Version July 2025
Tetrabenazine can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington disease. Anyone considering the use of tetrabenazine must balance the risks of depression and suicidality with the clinical need for control of chorea. Close observation of patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior should accompany therapy. Patients, their caregivers, and families should be informed of the risk of depression and suicidality, and should be instructed to report behaviors of concern promptly to the treating physician.
Particular caution should be exercised in treating patients with a history of depression or prior suicide attempts or ideation, which are increased in frequency in Huntington disease. Tetrabenazine is contraindicated in patients who are actively suicidal, and in patients with untreated or inadequately treated depression.
Huntington disease–associated chorea:
Initial: Oral: 12.5 mg once daily in the morning; may increase to 12.5 mg twice daily after 1 week. May increase daily dosage by 12.5 mg increments at weekly intervals up to 50 mg/day; divide daily doses >37.5 mg into 3 doses (maximum single dose: 25 mg).
Patients with chorea on 50 mg/day: Genotype for CYP2D6: Extensive/intermediate metabolizers: Oral: Maximum: 100 mg/day; 37.5 mg/dose.
Tardive dyskinesia (off-label use) (alternative agent): Oral: Initial: 50 mg/day in divided doses; may increase daily dose by 50 mg increments every 2 weeks up to maximum of 150 mg/day in divided doses (Ref).
Alternatively, an initial dose of 25 to 37.5 mg/day in 2 or 3 divided doses has been recommended with increases or decreases in increments of 12.5 mg/day at weekly intervals. Usual maximum tolerated dose: 75 mg/day in 3 divided doses; in very rare cases, doses up to 200 mg/day have been used (Ref).
Tourette syndrome (Canadian labeling): Initial: Oral: 12.5 mg 2 to 3 times daily; may increase daily dose by 12.5 mg increments at weekly intervals. Usual maximum tolerated dosage: 25 mg 3 times daily; maximum recommended dose: 200 mg/day.
Missed doses: If treatment is interrupted for >5 days, retitration is recommended. If treatment is interrupted for <5 days resume at previous maintenance dose.
Discontinuation of treatment: Treatment may be discontinued without tapering; chorea re-emergence may occur within 12 to 18 hours after the last dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Use is contraindicated.
For adverse reactions, including akathisia, restlessness, parkinsonism, insomnia, depression, suicidality, anxiety, sedation (intolerable): Suspend upward dosage titration and reduce dose; consider discontinuing therapy or treating symptoms if adverse reaction does not resolve (may be discontinued without tapering).
Refer to adult dosing; use with caution.
Tourette syndrome (Canadian labeling): Children and Adolescents: Oral: Administer 50% of adult dose. Initial: 6.25 mg 2 to 3 times daily; may be increased by 6.25 mg daily at weekly intervals; should be titrated slowly to maximal tolerated and effective dose (dose is individualized).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Children and Adolescents: 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).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Use is contraindicated.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Gastrointestinal: Nausea
Nervous system: Akathisia (including hyperkinetic muscle activity, restlessness), anxiety (including exacerbation of anxiety), depression (including exacerbation of depression), drowsiness, extrapyramidal reaction (including bradykinesia, hypertonia, parkinsonism), falling, fatigue, insomnia, sedated state
Respiratory: Upper respiratory tract infection
1% to 10%:
Dermatologic: Ecchymoses
Gastrointestinal: Decreased appetite, dysphagia, vomiting
Genitourinary: Dysuria
Nervous system: Balance impairment, dizziness, dysarthria, headache, irritability, obsessions, unsteady gait
Respiratory: Bronchitis, dyspnea
Frequency not defined:
Cardiovascular: Orthostatic dizziness, orthostatic hypotension, prolonged QT interval on ECG, syncope
Endocrine & metabolic: Hyperprolactinemia
Gastrointestinal: Diarrhea
Nervous system: Suicidal ideation, suicidal tendencies
Postmarketing:
Dermatologic: Hyperhidrosis, skin rash
Nervous system: Aggressive behavior (worsening), confusion, neuroleptic malignant syndrome, tremor
Respiratory: Pneumonia
Hepatic impairment; active suicidality or 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; coadministration with deutetrabenazine or valbenazine.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to tetrabenazine or any component of the formulation; history or current episode of clinical depression unless under the care of a psychiatrist who is familiar with the patient's disorder and tetrabenazine’s pharmacology.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). If sedation occurs during treatment, dosage reduction or discontinuation may be necessary.
• Depression/suicidal ideation: Use can increase risk for depression and suicidal thoughts and behavior in patients with Huntington disease. Dosage reduction, treatment of depression, or discontinuation may be necessary.
• 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: Use may be associated with neuroleptic malignant syndrome (NMS). 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.
• Parkinsonism: May cause parkinsonism symptoms (ie, bradykinesia, hypertonia, rigidity). Dose reduction, treatment of parkinsonism, or discontinuation of therapy may be necessary.
• Psychomotor stimulation: Use has been associated with akathisia, restless, and agitation. Dosage reduction, treatment of psychomotor effects, or discontinuation may be necessary.
• 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.
• Tardive dyskinesia: May cause dyskinetic movements; discontinue use if signs and symptoms of tardive dyskinesia occur.
Disease-related concerns:
• Prolactin-dependent tumors: Elevates prolactin levels; use with caution in patients with breast cancer or other prolactin-dependent tumors; dose discontinuation may be considered.
