Adult: For moderate to severe cases: Initially, 12.5 mg daily, then gradually titrate the dose according to response. Missed dose: If therapy is interrupted for >5 days, retitrate dose once resumed. If therapy is interrupted for <5 days, resume at the previous maintenance dose. Dosage and treatment recommendations may vary among countries and between individual products (refer to specific product guidelines).
Oral Movement disorders
Adult: In cases associated with organic central nervous system conditions (e.g. Huntington's chorea, hemiballismus and senile chorea): Initially, 12.5-25 mg up to tid, then may gradually increase in increments of 12.5-25 mg every 3-4 days based on response. Max: 200 mg daily. Further treatment is unlikely to be of benefit if patient does not respond within 7 days of receiving the Max dose. Missed dose: If therapy is interrupted for >5 days, retitrate dose once resumed. If therapy is interrupted for <5 days, resume at the previous maintenance dose. Dosage and treatment recommendations may vary among countries and between individual products (refer to specific product guidelines).
Special Patient Group
Patients taking strong CYP2D6 inhibitors: Max: 25 mg/dose or 50 mg daily. Dosage recommendations may vary among countries and between individual products (refer to specific product guidelines).
Pharmacogenomics:
Tetrabenazine is rapidly and extensively metabolised in the liver by carbonyl reductase into the active metabolites, α- and β-hydroxytetrabenazine, which are subsequently metabolised by CYP2D6 into 9-desmethyl-α-dihydrotetrabenazine (minor metabolite) and 9-desmethyl-β-dihydrotetrabenazine (major metabolite). The relative contribution of each isomer to clinical efficacy or adverse effects is currently unknown; however, CYP2D6 metaboliser status may be relevant for therapeutic response or the incidence of therapy-limiting adverse effects. The US Food and Drug Administration (US FDA) drug label recommends that patients requiring doses >50 mg daily should undergo genotyping for the drug metabolising enzyme CYP2D6 to determine if the patient is a poor, an intermediate or extensive metaboliser.
CYP2D6 poor metabolisers
Individuals who are CYP2D6 poor metabolisers will have significantly increased level of exposure to the primary metabolites as compared to CYP2D6 extensive metabolisers. The US FDA drug label recommends giving a Max of 50 mg daily dose with a Max of 25 mg single dose.
CYP2D6 intermediate or extensive metabolisers
The US FDA drug label recommends giving a Max of 100 mg daily dose with a Max of 37.5 mg single dose.
Dosage recommendations may vary between countries. Refer to specific country guidelines for the appropriate clinical recommendations.
Hepatic Impairment
Contraindicated.
Administration
Tetrabenazine May be taken with or without food.
Contraindications
Active suicidality, untreated or inadequately treated depression; parkinsonism and hypokinetic-rigid syndrome. Hepatic impairment. Concurrent use or within 14 days of discontinuing MAOIs. Concomitant use with reserpine, deutetrabenazine or valbenazine.
Special Precautions
Patient with history of depression or previous suicide attempts or ideation; prolactin-dependent tumours (e.g. breast cancer); at risk of aspiration pneumonia; congenital long QT syndrome, history of cardiac arrhythmias. CYP2D6 poor, intermediate or extensive metabolisers. Pregnancy and lactation. Concurrent use with strong CYP2D6 inhibitors.
Adverse Reactions
Significant: Orthostatic hypotension, postural dizziness, syncope; QT prolongation; oesophageal dysmotility, dysphagia, aspiration; may induce or exacerbate parkinsonism symptoms (e.g. bradykinesia, hypertonia, rigidity); sedation, somnolence; akathisia, restlessness, agitation; dyskinetic movements; hyperprolactinaemia; long-term ophthalmic effects; slight worsening in cognition, mood, rigidity and functional capacity (in patients with Huntington's disease); potential risk of anger and aggressive behaviour (particularly in patients with history of depression or other psychiatric illnesses). Eye disorders: Blepharospasm. Gastrointestinal disorders: Nausea, diarrhoea, vomiting, constipation. General disorders and administration site conditions: Fatigue, ecchymosis. Injury, poisoning and procedural complications: Fall, laceration, inflicted injury. Metabolism and nutrition disorders: Decreased appetite. Nervous system disorders: Drowsiness, dizziness, headache, dysarthria, lethargy. Psychiatric disorders: Anxiety, restlessness, confusion, insomnia, irritability, obsessive-compulsive disorder. Renal and urinary disorders: Dysuria. Respiratory, thoracic and mediastinal disorders: URTI, pneumonia, dyspnoea, bronchitis. Potentially Fatal: Increased risk for depression and suicidal ideation or behaviours; NMS.
This drug may cause drowsiness, if affected, do not drive or operate machinery.
