Deutetrabenazine

The precise mechanism by which deutetrabenazine exerts its effects in the treatment of tardive dyskinesia and chorea in patients with Huntington’s disease is unknown but is believed to be related to its effect as a reversible depletor of monoamines (such as dopamine, serotonin, norepinephrine, and histamine) from nerve terminals. The major circulating metabolites (α-dihydrotetrabenazine [HTBZ] and β-HTBZ) of deutetrabenazine, are reversible inhibitors of VMAT2, resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.

• AUSTEDO XR ® and AUSTEDO ® are indicated in adults for the treatment of: chorea associated with Huntington’s disease [see Clinical Studies ( 14.1 )] tardive dyskinesia [see Clinical Studies ( 14.2 )] AUSTEDO XR and AUSTEDO are vesicular monoamine transporter 2 (VMAT2) inhibitors indicated in adults for the treatment of: Chorea associated with Huntington’s disease ( 1 ) Tardive dyskinesia ( 1 )

• AUSTEDO XR and AUSTEDO are contraindicated in patients: With Huntington’s disease who are suicidal, or have untreated or inadequately treated depression [see Warnings and Precautions ( 5.1 )] . With hepatic impairment [see Use in Specific Populations ( 8.6 ), Clinical Pharmacology ( 12.3 )] .contraindicated

AUSTEDO XR AUSTEDO Recommended Starting Dosage 12 mg once daily (12 mg per day) 6 mg twice daily (12 mg per day) Titrate at weekly intervals by 6 mg per day based on reduction of chorea or tardive dyskinesia, and tolerability, up to a maximum recommended daily dosage of 48 mg ( 2.1 ) Administer AUSTEDO XR with or without food in once-daily doses ( 2.1 ) Administer AUSTEDO with food and administer total daily dosages of 12 mg or above in two divided doses ( 2.1 ) Swallow tablets whole; do not chew, crush, or break ( 2.1 ) If switching patients from tetrabenazine, discontinue tetrabenazine and initiate AUSTEDO XR or AUSTEDO the following day. See full prescribing information for recommended conversion table ( 2.2 ) Maximum recommended dosage of AUSTEDO XR or AUSTEDO in poor CYP2D6 metabolizers is 36 mg per day ( 2.4 , 8.7 ) 2.1 Dosing Information The dose of AUSTEDO XR and AUSTEDO is determined individually for each patient based on reduction of chorea or tardive dyskinesia and tolerability. Table 1 displays the recommended dosage and important administration instructions of AUSTEDO XR and AUSTEDO when first prescribed to patients who are not being switched from tetrabenazine (a related VMAT2 inhibitor).

QT Prolongation: Avoid use in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval ( 5.3 ) Neuroleptic Malignant Syndrome (NMS): Discontinue if this occurs ( 5.4 ) Akathisia, agitation, restlessness, and parkinsonism: Reduce dose or discontinue if this occurs ( 5.5 , 5.6 ) Sedation/somnolence: May impair the patient’s ability to drive or operate complex machinery ( 5.7 ) 5.1 Depression and Suicidality in Patients with Huntington’s Disease Patients with Huntington’s disease are at increased risk for depression, and suicidal ideation or behaviors (suicidality). AUSTEDO XR and AUSTEDO may increase the risk for suicidality in patients with Huntington’s disease. In a 12-week, double-blind, placebo-controlled trial, suicidal ideation was reported by 2% of patients treated with AUSTEDO, compared to no patients on placebo; no suicide attempts and no completed suicides were reported. Depression was reported by 4% of patients treated with AUSTEDO. When considering the use of AUSTEDO XR or AUSTEDO, the risk of suicidality should be balanced against the need for treatment of chorea. All patients treated with AUSTEDO XR or AUSTEDO should be observed for new or worsening depression or suicidality. If depression or suicidality does not resolve, consider discontinuing treatment with AUSTEDO XR or AUSTEDO.

