma proteins and concurrent administration of vilazodone in patients receiving another drug that is highly protein bound may result in increased free concentrations of the other drug.1

Alcohol

Alcohol does not appear to substantially alter the pharmacokinetics of vilazodone; therefore, dosage adjustment of vilazodone is not necessary during concurrent use.1 However, because of the risk of additive CNS depressant effects, the manufacturer recommends that alcohol be avoided during vilazodone therapy.1

Other Information ⬆ ⬇

Description

Vilazodone hydrochloride is an indolalkylamine antidepressant with a dual mechanism of action; the drug acts as a combined selective serotonin-reuptake inhibitor (SSRI) and as a serotonin type 1A (5-hydroxytryptamine [5-HT_1A]) receptor partial agonist.1,2,3,4,9,19,29,30 The precise mechanism of the antidepressant effect of vilazodone is not fully understood, but is thought to be related to enhancement of serotonergic activity in the CNS through selective inhibition of serotonin reuptake.1 Vilazodone is also a partial agonist at serotonergic 5-HT_1A receptors; however, the net result of this action on serotonergic transmission and its role in the drug's antidepressant effect currently are unknown.1

Vilazodone binds with high affinity to the serotonin reuptake site, but not to the norepinephrine or dopamine reuptake sites.1 The drug potently and selectively inhibits the reuptake of serotonin and binds selectively with high affinity to 5-HT_1A receptors.1,9,10

Absolute oral bioavailability of vilazodone hydrochloride is 72% when taken with food.1 Administration of the drug with food (a high-fat or light meal) increases its oral bioavailability (peak plasma concentrations increase by about 147-160% and area under the concentration-time curve [AUC] increases by about 64-85%).1 Plasma concentrations of vilazodone peak at a median of 4-5 hours after oral administration and decline with a terminal elimination half-life of about 25 hours.1 Vilazodone is widely distributed and approximately 96-99% protein bound.1 The drug is extensively metabolized through cytochrome P-450 (CYP), primarily by CYP3A4 with minor contributions from CYP2C19 and CYP2D6 and non-CYP pathways (possibly by carboxylesterase).1 Only 1% of an oral dose is recovered in the urine and 2% of the dose is recovered in the feces as unchanged vilazodone.1

Advice to Patients

Importance of providing a copy of written patient information (medication guide) each time vilazodone hydrochloride is dispensed.1,12,14,15 Importance of advising patients to read the patient information before taking vilazodone and each time the prescription is refilled.1

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.1,12,14,15 (See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)

Importance of advising patients to take vilazodone with food since the drug may be less effective when taken on an empty stomach.1 Importance of also informing patients that the dosage of vilazodone hydrochloride should be titrated when initiating therapy.1

Importance of instructing patients not to take vilazodone with or within 14 days of discontinuing a monoamine oxidase (MAO) inhibitor.1

Importance of informing patients of potential risk of serotonin syndrome and neuroleptic malignant syndrome (NMS)-like reactions, particularly with concurrent use of vilazodone hydrochloride and 5-HT₁ receptor agonists (also called triptans), tramadol, tryptophan, other serotonergic agents, or antipsychotic agents.1,18 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 blood pressure, diarrhea, coma, nausea, vomiting, confusion).1,18

Risk of seizures; importance of cautioning patients about use of vilazodone if they have a history of a seizure disorder.1

Importance of patients being aware that withdrawal effects may occur when stopping vilazodone, especially with abrupt discontinuance of the drug.1

Importance of informing patients that if they receive diuretics, are otherwise volume depleted, or are elderly, that they may be at greater risk of developing hyponatremia during vilazodone therapy.1

Risk of cognitive and motor impairment; importance of patients exercising caution while operating hazardous machinery, including driving a motor vehicle, until they are reasonably certain that vilazodone therapy does not adversely affect their ability to engage in such activities.1

Importance of avoiding alcohol during vilazodone therapy.1

Importance of advising patients to notify their clinician if any signs or symptoms of an allergic reaction develop during therapy (e.g., rash, hives, swelling, difficulty breathing).1

Importance of advising patients, their families, and caregivers to watch for signs of activation of mania/hypomania.1

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.1 Importance of advising patients about the risk of bleeding associated with concomitant use of vilazodone with aspirin or other nonsteroidal anti-inflammatory agents, warfarin, or other drugs that affect coagulation.1

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

Importance of informing patients of other important precautionary information.1 (See Cautions.)

