Vilazodone Hydrochloride - Uses, Warning Signs, and Precautions

Overview

Major depressive disorder is the major cause of morbidity, especially in the United States (U.S), which is common among fifteen to forty-four years of age. Additionally, the fourth most commonly prescribed drug in 2009 was antidepressants. Patients with depressive disorder present with depressed mood, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep, low energy, and poor concentration. Although the underlying pathophysiology of depression has not been clearly defined, some studies suggest that the disorder results from a disturbance in serotonin and norepinephrine neurotransmission in the central nervous system.

Successful pharmacological treatment of depression depends on tolerability, treatment resistance, and drug efficacy. Unfortunately, up to fifty percent of depressive patients do not respond to initial therapy. Sometimes, patients who do not respond to one antidepressant might benefit from another, even if it belongs to the same therapeutic group. This led to the development of antidepressants with improvements in efficacy and novel mechanism of action. Vilazodone offers a novel combination of selective serotonin reuptake inhibition and serotonergic receptor partial agonist activity and is called Serotonin Partial Agonist -Reuptake Inhibitor (SPARI). Vilazodone hydrochloride was approved by the U.S Food and Drug Administration (FDA) for the treatment of major depressive disorder for oral use in adults in January 2011.

Uses:

It is used for the treatment of major depressive disorder in adults.

What Is the Mechanism of Action?

Although the mechanism of action of Vilazodone hydrochloride is not fully understood. It works by enhancing serotonergic activity in the central nervous system through selective inhibition of serotonin reuptake.

What Are the Ingredients in Vilazodone Hydrochloride?

Active Ingredient: Vilazodone hydrochloride.

Inactive Ingredients: Colloidal silicon dioxide, magnesium stearate, lactose monohydrate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, titanium dioxide, talc, FD&C Red #40 (10 mg only), FD&C Yellow #6 (20 mg only), and FD&C Blue #1 (40 mg only).

For Patients:

What Are the Symptoms of Depression?

Patients with depressive disorder present with depressed mood, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep, low energy, and poor concentration.

What Is Vilazodone Hydrochloride?

It is a prescribed medication used to treat the major depressive disorder.

Who Should Not Take Vilazodone Hydrochloride?

• Persons who are taking Monoamine oxidase inhibitors.

• Persons who have stopped taking Monoamine oxidase inhibitors in the past fourteen days.

• Persons who are treated with Linezolid or intravenous Methylene blue.

What Is the Information One Should Know About the Vilazodone Hydrochloride?

• Increases the risk of suicidal thoughts and actions in adolescents and young adults (more common in twenty-four years or younger), especially in the first few months of treatment and when the dose is changed. Vilazodone hydrochloride is not recommended for children.

How to Prevent Suicidal Thoughts and Actions?

• One should pay attention to any sudden changes in mood, behavior, thoughts, feelings, or development of any suicidal thoughts.

• Immediately call a health care provider in case of changes in behavior.

• Should do follow-up visits regularly as scheduled by the healthcare providers.

What Is the History One Should Inform Healthcare Providers Before Starting to Take Vilazodone Hydrochloride?

• A family history of suicide, bipolar disorder, depression, mania, or hypomania.

• Having bleeding problems.

• Having seizures or convulsions.

• Having high pressure in the eye (glaucoma).

• Having seizures or convulsions.

• Having low sodium levels in the blood.

• Drinking alcohol.

• Pregnancy or planning to get pregnant.

• Breastfeeding.

• About all the medications the person intakes.

How to Take Vilazodone Hydrochloride?

• Take Vilazodone hydrochloride as per the physician's instructions.

• Do not change the dose or discontinue without the physician's advice.

• Should take one tablet each day with food.

• If a dose is missed, the person should take it as soon as possible once remembered, but if it is time for the next dose, they should skip it.

• If you take too many doses, call the healthcare provider immediately.

What to Avoid While Taking Vilazodone Hydrochloride?

• The person should not drive, operate heavy machinery, or do dangerous activities.

• Avoid drinking alcohol.

How to Store Vilazodone Hydrochloride?

• Store at a room temperature between 68°F and 77°F (20°-25° C).

• Keep out of reach of children.

For Doctors:

What Are the Uses?

It is used for the treatment of major depressive disorder in adults.

What Is the Dosage for the Treatment of Major Depressive Disorder?

• The recommended dosage is 10 mg to 40 mg orally once daily.

