Time to Onset of Action for Austedo (Deutetrabenazine)
Austedo begins working within the first week of treatment, with steady-state plasma concentrations of active metabolites achieved after approximately 4-7 days of consistent dosing. 1, 2
Pharmacokinetic Timeline
Steady-state achievement occurs within 4-7 days of regular dosing, at which point the active metabolites (α-HTBZ and β-HTBZ) reach consistent therapeutic levels in the bloodstream 1, 2
The deuterated active metabolites have an elimination half-life approximately twice as long as non-deuterated tetrabenazine metabolites, which contributes to more stable drug levels throughout the day 2, 3
Peak plasma concentrations (Cmax) occur within hours of each dose, but the clinical benefit accumulates as steady-state is reached over the first week 3
Clinical Response Timeline
In the pivotal FIRST-HD trial, deutetrabenazine was titrated over 8 weeks to optimal doses (12-48 mg/day) for chorea control, with the full 12-week study demonstrating significant efficacy 4
Clinical improvement in chorea symptoms becomes apparent during the titration period, though maximal benefit may require several weeks as the dose is optimized for each patient 4
The ARC-HD trial showed sustained improvements in chorea control at 54 weeks, indicating that benefits are maintained with continued treatment 4
Practical Dosing Considerations
Deutetrabenazine is administered twice daily with the standard formulation, though a once-daily extended-release formulation has been shown to be bioequivalent 1
Food has no effect on overall drug exposure (AUC), though it increases peak concentrations by approximately 50%, which remains lower than tetrabenazine peaks 3
The lower peak-to-trough fluctuation (11-fold lower than tetrabenazine) contributes to better tolerability while maintaining efficacy 3
Safety Profile During Initial Treatment
Most treatment-emergent adverse events are mild to moderate in severity, with somnolence being the most common neuropsychiatric effect 4
Individual neuropsychiatric adverse events typically occur in less than 7% of patients, with no significant difference from placebo in the FIRST-HD trial 4
The favorable pharmacokinetic profile permits lower dosing than tetrabenazine (approximately 11.4-13.2 mg deutetrabenazine provides comparable exposure to 25 mg tetrabenazine), potentially improving the safety profile 3