Austedo

Huntington's Disease Chorea

Austedo is used to manage chorea, which are jerky, involuntary movements that often occur in people with Huntington's disease. These movements can affect various parts of the body and may interfere with daily activities. While the medication helps control these movements, it is not a cure for Huntington's disease and does not slow the progression of the underlying condition.

Tardive Dyskinesia

This medication is also approved to treat tardive dyskinesia in adults. Tardive dyskinesia is a movement disorder characterized by repetitive, uncontrollable muscle movements. These movements often involve the face, tongue, and mouth, but can also affect the limbs or trunk. Common signs include:

• Uncontrolled blinking or grimacing
• Lip smacking or puckering
• Sticking out the tongue
• Jerking movements of the arms or legs

Tardive dyskinesia typically develops as a side effect of long-term use of certain medications, such as antipsychotics used for mental health conditions or certain drugs used to treat digestive issues.

Mechanism of Action

Austedo is classified as a vesicular monoamine transporter 2 (VMAT2) inhibitor. It targets a specific protein in the brain that is responsible for storing and releasing chemical messengers, particularly dopamine.

Dopamine plays a key role in how the brain sends signals to control physical movements. In conditions such as Huntington's disease chorea and tardive dyskinesia, these signals can become overactive, leading to uncontrollable or jerky movements. Austedo works by:

• Blocking the VMAT2 protein: This prevents the protein from moving dopamine into the areas of the nerve cells where it is stored for release.
• Reducing dopamine levels: By limiting the amount of dopamine available at the nerve endings, the medication helps dampen the overactive signals that cause involuntary movements.

While the exact way the drug improves movement disorders is not fully understood, it is believed that this reduction in dopamine activity is the primary reason for its effectiveness.

The Role of Deuterium

Austedo is a modified version of an older medication called tetrabenazine. It contains deuterium, a naturally occurring form of hydrogen. This structural change causes the body to break down the medication more slowly, which allows for more stable levels of the drug in the body over time.

Common Side Effects

The most frequently reported side effects of Austedo include:

• Sleepiness or drowsiness
• Dry mouth
• Diarrhea
• Fatigue or tiredness
• Difficulty sleeping (insomnia)
• Urinary tract infections

Serious Side Effects

Some side effects can be severe and require immediate medical attention. These include:

• Mood and mental health changes: New or worsening depression, anxiety, agitation, or thoughts of hurting yourself.
• Movement problems: Restlessness, an inability to sit still (akathisia), or symptoms similar to Parkinson's disease, such as tremors, body stiffness, or trouble with balance and walking.
• Neuroleptic Malignant Syndrome (NMS): A rare but life-threatening reaction that causes high fever, stiff muscles, confusion, and sweating.
• Heart rhythm changes: Austedo may cause a change in the electrical activity of the heart known as QT prolongation, which can affect the heartbeat.

Boxed Warning: Depression and Suicidality

Austedo can increase the risk of depression and suicidal thoughts or behavior in people with Huntington’s disease. Healthcare providers typically monitor patients closely for new or worsening depression, suicidal ideation, or unusual changes in behavior. This medication is generally avoided in patients who have untreated or inadequately treated depression or a history of suicidal attempts.

Contraindications

Austedo should not be used by individuals with certain medical conditions or those taking specific medications, including:

• Liver impairment (hepatic impairment).
• Current use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping an MAOI.
• Current use of reserpine, or use within 20 days of stopping reserpine.
• Current use of tetrabenazine or valbenazine.

Neuroleptic Malignant Syndrome (NMS)

A potentially fatal symptom complex known as Neuroleptic Malignant Syndrome has been reported with drugs that reduce dopaminergic transmission. Symptoms may include high fever, muscle rigidity, altered mental status, and evidence of autonomic instability, such as irregular pulse or blood pressure.

