Valbenazine

Tardive Dyskinesia

Valbenazine is primarily used to treat tardive dyskinesia (TD) in adults. TD is a movement disorder characterized by uncontrollable, repetitive muscle movements, which most commonly affect the:

• Face and mouth (such as blinking, grimacing, or sticking out the tongue)
• Arms and legs
• Torso

These movements often develop as a side effect of long-term use of certain medications, such as antipsychotics used to treat mental health conditions like schizophrenia or bipolar disorder.

Huntington's Disease Chorea

This medication is also approved to treat chorea associated with Huntington's disease. Chorea refers to involuntary, jerky, or irregular movements that can occur in people with this genetic condition. Valbenazine helps reduce the severity of these movements, though it does not cure the underlying disease.

Mechanism of Action

Valbenazine belongs to a class of drugs called vesicular monoamine transporter 2 (VMAT2) inhibitors. It is used to treat movement disorders characterized by uncontrollable body movements, such as tardive dyskinesia.

While the exact way valbenazine works is not completely understood, it is believed to function by:

• Targeting VMAT2: The drug blocks a specific protein in the brain called VMAT2. This protein is responsible for transporting and storing chemical messengers, such as dopamine, within nerve cells.
• Regulating Dopamine: By inhibiting this protein, valbenazine reduces the amount of dopamine available for release in the parts of the brain that control muscle movement.
• Reducing Involuntary Movements: Lowering the levels of these chemicals helps calm the overactive nerve signals that cause jerky, repetitive, or uncontrollable muscle movements.

Common Side Effects

The most common side effect of valbenazine is sleepiness or somnolence. Other frequent side effects may include:

• Dry mouth
• Constipation
• Blurred vision
• Dizziness or lightheadedness
• Nausea or vomiting
• Joint pain
• Headache

Serious Side Effects

While less common, some side effects can be serious. Seek medical attention right away if you experience any of the following:

• Movement problems: New or worsening tremors, muscle stiffness, drooling, or difficulty with balance and walking (parkinsonism).
• Heart rhythm issues: A fast, pounding, or irregular heartbeat, or feeling faint.
• Allergic reactions: Swelling of the face, lips, or throat, or a severe skin rash.
• Mental health changes: New or worsening depression, anxiety, or thoughts of hurting yourself.
• Neuroleptic Malignant Syndrome: A rare but life-threatening reaction that causes high fever, stiff muscles, confusion, and sweating.

Somnolence and Sedation

Valbenazine can cause significant drowsiness or sleepiness. This effect may impair the ability to perform tasks that require mental alertness, such as driving or operating heavy machinery. These effects may be more pronounced when first starting the medication or after a dose increase.

Heart Rhythm Changes

This medication may cause a condition called QT prolongation, which affects the heart's electrical rhythm. The risk of this condition may be higher for individuals who have a history of certain heart rhythm problems, have congenital long QT syndrome, or take other medications known to affect heart rhythm.

Parkinsonism

Valbenazine can cause symptoms similar to Parkinson's disease, a condition known as parkinsonism. Symptoms may include shaking (tremors), body stiffness, drooling, or trouble with balance and walking. These issues typically resolve after the medication is stopped.

Mood and Mental Health

It is important to monitor for changes in mood or behavior while taking this medication. Patients and caregivers should watch for signs of depression, anxiety, or suicidal thoughts and report these changes to a healthcare provider.

Genetic and Organ Considerations

The way the body processes valbenazine can be affected by genetics and organ function:

• CYP2D6 Metabolism: Individuals who are known poor metabolizers of the CYP2D6 enzyme may have higher levels of the drug in their system, which may require a dosage adjustment.
• Liver Impairment: People with moderate to severe liver disease may require a reduced dose of valbenazine.

Pregnancy

The effects of valbenazine on human pregnancy are not well-studied. Animal studies have shown that high doses of the medication may lead to issues such as reduced fetal weight or an increase in stillbirths. Because there is no adequate data on use in pregnant women, it is important to discuss the potential risks and benefits with a healthcare provider if you are pregnant or planning to become pregnant.

Breastfeeding

It is not known if valbenazine passes into human breast milk. However, due to the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended while taking this medication and for at least 5 days after the final dose. Patients should consult with their doctor to determine the best way to feed their baby while undergoing treatment.

Available Forms

Valbenazine is provided as an oral medication in the following formats:

• Capsules: Standard capsules designed to be swallowed whole.
• Sprinkle capsules: A specialized capsule form that can be swallowed whole or opened to have the contents mixed with soft food for individuals who have difficulty swallowing.

FDA Approval and Indications

Valbenazine was first approved by the U.S. Food and Drug Administration (FDA) in April 2017. It is indicated for the treatment of adults with tardive dyskinesia, a movement disorder characterized by involuntary movements often caused by long-term use of antipsychotic medications. In August 2023, the FDA expanded its approval to include the treatment of chorea (involuntary, irregular movements) associated with Huntington’s disease.

Boxed Warning

The FDA has issued a boxed warning for valbenazine when used to treat chorea associated with Huntington’s disease. This warning states that the medication can increase the risk of depression and suicidal thoughts or behavior in these patients. Healthcare providers are advised to balance the risks of depression and suicide with the clinical need for chorea treatment. Patients should be closely monitored for new or worsening depression, suicidal ideation, or unusual changes in behavior.

Pharmacogenomic Considerations

The FDA-approved labeling includes specific guidance for patients based on their genetic metabolism. Individuals identified as CYP2D6 poor metabolizers may require a reduced dosage. Because these patients process the drug more slowly, they are at a higher risk for increased drug exposure and associated side effects, such as heart rhythm changes (QT prolongation).

Regulatory Status

• Prescription Requirement: Valbenazine is available only by prescription from a licensed healthcare provider.
• Controlled Substance Status: It is not classified as a controlled substance.
• Contraindications: It is contraindicated in patients with Huntington’s disease who have untreated or inadequately treated depression or who are actively suicidal.

Brand and Generic Availability

Valbenazine is currently available only as the brand-name medication Ingrezza. There is no generic version available at this time. Brand-name drugs typically cost more than their generic counterparts because they are protected by patents that prevent other companies from making the same medication.

Insurance Coverage

Most insurance plans, including Medicare and Medicaid, cover valbenazine, but the out-of-pocket cost depends on your specific plan's formulary. Many insurance providers require prior authorization before they will approve coverage for this medication. This process involves your healthcare provider submitting documentation to prove the medical necessity of the drug.

Specialty Pharmacy Requirements

Valbenazine is usually dispensed through specialty pharmacies rather than standard retail pharmacies. Specialty pharmacies handle medications that are high-cost or require special handling. These pharmacies often provide additional services, such as help with insurance navigation and financial assistance applications.

Financial Assistance Programs

Because the list price for valbenazine can be high, several options may help reduce the cost:

• Copay Savings Cards: The manufacturer may offer savings cards for patients with commercial insurance that can significantly lower monthly copayments.
• Patient Assistance Programs: For individuals who are uninsured or underinsured, the manufacturer or independent non-profit organizations may offer programs that provide the medication at a reduced cost or for free, based on financial need.
• Support Services: Dedicated support programs can help patients identify which financial resources they are eligible for and assist with the application process.