Additional Information

Overview^® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

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	Tablets, film-coated	10 mg	Viibryd^®	Forest
		20 mg	Viibryd^®	Forest
		40 mg	Viibryd^®	Forest

References ⬆

1. Forest Pharmaceuticals, Inc. Viibryd^® (vilazodone hydrochloride) tablets prescribing information. St Louis, MO; 2011 Apr.

2. Rickels K, Athanasiou M, Robinson DS et al. Evidence for efficacy and tolerability of vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry . 2009; 70:326-33. [PubMed 19284933]

3. Khan A, Cutler AJ, Kajdasz DK et al. A randomized, double-blind, placebo-controlled, 8-week study of vilazodone, a serotonergic agent for the treatment of major depressive disorder. J Clin Psychiatry . 2011; 72:441-7. [PubMed 21527122]

4. Robinson DS, Kajdasz DK, Gallipoli S et al. A 1-year, open-label study assessing the safety and tolerability of vilazodone in patients with major depressive disorder. J Clin Psychopharmacol . 2011; 31:643-6. [PubMed 21869687]

5. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder, third edition. Am J Psychiatry . 2010; 167(suppl) [Web]

6. The European Agency for the Evaluation of Medicinal Products (EMEA). Committee for proprietary medicinal products (CPMP) position paper on selective serotonin uptake inhibitors (SSRIs) and dependency/withdrawal reactions. London, UK; 2000 Apr 12. From EMEA web site. [Web]

7. Lazowick AL, Levin GM. Potential withdrawal syndrome associated with SSRI discontinuation. Ann Pharmacother. 1995; 29:1284-5.

8. Longstreth J, Alcorn H, Adams MH, et al.. Vilazodone pharmacokinetics in subjects with mild to moderate hepatic impairment [abstract]. Presented at the American Psychiatric Association annual meeting. New Orleans, LA: 2010 May 22-26. Abstract NR4-37. [Web]

9. Hughes ZA, Starr KR, Langmead CJ et al. Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone. Eur J Pharmacol . 2005; 510:49-57. [PubMed 15740724]

10. Page ME, Cryan JF, Sullivan A et al. Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist. J Pharmacol Exp Ther . 2002; 302:1220-7. [PubMed 12183683]

11. Novartis Pharmaceuticals Corporation. Tegretol^® (carbamazepine) chewable tablets, suspension, and tablets and Tegretol^®-XR (carbamazepine) extended-release tablets prescribing information. East Hanover, NJ; 2011 Mar.

12. US Food and Drug Administration. FDA news: FDA proposes new warnings about suicidal thinking, behavior in young adults who take antidepressant medications. Rockville, MD; 2007 May 2. From the FDA website. [Web]

14. US Food and Drug Administration. Antidepressant use in children, adolescents, and adults: class revisions to product labeling. Rockville, MD; 2007 May 2. From the FDA website. [Web]

15. US Food and Drug Administration. Revisions to medication guide: antidepressant medicines, depression and other serious mental illnesses and suicidal thoughts or actions. Rockville, MD; 2007 May 2. From the FDA website. [Web]

16. US Food and Drug Administration. Drug Safety Communication: Serious CNS reactions possible when linezolid (Zyvox) is given to patients taking certain psychiatric medications. 2011 Jul 26. From FDA website. [Web]

17. US Food and Drug Administration. Drug Safety Communication: Updated information about the drug interaction between linezolid (Zyvox^®) and serotonergic psychiatric medications. 2011 Oct 20. From FDA website. [Web]

18. Food and Drug Administration. Public health advisory: combined use of 5-hydroxytryptamine receptor agonists (triptans), selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs) may result in life-threatening serotonin syndrome. Rockville, MD; 2006 Jul 19. From the FDA website. [Web]

19. Anon. Vilazodone (Viibryd®) — a new antidepressant. Med Lett Drugs Therapeutics . 2011; 53:53-4.

21. Meijer WEE, Heerdink ER, Nolen WA et al. Association of risk of abnormal bleeding with degree of serotonin reuptake inhibition by antidepressants. Arch Intern Med . 2004; 164:2367-70. [PubMed 15557417]

22. Morag I, Batash D, Keidar R et al. Paroxetine use throughout pregnancy: does it pose any risk to the neonate? J Toxicol Clin Toxicol . 2004; 42:97-100.

