From the FDA Drug Label
The chronic daily dose of tetrabenazine tablets used to treat chorea associated with Huntington’s disease (HD) is determined individually for each patient. When first prescribed, tetrabenazine tablets therapy should be titrated slowly over several weeks to identify a dose of tetrabenazine tablets that reduces chorea and is tolerated.
The starting dose should be 12.5 mg per day given once in the morning. After one week, the dose should be increased to 25 mg per day given as 12.5 mg twice a day. Tetrabenazine tablets should be titrated up slowly at weekly intervals by 12. 5 mg daily, to allow the identification of a tolerated dose that reduces chorea.
If a dose of 37. 5 to 50 mg per day is needed, it should be given in a three times a day regimen. The maximum recommended single dose is 25 mg.
Patients who require doses of tetrabenazine tablets greater than 50 mg per day should be first tested and genotyped to determine if they are poor metabolizers (PMs) or extensive metabolizers (EMs) by their ability to express the drug metabolizing enzyme, CYP2D6
The dose of tetrabenazine tablets should then be individualized accordingly to their status as PMs or EMs.
The treatment regimen for Huntington's disease chorea using Tetrabenazine is as follows:
- Starting dose: 12.5 mg per day given once in the morning
- Dose titration: Increase dose to 25 mg per day given as 12.5 mg twice a day after one week, then titrate up slowly at weekly intervals by 12.5 mg daily
- Maximum recommended single dose: 25 mg for doses up to 50 mg per day, and 37.5 mg for doses above 50 mg per day
- Dosing frequency: Three times a day for doses of 37.5 to 50 mg per day, and for doses above 50 mg per day
- Genotyping: Required for patients who require doses greater than 50 mg per day to determine if they are poor metabolizers (PMs) or extensive metabolizers (EMs)
- Maximum daily dose: 50 mg for PMs, and 100 mg for EMs and intermediate metabolizers (IMs) 1, 1, 1
From the Research
Tetrabenazine is the first-line medication for treating chorea in Huntington's disease, typically started at 12.5 mg once daily and gradually increased to an effective dose, as supported by the most recent and highest quality study 2.
Treatment Regimen
The recommended approach involves weekly dose increases of 12.5 mg, dividing the total daily dose into two or three administrations per day. Most patients require 25-100 mg daily, with a maximum of 100 mg per day or 37.5 mg in a single dose.
Dose Adjustments
Dose adjustments should be made based on symptom control and side effects, with slower titration for elderly patients or those with hepatic impairment.
Mechanism of Action
Tetrabenazine works by depleting presynaptic dopamine and inhibiting vesicular monoamine transporter 2 (VMAT2), which helps reduce the involuntary movements characteristic of Huntington's chorea.
Common Side Effects
Common side effects include sedation, depression, akathisia, and parkinsonism, requiring careful monitoring, especially in patients with pre-existing depression or suicidal thoughts.
Alternative Options
If side effects become problematic, dose reduction is recommended before discontinuation. For patients who don't respond adequately to tetrabenazine, alternative options include deutetrabenazine, which has a similar mechanism but potentially fewer side effects, or antipsychotics like risperidone or olanzapine, as noted in studies 3, 4, 5, 6. Some key points to consider when treating chorea in Huntington's disease with tetrabenazine include:
- The importance of individualized dosing based on ongoing assessment of possible adverse side effects, as highlighted in the study 3.
- The need for careful monitoring of side effects, particularly in patients with pre-existing depression or suicidal thoughts, as noted in the study 6.
- The potential for long-term improvement in chorea with tetrabenazine treatment, as demonstrated in the study 4.