(tet ra BEN a zeen)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Xenazine: 12.5 mg
Xenazine: 25 mg [scored]
Generic: 12.5 mg, 25 mg
Brand Names: U.S.
- Central Monoamine-Depleting Agent
Acts as a reversible inhibitor of the human vesicular monamine transporter type 2 (VMAT-2) and thereby decreases the uptake of monoamines (including dopamine, serotonin, norepinephrine, and histamine) into synaptic vesicles and depletes the monoamine stores; hydroxytetrabenazine (HTBZ) also inhibits VMAT-2; weak binding affinity for dopamine D2 receptors.
Hepatic (rapid and extensive), to active metabolites: Alpha and beta hydroxytetrabenazine (HTBZ) via CYP2D6 (primary active moiety)
Urine (75% as metabolites, <10% as alpha and beta HTBZ); feces (7% to 16%)
Time to Peak
Metabolites: Within 1 to 1.5 hours
Duration of Action
16 to 24 hours (at steady-state); chorea may recur within 12 to 18 hours after discontinuation
Alpha-HTBZ: 7 hours; 10 hours (hepatic impairment); Beta-HTBZ: 5 hours, 8 hours (hepatic impairment); Terabenazine: ~17.5 hours (hepatic impairment)
82% to 85%; Metabolites: 59% to 68%
Special Populations: Hepatic Function Impairment
Metabolism of tetrabenazine is decreased in patients with hepatic function impairment and the Cmax is 7- to 190-fold higher compared with healthy subjects.
Use: Labeled Indications
Chorea associated with Huntington disease: Treatment of chorea associated with Huntington disease
Canadian labeling: Treatment of hyperkinetic movement disorders, including Huntington chorea, hemiballismus, senile chorea, Tourette syndrome, and tardive dyskinesia
Hepatic impairment; patients who are actively suicidal or who have untreated or inadequately treated depression; coadministration of monoamine oxidase inhibitors (MAOIs) or use of tetrabenazine within 2 weeks of discontinuation of MAOI therapy; coadministration with reserpine, ≥20 days should pass after discontinuing reserpine before initiating tetrabenazine therapy
Canadian labeling: Hypersensitivity to tetrabenazine or any component of the formulation; history or current episode of clinical depression
Oral: Dose should be individualized; titrate slowly
Chorea associated with Huntington disease: Adults:
Initial: 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: Genotype for CYP2D6:
Extensive/intermediate metabolizers: Maximum: 100 mg/day; 37.5 mg/dose
Poor metabolizers: Maximum: 50 mg/day; 25 mg/dose
Concomitant use with strong CYP2D6 inhibitors (eg, fluoxetine, paroxetine, quinidine): Maximum: 50 mg/day; 25 mg dose
Note: If treatment is interrupted for >5 days, retitration is recommended. If treatment is interrupted for <5 days resume at previous maintenance dose.
Canadian labeling: Hyperkinetic movement disorders:
Adults: Initial: 12.5 mg 2 to 3 times daily; may be increased by 12.5 mg daily at weekly intervals; should be titrated slowly to maximal tolerated and effective dose (dose is individualized)
Usual maximum tolerated dosage: 25 mg 3 times daily; maximum recommended daily dose: 200 mg
Note: If there is no improvement at the maximum tolerated dose after 7 days, improvement is unlikely.
Elderly and/or debilitated patients: Consider initiation at lower doses; must be titrated slowly to individualize dosage
Dosage adjustment for toxicity: For toxicity/adverse reaction, including akathisia, restlessness, parkinsonism, insomnia, depression, suicidality, anxiety, sedation (intolerable): Suspend upward dosage titration and reduce dose; consider discontinuing if adverse reaction does not resolve (may be discontinued without tapering).
Dosage adjustment in renal impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Dosage adjustment in hepatic impairment: Use is contraindicated
May administer without regard to meals.
May be taken without regard to meals.
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Antipsychotic Agents: Tetrabenazine may enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Monitor therapy
Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Tetrabenazine adult dose should be reduced by 50% when starting a strong CYP2D6 inhibitor. Maximum tetrabenazine adult dose is 50 mg/day when used with a strong CYP2D6 inhibitor. Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Highest Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Highest Risk QTc-Prolonging Agents. Avoid combination
Hydrocodone: CNS Depressants may enhance the CNS depressant effect of Hydrocodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
Ivabradine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
MAO Inhibitors: Tetrabenazine may enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
Metoclopramide: May enhance the adverse/toxic effect of Tetrabenazine. Avoid combination
Metyrosine: May enhance the adverse/toxic effect of Tetrabenazine. Monitor therapy
Mifepristone: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
Reserpine: May enhance the adverse/toxic effect of Tetrabenazine. Avoid combination
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification
Note: Many adverse effects are dose-related and may resolve at lower dosages. Adverse effects reported for adults with chorea associated with Huntington’s disease.