• First, the patient should be advised to take 10 mg orally once daily for seven days.

• Then the dose is increased to 20 mg for the next seven days.

• Then the dose is increased to 40 mg orally once daily.

• The physician should give a seven days interval between dose increases.

What to Do in Case a Dose Is Missed?

• If a dose is missed, the patient should take it as soon as they remember.

• If it is time for the next dose, the patient is advised to skip and take the next dose at regular intervals.

• It is not advised to take two doses at the same time.

What Points should the physician be aware of Before Starting and Discontinuing the Vilazodone Hydrochloride?

Before Start:

• Screen for Bipolar Disorder: Prior to starting treatment with Vilazodone hydrochloride, the physician should screen the patient for a family history of any bipolar disorder, mania, and hypomania.

• Switching From or to a Monoamine Oxidase Inhibitor Receptor Antidepressant: Fourteen days must elapse after stopping the monoamine oxidase inhibitor and before starting Vilazodone hydrochloride or vice-versa.

Dosage Adjustment With CYP3A4 Inhibitors or Inducers:

• For Patients Receiving CYP3A4 Inhibitor: During concomitant use of CYP3A4 inhibitor, the dose of Vilazodone hydrochloride should not exceed 20 mg. The initial dose is resumed once after stopping the CYP3A4 inhibitor.

• For Patients Receiving CYP3A4 Inducers: Based on clinical response, the doctor should increase the dose of Vilazodone hydrochloride by two-fold up to a maximum of 80 mg once daily in patients taking CYP3A4 inducer for more than two weeks. If the CYP3A4 inducer is stopped, the Vilazodone hydrochloride dose should be reduced to a normal range over one to two weeks.

After Discontinuing the Treatment:

• Adverse reactions appear on discontinuation of Vilazodone hydrochloride.

• A gradual reduction is recommended rather than abrupt discontinuation.

• Patients taking 40 mg doses should be reduced to 20 mg once daily for four days, and patients taking 20 mg should be reduced to 10 mg once daily for seven days.

What Are Dosages and Strengths?

• Vilazodone hydrochloride is available in 10 mg, 20 mg, and 40 mg film-coated tablets.

• 10 mg pink, oval shape, debossed with ten on one side.

• 20 mg orange, oval shape, debossed with twenty on one side.

• 40 mg blue, oval shape, debossed with forty on one side.

What Are the Contraindications for Vilazodone Hydrochloride?

• Contraindicated in patients under Monoamine oxidase inhibitors, including Linezolid and intravenous Methylene blue - who are taking or stopped taking before fourteen days.

What Are the Warning Signs and Precautions?

Suicidal Thoughts And Behaviour in Adolescents and Young Adults:

• In a pooled analysis of placebo-controlled trials of antidepressant drugs that include seventy-seven thousand adult patients and four thousand five hundred young patients and from the analysis, the incidence of suicidal thoughts and behavior was greater among antidepressant-treated patients who were twenty-four years and younger.

• Monitor all antidepressant-treated patients for suicidal thoughts and behavior, especially during the initial few months and when changing dosage. Counseling should be given to parents and caregivers of patients to monitor changes in behavior and to alert healthcare providers. Additionally, the physician should discontinue the usage when the depression becomes worse.

Serotonin Syndrome:

• Serotonin syndrome is a life-threatening disorder. The risk is increased in concomitance use of serotonin drugs like Triptans, Tricyclic Antidepressants, Fentanyl, Lithium, Tramadol, Tryptophan, and drugs that impair the metabolism of serotonin. However, Serotonin syndrome occurs even when the drugs are used alone.

• The signs and symptoms include mental status changes, autonomic instability, and neuromuscular and gastrointestinal symptoms.

• The physician should monitor patients with Serotonin syndrome and immediately discontinue the medicine if any above symptoms develop.

• If Vilazodone hydrochloride with other drugs is warranted, then the patient should be informed about the Serotonin syndrome.

Increased Risk of Bleeding:

• Vilazodone hydrochloride interrupts Serotonin reuptake and increases the risk of bleeding. When taken with antiplatelets, anti-inflammatory drugs, and anticoagulants, this drug increases the risk of bleeding. Bleeding events range from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages.

• The healthcare providers should inform the patient about the risk of bleeding when concomitant usage with other antiplatelet drugs.