23. Haddad PM, Pal BR, Clarke P et al. Neonatal symptoms following maternal paroxetine treatment: serotonin toxicity or paroxetine discontinuation syndrome? J Psychopharmacol . 2005; 19:554-7.

24. Moses-Kolko EL, Bogen D, Perel J et al. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. JAMA . 2005; 292:2372-85.

25. Sanz EJ, De-Las-Cuevas C, Kiuru A et al. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet . 2005; 365:482-7. [PubMed 15705457]

26. Nordeng H, Lindemann R, Perminov KV et al. Neonatal withdrawal syndrome after in utero exposure to selective serotonin-reuptake inhibitors. Acta Paediatr . 2001; 90:288-91. [PubMed 11332169]

27. Dahl ML, Olhager E, Ahlner J. Paroxetine withdrawal syndrome in a neonate. Br J Psychiatr . 1997; 171:391-2.

28. Bridge JA, Iyengar S, Salary CB. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA . 2007; 297:1683-96. [PubMed 17440145]

29. Lindsey WT. Vilazodone for the treatment of depression. Ann Pharmacother . 2011; 45:946-53. [PubMed 21672888]

30. Frampton JE. Vilazodone in major depressive disorder. CNS Drugs . 2011; 25:615-27. [PubMed 21699273]

31. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med . 2005; 352:1112-20. [PubMed 15784664]

32. US Food and Drug Administration. Drug Safety Communication: Selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and reports of a rare heart and lung condition in newborn babies. 2011 Dec 14. From the FDA website. [Web]

33. US Food and Drug Administration. Public health advisory: treatment challenges of depression in pregnancy and the possibility of persistent pulmonary hypertension in newborns. Rockville, MD; 2006 Jul 19. From the FDA website. [Web]

34. Chambers CD, Hernandez-Diaz S, Van Marter LJ et al. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. New Engl J Med . 2006; 354:579-87. [PubMed 16467545]

35. Yonkers KA, Wisner KL, Stewart DE et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Obstet Gynecol . 2009; 114:703-13. [Web][PubMedCentral][PubMed 19701065]

36. Roerig, Division of Pfizer Inc. Zoloft^® (sertraline hydrochloride) tablets and oral concentrate. 2011 Sep.

37. Källén B, Olausson PO. Maternal use of selective serotonin re-uptake inhibitors and persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf . 2008; 17:801-6. [PubMed 18314924]

38. Wichman CL, Moore KM, Lang TR et al. Congenital heart disease associated with selective serotonin reuptake inhibitor use during pregnancy. Mayo Clin Proc . 2009; 84:23-7. [PubMedCentral][PubMed 19121250]

39. Andrade SE, McPhillips H, Loren D et al. Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf . 2009; 18:246-52. [PubMed 19148882]

40. Wilson KL, Zelig CM, Harvey JP et al. Persistent pulmonary hypertension of the newborn is associated with mode of delivery and not with maternal use of selective serotonin reuptake inhibitors. Am J Perinatol . 2011; 28:19-24. [PubMed 20607643]

41. Cohen LS, Altshuler LL, Harlow BL et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA . 2006; 295:499-507. [PubMed 16449615]

42. Kieler H, Artama M, Engeland A et al. Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries. Br Med J . 2012; 344:d8012.

section name header

Introduction ⬇

AHFS Class:

Generic Name(s):

Chemical Name:

Molecular Formula:

Uses ⬆ ⬇

Dosage and Administration ⬆ ⬇

Cautions ⬆ ⬇

Drug Interactions ⬆ ⬇

Other Information ⬆ ⬇

Preparations ⬆ ⬇

Vilazodone Hydrochloride

Copyright ⬆ ⬇

References ⬆