Monitoring Parameters
Perform CYP2D6 genotyping for evaluation of metaboliser status (in patients requiring doses >50 mg daily). Monitor LFT (at baseline and as clinically indicated), orthostatic blood pressure (as clinically indicated), and ECG (as clinically indicated for QT prolongation). Assess for signs or symptoms of depression or suicide ideation and changes in CNS function.
Management: Symptomatic and supportive treatment. Monitor cardiac rhythm and vital signs.
Drug Interactions
Concomitant use with strong CYP2D6 inhibitors (e.g. fluoxetine, paroxetine, quinidine) may increase the exposure of the active metabolites of tetrabenazine. May enhance adverse effects with reserpine; at least 20 days should pass after stopping reserpine before initiating tetrabenazine. Increased risk of QT prolongation with agents known to cause QT prolongation such as antipsychotics (e.g. chlorpromazine, thioridazine), class IA antiarrhythmics (e.g. quinidine, procainamide), class III antiarrhythmics (e.g. amiodarone, sotalol), and antibiotics (e.g. gatifloxacin, moxifloxacin). Additive sedative effects with CNS depressants (e.g. neuroleptics, hypnotics, opioids). Increased risk of parkinsonism, NMS and akathisia with dopamine antagonists or antipsychotics (e.g. haloperidol, chlorpromazine, olanzapine, risperidone, thioridazine, ziprasidone). May reduce the therapeutic effect of levodopa. Increased risk of orthostatic hypotension with antihypertensive agents (e.g. β-blockers). Increased risk of adverse effects with deutetrabenazine. May increase the adverse effects of valbenazine. Potentially Fatal: Increased risk of hypertensive crisis with MAOIs.
Food Interaction
Additive sedative effects with alcohol.
Action
Description: Overview: Tetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is a selective, reversible, and centrally-acting dopamine depleting agent. Mechanism of Action: The exact mechanism of action of tetrabenazine has not been fully established; however, it is believed to be related to its effect as a reversible inhibitor of VMAT2 which decreases the uptake of monoamines (including dopamine, serotonin, norepinephrine, histamine) into synaptic vesicles and depletes the monoamine stores. Duration: 16-24 hours. Pharmacokinetics: Absorption: Immediately and mostly absorbed. Bioavailability: Low and erratic. Time to peak plasma concentration: Within 1-1.5 hours (metabolites). Distribution: Plasma protein binding: 82-85% (tetrabenazine); 59-68% (metabolites). Metabolism: Rapidly and extensively metabolised in the liver by carbonyl reductase into α- and β-hydroxytetrabenazine (HTBZ) (major active metabolites), which are subsequently metabolised by CYP2D6 into 9-desmethyl-α-dihydrotetrabenazine (minor metabolite) and 9-desmethyl-β-dihydrotetrabenazine (major metabolite). Excretion: Mainly via urine (approx 75% as metabolites, <10% as α- and β-HTBZ); faeces (approx 7-16%). Elimination half-life: 7 hours (α-HTBZ); 5 hours (β-HTBZ); 12 hours (9-desmethyl-β-dihydrotetrabenazine).
Chemical Structure
Tetrabenazine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 6018, Tetrabenazine. https://pubchem.ncbi.nlm.nih.gov/compound/Tetrabenazine. Accessed Feb. 24, 2026.
N07XX06 - tetrabenazine ; Belongs to the class of other nervous system drugs.
References
Whirl-Carillo M, Huddart R, Gong L et al. An Evidence-Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine. Clin Pharmacol Ther. 2021 Sep;110(3):563-572. doi: 10.1002/cpt.2350. Accessed 10/12/2025. PMID: 34216021Annotation of FDA Label for Tetrabenazine and CYP2D6. ClinPGx. https://www.clinpgx.org. Accessed 10/12/2025.Annotation of HCSC Label for Tetrabenazine and CYP2D6. ClinPGx. https://www.clinpgx.org. Accessed 10/12/2025.Annotation of PMDA Label for Tetrabenazine and CYP2D6. ClinPGx. https://www.clinpgx.org. Accessed 10/12/2025.Annotation of Swissmedic Label for Tetrabenazine and CYP2D6. ClinPGx. https://www.clinpgx.org. Accessed 10/12/2025.Brayfield A, Cadart C (eds). Tetrabenazine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/12/2025.CYP2D6 - Tetrabenazine. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 10/12/2025.Douglas Pharmaceuticals Ltd. Motetis 25 mg Tablet data sheet 05 May 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 10/12/2025.Joint Formulary Committee. Tetrabenazine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/12/2025.Tetrabenazine 25 mg Tablets (Sandretto Building). MHRA. https://products.mhra.gov.uk. Accessed 10/12/2025.Tetrabenazine Tablet (Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/12/2025.Tetrabenazine. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 10/12/2025.Tetrabenazine. UpToDate Lexidrug, AHFS DI (Adult and Pediatric) Online. American Society of Health-System Pharmacists, Inc. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 10/12/2025.Tetrabenazine. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 10/12/2025.
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