• Monitor patients taking Warfarin for coagulation indices while initiating, titrating, and discontinuing Vilazodone hydrochloride.

Activation of Mania or Hypomania:

• In patients with bipolar disorder, treatment with Vilazodone hydrochloride or other antidepressants may precipitate a mixed manic episode.

• In controlled clinical trials, patients with bipolar disorder are excluded.

• Prior to starting the treatment with Vilazodone hydrochloride, it is important to check the family history of bipolar disorder or mania.

Discontinuation Syndrome:

• Adverse reactions to abrupt discontinuation of the drug lead to nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances, tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures.

• Hence, a gradual reduction in dosage is recommended.

Seizures:

• Patients with seizures are excluded from the clinical trials.

• Hence, Vilazodone hydrochloride should be prescribed with caution in patients with a seizure disorder, although it is not evaluated systemically.

Angle-Closure Glaucoma:

• Following Vilazodone hydrochloride or other antidepressant administration causes pupillary dilatation, which triggers angle closure attacks in patients with anatomically narrow angles who do not have a patent iridectomy.

• Should avoid using Vilazodone hydrochloride in patients with untreated narrow angles.

Hyponatremia:

• The use of Vilazodone hydrochloride causes hyponatremia. Cases of serum sodium less than ten mmol/L have been reported.

• Signs and symptoms include headache, memory impairment, difficulty concentrating, confusion, weakness, and unsteadiness which leads to falls.

• Signs and symptoms of acute cases include hallucination, seizure, syncope, coma, respiratory arrest, and death. In many cases, hyponatremia occurs due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

• Elderly patients taking diuretics and those who are volume-depleted are at high risk of developing hyponatremia.

• Hence, Vilazodone hydrochloride should be discontinued in patients showing symptoms of hyponatremia and institute appropriate medical intervention.

Sexual Dysfunction:

• The use of Vilazodone hydrochloride may cause a sexual disturbance.

• In males, it causes ejaculatory delay, decreased libido, and erectile dysfunction, whereas, in females, it caused decreased libido and delayed or absent orgasm.

• The physician must enquire about sexual function before starting treatment with Vilazodone hydrochloride.

• Also, the physician should discuss potential management strategies to support patients in making informed treatment decisions.

What Are the Adverse Reactions?

• Suicidal thoughts and behavior in young adults and adolescents.

• Serotonin syndrome.

• Increased risk of bleeding.

• Activation of mania or hypomania.

• Discontinuation syndrome.

• Seizures.

• Angle-closure glaucoma.

• Hyponatremia.

• Sexual dysfunction.

Clinical Trials Experiences:

• From the clinical studies, the common adverse effects are diarrhea, nausea, vomiting, insomnia, dry mouth, abdominal pain, dyspepsia, flatulence, gastroenteritis, headache, dizziness, somnolence, paraesthesia, abnormal dreams, restlessness, fatigue, palpitation, increased appetite, arthralgia, and increased weight.

Post-Administration Adverse Effects:

• Irritability, sleep paralysis, hallucinations, suicide attempt, suicidal ideation, generalized rash, urticaria, drug eruption, and acute pancreatitis.

What Are the Drug Interactions?

• Drugs that have clinical interactions with Vilazodone hydrochloride are Monoamine oxidase inhibitors, other Serotonergic drugs, Antiplatelets and Anticoagulants, CYP3A4 inhibitors and inducers, and Digoxin.

• The drugs which do not interact with Vilazodone hydrochloride are substrates of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and P-glycoprotein except Digoxin.

What Are the Uses in Special Populations?

Pregnancy:

• Patients taking Vilazodone hydrochloride in late pregnancy may have an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding, and persistent pulmonary hypertension of the newborn.

• Monitor neonates exposed to Vilazodone hydrochloride in the third trimester of pregnancy for drug discontinuation syndrome and persistent pulmonary hypertension of the newborn.

• Additionally, the women who discontinued the use of antidepressants in early pregnancy are more likely to experience a relapse of major depressive disorder than one who takes it throughout pregnancy.

Lactation:

• There is no data on the presence of Vilazodone in human milk.

• Also, there is no effect on the breastfed infant and the effect of drugs on milk production.

• The health benefits of breastfeeding should be considered, along with the mother's clinical need and the adverse effects of Vilazodone hydrochloride on the breastfed child.

Pediatric Use:

• The safety of Vilazodone hydrochloride has not been established in pediatric patients to treat the major depressive disorder.