Movement and Neurological Effects

Austedo may cause movement-related side effects, including:

• Akathisia: Some patients may experience restlessness, agitation, or a compelling need to move.
• Parkinsonism: The medication can cause symptoms similar to Parkinson’s disease, such as tremors, body stiffness, or trouble with balance and walking.

Heart Rhythm Changes (QT Prolongation)

Austedo may prolong the QT interval, which is a measure of the heart's electrical activity. This can lead to serious heart rhythm disturbances. The risk may be higher in patients taking certain other medications or those with specific heart conditions or liver issues.

Sedation and Somnolence

Drowsiness or sedation is a common side effect. Patients are typically advised to avoid performing activities that require mental alertness, such as driving or operating heavy machinery, until they know how the medication affects them.

Pregnancy

It is currently unknown if Austedo will cause harm to an unborn baby, as there are no adequate and well-controlled studies in pregnant women. If you are pregnant or planning to become pregnant, you should inform your healthcare provider to determine if the benefits of the medication outweigh the potential risks.

Breastfeeding

It is not known whether Austedo passes into human breast milk or how it might affect a nursing infant. Because of the potential for serious adverse reactions in a breastfed child, the following precautions are generally recommended:

• Breastfeeding is not recommended during treatment with Austedo.
• Avoid breastfeeding for at least 14 days after taking the final dose of the medication.

The decision to breastfeed while taking this medication should involve a discussion with a healthcare professional regarding the clinical need for the drug and the health benefits of breastfeeding for the infant.

Available Forms

Austedo is provided in the following oral dosage forms:

• Tablets: An immediate-release formulation.
• Extended-release tablets: A formulation designed to release the medication over a longer period, marketed as Austedo XR.

FDA Approval History

The U.S. Food and Drug Administration (FDA) first approved Austedo in April 2017. It was the first deuterated drug product approved by the FDA. Initially indicated for the treatment of chorea associated with Huntington’s disease, its approval was expanded in August 2017 to include the treatment of tardive dyskinesia in adults. In February 2023, the FDA approved a once-daily extended-release formulation known as Austedo XR.

Boxed Warning

Austedo contains a boxed warning, the FDA’s most serious type of warning, regarding the risk of depression and suicidality in patients with Huntington’s disease. Clinical trials showed an increased risk of suicidal thoughts and behaviors in patients taking this class of medication for Huntington’s chorea. Healthcare providers are advised to balance the risks of depression and suicide with the clinical need for chorea treatment and to monitor patients closely for new or worsening symptoms.

Regulatory Requirements

Austedo is a prescription-only medication. While it does not require a specific Risk Evaluation and Mitigation Strategy (REMS) program, it must be dispensed with a Medication Guide that explains its risks and proper use. The medication is contraindicated in patients who are actively suicidal or who have untreated or inadequately treated depression. It is also contraindicated in patients with hepatic impairment and those taking certain other medications, such as monoamine oxidase inhibitors (MAOIs) or reserpine.

Insurance and Coverage

The out-of-pocket cost for Austedo is largely determined by an individual's health insurance plan. Most commercial insurance, Medicare, and Medicaid plans cover the medication, though it is often classified as a specialty drug. This classification may require patients to obtain prior authorization from their insurance provider before the prescription is approved for coverage.

Specialty Pharmacy Access

Austedo is typically dispensed through specialty pharmacies rather than standard retail locations. These pharmacies specialize in medications for complex conditions and can often assist with navigating insurance requirements and identifying financial support options.

Financial Assistance

For those who are uninsured or have high copays, several options may help manage expenses:

• Copay Savings Cards: Eligible patients with commercial insurance may use manufacturer copay cards to lower their monthly out-of-pocket costs.
• Patient Assistance Programs: Programs may be available for individuals who meet specific income and eligibility criteria, providing the medication at a reduced cost or for free.

The total price also depends on the prescribed strength and whether the patient is taking the standard tablets or the extended-release (XR) version of the medication.