What is Austedo (Deutetrabenazine)?

From the Guidelines

Austedo (deutetrabenazine) is a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2) used to treat chorea in Huntington's disease and tardive dyskinesia, with a recommended treatment approach based on the American Psychiatric Association's guidelines for managing tardive dyskinesia associated with antipsychotic therapy 1. When considering the use of Austedo, it's essential to assess the patient's overall health and treatment history, including any previous use of antipsychotic medications and the presence of any movement disorders. Key points to consider when prescribing Austedo include:

• Starting dose: 6 mg twice daily, which can be gradually increased to a maximum of 48 mg per day (24 mg twice daily) for Huntington's chorea, or 36 mg per day (18 mg twice daily) for tardive dyskinesia 1.
• Dosage adjustments: should be made weekly based on response and tolerability.
• Mechanism of action: Austedo works by reducing the amount of dopamine available in the brain, which helps control involuntary movements.
• Common side effects: include drowsiness, dry mouth, and fatigue.
• Important administration instructions: take Austedo with food and avoid alcohol while using this medication.
• Monitoring requirements: patients should be monitored for depression and suicidal thoughts, especially those with a history of depression or Huntington's disease.
• Contraindications: Austedo should not be used in combination with MAO inhibitors or other VMAT2 inhibitors. Regular follow-ups with a healthcare provider are necessary to assess the medication's effectiveness and manage any side effects, as recommended by the American Psychiatric Association's guidelines for treating patients with schizophrenia and associated movement disorders 1.

From the FDA Drug Label

AUSTEDO XR extended-release tablets and AUSTEDO tablets are formulated with deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor for oral administration. Deutetrabenazine is a hexahydro-dimethoxybenzoquinolizine derivative and has the following chemical name: (RR, SS)-1,3,4,6,7, 11b-hexahydro-9,10-di(methoxy-d3)-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-one.

• AUSTEDO (Deutetrabenazine) is a vesicular monoamine transporter 2 (VMAT2) inhibitor for oral administration.
• It is used in the treatment of tardive dyskinesia and chorea in patients with Huntington’s disease.
• The precise mechanism by which deutetrabenazine exerts its effects is unknown but is believed to be related to its effect as a reversible depletor of monoamines. 2

From the Research

Overview of Austedo (Deutetrabenazine)

• Austedo, also known as deutetrabenazine, is a medication used to treat certain movement disorders, including chorea associated with Huntington's disease and tardive dyskinesia 3, 4.
• It is a reversible inhibitor of vesicular monoamine transporter type 2 (VMAT2) and is structurally related to tetrabenazine, another medication used to treat similar conditions 3.

Mechanism of Action and Pharmacokinetics

• Deutetrabenazine works by inhibiting the VMAT2 protein, which is involved in the regulation of monoamine neurotransmitters in the brain 3.
• The medication has a favorable pharmacokinetic profile, with a longer half-life and lower peak-to-trough fluctuations compared to tetrabenazine 5.
• Food does not affect the exposure to deutetrabenazine, and the medication can be taken with or without food 5.

Clinical Trials and Efficacy

• Deutetrabenazine has been shown to be effective in controlling chorea symptoms in patients with Huntington's disease in clinical trials, including the FIRST-HD and ARC-HD trials 3, 4.
• The medication has also been shown to be effective in treating tardive dyskinesia, with consistent efficacy across patient types and regardless of underlying psychiatric illness or use of dopamine-receptor antagonists 4.
• Long-term extension studies have demonstrated consistent efficacy and safety of deutetrabenazine in both Huntington's disease-associated chorea and tardive dyskinesia 4.

Safety Profile

• Deutetrabenazine has a similar safety profile to placebo, with most treatment-emergent adverse events being mild or moderate in severity 3, 4.
• The medication does not have a clinically relevant effect on QT prolongation at maximum recommended doses, according to a concentration-QTc analysis study 6.
• Adverse events may increase with higher exposure to deutetrabenazine, but no clinically relevant ECG findings have been reported 6.