Deutetrabenazine
Austedo · Austedo XR
VMAT2 Inhibitor
Deutetrabenazine is a deuterated analog of tetrabenazine that inhibits vesicular monoamine transporter 2 (VMAT2), decreasing monoamine (primarily dopamine) packaging into synaptic vesicles. Deuterium substitution slows CYP2D6-mediated O-demethylation of the active metabolites, resulting in longer half-life, more stable plasma levels, and BID (vs TID) dosing compared to tetrabenazine.
Compare Deutetrabenazine →FDA-Approved Indications
- Tardive dyskinesia
- Chorea associated with Huntington disease
What Sets This Drug Apart
- Dual FDA indications — tardive dyskinesia AND Huntington disease chorea (valbenazine is TD only)
- Deuterium substitution provides longer half-life and more stable plasma levels than tetrabenazine — enabling BID vs TID dosing
- Boxed warning for depression and suicidality (HD indication) — stricter than valbenazine's warning
- Contraindicated in ANY hepatic impairment — unique among VMAT2 inhibitors (valbenazine is OK in mild impairment)
- CYP2D6 genotype-guided dosing recommended — poor metabolizers capped at 36 mg/day
- Now available as once-daily XR formulation (Austedo XR) — bridging the dosing frequency gap with valbenazine
Boxed Warning
Depression and suicidality in patients with Huntington disease — VMAT2 inhibitors increase risk