Reviewed on 5/24/2022

What Is Tetrabenazine and How Does It Work?

Tetrabenazine is a prescription medication used for the treatment of Huntington’s disease.

  • Tetrabenazine is available under the following different brand names: Xenazine

What Are Dosages of Tetrabenazine?

Adult dosage


  • 12.5mg
  • 25mg

Huntington Disease

Adult dosage

  • Total daily dose up to 50 mg/day
    • 12.5 mg orally every day initially; after 1 week, the dose should be increased to 12.5 mg every 12 hours
    • Maintenance: Titrate slowly by weekly intervals of 12.5 mg/day to identify a dose that reduces chorea and is tolerated
    • If the daily dose is 37.5 to 50 mg/day, administered in divided doses q8hr
    • Not to exceed 25 mg per single dose for a total daily dosage between 37.5-50 mg/day
  • Total Daily dose is more than 50 mg/day
  • If the dose is more than 50 mg/day is required, test and genotype to determine if poor or extensive metabolizers of CYP2D6; are not to exceed 100 mg/day or 37.5 mg/dose

Dosage Considerations – Should be Given as Follows: 

  • See “Dosages”

What Are Side Effects Associated with Using Tetrabenazine?

Common side effects of the Tetrabenazine include:

  • drowsiness, tiredness;
  • depressed mood;
  • nausea; or
  • feeling anxious, agitated, or restless.

Serious side effects of the Tetrabenazine include:

  • tremors, shaking, restless movement, problems with balance;
  • uncontrolled muscle movements in the face (chewing, lip smacking, frowning, tongue movement, blinking or eye movement);
  • trouble swallowing;
  • fast or pounding heartbeats;
  • a light-headed feeling, or
  • severe nervous system reaction--very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats.

Rare side effects of the Tetrabenazine include:

  • none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Other Drugs Interact with Tetrabenazine?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

What Are Warnings and Precautions for Tetrabenazine?


  • Hypersensitivity
  • Hepatic impairment
  • Patients who are actively suicidal, or who have untreated or inadequately treated depression (see Black Box Warnings)
  • Coadministration with deutetrabenazine or valbenazine
  • Concomitant MAO inhibitor or within 14 days of discontinuing MAO inhibitor
  • Concomitant use with reserpine

Effects of drug abuse

  • None

Short-Term Effects

  • See “What Are Side Effects Associated with Using Tetrabenazine?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Tetrabenazine?”


