Austedo for Treating Chorea in Huntington’s Disease and Tardive Dyskinesia

Austedo is an oral medication containing deutetrabenazine, used primarily to treat movement disorders such as chorea associated with Huntington’s disease and tardive dyskinesia in adults. It works by regulating neurotransmitter activity involved in these involuntary movements. Austedo is available as both immediate-release tablets and extended-release tablets, allowing for flexible dosing schedules.

Austedo is approved for use in adults for:

• Treatment of chorea associated with Huntington’s disease.
• Treatment of tardive dyskinesia, a movement disorder caused by certain medications.

deutetrabenazine

Austedo is a vesicular monoamine transporter 2 (VMAT2) inhibitor. It reduces the uptake of monoamines like dopamine into synaptic vesicles, thereby decreasing the release of these neurotransmitters in the brain. This mechanism helps control abnormal involuntary movements seen in Huntington’s disease and tardive dyskinesia.

The starting dose of Austedo depends on the formulation:

• Austedo XR (extended-release tablets): Start at 12 mg once daily.
• Austedo (immediate-release tablets): Start at 6 mg twice daily (12 mg total daily).

Doses may be increased weekly by 6 mg per day based on symptom response and tolerability, up to a maximum of 48 mg daily.

For patients taking strong CYP2D6 inhibitors or those who are poor CYP2D6 metabolizers, the maximum recommended dose is 36 mg daily.

Administration instructions:

• Austedo XR tablets should be swallowed whole, with or without food, once daily.
• Austedo tablets should be taken with food, swallowed whole, and if total daily dose is 12 mg or higher, divided into two doses.

If switching from tetrabenazine, discontinue tetrabenazine and start Austedo XR or Austedo the following day using recommended conversion doses.

Treatment interruption over 1 week requires re-titration upon resuming therapy; shorter interruptions can resume the previous dose without titration.

• Patients with Huntington’s disease who are suicidal or have untreated or inadequately treated depression.
• Patients with hepatic impairment.
• Concurrent use with reserpine (initiate Austedo at least 20 days after stopping reserpine).
• Use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOIs.
• Use with tetrabenazine or valbenazine.

Depression and suicidal thoughts: Austedo can increase the risk of depression and suicidality in patients with Huntington’s disease. Close monitoring for new or worsening depression, suicidal ideation, or behavioral changes is essential. Inform patients and caregivers about this risk and instruct them to report concerns promptly.

Contraindications: Do not use in patients with Huntington’s disease who are suicidal or have untreated/inadequately treated depression.

QT prolongation: Avoid use in patients with congenital long QT syndrome or arrhythmias related to prolonged QT interval.

Neuroleptic malignant syndrome (NMS): Discontinue Austedo if symptoms of NMS occur.

Movement disorders: May cause or worsen akathisia, agitation, restlessness, parkinsonism, and sedation. Dose reduction or discontinuation should be considered if these occur.

Periodic reassessment of the need for treatment and monitoring for adverse effects is important.

Common side effects: Depression (4% in clinical trial), suicidal ideation (2% with Austedo vs none with placebo in a 12-week trial), sedation, akathisia, restlessness, and parkinsonism.

Serious side effects: Neuroleptic malignant syndrome, QT interval prolongation.

Strong CYP2D6 inhibitors: May increase Austedo plasma levels; maximum dose should not exceed 36 mg daily.

Reserpine: At least 20 days must elapse after stopping reserpine before starting Austedo.

Monoamine oxidase inhibitors (MAOIs): Austedo is contraindicated during use and within 14 days of stopping MAOIs.

Tetrabenazine and valbenazine: Do not use concurrently with Austedo.