DEUTETRABENAZINE TAB
Clinical Criteria Summary
Document 276: Deutetrabenazine AUSTEDO and AUSTEDO XR Criteria
Exclusion Criteria
- Actively suicidal or has untreated or inadequately treated depression
- Congenital long QT interval, or a QTc >450 ms for men or QTc >470 ms for women
- History of cardiac arrhythmias (ventricular), cardiac conduction system disease (LBBB or RBBB), or cardiac device (can be considered candidates with cardiology evaluation)
- Concurrent use of a monoamine oxidase inhibitor (MAOI) or within 14 days of discontinuing therapy with an MAOI
- Current or use of reserpine within the past 20 days
- Concurrent use of another VMAT2 inhibitor (i.e., tetrabenazine, valbenazine)
- History of neuroleptic malignant syndrome (NMS)
- Current clinically significant hyperprolactinemia
- Pregnant or lactating
- Hepatic impairment
Inclusion Criteria: Treatment of Huntington Disease
- Initial prescriber is a resident, fellow, or other trainee: an attending psychiatrist or neurologist has verified the diagnosis and need for deutetrabenazine
- Diagnosis of Huntington disease documented in the medical record
- Chorea is disabling or painful and interferes with functional status (including self-care and ambulation), quality of life, or creates a social stigma sufficient to cause social isolation or embarrassment
- Prescriber has documented specific movement(s) (e.g., facial, oral, extremity, or trunk) in the medical record along with how the chorea is affecting function, quality of life, or socialization
Inclusion Criteria: Treatment of Dystonia
- Initial prescriber is a resident, fellow, or other trainee: an attending psychiatrist or neurologist has verified the diagnosis and need for deutetrabenazine
- No response or intolerant to alternative agents (local botulinum toxin injections, anticholinergics, or benzodiazepines)
Inclusion Criteria: Treatment of Tardive Dyskinesia
- Diagnosis of tardive dyskinesia (TD) secondary to a dopaminergic blocking agent (e.g., antipsychotic or metoclopramide)
- TD interferes with functional status (including self-care and ambulation), quality of life, or creates a social stigma sufficient to cause social isolation or embarrassment
- Prescriber has documented specific movement(s) (e.g., facial, oral, extremity, or trunk) in the medical record along with how TD is affecting function, quality of life, or socialization
- Recent Abnormal Involuntary Movement Scale (AIMS) score is recorded in the medical record
- ECG performed to confirm a QTc <450 ms for men or QTc <470 ms for women
- Initial prescriber is a resident, fellow, or other trainee: an attending psychiatrist or neurologist has verified the diagnosis and need for deutetrabenazine
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.