Tetrabenazine

The precise mechanism by which tetrabenazine exerts its anti-chorea effects 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. Tetrabenazine reversibly inhibits the human vesicular monoamine transporter type 2 (VMAT2) (K i ≈ 100 nM), resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.

• Tetrabenazine tablets are indicated for the treatment of chorea associated with Huntington's disease.

• Tetrabenazine tablets are contraindicated in patients: Who are actively suicidal, or in patients with 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

Individualization of dose with careful weekly titration is required. The 1 st week's starting dose is 12.5 mg daily; 2 nd week, 25 mg (12.5 mg twice daily); then slowly titrate at weekly intervals by 12.5 mg to a tolerated dose that reduces chorea. ( 2.1 , 2.2 ) Doses of 37.5 mg and up to 50 mg per day should be administered in three divided doses per day with a maximum recommended single dose not to exceed 25 mg. ( 2.2 ) Patients requiring doses above 50 mg per day should be genotyped for the drug metabolizing enzyme CYP2D6 to determine if the patient is a poor metabolizer (PM) or an extensive metabolizer (EM). ( 2.2 , 5.3 ) Maximum daily dose in PMs: 50 mg with a maximum single dose of 25 mg. ( 2.2 ) Maximum daily dose in EMs and intermediate metabolizers (IMs): 100 mg with a maximum single dose of 37.5 mg. ( 2.2 ) If serious adverse reactions occur, titration should be stopped and the dose should be reduced. If the adverse reaction(s) do not resolve, consider withdrawal of tetrabenazine tablets. ( 2.2 ) 2.1 General Dosing Considerations The chronic daily dose of tetrabenazine tablets used to treat chorea associated with Huntington's disease (HD) is determined individually for each patient. When first prescribed, tetrabenazine therapy should be titrated slowly over several weeks to identify a dose of tetrabenazine tablets that reduces chorea and is tolerated. Tetrabenazine tablets can be administered without regard to food [see Clinical Pharmacology ( 12.3 )] . 2.2 Individualization of Dose The dose of tetrabenazine tablets should be individualized.

Periodically reevaluate the benefit and potential for adverse effects such as worsening mood, cognition, rigidity, and functional capacity. ( 5.2 ) Do not exceed 50 mg/day and the maximum single dose should not exceed 25 mg if administered in conjunction with a strong CYP2D6 inhibitor (e.g., fluoxetine, paroxetine). ( 5.3 , 7.1 ) Neuroleptic Malignant Syndrome (NMS): Discontinue if this occurs. ( 5.4 , 7.6 ) Restlessness, agitation, akathisia and parkinsonism: Reduce dose or discontinue if occurs. ( 5.5 , 5.6 ) Sedation/Somnolence: May impair patient’s ability to drive or operate complex machinery. ( 5.7 ) QTc prolongation: Not recommended in combination with other drugs that prolong QTc. ( 5.8 ) 5.1 Depression and Suicidality Patients with Huntington’s disease are at increased risk for depression, suicidal ideation or behaviors (suicidality). Tetrabenazine increases the risk for suicidality in patients with HD. In a 12-week, double-blind, placebo-controlled study in patients with chorea associated with Huntington’s disease, 10 of 54 patients (19%) treated with tetrabenazine were reported to have an adverse event of depression or worsening depression compared to none of the 30 placebo-treated patients. In two open-label studies (in one study, 29 patients received tetrabenazine for up to 48 weeks; in the second study, 75 patients received tetrabenazine for up to 80 weeks), the rate of depression/worsening depression was 35%. In all of the HD chorea studies of tetrabenazine (n=187), one patient committed suicide, one attempted suicide, and six had suicidal ideation.

The following serious adverse reactions are described below and elsewhere in the labeling: Depression and Suicidality [see Warnings and Precautions ( 5.1 )] Neuroleptic Malignant Syndrome (NMS) [see Warnings and Precautions ( 5.4 )] Akathisia, Restlessness, and Agitation [see Warnings and Precautions ( 5.5 )] Parkinsonism [see Warnings and Precautions ( 5.6 )] Sedation and Somnolence [see Warnings and Precautions ( 5.7 )] QTc Prolongation [see Warnings and Precautions ( 5.8 )] Hypotension and Orthostatic Hypotension [see Warnings and Precautions ( 5.9 )] Hyperprolactinemia [see Warnings and Precautions ( 5.10 )] Binding to Melanin-Containing Tissues [see Warnings and Precautions ( 5.11 )] Most common adverse reactions (>10% and at least 5% greater than placebo) were: Sedation/somnolence, fatigue, insomnia, depression, akathisia, anxiety/anxiety aggravated, nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 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. During its development, tetrabenazine was administered to 773 unique subjects and patients.

