Deutetrabenazine

Huntington's Disease

Deutetrabenazine is used to treat chorea in adults with Huntington's disease. Chorea is a movement disorder characterized by jerky, involuntary, and unpredictable muscle movements. While the medication helps reduce the severity of these movements, it does not cure Huntington's disease or slow the progression of the underlying condition.

Tardive Dyskinesia

This medication is also indicated for the treatment of tardive dyskinesia in adults. Tardive dyskinesia is a condition that causes repetitive, uncontrollable muscle movements, which may include:

• Grimacing or puckering the lips
• Rapid eye blinking
• Tongue movements or protrusion
• Involuntary movements of the arms, legs, or torso

This condition typically develops as a side effect of long-term use of certain medications, such as antipsychotics used to treat mental health disorders or certain drugs used for gastrointestinal issues.

Mechanism of Action

Deutetrabenazine is a vesicular monoamine transporter 2 (VMAT2) inhibitor. While the exact way it works to treat movement disorders is not fully understood, it is believed to function by regulating the levels of certain chemicals in the brain.

The medication targets neurotransmitters like dopamine, serotonin, and norepinephrine, which are responsible for sending signals between nerve cells. It works through the following actions:

• Inhibiting VMAT2: The drug blocks a specific protein called VMAT2. This protein normally helps package and store dopamine and other chemicals within nerve cells so they can be released later.
• Reducing Chemical Release: By blocking this storage process, the medication reduces the amount of these chemicals that can be released to send signals to other nerves.
• Calming Involuntary Movements: Lowering the levels of dopamine at the nerve endings helps to decrease the overactive signaling that causes involuntary, jerky movements (chorea) in Huntington’s disease and the repetitive movements seen in tardive dyskinesia.

Deutetrabenazine contains deuterium, a form of hydrogen that slows down the rate at which the body breaks down the medication. This allows for more stable levels of the drug in the bloodstream.

Common Side Effects

Commonly reported side effects of deutetrabenazine include:

• Sleepiness or drowsiness
• Tiredness
• Dry mouth
• Diarrhea
• Bruising
• Insomnia
• Cold-like symptoms, such as a runny nose or sore throat

Serious Side Effects

Seek medical help immediately if you experience any of the following serious symptoms:

• Mental health changes: New or worsening depression, anxiety, or suicidal thoughts and behaviors.
• Neuroleptic Malignant Syndrome: Symptoms include high fever, muscle stiffness, confusion, sweating, and changes in pulse or blood pressure.
• Movement disorders: Restlessness, agitation, or an inability to sit still (akathisia), as well as Parkinson-like symptoms such as tremors, body stiffness, or difficulty moving.
• Heart rhythm issues: Dizziness, fainting, or a fast or irregular heartbeat.
• Severe allergic reactions: Rash, itching, or swelling of the face, lips, or throat.

Boxed Warning: Depression and Suicidality

Deutetrabenazine can increase the risk of depression and suicidal thoughts and behavior in patients with Huntington’s disease. Healthcare providers typically weigh these risks against the clinical need for treatment. Patients, caregivers, and families should remain alert for the emergence or worsening of depression, suicidal ideation, or unusual changes in behavior.

Contraindications

This medication is contraindicated in several situations, including:

• Patients with Huntington’s disease who are suicidal or have untreated or inadequately treated depression.
• Patients with moderate to severe liver impairment.
• Patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOI therapy.
• Patients taking reserpine, or within 20 days of stopping reserpine.
• Patients taking tetrabenazine or valbenazine.

Clinical Monitoring and Safety

Several serious conditions may occur during treatment that require medical attention or dose adjustments:

• Neuroleptic Malignant Syndrome (NMS): This is a rare but life-threatening reaction. Symptoms include high fever, muscle rigidity, altered mental status, and irregular pulse or blood pressure.
• Akathisia and Restlessness: Some patients may experience agitation or a physical inability to remain still.
• Parkinsonism: The medication may cause or worsen symptoms such as tremors, muscle stiffness, and difficulty with balance.
• QT Prolongation: This drug may affect the heart's electrical rhythm. Caution is used in patients with certain heart conditions or those taking other medications that also affect heart rhythm.

Sedation and Somnolence

Sedation and drowsiness are common side effects. Patients should be cautious when performing tasks that require mental alertness, such as driving or operating machinery, until they know how the medication affects them.

Pregnancy

There is currently no adequate research on the use of deutetrabenazine in pregnant women. In animal studies, high doses of the medication were associated with an increase in stillbirths and postnatal mortality, although no structural birth defects were reported. Because the effects on a human pregnancy are unknown, it is important to discuss the potential risks and benefits with a healthcare provider before using this medication.

Breastfeeding

It is not known whether deutetrabenazine passes into human breast milk or how it might affect a nursing infant or milk production. Because of the risk of serious adverse reactions in a breastfed child, the following precautions are typically advised:

• Do not breastfeed while taking this medication.
• Wait at least 14 days after the last dose of deutetrabenazine before starting or resuming breastfeeding.

Patients who are pregnant, planning to become pregnant, or breastfeeding should consult their medical team to evaluate their treatment options and determine the safest course of action.

Available Forms

Deutetrabenazine is available for oral administration in the following formats:

• Tablets: Standard oral tablets.
• Extended-release tablets: Tablets designed to release the medication gradually after ingestion.

FDA Approval and Indications

Deutetrabenazine was first approved by the U.S. Food and Drug Administration (FDA) in 2017. It is indicated for the treatment of chorea (involuntary movements) associated with Huntington’s disease and for the treatment of tardive dyskinesia in adults.

Boxed Warning

The FDA has required a boxed warning for deutetrabenazine due to the increased risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Healthcare providers must balance the risks of these serious side effects against the clinical need for chorea control. Patients, caregivers, and families should be alert to the emergence or worsening of depression, suicidal ideation, or unusual changes in behavior.

Contraindications and Safety

The medication is contraindicated in patients who are suicidal or who have untreated or inadequately treated depression. It is also contraindicated in patients with hepatic impairment and those taking monoamine oxidase inhibitors (MAOIs), reserpine, or tetrabenazine.

Regulatory Classification

• Deutetrabenazine is available only by prescription.
• It is not classified as a controlled substance.
• There is currently no Risk Evaluation and Mitigation Strategy (REMS) program required for this medication, though it must be dispensed with a Medication Guide.

Stopping Treatment

If you need to stop taking deutetrabenazine, it is important to consult your doctor first. While this medication generally does not require a gradual dose reduction (tapering) to avoid physical withdrawal symptoms, stopping the drug can affect the condition it was treating.

Recurrence of Symptoms

The main concern when discontinuing deutetrabenazine is the return of the symptoms that the medication was managing. This may include:

• Chorea: In patients with Huntington's disease, the involuntary, jerky movements may reappear or worsen after the medication is stopped.
• Tardive Dyskinesia: For those treated for tardive dyskinesia, the involuntary facial or body movements may return.

Your healthcare provider will monitor your condition closely after you stop taking the medication to manage any returning symptoms and determine the next steps for your treatment plan.