The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Depression and Suicidality in Patients with Huntington’s disease [see Warnings and Precautions ( 5.1 )] QTc Prolongation [see Warnings and Precautions ( 5.3 )] Neuroleptic Malignant Syndrome (NMS) [see Warnings and Precautions ( 5.4 )] Akathisia, Agitation, and Restlessness [see Warnings and Precautions ( 5.5 )] Parkinsonism [see Warnings and Precautions ( 5.6 )] Sedation and Somnolence [see Warnings and Precautions ( 5.7 )] Hyperprolactinemia [see Warnings and Precautions ( 5.8 )] Binding to Melanin-Containing Tissues [see Warnings and Precautions ( 5.9 )] Most common adverse reactions (>8% of AUSTEDO-treated patients with Huntington’s disease and greater than placebo): somnolence, diarrhea, dry mouth, and fatigue ( 6.1 ) Most common adverse reactions (that occurred in 4% of AUSTEDO-treated patients with tardive dyskinesia and greater than placebo): nasopharyngitis and insomnia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals at 1-888-483-8279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ) 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of AUSTEDO XR or AUSTEDO in pregnant women. Administration of deutetrabenazine to rats during organogenesis produced no clear adverse effect on embryofetal development. However, administration of tetrabenazine to rats throughout pregnancy and lactation resulted in an increase in stillbirths and postnatal offspring mortality [see Data]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of deutetrabenazine (5, 10, or 30 mg/kg/day) or tetrabenazine (30 mg/kg/day) to pregnant rats during organogenesis had no clear effect on embryofetal development. The highest dose tested was 6 times the maximum recommended human dose of 48 mg/day, on a body surface area (mg/m 2 ) basis. The effects of deutetrabenazine when administered during organogenesis to rabbits or during pregnancy and lactation to rats have not been assessed.

Metabolism

After oral dosing, plasma concentrations of deutetrabenazine are low compared to that of the active deuterated metabolites because of the extensive hepatic metabolism of deutetrabenazine. AUSTEDO XR Systemic exposure (i.e., peak plasma concentrations [C max ] and the area under the plasma concentration-time curve [AUC]) for deutetrabenazine and the active, deuterated dihydro metabolites (HTBZ), α-HTBZ and β-HTBZ, increased proportionally to dose following single doses of AUSTEDO XR over the recommended clinical dosage range (6 mg to 48 mg).

Overdoses ranging from 100 mg to 1 g have been reported in the literature with tetrabenazine, a closely related VMAT2 inhibitor. The following adverse reactions occurred with overdosing: acute dystonia, oculogyric crisis, nausea and vomiting, sweating, sedation, hypotension, confusion, diarrhea, hallucinations, rubor, and tremor. Treatment should consist of those general measures employed in the management of overdosage with any central nervous system-active drug. General supportive and symptomatic measures are recommended. Cardiac rhythm and vital signs should be monitored. In managing overdosage, the possibility of multiple drug involvement should always be considered. The physician should consider contacting a poison control center on the treatment of any overdose. Telephone numbers for certified poison control centers are listed on the American Association of Poison Control Centers website www.aapcc.org.

• Apr 3, 2017NDANDA208082Teva Branded Pharm
• Feb 17, 2023NDANDA216354Teva

1. 1Drug Ineffective96214%
2. 2Depression4817.1%
3. 3Death4596.8%
4. 4Dyskinesia4316.3%
5. 5Product Use Issue3595.3%
6. 6Tremor3465.1%
7. 7Somnolence3184.7%
8. 8Suicidal Ideation3084.5%
9. 9Fatigue3054.5%
10. 10Insomnia3034.5%
11. 11Fall2824.2%
12. 12Off Label Use2774.1%
13. 13Product Use In Unapproved Indication2623.9%
14. 14Tardive Dyskinesia2403.5%
15. 15Dizziness2233.3%

