Austedo Deutetrabenazine Tablets

1. Indications and Usage
Huntington’s Disease (HD):
Treatment of chorea associated with Huntington’s disease in adults.
Tardive Dyskinesia (TD):
Treatment of adult patients with tardive dyskinesia.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Recommended Dosage:
Huntington’s Disease:
Starting Dose: 6 mg once daily for 1 week, then 6 mg twice daily (12 mg/day).
Titration: Increase by 6 mg/day at weekly intervals based on response and tolerability.
Maximum Dose: 48 mg/day (24 mg twice daily).
Tardive Dyskinesia:
Starting Dose: 6 mg twice daily (12 mg/day).
Titration: Increase by 6 mg/day at weekly intervals.
Maximum Dose: 36 mg/day (18 mg twice daily).
Administration:
Swallow tablets whole; do not chew, crush, or split.
Can be taken with or without food.
3. Mechanism of Action
VMAT2 Inhibition:
Deutetrabenazine is a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2).
Depletion of Monoamines:
By inhibiting VMAT2, it prevents the uptake of monoamines (dopamine, serotonin, norepinephrine, histamine) into presynaptic storage vesicles.
Therapeutic Effect:
This leads to a depletion of these neurotransmitters in the synaptic cleft. The reduction of dopamine transmission is primarily responsible for the therapeutic effect on hyperkinetic movement disorders (chorea and TD).
Deuterium Advantage:
The substitution of hydrogen with deuterium slows down metabolism by CYP2D6, resulting in a longer half-life (~8.6 hours vs ~4.8 hours for tetrabenazine) and reduced peak-trough fluctuations.
4. Safety and Warnings
Depression and Suicidality (Boxed Warning):
May worsen depression or increase suicidality.
Contraindication: Do not use in patients with untreated or inadequately treated depression or suicidal ideation.
Somnolence:
May cause drowsiness and fatigue. Patients should avoid driving or operating machinery until established on the drug.
Parkinsonism:
Can cause or worsen parkinsonian symptoms (rigidity, bradykinesia, tremor).
QT Prolongation:
May cause QT prolongation; caution is advised in patients with cardiac conduction abnormalities.
5.Adverse Reactions
Most Common:
Somnolence, sedation, fatigue, insomnia, anxiety, upper abdominal pain, diarrhea, dry mouth, and increased appetite.
6.Drug Interactions
MAO Inhibitors (Contraindicated):
Do not use within 14 days of stopping an MAO inhibitor due to the risk of severe neuroleptic malignant syndrome-like reactions.
CYP2D6 Inhibitors:
Strong inhibitors (e.g., fluoxetine, paroxetine) may increase exposure; dose limitations apply.
7.Pharmaceutical Information
Chemical Composition:
Active Ingredient: Deutetrabenazine.
Available Strength: 6 mg, 9 mg, 12 mg tablets.
Appearance: Film-coated tablets.
Storage: Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F).