Central nervous system: Drowsiness (≤17% to ≤57%), sedation (≤17% to ≤57%), depression (19% to 35%), extrapyramidal reaction (15% to 33%), fatigue (22%), insomnia (22%), akathisia (19% to 20%), anxiety (15%), falling (15%)
Gastrointestinal: Nausea (13%)
Respiratory: Upper respiratory tract infection (11%)
1% to 10%:
Central nervous system: Drug-induced Parkinson's disease (3% to 10%), equilibrium disturbance (9%), irritability (9%), abnormal gait (4%), dizziness (4%), dysarthria (4%), headache (4%), obsessive rumination (4%)
Gastrointestinal: Dysphagia (4% to 10%), vomiting (6%), decreased appetite (4%), diarrhea (2%)
Genitourinary: Dysuria (4%)
Hematologic & oncologic: Bruise (6%)
Neuromuscular & skeletal: Bradykinesia (9%)
Respiratory: Bronchitis (4%), dyspnea (4%)
Miscellaneous: Laceration (6%, head)
<1% (Limited to important or life-threatening): Aggressive behavior (worsening), aspiration pneumonia, confusion, hyperhidrosis, hyperprolactinemia, increased serum transaminases, orthostatic dizziness, orthostatic hypotension, neuroleptic malignant syndrome, pneumonia, prolonged QT interval on ECG, restlessness, skin rash, suicidal ideation, syncope, tremor
Concerns related to adverse effects:
• Akathisia: Use has been associated with akathisia; monitor for signs and symptoms of restlessness and agitation. Dosage reduction or discontinuation may be necessary.
• Depression/suicidal ideation: [US Boxed Warning]: Use can increase risk for depression and suicidal thoughts and behavior; closely monitor for emergence or worsening of depression, suicidality, or unusual behavioral changes. Use with caution in patients with a history of depression or prior suicide attempts or ideation; monitor patients closely for new or worsening signs or symptoms of depression. Use is contraindicated in patients who are actively suicidal, and in patients with untreated or inadequately treated depression. Consider discontinuing use if depression/suicidal ideation does not resolve.
• Esophageal dysmotility/aspiration: Use has been associated with esophageal dysmotility, dysphagia, and aspiration; use with caution in patients at risk of aspiration pneumonia.
• Neuroleptic malignant syndrome (NMS): Use may be associated with NMS; monitor for mental status changes, fever, muscle rigidity and/or autonomic instability. Discontinue with confirmed NMS; may recur with reintroduction of treatment; monitor carefully.
• Ophthalmic effects: Binds to melanin-containing tissues in animal studies; may result in accumulation and toxicity with extended use and long-term ophthalmic effects. Clinical relevance and monitoring recommendations are unknown.
• Orthostatic hypotension: May cause orthostatic hypotension; monitor patients at risk closely.
• QT prolongation: Has been shown to prolong the QT interval alone (minimal) and with other drugs with comparable effects on the QT interval (additive). Avoid use in patients with congenital QT prolongation, a history of cardiac arrhythmias, or concomitant drugs known to cause QT prolongation.
• Sedation: Most common dose-limiting adverse effect; sedation has occurred at lower than recommended doses. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Dose reduction or discontinuation of therapy may be necessary.
• Tardive dyskinesia: May cause dyskinetic movements; discontinue use if signs and symptoms of tardive dyskinesia occur.
• Parkinsonism: May cause parkinsonism symptoms (ie, bradykinesia, hypertonia, rigidity). Dose reduction or discontinuation of therapy may be necessary.
• Prolactin-dependent tumors: Elevates prolactin levels; use with caution in patients with breast cancer or other prolactin; dose discontinuation may be considered.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• CYP2D6 poor metabolizers: CYP2D6 poor metabolizers have increased levels of primary drug metabolites. Patients should be tested for the CYP2D6 gene prior to initiating doses >50 mg/day; maximum dosage should not exceed 50 mg/day in poor metabolizers.
• Appropriate use: Should not be used to treat levodopa-induced dyskinesia.
Improvement in movement disorder; signs and/or symptoms of depression or suicide ideation; signs and/or symptoms of NMS; orthostatic blood pressure. Due to the possibility of comorbid psychiatric disorders, and potential psychiatric adverse effects, patients should be carefully monitored for potential changes in psychiatric status during therapy. CYP2D6 genotyping for evaluation of metabolizer status (for patients requiring >50 mg/day).
Pregnancy Risk Factor
Adverse events were observed in some animal reproduction studies. Limited information related to the use of tetrabenazine in pregnancy has been located (Lubbe, 1983).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience fatigue, fasciculations, bradykinesia, anxiety, nausea, or insomnia. Have patient report immediately to prescriber tachycardia, arrhythmia, severe dizziness, syncope, dysphagia, signs of neuroleptic malignant syndrome, ot signs of tardive dyskinesia (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about tetrabenazine
- Other brands: Xenazine