FDA

Vilazodone Hydrochloride

Approved 7 Jul 2023OralTablet

The FDA lists this product in 15 strengths and forms.

Indications

Vilazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD) in adults [see Clinical Studies (14) ]. Vilazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD) in adults ( 1 ).

Contraindications

Vilazodone hydrochloride tablets are 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) ]. 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, amphetamines), but also when taken alone. If it occurs, discontinue vilazodone hydrochloride 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 vilazodone hydrochloride, in patients with untreated anatomically narrow angles. ( 5.7 ). Sexual Dysfunction: Vilazodone hydrochloride may cause symptoms of sexual dysfunction ( 5.9 ).

5.1Suicidal 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 Patients 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.

At a glance

Brand name: Vilazodone Hydrochloride
Route: Oral
Dosage form: Tablet
Applicant: Apotex
Status: Prescription
FDA approval: 7 Jul 2023
Application: ANDA208228-002

Contraindications

Warnings and precautions

5.1Suicidal Thoughts and Behavior in Adolescents and Young Adults

Interactions

CYP3A4 Inhibitors: The vilazodone hydrochloride dose should not exceed 20 mg once daily when co-administered with strong CYP3A4 inhibitors ( 2.4 , 7 ). CYP3A4 Inducers: Consider increasing vilazodone hydrochloride 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 ).

7.1 Drugs Having Clinically Important Interactions With Vilazodone Hydrochloride Table 4: Clinically Important Drug Interactions with Vilazodone Hydrochloride Concomitant Drug Name or Drug Class Clinical Rationale Clinical Recommendation Monoamine Oxidase Inhibitors (MAOIs) The concomitant use of MAOIs and serotonergic drugs including vilazodone hydrochloride increases the risk of serotonin syndrome. Vilazodone hydrochloride 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)] .

Other Serotonergic Drugs The concomitant use of serotonergic drugs including vilazodone hydrochloride and other serotonergic drugs increases the risk of serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during vilazodone hydrochloride initiation. If serotonin syndrome occurs, consider discontinuation of vilazodone hydrochloride and/or concomitant serotonergic drugs [ see Warnings and Precautions (5.2) ].

Antiplatelet Agents and Anticoagulants Serotonin release by platelets plays an important role in hemostasis. The concurrent use of an antiplatelet agent or anticoagulant with vilazodone hydrochloride may potentiate the risk of bleeding. Inform patients of the increased risk of bleeding with the concomitant use of vilazodone hydrochloride and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio (INR) when initiating, titrating, or discontinuing vilazodone hydrochloride [ see Warnings and Precautions (5.3) ] .

Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin, voriconazole) The concomitant use of vilazodone hydrochloride and strong CYP3A4 inhibitors increased the exposure of vilazodone compared to the use of vilazodone hydrochloride alone [ see Clinical Pharmacology (12.3) ]. The vilazodone hydrochloride 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) ].

Strong CYP3A4 Inducers (e.g., carbamazepine, phenytoin, rifampin) The concomitant use of vilazodone hydrochloride and strong CYP3A4 inducers decreased the exposure of vilazodone compared to the use of vilazodone hydrochloride alone [ see Clinical Pharmacology (12.3) ]. Based on clinical response, consider increasing the dosage of vilazodone hydrochloride, over 1 to 2 weeks inpatients taking strong CYP3A4 inducers for greater than 14 days [ see Dosage and Administration (2.4), Clinical Pharmacology (12.3) ].

Digoxin Digoxin is a narrow therapeutic index drug. Concomitant use of vilazodone hydrochloride increased digoxin concentrations [ see Clinical Pharmacology (12.3) ] . Measure serum digoxin concentrations before initiating concomitant use of vilazodone hydrochloride. Continue monitoring and reduce digoxin dose as necessary.

7.2Drugs Having No Clinically Important Interactions With Vilazodone Hydrochloride 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 vilazodone hydrochloride is administered concomitantly [see Drug Interactions (7.1) , Clinical Pharmacology (12.3)] .

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405- 6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants. Risk Summary There are no adequate and well-controlled studies of vilazodone hydrochloride 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 to 4% and of miscarriage is 15 to 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 vilazodone hydrochloride, 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 vilazodone hydrochloride 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 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 to 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 to infants who had not been exposed to antidepressants during pregnancy.

A study of 831,324 infants born in Sweden in 1997-2005 found a PPHN risk ratio of 2.4 (95% CI 1.2 to 4.3) associated with patient-reported maternal use of SSRIs “in early pregnancy” and a PPHN risk ratio of 3.6 (95% CI 1.2 to 8.3) associated with a combination of patient-reported maternal use of SSRIs “in early pregnancy” and an antenatal SSRI prescription “in later pregnancy.” Animal Data No teratogenic effects were observed when vilazodone was given to pregnant rats or rabbits during the period of organogenesis at oral doses up to 200 and 36 mg/kg/day, respectively.

