Dosing of Ingrezza (Valbenazine) in Your Patient
Start valbenazine at 40 mg once daily for one week, then increase to the recommended dose of 80 mg once daily. 1
Standard Dosing Regimen
The FDA-approved dosing for tardive dyskinesia follows a simple two-step approach 1:
- Week 1: 40 mg once daily
- Week 2 onward: 80 mg once daily (recommended target dose)
- Alternative maintenance doses: 40 mg or 60 mg once daily may be considered based on individual response and tolerability
Valbenazine can be taken with or without food, providing flexibility in administration 1.
Critical Drug Interaction Considerations
Your patient's current medication regimen requires careful attention:
Depakote (Valproic Acid)
No dose adjustment of valbenazine is needed. While one case report describes possible serotonin syndrome when trazodone was added to lurasidone and valproic acid 2, valproic acid itself does not significantly interact with valbenazine through CYP pathways.
Latuda (Lurasidone)
No dose adjustment of valbenazine is needed. Lurasidone is not a strong CYP3A4 or CYP2D6 inhibitor. However, be aware that one case report documented acute worsening of depression when valbenazine was added to lurasidone in a patient with major depressive disorder 3. Monitor mood closely during initiation.
Trazodone
No dose adjustment of valbenazine is needed. Trazodone is not a strong CYP inhibitor.
The standard 40 mg → 80 mg titration schedule is appropriate for your patient since none of the concurrent medications are strong CYP3A4 or CYP2D6 inhibitors 1.
When Dose Reduction to 40 mg is Required
Reduce the maximum dose to 40 mg once daily in these specific situations 1:
- Strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, clarithromycin)
- Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine, bupropion)
- Known CYP2D6 poor metabolizers
- Moderate to severe hepatic impairment (Child-Pugh score 7-15)
Monitoring Priorities
Depression and Suicidality
This is the most critical safety concern. Valbenazine carries a boxed warning for depression and suicidal ideation in Huntington's disease patients 1. While your patient likely has tardive dyskinesia (not Huntington's), one recent case report documented acute mood deterioration within hours of starting valbenazine 40 mg in a patient with major depressive disorder on lurasidone 3. The patient's Hamilton Depression Rating Scale increased from 30 to 40 overnight, requiring discontinuation.
Monitor closely for:
- Emergence or worsening of depression
- Suicidal thoughts or behavior
- Unusual behavioral changes
- Increased anxiety or functional decline
QTc Prolongation
Valbenazine may prolong QTc interval, particularly at higher exposures 1. At 80 mg daily in typical patients, mean QTc prolongation is 6.7 msec (upper CI: 8.4 msec). Consider baseline ECG if the patient has cardiac risk factors.
Extrapyramidal Symptoms
While valbenazine treats tardive dyskinesia, paradoxically it can cause parkinsonism, akathisia, or other movement disorders in some patients 1. Monitor for new or worsening motor symptoms.
Timeline for Response
- Steady-state exposure: Achieved within 1 week 1
- Clinical improvement: May be observed as early as week 2, with continued improvement over subsequent weeks 4
- Long-term data: In open-label studies, 64.3% of patients achieved CGIS-TD scores of "normal/not ill" or "borderline ill" by week 48 4
Practical Considerations
Once-daily dosing is a significant advantage over deutetrabenazine (twice-daily) 5. Valbenazine does not require titration to individual tolerability—the goal is to reach 80 mg unless specific contraindications exist 5, 6.
If inadequate response at 80 mg: Consider whether the patient is truly adherent, whether there are unrecognized drug interactions, or whether the diagnosis of tardive dyskinesia is correct. The 60 mg dose was approved based on modeling showing efficacy between 40 mg and 80 mg 6, providing an intermediate option if 80 mg causes tolerability issues.
Key Pitfall to Avoid
Do not avoid strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) with valbenazine—they significantly reduce exposure and are not recommended for concomitant use 1. Your patient is not on any such medications, but this is important if future medication changes are considered.