Special populations:
• 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.
• Huntington disease: May worsen mood, cognition, rigidity, and functional capacity in patients with Huntington disease, which can be difficult to differentiate from progression of the underlying disease. Underlying chorea may improve over time in some patients, thereby decreasing the need for therapy. Re-evaluate patients need for treatment by periodically assessing the effect on chorea and possible adverse effects. Dose reduction or discontinuation of therapy may be necessary.
Other warnings/precautions:
• Appropriate use: Should not be used to treat levodopa-induced dyskinesia.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Xenazine: 12.5 mg [contains corn starch]
Xenazine: 25 mg [scored; contains corn starch]
Generic: 12.5 mg, 25 mg
Yes
Tablets (Tetrabenazine Oral)
12.5 mg (per each): $2.13 - $78.81
25 mg (per each): $4.27 - $157.62
Tablets (Xenazine Oral)
12.5 mg (per each): $227.88
25 mg (per each): $455.76
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Nitoman: 25 mg [contains corn starch]
Generic: 25 mg
Oral: May administer without regard to meals.
Oral: Nitroman [Canadian labeling]: Administer without regard to meals.
An FDA-approved patient medication guide, which is available with the product and as follows, must be dispensed with this medication:
Xenazine: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021894s013lbl.pdf#page=24
Chorea associated with Huntington disease: Treatment of chorea associated with Huntington disease
Canadian labeling: Additional use (not in US labeling):Treatment of chronic tic disorders, including Tourette syndrome
Tardive dyskinesia
Substrate of CYP2D6 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits VMAT2;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ajmaline: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Antipsychotic Agents: Tetrabenazine may increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for NMS and extrapyramidal symptoms may be increased. Risk C: Monitor
Artemether and Lumefantrine: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase adverse/toxic effects of Tetrabenazine. Risk X: Avoid
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
CYP2D6 Inhibitors (Moderate): May increase active metabolite exposure of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Risk C: Monitor
CYP2D6 Inhibitors (Strong): May increase active metabolite exposure of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Limit the tetrabenazine dose to 50 mg per day (25 mg per single dose) in patients taking strong CYP2D6 inhibitors. Risk D: Consider Therapy Modification
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Deutetrabenazine: May increase adverse/toxic effects of Tetrabenazine. Risk X: Avoid
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Levodopa-Foslevodopa: Vesicular Monoamine Transporter 2 (VMAT2) Inhibitors may decrease therapeutic effects of Levodopa-Foslevodopa. Management: Consider alternatives to the coadministration of levodopa and vesicular monoamine transporter 2 (VMAT2) inhibitors. If combined, monitor for reduced levodopa efficacy. Risk D: Consider Therapy Modification
Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of Levoketoconazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mavorixafor: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metoclopramide: May increase adverse/toxic effects of Tetrabenazine. Risk X: Avoid
MetyroSINE: May increase adverse/toxic effects of Vesicular Monoamine Transporter 2 (VMAT2) Inhibitors. Specifically, the risk for extrapyramidal symptoms and excessive sedation may be increased. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Monoamine Oxidase Inhibitors: Tetrabenazine may increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification
OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Peginterferon Alfa-2b: May decrease serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: Tetrabenazine may decrease therapeutic effects of Piribedil. Piribedil may decrease therapeutic effects of Tetrabenazine. Risk X: Avoid
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QuiNIDine: Tetrabenazine may increase QTc-prolonging effects of QuiNIDine. QuiNIDine may increase active metabolite exposure of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Limit the tetrabenazine dose to 50 mg per day (25 mg per single dose) in patients taking quinidine. Additionally, monitor for QTc interval prolongation and ventricular arrhythmias (including torsades de pointes) when these drugs are combined. Risk D: Consider Therapy Modification
Reserpine: May increase adverse/toxic effects of Tetrabenazine. Risk X: Avoid
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Suvorexant: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valbenazine: Tetrabenazine may increase adverse/toxic effects of Valbenazine. Risk X: Avoid
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Adverse events were observed in some animal reproduction studies. Limited information related to the use of tetrabenazine in pregnancy has been located (Lubbe 1983).
It is not known if tetrabenazine is present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Liver function (baseline and as clinically indicated); orthostatic BP (as clinically indicated); CYP2D6 genotyping for evaluation of metabolizer status (for patients requiring >50 mg/day); EKG (as clinically indicated for QT prolongation); signs/symptoms of suicidal ideation.
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.
Duration: 16 to 24 hours (at steady-state); chorea may recur within 12 to 18 hours after discontinuation
Protein binding: 82% to 85%; Metabolites: 59% to 68%
Metabolism: Hepatic (rapid and extensive), to active metabolites: Alpha and beta hydroxytetrabenazine (HTBZ) via CYP2D6 (primary active moiety)
Bioavailability: Low and erratic (due to extensive first-pass effects); unaffected by food
Half-life elimination: Alpha-HTBZ: 7 hours, 10 hours (hepatic impairment); Beta-HTBZ: 5 hours, 8 hours (hepatic impairment); Terabenazine: ~17.5 hours (hepatic impairment)
Time to peak, plasma: Metabolites: Within 1 to 1.5 hours
Excretion: Urine (~75% as metabolites, <10% as alpha and beta HTBZ); feces (~7% to 16%)
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.