These doses are 48 and 17 times, in rats and rabbits, respectively, the maximum recommended human dose (MRHD) of 40 mg on a mg/m2 basis. Fetal body weight gain was reduced, and skeletal ossification was delayed in both rats and rabbits at these doses; these effects were not observed at doses up to 10 times the MRHD in rats or 4 times the MRHD in rabbits. When vilazodone was administered to pregnant rats at an oral dose of 30 times the MRHD during the period of organogenesis and throughout pregnancy and lactation, the number of live born pups was decreased.

There was an increase in early postnatal pup mortality, and among surviving pups there was decreased body weight, delayed maturation, and decreased fertility in adulthood. There was some maternal toxicity at this dose. These effects were not seen at 6 times the MRHD.

Adverse reactions

The following adverse reactions are discussed in greater detail in other sections of the labeling: Suicidal Thoughts and Behaviors in 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) ]. Angle-Closure Glaucoma [ see Warnings and Precautions (5.7) ]. Hyponatremia [ see Warnings and Precautions (5.8) ]. Sexual Dysfunction [ see Warnings and Precautions (5.9) ]. 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 Novadoz Pharmaceuticals LLC at 1-855-668-2369 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience

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 vilazodone hydrochloride-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 vilazodone hydrochloride was evaluated in 3,007 patients (18 to 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 vilazodone hydrochloride for a total of 348 patient-years. The adverse reaction information presented below was derived from studies of vilazodone hydrochloride 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 vilazodone hydrochloride-treated patients; and
An open-label 52-week study of 599 vilazodone hydrochloride-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, vilazodone hydrochloride was administered with food. Adverse reactions reported as reasons for discontinuation of treatment In these studies, 7.3% of the vilazodone hydrochloride-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 vilazodone hydrochloride-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 occurring in ≥ 2% of vilazodone hydrochloride-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 Vilazodone Hydrochloride-treated Patients and Greater than the Rate of Placebo-Treated Patients System Organ Class Preferred Term Placebo N=967 Vilazodone Hydrochloride 20 mg/day N=288 Vilazodone Hydrochloride 40 mg/day N=978 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 Gastrointestinal disorders Diarrhea 10% 26% 29% Nausea 7% 22% 24% Dry mouth 5% 8% 7% Vomiting 2% 4% 5% Abdominal pain1 3% 7% 4% Dyspepsia 2% 2% 3% Flatulence 1% 3% 3% Gastroenteritis 1% 1% 2% Abdominal distension 1% 2% 1% Nervous system disorders Headache2 14% 15% 14% Dizziness 5% 6% 8% Somnolence 2% 4% 5% Paresthesia 1% 1% 2% Psychiatric disorders Insomnia 2% 7% 6% Abnormal dreams 2% 2% 3% Restlessness3 1% 2% 3% General disorders Fatigue 3% 4% 3% Cardiac disorders Palpitations <1% 1% 2% Metabolism and nutrition disorders Increased appetite 1% 1% 3% Musculoskeletal and connective tissue disorders Arthralgia 1% 2% 1% Investigations Increased weight 1% 1% 2% 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 Vilazodone Hydrochloride-treated Patients and Greater than the Rate of Placebo-Treated Patients − Not applicable *Includes abnormal orgasm and anorgasmia Preferred Term Males Females Placebo N=416 Vilazodone Hydrochloride 20 mg/day N=122 Vilazodone Hydrochloride 40 mg/day N=417 Placebo N=551 Vilazodone Hydrochloride 20 mg/day N=166 Vilazodone Hydrochloride 40 mg/day N=561 Abnormal Orgasm* <1% 2% 2% 0% 1% 1% Erectile dysfunction 1% 0% 3% - - - Libido decreased <1% 3% 4% <1% 2% 2% Ejaculation disorder 0% 1% 2% - - - Other adverse reactions observed in clinical studies The following list does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications, or 5) which occurred at a rate equal to or less than placebo. Reactions are categorized by body system according to the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients: Cardiac disorders: infrequent: ventricular extrasystoles Eye disorders: infrequent: dry eye, vision blurred, rare: cataracts Nervous System: frequent: sedation, tremor; infrequent: migraine Psychiatric disorders: infrequent: panic attack Skin and subcutaneous tissue disorders: infrequent: hyperhidrosis, night sweats

6.2Post-marketing Experience

The following adverse reactions have been identified during post-approval use of vilazodone hydrochloride. 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 vilazodone hydrochloride 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

Vilazodone Hydrochloride

Indications

Contraindications

Warnings and precautions

5.1Suicidal Thoughts and Behavior in Adolescents and Young Adults

At a glance

Two medicines in one question?

Vilazodone Hydrochloride

Indications

Contraindications

Warnings and precautions

5.1Suicidal Thoughts and Behavior in Adolescents and Young Adults

At a glance

Two medicines in one question?

5.2Serotonin Syndrome Serotonin

5.3Increased Risk of Bleeding

5.4Activation of Mania or Hypomania

5.5Discontinuation Syndrome

5.6Seizures

5.7Angle-Closure Glaucoma

Interactions

7.2Drugs Having No Clinically Important Interactions With Vilazodone Hydrochloride Based

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Exposure Registry

Adverse reactions

6.1Clinical Trials Experience

6.2Post-marketing Experience

Composition

Strengths and forms

Official product information