Deutetrabenazine (Austedo)

VMAT2 inhibitor • Last reviewed 2025-09-26

General information

Deutetrabenazine (Austedo, Austedo XR) is a vesicular monoamine transporter 2 (VMAT2) inhibitor indicated for the treatment of tardive dyskinesia and chorea associated with Huntington disease. Deuterium substitution prolongs half-life compared with tetrabenazine, allowing twice-daily or once-daily XR dosing.

Common adverse effects include somnolence, diarrhea, dry mouth, nasopharyngitis, and fatigue. Deutetrabenazine carries a boxed warning for depression and suicidality in Huntington disease; monitor mood closely.

It is contraindicated in patients with hepatic impairment or on monoamine oxidase inhibitors.

Gradual titration improves tolerability; patients switching from tetrabenazine can convert by halving the total daily tetrabenazine dose and dividing BID.

Dosing & administration

Tardive dyskinesia: start 6 mg twice daily; increase by 6 mg/day at weekly intervals to a maximum of 48 mg/day (divided BID or once-daily XR).

Reduce dose in poor CYP2D6 metabolizers or with strong CYP2D6 inhibitors (max 36 mg/day).

Take with food to reduce GI upset.

Dose adjustments

Strong CYP2D6 inhibitors: Max 36 mg/day
Hepatic impairment: Contraindicated

Mechanism of action

Reversibly inhibits VMAT2, decreasing presynaptic packaging of dopamine into synaptic vesicles and thereby dampening hyperkinetic movements.

Metabolism & pharmacokinetics

Deuterium substitution slows metabolism; peak levels occur 3–4 h post-dose (IR) with half-life ~9–10 h.

Metabolized primarily via CYP2D6 to active metabolites (α-HTBZ, β-HTBZ).

Excreted in urine (~75%) and feces (~7%).

Tmax: 3–4 h
Half-life: ~9–10 h
Metabolism: CYP2D6

Drug interactions

Strong CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine) increase exposure; limit dose to 36 mg/day.

Concomitant MAOIs, reserpine, or tetrabenazine increase risk of monoamine depletion; contraindicated.

CNS depressants may enhance sedation.

Mechanism	Agents / factors	Management
CYP2D6 inhibition	Fluoxetine, paroxetine	Max 36 mg/day
Monoamine depletion	MAOIs, reserpine	Contraindicated
CNS depression	Alcohol, benzodiazepines	Counsel on sedation

Monitoring & safety checks

Mood/depression assessment
Baseline and each visit • Boxed warning
Tardive dyskinesia severity
Baseline and periodic • Evaluate benefit
Hepatic function
Baseline • Contraindicated if hepatic impairment

If therapy is interrupted >1 week, retitrate.

Educate patients/caregivers to report mood changes promptly.

Discontinuation guidance

Taper over 1 week if possible; sudden stop may lead to return of dyskinesia.

Adverse effects

Common: somnolence, diarrhea, dry mouth, fatigue.

Serious: depression, suicidality (Huntington disease), QT prolongation.

References

Austedo (deutetrabenazine) Prescribing Information — DailyMed (2024)
Deutetrabenazine in tardive dyskinesia: 2022 evidence review — CNS Drugs (2022) DOI: 10.1007/s40263-022-00958-0
Deutetrabenazine for the treatment of tardive dyskinesia — New England Journal of Medicine (2017) DOI: 10.1056/NEJMoa1500854

Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.