Ingrezza (Valbenazine) Dosing and Monitoring for Tardive Dyskinesia
Start Ingrezza at 40 mg once daily for one week, then increase to the recommended dose of 80 mg once daily; adjust to 40 mg or 60 mg based on response and tolerability. 1
Standard Dosing Protocol
For adults with tardive dyskinesia:
- Week 1: 40 mg once daily
- Week 2 onward: 80 mg once daily (recommended dose)
- Alternative maintenance doses: 40 mg or 60 mg once daily may be used depending on individual response and tolerability 1
Administer with or without food. The capsule may be swallowed whole or, if using INGREZZA SPRINKLE formulation, the contents can be sprinkled on soft food (applesauce, yogurt, pudding) and consumed immediately 1.
Dose Adjustments for Special Populations
Hepatic Impairment
Reduce to 40 mg once daily for moderate or severe hepatic impairment (Child-Pugh score 7-15) due to increased drug exposure 1. This is a critical adjustment—patients with compromised liver function have significantly higher valbenazine and active metabolite levels.
CYP2D6 Poor Metabolizers
Reduce to 40 mg once daily for known CYP2D6 poor metabolizers 1. These patients have increased exposure to the active metabolite, raising the risk of dose-related adverse effects.
Renal Impairment
No dose adjustment needed for any degree of renal impairment (mild, moderate, or severe) 1. Valbenazine does not undergo primary renal clearance, making it safe across all levels of kidney function.
Drug Interaction Adjustments
Strong CYP3A4 Inhibitors
Reduce to 40 mg once daily when co-administered with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir) 1.
Strong CYP2D6 Inhibitors
Reduce to 40 mg once daily when co-administered with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine) 1.
Strong CYP3A4 Inducers
Avoid concomitant use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) as they significantly reduce valbenazine efficacy 1.
Clinical Monitoring and Safety
Efficacy Assessment
The APA guidelines recommend treating moderate to severe or disabling tardive dyskinesia with a VMAT2 inhibitor like valbenazine (1B recommendation) 2. Monitor treatment response using:
- Abnormal Involuntary Movement Scale (AIMS): Expect ≥50% improvement in 40% of patients by week 6 on 80 mg 3. By week 48,86% of completers achieve ≥50% improvement 4.
- Clinical Global Impression of Change-TD (CGI-TD): 82.8% of patients show "much improved" or "very much improved" ratings at 48 weeks 5
- Early response prediction: 55% of patients who complete 48 weeks show clinically meaningful improvement (≥2-point AIMS reduction) by week 4; 97% meet this threshold by week 48 4
Safety Monitoring
Key adverse effects to monitor:
- Somnolence/sedation: Most common adverse effect (10.9% vs 4.2% placebo), with NNH of 15 3. This typically occurs after dose escalation to 80 mg.
- QT prolongation: Monitor ECG in patients with cardiac risk factors, though no specific contraindications exist 3
- Depression/suicidal ideation: While the boxed warning applies specifically to Huntington's disease patients, remain vigilant in all patients with psychiatric comorbidities 1
- SIADH: One case report suggests possible association with severe hyponatremia 6. Consider monitoring sodium levels in symptomatic patients, particularly within the first 6 weeks of treatment.
Discontinuation Rates
Treatment discontinuation due to adverse events is low (2.9% vs 1.6% placebo), yielding an NNH of 76 (not statistically significant) 3. The number needed to treat (NNT) is 4 for achieving ≥50% AIMS improvement, making valbenazine approximately 15 times more likely to produce therapeutic response than cause discontinuation 3.
Long-term Treatment Considerations
Sustained response is the rule, not the exception. Of patients achieving ≥50% AIMS response at week 8,95% maintain this response at week 48 4. Even among those not responding at week 8,81% eventually achieve ≥50% improvement by week 48 4. This supports continuing treatment beyond initial weeks even if early response is modest.
Quality of life improvements are substantial and clinically meaningful, with validated patient-reported outcomes showing significant benefits in the TDIS scale, Sheehan Disability Scale, and EQ-VAS 7.
Common Pitfalls to Avoid
- Premature discontinuation: Don't stop treatment if response at 4-8 weeks is suboptimal; most patients eventually respond with continued treatment 4
- Overlooking dose reduction needs: Always reduce to 40 mg for hepatic impairment, CYP2D6 poor metabolizers, and strong CYP3A4/CYP2D6 inhibitor co-administration
- Ignoring drug interactions: Strong CYP3A4 inducers can render valbenazine ineffective—avoid this combination entirely
- Enteral tube administration: Never administer INGREZZA SPRINKLE via feeding tubes as it causes obstruction 1