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 tetrabenazine in pregnant women. Administration of tetrabenazine to rats throughout pregnancy and lactation resulted in an increase in stillbirths and postnatal offspring mortality. Administration of a major human metabolite of tetrabenazine to rats during pregnancy or during pregnancy and lactation produced adverse effects on the developing fetus and offspring (increased mortality, decreased growth, and neurobehavioral and reproductive impairment). The adverse developmental effects of tetrabenazine and a major human metabolite of tetrabenazine in rats occurred at clinically relevant doses [see Data] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Tetrabenazine had no clear effects on embryofetal development when administered to pregnant rats throughout the period of organogenesis at oral doses up to 30 mg/kg/day (or 3 times the maximum recommended human dose [MRHD] of 100 mg/day on a mg/m 2 basis).

Metabolism

Absorption Following oral administration of tetrabenazine, the extent of absorption is at least 75%. After single oral doses ranging from 12.5 to 50 mg, plasma concentrations of tetrabenazine are generally below the limit of detection because of the rapid and extensive hepatic metabolism of tetrabenazine by carbonyl reductase to the active metabolites α-HTBZ and β-HTBZ.

Three episodes of overdose occurred in the open-label trials performed in support of registration. Eight cases of overdose with tetrabenazine have been reported in the literature. The dose of tetrabenazine in these patients ranged from 100 mg to 1 g. Adverse reactions associated with tetrabenazine overdose include 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 CNS-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.

• Aug 15, 2008NDANDA021894Bausch
• Aug 17, 2015ANDAANDA206129Sun Pharm
• Feb 3, 2016ANDAANDA204574Hetero Labs Ltd V
• Jan 31, 2017ANDAANDA207682Mylan
• Dec 18, 2017ANDAANDA208826Bionpharma
• Jan 8, 2018ANDAANDA209284Dr Reddys
• Jan 22, 2020ANDAANDA213316Adaptis
• Mar 17, 2020ANDAANDA206093Apotex

1. 1Death1,21417%
2. 2Off Label Use1,12615%
3. 3Drug Ineffective7019.6%
4. 4Depression4756.5%
5. 5Somnolence4516.2%
6. 6Fatigue3615.0%
7. 7Fall3164.3%
8. 8Hospitalisation2974.1%
9. 9Insomnia2763.8%
10. 10Intentional Product Use Issue2743.8%
11. 11Anxiety2633.6%
12. 12Drug Administration Error2413.3%
13. 13Condition Aggravated2273.1%
14. 14Drug Dose Omission2243.1%
15. 15Dyskinesia2233.1%

Recent PubMed references pinned to Tetrabenazine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Measuring What Matters: Further Validation for the Tardive Dyskinesia Impact Scale, a Novel Patient-Reported Outcome Measure in Valbenazine Clinical Trials.
  The Journal of clinical psychiatry · 2026 · Bron M, Mathias SD, Stull DE, et al.
  PMID 42095693DOI 10.4088/JCP.25nr16047
• Pharmacokinetics and Bioequivalence of 2 Deutetrabenazine Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions.
  Clinical pharmacology in drug development · 2026 · Xu D, Wang P, Li Y, et al.
  PMID 41866636DOI 10.1002/cpdd.70054
• Safety and efficacy of VMAT2 inhibitors in Huntington Disease: A systematic review.
  Parkinsonism & related disorders · 2026 · Baghaei A, Dehnavi AZ, Hashempour Z, et al.
  PMID 41651710DOI 10.1016/j.parkreldis.2026.108209
• The Use of VMAT2 Inhibitors for Tardive Dyskinesia.
  Journal of clinical psychopharmacology · 2026 · Alabaku O, Olfson M, Stroup TS, et al.
  PMID 41626799DOI 10.1097/JCP.0000000000002139
• Optimization of Ionic Liquid Based NLC for Nose-To-Brain Delivery of Tetrabenazine Hydrochloride.
  AAPS PharmSciTech · 2026 · Jadhav NR, Yede SR, Jadhav AS, et al.
  PMID 41507583DOI 10.1208/s12249-025-03313-2
• Physician experience and perceptions of tetrabenazine for the treatment of tardive dyskinesia and Huntington's chorea: a survey of neurologists and psychiatrists.
  Expert review of neurotherapeutics · 2026 · Sung VW, Claassen DO, Ribalov R, et al.
  PMID 41414855DOI 10.1080/14737175.2025.2602188
• Theta oscillations vary with local response rate and are moderated by the dopamine-depleting agent, tetrabenazine, during effort-based behavior.
  Cognitive, affective & behavioral neuroscience · 2026 · Ecevitoglu A, Mankili A, Ren N, et al.
  PMID 41345329DOI 10.3758/s13415-025-01367-0
• Valbenazine Sprinkle: An Alternative Formulation of Valbenazine for Oral Administration in Patients With Dysphagia.
  Clinical and translational science · 2025 · Giri N, Jimenez R, Rees L, et al.
  PMID 41215526DOI 10.1111/cts.70390

