Section 03 · Monograph

Deutetrabenazine

Reviewed Nov 2026FDA label

AustedoVMAT2 inhibitor

Black Box Warning

AUSTEDO XR and AUSTEDO can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington's disease
Monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior
Balance the risks of depression and suicidality against the clinical need for treatment of chorea when using AUSTEDO/AUSTEDO XR
Patients, caregivers, and families should be informed of the risk and instructed to report behavioral changes promptly

Reversible, selective inhibitor of vesicular monoamine transporter 2 (VMAT2)
Deuterium substitution slows CYP2D6-mediated metabolism of the active metabolites relative to tetrabenazine, prolonging half-life and allowing less frequent dosing
Depletes presynaptic stores of monoamines (dopamine, serotonin, norepinephrine, histamine) by inhibiting their transport into synaptic vesicles
Reduced dopaminergic transmission is believed to underlie the antichoreic and antidyskinetic effects

AUSTEDO (immediate-release): initiate at 6 mg twice daily (12 mg/day); titrate in weekly increments of 6 mg/day as needed
AUSTEDO (immediate-release): maximum recommended dose 48 mg/day; doses ≥12 mg/day should be given in divided doses (2–3x/day) with food
AUSTEDO XR (extended-release): initiate at 12 mg once daily; titrate in weekly increments of 6 mg/day; maximum 48 mg/day once daily, with or without food
For CYP2D6 poor metabolizers, or when co-administered with a strong CYP2D6 inhibitor, maximum recommended dose is 36 mg/day
Chorea and tardive dyskinesia dosing/titration schedules differ slightly by indication per full prescribing information — titrate to optimal reduction of chorea/dyskinesia while minimizing adverse effects

Patients with Huntington's disease who are suicidal, or who have untreated or inadequately treated depression
Hepatic impairment
Concomitant use with reserpine or within 20 days of discontinuing reserpine (risk of VMAT2 depletion and NMS-like reactions)
Concomitant use of a monoamine oxidase inhibitor (MAOI), or use within 14 days of discontinuing an MAOI
Concomitant use with tetrabenazine or valbenazine

Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, bupropion, quinidine) increase active metabolite exposure ~3-fold — cap dose at 36 mg/day
Reserpine — contraindicated; do not administer within 20 days of stopping reserpine due to irreversible VMAT2 binding
MAOIs — contraindicated concurrently or within 14 days of MAOI use
Alcohol and other CNS depressants — additive sedation/somnolence risk
Drugs that prolong QT interval — additive QTc prolongation risk

Monitor for new-onset or worsening depression and suicidal ideation throughout treatment
Monitor for akathisia, restlessness, and agitation; reduce dose or discontinue if severe
Monitor for drug-induced parkinsonism, which may emerge within weeks of initiation or dose increase
Monitor for signs/symptoms of neuroleptic malignant syndrome (NMS); discontinue immediately if suspected
Consider ECG monitoring in patients at risk for QTc prolongation (e.g., with CYP2D6 inhibitors, other QT-prolonging drugs, or electrolyte abnormalities)

Pregnancy: no adequate human data; the related compound tetrabenazine increased stillbirths and postnatal mortality in animal studies — weigh maternal benefit against potential fetal risk
A pregnancy exposure registry is available for AUSTEDO/AUSTEDO XR
Lactation: no data on presence in human milk, effects on the breastfed infant, or milk production — weigh developmental/health benefits of breastfeeding against the mother's clinical need and potential infant exposure