Starting Dose of Ingrezza (Valbenazine)
The starting dose of Ingrezza is 40 mg once daily for both tardive dyskinesia and chorea associated with Huntington's disease 1.
Dosing Algorithm by Indication
For Tardive Dyskinesia
- Start: 40 mg once daily
- After 1 week: Increase to the recommended dose of 80 mg once daily
- Alternative maintenance doses: 40 mg or 60 mg once daily may be considered based on individual response and tolerability 1
For Chorea Associated with Huntington's Disease
- Start: 40 mg once daily
- Titration: Increase in 20 mg increments every 2 weeks
- Target dose: 80 mg once daily
- Alternative maintenance doses: 40 mg or 60 mg once daily may be considered based on response and tolerability 1
Administration Details
Ingrezza can be taken with or without food 1. Both the standard capsule and sprinkle formulation are available, with the sprinkle version designed for patients with dysphagia who can either swallow the capsule whole or sprinkle the contents on soft food like applesauce, yogurt, or pudding 1, 2.
Critical Dose Adjustments
Reduce Starting Dose to 40 mg Once Daily (and maintain) in:
- Moderate to severe hepatic impairment (Child-Pugh score 7-15) 1
- Known CYP2D6 poor metabolizers 1
- Patients taking strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin) 1
- Patients taking strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine) 1
Avoid Concomitant Use:
Do not use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) as they significantly reduce valbenazine exposure 1.
Clinical Evidence Supporting This Dosing
The 40 mg starting dose is supported by phase 3 trials showing dose-dependent efficacy. In KINECT 3, the 80 mg dose demonstrated a clinically significant effect size (d=0.90) for tardive dyskinesia improvement, while the 40 mg dose showed a moderate effect (d=0.52) 3, 4. Long-term studies (KINECT 4) demonstrated that most patients achieved substantial improvement by week 48, with 89-90% showing ≥50% improvement in AIMS scores regardless of whether they remained on 40 mg or escalated to 80 mg 5.
Safety Considerations
The gradual titration schedule minimizes adverse effects. In clinical trials, starting at 40 mg with weekly (tardive dyskinesia) or biweekly (Huntington's chorea) escalation was generally well-tolerated, with the most common side effects being somnolence and fatigue 5, 3. Importantly, psychiatric stability was maintained throughout long-term treatment, and no new safety signals emerged with extended use up to 48 weeks 5, 6.
Special Warning for Huntington's Disease: VMAT2 inhibitors including Ingrezza carry a boxed warning for increased risk of depression and suicidal ideation in patients with Huntington's disease. Close monitoring is essential, particularly in those with prior depression or suicide attempts 1.