What is the recommended treatment and dosage of Tetrabenazine (Xenazine) for chorea associated with Huntington's disease?

Tetrabenazine Treatment for Chorea in Huntington's Disease

Tetrabenazine is the recommended first-line pharmacological treatment for chorea associated with Huntington's disease, with an initial dose of 12.5 mg once daily, gradually titrated to an effective dose that typically ranges from 25-100 mg per day based on patient response and CYP2D6 metabolizer status. 1

Dosing Protocol

Initial Titration (Up to 50 mg/day)

• Start with 12.5 mg once daily in the morning for one week 1
• Increase to 25 mg/day (12.5 mg twice daily) after one week 1
• Titrate upward slowly at weekly intervals by 12.5 mg daily until identifying a tolerated dose that effectively reduces chorea 1
• For doses of 37.5-50 mg/day, administer in three divided doses throughout the day 1
• Maximum recommended single dose is 25 mg 1

Dosing Above 50 mg/day

• Patients requiring doses above 50 mg/day must be genotyped for CYP2D6 enzyme activity to determine metabolizer status 1
• For extensive or intermediate metabolizers:
  • Continue titration at weekly intervals by 12.5 mg daily 1
  • Maximum daily dose: 100 mg 1
  • Maximum single dose: 37.5 mg 1
  • Administer in three divided doses per day 1
• For poor metabolizers:
  • Maximum daily dose: 50 mg 1
  • Maximum single dose: 25 mg 1

Efficacy

• Clinical trials demonstrate significant reduction in chorea severity compared to placebo 2
• In randomized controlled trials, tetrabenazine reduced chorea scores by 5.0 units compared to 1.5 units with placebo (p<0.0001) 2
• Long-term studies show sustained efficacy, with 75% of patients achieving marked or very good responses at optimal dosages 3
• Improvement in chorea can be maintained for up to 80 weeks with continued treatment 4

Adverse Effects and Monitoring

Common Adverse Effects

• Sedation/somnolence (39%) 3
• Insomnia (33%) 3
• Depression (31%) 3
• Akathisia/restlessness 1, 4
• Parkinsonism 4
• Anxiety 4

Serious Concerns

• Depression and suicidality - requires careful monitoring 1
• Contraindicated in:
  • Actively suicidal patients 1
  • Untreated or inadequately treated depression 1
  • Hepatic impairment 1
  • Patients taking MAOIs or reserpine 1
  • Patients taking deutetrabenazine or valbenazine 1

Dose Adjustment

• If adverse reactions occur, stop titration and reduce the dose 1
• If adverse reactions persist despite dose reduction, consider discontinuation or alternative treatment 1
• Do not exceed 50 mg/day when co-administered with strong CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) 1

Treatment Considerations

• Tetrabenazine is one of three major treatments for alleviating chorea in Huntington's disease, alongside deutetrabenazine and valbenazine 5
• Real-world data shows that approximately 66.5% of patients receive tetrabenazine doses ≤50 mg/day 6
• Common reasons for stopping dose titration include optimal chorea control (55.5%), intolerability of higher doses (31.2%), and reaching maximum recommended dosage despite suboptimal control (11.4%) 6
• Patients should be monitored for emergence or worsening of depression, suicidality, or unusual changes in behavior 1
• Personalized management requires consideration of symptom variations and careful management of adverse drug reactions 5

Alternative Options

• If tetrabenazine is not tolerated or ineffective, consider deutetrabenazine (Austedo) or valbenazine (Ingrezza) 5
• Antipsychotics such as haloperidol, sulpiride, and quetiapine may also improve chorea and psychiatric symptoms 5