The 10 most recently updated of 17 ClinicalTrials.gov registrations naming Tetrabenazine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Xenazine in Late Dyskinetic Syndrome With Neuroleptics
  Completed · Phase 3 · Interventional · 54 enrolled · Centre Hospitalier Universitaire, Amiens
  NCT01543321updated 2025-11-19
• Effect of Tetrabenazine on Stroop Interference in HD
  Completed · Phase 4 · Interventional · 2 enrolled · New York Medical College
  NCT01834911updated 2025-05-28
• Efficacy, Safety, and Tolerability of Valbenazine for the Treatment of Chorea Associated With Huntington Disease
  Completed · Phase 3 · Interventional · 128 enrolled · Neurocrine Biosciences
  NCT04102579updated 2023-10-11
• Compassionate Use of Tetrabenazine in the Treatment of Abnormal Movements
  No longer available · Expanded access · Joseph Jankovic
  NCT00642057updated 2023-03-24
• A Pilot Study Assessing Impulsivity in Patients With Huntington's Disease on Xenazine (Tetrabenazine)
  Unknown · Phase 4 · Interventional · 20 enrolled · William Ondo, MD
  NCT02509793updated 2022-09-02
• Alternatives for Reducing Chorea in Huntington Disease
  Completed · Phase 3 · Interventional · 119 enrolled · Auspex Pharmaceuticals, Inc.
  NCT01897896updated 2021-11-09
• Excessive Crying in Children With Cerebral Palsy and Communication Deficits
  Completed · Phase 4 · Interventional · 131 enrolled · Sathbhavana Brain Clinic
  NCT04523935updated 2021-10-28
• A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette's Syndrome
  Withdrawn · Phase 2 · Interventional · 0 enrolled · Bausch Health Americas, Inc.
  NCT01133353updated 2019-11-29
• Bioequivalence Study of Tetrabenazine Tablets 25 mg Under Fasting Conditions
  Completed · Phase 1 · Interventional · 48 enrolled · Dr. Reddy's Laboratories Limited
  NCT03696329updated 2018-10-18
• Bioequivalence Study of Tetrabenazine Tablets 25 mg Under Fed Conditions
  Completed · Phase 1 · Interventional · 48 enrolled · Dr. Reddy's Laboratories Limited
  NCT03702855updated 2018-10-11

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

• CYP2D6CPIC A/B (provisional)FDA label: Testing Required

Frequently asked questions

How does Tetrabenazine work?

The precise mechanism by which tetrabenazine exerts its anti-chorea effects 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. Tetrabenazine reversibly inhibits the human vesicular monoamine transporter type 2 (VMAT2) (K i ≈ 100 nM), resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.

What is Tetrabenazine used for?

According to FDA labeling, Tetrabenazine carries indications including: Tetrabenazine tablets are indicated for the treatment of chorea associated with Huntington's disease.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Tetrabenazine?

Tetrabenazine is classified as Other nervous system drugs, Vesicular Monoamine Transporter 2 Inhibitor, 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 Tetrabenazine?

Tetrabenazine is marketed under brand names including Xenazine.

What are the contraindications for Tetrabenazine?

Tetrabenazine labeling lists contraindications including: Tetrabenazine tablets are contraindicated in patients: Who are actively suicidal, or in patients with 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.