• The adverse reactions in pediatric patients include nausea, vomiting, diarrhea, abdominal pain/discomfort, and dizziness.

Geriatric Use:

• No dose changes are recommended on an age basis.

• Clinical studies do not include subjects aged 65 and over to determine whether they respond differently from younger subjects. Of the 3,007 patients in clinical studies, 65 patients were 65 years of age or older, and 378 patients were 55 to 64 years of age.

• Therefore, the dose selection for an elderly patient should be conservative, starting at a low dosing range that reflects the increased frequency of reduced hepatic, renal, and cardiac function.

Use in Other Patient Populations:

• No dose adjustment is required on a gender basis and based on renal and hepatic functions.

What Is the Information to Know About Vilazodone Hydrochloride?

Drug Abuse and Dependence:

Drug abuse and dependence have not been systematically studied in humans, and there was no suggested evidence of drug-seeking behavior in clinical studies.

Overdosage:

There is limited clinical experience regarding drug overdose.

Drug Description:

• Vilazodone hydrochloride tablets for oral administration contain polymorph form IV Vilazodone hydrochloride, a selective serotonin reuptake inhibitor, and a 5HT1A receptor partial agonist.

• Vilazodone HCl is 2-benzofuran carboxamide, 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-1-piperazinyl]-, hydrochloride (1:1). Its molecular weight is 477.99.

• Vilazodone hydrochloride tablets are available as 10 mg, 20 mg, and 40 mg film-coated tablets containing 10 mg, 20 mg, and 40 mg of vilazodone hydrochloride, respectively.

Mechanism of Action:

Although the mechanism of action of Vilazodone hydrochloride is not fully understood. It works by enhancing serotonergic activity in the central nervous system through selective inhibition of serotonin reuptake.

Pharmacokinetics:

Absorption:

• Vilazodone hydrochloride concentrations peaked at a median of 4 to 5 hours after administration and declined with a half-life of 25 hours.

• The bioavailability of Vilazodone hydrochloride with food is 72 %.

• Inadequate drug concentrations and reduced effectiveness occur when administered without food.

• Co-administration with ethanol or with a proton pump inhibitor (pantoprazole) did not affect the rate or extent of Vilazodone absorption.

• After 7 hours of ingestion, vomiting decreases absorption, and no replacement dose is needed.

Distribution:

• Vilazodone is distributed widely and 96% to 99% protein-bound.

• Administration to a patient taking another drug with protein bound may cause increased free concentrations of the other drug because Vilazodone is highly bound to plasma protein. The interaction between Vilazodone and other protein-bound other medicines has not been evaluated.

Metabolism and Elimination:

• It is extensively metabolized through CYP and non-CYP pathways (possibly by carboxylesterase), with only 1 % of the dose recovered in the urine and 2 % of the dose recovered in the feces as unchanged Vilazodone.

Pharmacodynamics:

• Vilazodone binds highly with the serotonin reuptake site but not to the norepinephrine or dopamine reuptake sites.

• Vilazodone potently inhibits the reuptake of serotonin.

• Vilazodone also binds selectively with high affinity to 5-HT1A receptors and is a 5-HT1A receptor, a partial agonist.

Clinical Studies:

• The drug's efficacy was demonstrated in four multicenter, randomized, double-blind, placebo-controlled studies in adult (18 to 70 years of age) outpatients who met the Diagnostic and Statistical Manual of Mental Disorders criteria for major depressive disorder.

• Three eight-week studies evaluated the efficacy of Vilazodone hydrochloride 40 mg (Studies 1-3), and one ten-week study (Study 4) evaluated the efficacy of Vilazodone hydrochloride 20 mg and 40 mg. These studies include patients exposed to either 20 mg or 40 mg or a placebo once daily with food. Patients were either titrated over one week to a dose of 20 mg daily or over two weeks to a dose of 40 mg once daily with food.

• Vilazodone hydrochloride was superior to placebo in improving depressive symptoms as measured by the change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score for both doses.

• The Montgomery-Asberg Depression Rating Scale is a ten-item, clinician-rated scale used to assess the severity of depressive symptoms.

• The Montgomery-Asberg Depression Rating Scale ranges from 0 to 60.

• The higher the score, the more severe the depression rating.

• Vilazodone hydrochloride 20 mg and 40 mg demonstrated superiority over placebo as measured by improved clinical global impression-severity score.