  • Not indicated for the treatment of levodopa-induced dyskinetic movements
  • Should only be used by physicians experienced with the treatment of hyperkinetic disorders
  • Induced postural dizziness was reported; however, blood pressure has not been measured during such events; monitoring of vital signs on standing should be considered in patients who are vulnerable to hypotension
  • Depression and suicidality
    • Patients with Huntington’s disease (HD) are at increased risk for depression, suicidal ideation, or behaviors (suicidality); this drug increases the risk for suicidality in patients with HD
    • When considering therapy, the risk of suicidality should be balanced against the need for treatment of chorea; all patients should be observed for new or worsening depression or suicidality; if depression or suicidality does not resolve, consider discontinuing treatment
    • Patients, their caregivers, and families should be informed of the risks of depression, worsening depression, and suicidality associated with therapy, and should be instructed to report behaviors of concern promptly to the treating physician; patients with HD who express suicidal ideation should be evaluated immediately
  • Clinical worsening and adverse effects
    • Huntington’s disease is a progressive disorder characterized by changes in mood, cognition, chorea, rigidity, and functional capacity over time; overtime also caused a slight worsening in mood, cognition, rigidity, and functional capacity
    • Whether these effects persist, resolve, or worsen with continued treatment is unknown; prescribers should periodically reevaluate the need for therapy by assessing the effect on chorea and possible adverse effects, including depression and suicidality, cognitive decline, parkinsonism, dysphagia, sedation/somnolence, akathisia, restlessness, and disability
    • It may be difficult to distinguish between adverse reactions and progression of underlying disease; decreasing the dose or stopping the drug may help the clinician distinguish between the two possibilities; in some patients, underlying chorea itself may improve over time, decreasing the need for therapy
  • Poor and extensive metabolizers
    • Before prescribing a daily dose that is greater than 50 mg per day, patients should be genotyped to determine if they express the drug-metabolizing enzyme, CYP2D6; CYP2D6 testing is necessary to determine whether patients are poor metabolizers (PMs), extensive (EMs) or intermediate metabolizers (IMs) of this drug
    • Patients who are PMs will have substantially higher levels of the primary drug metabolites (about 3-fold for α-HTBZ and 9-fold for β-HTBZ) than patients who are Ems; the dosage should be adjusted according to the patient’s CYP2D6 metabolizer status; in patients who are identified as CYP2D6 PMs, the maximum recommended total daily dose is 50 mg and the maximum recommended single dose is 25 mg
  • Neuroleptic malignant syndrome (NMS)
    • A potentially fatal symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS) has been reported in association with the drug and other drugs that reduce dopaminergic transmission
    • Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia); additional signs may include elevated creatinine phosphokinase, myoglobinuria, rhabdomyolysis, and acute renal failure
    • The diagnosis of NMS can be complicated; other serious medical illnesses (eg, pneumonia, systemic infection), and untreated or inadequately treated extrapyramidal disorders can present with similar signs and symptoms
    • Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology
    • The management of NMS should include immediate discontinuation of the drug, intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems for which specific treatments are available
    • There is no general agreement about specific pharmacological treatment regimens for NMS; recurrence of NMS has been reported with resumption of drug therapy; if treatment is needed after recovery from NMS, patients should be monitored for signs of recurrence
  • Parkinsonism
    • Therapy may cause parkinsonism; because rigidity can develop as part of the underlying disease process in Huntington’s disease, it may be difficult to distinguish between this drug-induced adverse reaction and progression of the underlying disease process
    • Drug-induced parkinsonism has the potential to cause more functional disability than untreated chorea for some patients with Huntington’s disease; if a patient develops parkinsonism during treatment, dose reduction should be considered; in some patients, discontinuation of therapy may be necessary
    • Sedation and somnolence
    • Sedation is the most common dose-limiting adverse reaction of this drug; in clinical trials, sedation was the reason upward titration was stopped and/or the dose decreased; in some patients, sedation has occurred at doses lower than recommended doses
    • Patients should not perform activities requiring mental alertness to maintain the safety of themselves or others, such as operating a motor vehicle or operating hazardous machinery, until they are on a maintenance dose and know how the drug affects them
  • QTc prolongation
    • The drug causes a small increase (about 8 msec) in corrected QT (QTc) interval; QT prolongation can lead to the development of torsade de pointes-type ventricular tachycardia with the risk increasing as the degree of prolongation increases
    • Use of this drug should be avoided in combination with other drugs known to prolong QTc, including antipsychotic medications (e.g., chlorpromazine, haloperidol, thioridazine, ziprasidone), antibiotics (e.g., moxifloxacin), Class 1A (eg, quinidine, procainamide), and Class III (eg, amiodarone, sotalol) antiarrhythmic medications or any other medications known to prolong the QTc interval
    • The drug should be avoided in patients with congenital long QT syndrome and patients with a history of cardiac arrhythmias; certain circumstances may increase the risk of occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including bradycardia, hypokalemia or hypomagnesemia, concomitant use of other drugs that prolong the QTc interval, and presence of congenital prolongation of the QT interval
  • Hyperprolactinemia
    • Therapy elevates serum prolactin concentrations in humans; peak plasma prolactin levels have increased after administration of the drug; although amenorrhea, galactorrhea, gynecomastia, and impotence can be caused by elevated serum prolactin concentrations, the clinical significance of elevated serum prolactin concentrations for most patients is unknown
    • Chronic increase in serum prolactin levels (although not evaluated) has been associated with low levels of estrogen and increased risk of osteoporosis; if there is a clinical suspicion of symptomatic hyperprolactinemia, appropriate laboratory testing should be done and consideration should be given to discontinuation of therapy
  • Binding to melanin-containing tissues
    • Since the drug or its metabolites bind to melanin-containing tissues, it could accumulate in these tissues over time; this raises the possibility that the drug may cause toxicity in these tissues after extended use; neither ophthalmologic nor microscopic examination of the eye has been conducted in chronic toxicity studies in a pigmented species, such as dogs
    • Ophthalmologic monitoring in humans was inadequate to exclude the possibility of an injury occurring after long-term exposure; the clinical relevance of this drug binding to melanin-containing tissues is unknown
    • Although there are no specific recommendations for periodic ophthalmologic monitoring, prescribers should be aware of the possibility of long-term ophthalmologic effects
  • Drug interaction overview
    • Concomitant use of neuroleptics (eg, haloperidol, chlorpromazine, risperidone, olanzapine) may cause additive effects of QTc prolongation, NMS, and extrapyramidal disorders
    • Caution with poor CYP2D6 metabolizers or drugs that inhibit CYP2D6 (eg, fluoxetine, paroxetine, quinidine); may markedly increase exposure to tetrabenazine active metabolites (alpha- and beta-HTBZ)
  • Reserpine
    • Do not use tetrabenazine and reserpine concomitantly
    • Reserpine binds irreversibly to VMAT2 and the duration of its effect is several days
    • Caution when switching from reserpine to tetrabenazine; wait for chorea to re-emerge before administering tetrabenazine to avoid overdosage and major CNS depletion of serotonin and norepinephrine
    • At least 20 days should elapse after stopping reserpine before starting tetrabenazine

Pregnancy and Lactation

  • There are no adequate data on the developmental risk associated with therapy in pregnant women; administration of tetrabenazine to rats throughout pregnancy and lactation increased stillbirths and postnatal offspring mortality
  • Lactation
    • There are no data on the presence of tetrabenazine or metabolites in human milk, effects on the breastfed infant or milk production; developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and potential adverse effects on the breastfed infant or underlying maternal condition.

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