The 10 most recently updated of 18 ClinicalTrials.gov registrations naming Deutetrabenazine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Evaluate the Effectiveness of Valbenazine in Adult Participants With Tardive Dyskinesia (TD) Who Remain Symptomatic While Receiving or After Stopping a Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor
  Recruiting · Phase 4 · Interventional · 50 enrolled · Neurocrine Biosciences
  NCT07105111updated 2026-06-11
• Real World Effectiveness and Safety of Deutetrabenazine in Adult Chinese Patients With Huntington's Disease (HD) Chorea in China
  Completed · Phase 4 · Interventional · 50 enrolled · Teva Branded Pharmaceutical Products R&D LLC
  NCT07601516updated 2026-06-09
• Impact of Deutetrabenazine on Functional Speech and Gait Dynamics in Huntington Disease
  Active not recruiting · Phase 2 · Phase 3 · Interventional · 30 enrolled · Vanderbilt University Medical Center
  NCT04713982updated 2026-04-14
• Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
  Not yet recruiting · Phase 4 · Interventional · 25 enrolled · University Hospitals Cleveland Medical Center
  NCT06997198updated 2026-04-09
• Efficacy of Deutetrabenazine to Control Symptoms of Dysphagia Associated with HD
  Terminated · Phase 1 · Interventional · 36 enrolled · Fundacion Huntington Puerto Rico
  NCT04301726updated 2025-02-27
• An Open-label Study to Define the Safety, Tolerability and Clinical Activity of Deutetrabenazine (AUstedo) in Adult Study Subjects With DYsTonia
  Completed · Phase 1 · Phase 2 · Interventional · 15 enrolled · University of Pennsylvania
  NCT04173260updated 2024-09-20
• A Study to Test if TEV-50717 is Safe and Effective in Relieving Abnormal Involuntary Movements in Cerebral Palsy
  Terminated · Phase 3 · Interventional · 44 enrolled · Teva Branded Pharmaceutical Products R&D, Inc.
  NCT04200352updated 2024-04-22
• A Study of TEV-50717 (Deutetrabenazine) for the Treatment of Dyskinesia in Cerebral Palsy in Children and Adolescents
  Completed · Phase 3 · Interventional · 63 enrolled · Teva Branded Pharmaceutical Products R&D, Inc.
  NCT03813238updated 2023-09-08
• Reducing Involuntary Movements in Participants With Tardive Dyskinesia
  Completed · Phase 3 · Interventional · 343 enrolled · Auspex Pharmaceuticals, Inc.
  NCT02198794updated 2022-04-01
• A Pilot Study Of SD-809 (Deutetrabenazine) In Moderate To Severe Tourette Syndrome (TS)
  Completed · Phase 1 · Interventional · 23 enrolled · Auspex Pharmaceuticals, Inc.
  NCT02674321updated 2021-11-09

CPIC-curated drug–gene pairs for Deutetrabenazine. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• CYP2D6CPIC B/C (provisional)FDA label: Actionable PGx

Frequently asked questions

How does Deutetrabenazine work?

The precise mechanism by which deutetrabenazine exerts its effects in the treatment of tardive dyskinesia and chorea in patients with Huntington’s disease is unknown but is believed to be related to its effect as a reversible depletor of monoamines (such as dopamine, serotonin, norepinephrine, and histamine) from nerve terminals. The major circulating metabolites (α-dihydrotetrabenazine [HTBZ] and β-HTBZ) of deutetrabenazine, are reversible inhibitors of VMAT2, resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.

What is Deutetrabenazine used for?

According to FDA labeling, Deutetrabenazine carries indications including: AUSTEDO XR ® and AUSTEDO ® are indicated in adults for the treatment of: chorea associated with Huntington’s disease [see Clinical Studies ( 14.1 )] tardive dyskinesia [see Clinical Studies ( 14.2 )] AUSTEDO XR and AUSTEDO are vesicular monoamine transporter 2 (VMAT2) inhibitors indicated in adults for the treatment of: Chorea associated with Huntington’s disease ( 1 ) Tardive dyskinesia ( 1 ). This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Deutetrabenazine?

Deutetrabenazine is classified as Other nervous system drugs, Monoamine Oxidase Inhibitors, Vesicular Monoamine Transporter 2 Inhibitors, Decreased Dopamine Activity, Decreased Histamine Activity, Decreased Norepinephrine Activity, Decreased Serotonin Activity.

What are the brand names for Deutetrabenazine?

Deutetrabenazine is marketed under brand names including Austedo.

What are the contraindications for Deutetrabenazine?

Deutetrabenazine labeling lists contraindications including: AUSTEDO XR and AUSTEDO are contraindicated in patients: With Huntington’s disease who are suicidal, or have untreated or inadequately treated depression [see Warnings and Precautions ( 5.1 )] . With hepatic impairment [see Use in Specific Populations ( 8.6 ), Clinical Pharmacology ( 12.3 )] .. Always consult the full prescribing information and a clinician.