VALBENAZINE CAP,ORAL
Clinical Criteria Summary
Document 267: Valbenazine INGREZZA Criteria Huntington Disease
Exclusion Criteria
- Active suicidality or untreated/inadequately treated depression
- Congenital long QT interval or QTc >450 ms (men) / >470 ms (women)
- History of cardiac arrhythmias (ventricular), cardiac conduction system disease (LBBB/RBBB), or presence of a cardiac device (requires cardiology evaluation for consideration)
- Concurrent use of monoamine oxidase inhibitors (MAOIs)
- Current or recent reserpine use within the past 20 days
- Concurrent use of another VMAT2 inhibitor
- History of neuroleptic malignant syndrome (NMS)
- Current clinically significant hyperprolactinemia
- Pregnancy or lactation
- Concurrent use of strong CYP3A4 inducers
Inclusion Criteria
- Documented diagnosis of Huntington disease in the medical record
- Disabling or painful chorea that interferes with functional status (self-care, ambulation), quality of life, or causes social stigma/isolation/embarrassment
- Documentation of specific movement(s) (facial, oral, extremity, trunk) and their impact on function, quality of life, or socialization
- Verification by an attending psychiatrist or neurologist if the initial prescriber is a resident, fellow, or other trainee
Document 299: DCR VMAT 2 Inhibitor Apr22
Criteria for Chorea Associated with Huntington Disease
- Deutetrabenazine: FDA approved; 6 mg once daily; may increase dose weekly based on response and tolerability in increments of 6 mg/day; administer in two divided doses if total daily dose ≥12 mg; maximum recommended dose: 48 mg/day.
- Tetrabenazine: FDA approved; 12.5 mg once daily in the morning, may increase to 12.5 mg twice daily after 1 week; dosage may be increased by 12.5 mg daily at weekly intervals; daily doses >37.5 mg should be divided into 3 doses (maximum single dose: 25 mg); patients requiring doses >50 mg/day should be genotyped for CYP2D6.
- Valbenazine: Not approved for Huntington disease-related chorea.
Criteria for Tardive Dyskinesia
- Deutetrabenazine: FDA approved; 6 mg twice daily; may increase dose weekly based on response and tolerability in increments of 6 mg/day; administer in two divided doses if total daily dose ≥12 mg; maximum recommended dose: 48 mg/day.
- Tetrabenazine: Used off-label; 12.5 mg daily for one week and increased by 12.5 mg increments every few days, according to clinical response and as tolerated, to a usual effective dose of 75 to 150 mg daily; daily doses >37.5 mg should be divided into three doses; maximum recommended single and daily doses are lower (25 and 50 mg, respectively) for patients taking strong CYP2D6 inhibitors.
- Valbenazine: FDA approved; 40 mg once daily; after 1 week, increase to 80 mg once daily; continuation of 40 or 60 mg once daily may be considered for some patients based on response and tolerability.
General Criteria (All VMAT-2 Inhibitors)
- Contraindications:
- Deutetrabenazine and Tetrabenazine: Suicidal/untreated depression, hepatic impairment, taking reserpine, taking MAOI, taking another VMAT-2 inhibitor.
- Valbenazine: Hypersensitivity to valbenazine.
- Warnings and Precautions:
- All three drugs: Depression and suicidality (box warning), neuroleptic malignant syndrome, akathisia/restlessness/agitation, Parkinsonism, sedation/somnolence, QTc prolongation.
- Tetrabenazine only: Hypotension/orthostatic hypotension, hyperprolactinemia, binding to melanin-containing tissues.
- Significant Drug Interactions:
- All three drugs: Strong CYP2D6 inhibitors, MAOI.
- Deutetrabenazine and Tetrabenazine: Reserpine, alcohol/sedating drugs, neuroleptic drugs, concomitant VMAT-2 inhibitors.
- Tetrabenazine only: Strong CYP3A4 inhibitors/inducers, digoxin.
- Formulary and Place in Therapy Considerations:
- All three are non-formulary with separate CFU.
- Sequencing does not appear warranted for either indication based on current evidence and utilization data.
- Huntington disease: Tetrabenazine is the workhorse agent followed by deutetrabenazine and valbenazine; indirect evidence suggests better tolerability with deutetrabenazine (not supported by VA ADERS).
- Tardive dyskinesia: Deutetrabenazine and valbenazine have similar efficacy and tolerability; lack of high-quality data exists for tetrabenazine. VA ADERS shows higher adverse drug event rates for valbenazine compared to deutetrabenazine. Majority of patients with TD receive valbenazine, followed by tetrabenazine and deutetrabenazine.
Document 642: Valbenazine INGREZZA Criteria Tardive Dyskinesia
Exclusion Criteria
- Patient is actively suicidal or has untreated/inadequately treated depression
- Congenital long QT interval, or QTc >450 ms (men) / >470 ms (women)
- History of cardiac arrhythmias (ventricular), cardiac conduction system disease (LBBB/RBBB), or cardiac device (candidates may be considered with cardiology evaluation)
- Concurrent use of a monoamine oxidase inhibitor (MAOI)
- Current or recent reserpine use within the past 20 days
- Concurrent use of another VMAT2 inhibitor
- History of neuroleptic malignant syndrome (NMS)
- Current clinically significant hyperprolactinemia
- Pregnant or lactating
- Concurrent use of a strong CYP3A4 inducer
Inclusion Criteria
- Diagnosis of tardive dyskinesia secondary to a dopaminergic blocking agent (e.g., antipsychotic or metoclopramide)
- TD interferes with functional status (self-care, ambulation), quality of life, or causes social stigma/isolation/embarrassment
- Prescriber has documented specific movement(s) (facial, oral, extremity, trunk) in medical record along with impact on function, quality of life, or socialization
- Recent Abnormal Involuntary Movement Scale (AIMS) score recorded in medical record
- ECG performed to confirm QTc <450 ms (men) / <470 ms (women)
- If initial prescriber is a resident/fellow/trainee, attending psychiatrist or neurologist must verify diagnosis and need for valbenazine