What is the recommended treatment and dosage of Ingrezza (valbenazine) for an adult patient with tardive dyskinesia?

Ingrezza (Valbenazine) for Tardive Dyskinesia

For adults with tardive dyskinesia, start Ingrezza at 40 mg once daily, then increase to the recommended dose of 80 mg once daily after one week. 1

Standard Dosing Regimen

• Initial dose: 40 mg once daily for the first week 1
• Target dose: 80 mg once daily (recommended maintenance dose) 1
• Alternative maintenance doses: 40 mg or 60 mg once daily may be considered based on individual response and tolerability 1
• Administration: Take with or without food 1

Dose Modifications for Specific Populations

Hepatic Impairment

• Moderate to severe hepatic impairment (Child-Pugh score 7-15): Reduce dose to 40 mg once daily 1

CYP2D6 Poor Metabolizers

• Known CYP2D6 poor metabolizers: Limit dose to 40 mg once daily 1

Drug Interactions Requiring Dose Adjustment

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): Reduce dose to 40 mg once daily 1
• Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine): Reduce dose to 40 mg once daily 1
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin): Concomitant use is not recommended 1

Clinical Context and Evidence

Valbenazine is a first-line FDA-approved VMAT2 inhibitor specifically indicated for tardive dyskinesia treatment. 2, 3 This recommendation is supported by multiple clinical guidelines identifying VMAT2 inhibitors as the preferred pharmacotherapy for moderate to severe or disabling TD. 3

Long-Term Efficacy Data

• Sustained improvement: Long-term studies demonstrate substantial and sustained TD improvements with both 40 mg and 80 mg doses over 48 weeks of treatment 4, 5
• Response rates at 48 weeks: Approximately 89-90% of patients achieved ≥50% improvement in AIMS total score 5
• Elderly patients (≥65 years): At week 48,82.1% achieved ≥50% AIMS improvement and 92.9% were rated as "much improved" or "very much improved" on CGI-TD 6
• Washout effects: TD symptoms return toward baseline after 4 weeks of valbenazine discontinuation, indicating ongoing need for treatment 4

Safety Profile

• Most common adverse effect: Somnolence (occurs in >5% of patients) 1
• Movement disorder risk: Long-term valbenazine does not appear to induce or worsen akathisia or parkinsonism 4
• Psychiatric stability: Patients generally remain psychiatrically stable during treatment 4, 6
• Long-term tolerability: After the initial 4-week dose escalation period, <15% of participants experienced serious TEAEs (13.7%) or discontinued due to TEAEs (11.8%) 5

Critical Safety Warnings

Boxed Warning for Huntington's Disease Patients

• Depression and suicidal ideation risk: VMAT2 inhibitors increase the risk of depression and suicidal thoughts/behavior specifically in patients with Huntington's disease 1
• This warning does NOT apply to tardive dyskinesia patients without Huntington's disease 1

Other Important Warnings

• Hypersensitivity reactions: Discontinue immediately if angioedema occurs 1
• QT prolongation: Avoid use in patients with congenital long QT syndrome or arrhythmias associated with prolonged QT interval 1
• Neuroleptic malignant syndrome: Discontinue if this occurs 1
• Parkinsonism: Postmarketing reports of severe parkinson-like symptoms; reduce dose or discontinue if clinically significant signs develop 1

Administration Options

INGREZZA SPRINKLE Formulation

• For patients with swallowing difficulties: Open capsule and sprinkle entire contents over 1 tablespoon of soft food (applesauce, yogurt, or pudding) 1
• Do NOT use milk or drinking water 1
• Storage: Drug/food mixture can be stored up to 2 hours at room temperature; discard unused portion after 2 hours 1
• Alternative: INGREZZA SPRINKLE may be swallowed whole with water; do not crush or chew 1
• Enteral tube warning: Do not administer via nasogastric, gastrostomy, or other enteral tubes due to obstruction risk 1

Common Pitfalls to Avoid

• Do NOT use anticholinergics (benztropine, trihexyphenidyl) to treat tardive dyskinesia - these medications can worsen TD 7, 2, 3
• Do NOT confuse TD with acute dystonia or drug-induced parkinsonism - anticholinergics may help the latter but worsen TD 2
• Do NOT use MAOIs concomitantly with valbenazine 1
• Do NOT exceed 40 mg daily in patients on strong CYP3A4 or CYP2D6 inhibitors - this prevents excessive drug accumulation 1