Austedo (Deutetrabenazine) Dosing
Start Austedo at 12 mg per day (6 mg twice daily with food for immediate-release tablets, or 12 mg once daily with or without food for extended-release tablets), then titrate weekly by 6 mg/day increments based on symptom control and tolerability, up to a maximum of 48 mg per day. 1
Initial Dosing
- Immediate-release Austedo tablets: Begin with 6 mg twice daily (12 mg total per day), administered with food 1
- Extended-release Austedo XR tablets: Begin with 12 mg once daily, which can be taken with or without food 1
- Swallow tablets whole—do not chew, crush, or break 1
Dose Titration
- Increase the dose at weekly intervals in 6 mg/day increments based on reduction of chorea (in Huntington's disease) or tardive dyskinesia symptoms, and patient tolerability 1
- The maximum recommended daily dose is 48 mg 1
- For immediate-release formulation, total daily doses of 12 mg or above should be divided into two doses 1
- Most patients in clinical trials achieved optimal response at doses between 24-48 mg/day 2
Special Dosing Considerations
Switching from Tetrabenazine
When converting patients from tetrabenazine to Austedo, discontinue tetrabenazine and start Austedo the following day using the conversion table below 1:
- Tetrabenazine 12.5 mg/day → Austedo 6 mg once daily (or 6 mg once daily for immediate-release)
- Tetrabenazine 25 mg/day → Austedo XR 12 mg once daily (or 6 mg twice daily)
- Tetrabenazine 37.5 mg/day → Austedo XR 18 mg once daily (or 9 mg twice daily)
- Tetrabenazine 50 mg/day → Austedo XR 24 mg once daily (or 12 mg twice daily)
- Tetrabenazine 100 mg/day → Austedo XR 48 mg once daily (or 24 mg twice daily)
CYP2D6 Considerations
- In patients taking strong CYP2D6 inhibitors or who are poor CYP2D6 metabolizers, the maximum daily dose should not exceed 36 mg 1
- This dose restriction is critical to avoid excessive drug accumulation and adverse effects 1
Treatment Interruption and Discontinuation
- Treatment can be discontinued without tapering 1
- If treatment is interrupted for less than one week, resume at the previous maintenance dose without re-titration 1
- If treatment is interrupted for greater than one week, re-titrate from the starting dose when resuming therapy 1
Clinical Efficacy Data
- In the pivotal ARM-TD and AIM-TD studies for tardive dyskinesia, 34% of patients achieved ≥50% improvement in AIMS scores with deutetrabenazine 12-18 mg twice daily versus 12% with placebo (NNT = 5) 3
- In the First-HD study for Huntington's disease chorea, 46% of patients were rated as "much improved" or "very much improved" with deutetrabenazine versus 26% with placebo (NNT = 5) 3
- Most patients who achieved therapeutic response required doses between 24-48 mg/day 2
Safety Monitoring
Common Adverse Events
The most common adverse events (≥4% and greater than placebo) include 1, 4:
- For tardive dyskinesia: nasopharyngitis and insomnia
- For Huntington's disease: somnolence, diarrhea, dry mouth, and fatigue
Critical Safety Warnings
- Boxed Warning: Austedo increases the risk of depression and suicidal thoughts/behavior in patients with Huntington's disease 1
- Contraindicated in patients with Huntington's disease who are suicidal or have untreated/inadequately treated depression 1
- Monitor closely for emergence or worsening of depression, suicidality, or unusual behavioral changes 1
- Avoid use in patients with congenital long QT syndrome or arrhythmias associated with QT prolongation 1
Hepatic Impairment
- Austedo is contraindicated in patients with any degree of hepatic impairment 1
Pharmacokinetic Advantages Over Tetrabenazine
- Deutetrabenazine has a 3-4 fold longer half-life for active metabolites compared to tetrabenazine 5
- This results in 11-fold lower peak-to-trough fluctuations at steady state 5
- The improved pharmacokinetic profile allows for lower total daily doses and potentially better tolerability while maintaining efficacy 5, 6
- Food has no effect on total drug exposure (AUC), though it increases peak concentration (Cmax) by approximately 50%—which remains lower than tetrabenazine's Cmax 5