tetrabenazine

Absorption: ≥75% absorbed following oral administration.

Distribution: Crosses the blood-brain barrier.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP2D6 isoenzyme; the CYP2D6 isoenzyme exhibits genetic polymorphism (∼7% of population may be poor metabolizers and may have significantly ↑ tetrabenazine concentrations and an ↑ risk of adverse effects). Metabolites are renally excreted. Two metabolites α-dihydrotetrabenazine (α-HTBZ) and β-HTBZ bind to VMAT-2 and are pharmacologically active.

Half-Life: α-HTBZ: 4–8 hr; β-HTBZ: 2–4 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1.0–1.5 hr	12–18 hr*

*Return of symptoms following discontinuation.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hepatic impairment;
Concurrent use of MAO inhibitors, deutetrabenazine, or valbenazine;
Actively suicidal or with untreated depression.

Use Cautiously in:

History of/propensity for depression or history of psychiatric illness; history of suicidality;
Poor CYP2D6 metabolizers; initial dose ↓ required;
Recent history of MI or unstable heart disease;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, QT interval prolongation

GI: nausea, dysphagia

Neuro: akathisia, anxiety, depression, fatigue, insomnia, sedation, balance difficulty, cognitive defects, dizziness, dysarthria, headache, NEUROLEPTIC MALIGNANT SYNDROME, parkinsonism, unsteady gait

Resp: dyspnea

Interactions ⬆ ⬇

Drug-drug:

Concurrent use of MAO inhibitors↑ risk of serious adverse reactions and is contraindicated; wait at least 14 days after discontinuing to initiate tetrabenazine.
Concurrent use of deutetrabenazine or valbenazine is contraindicated.
CYP2D6 inhibitors, including fluoxetine, paroxetine, and quinidine, may ↑ levels and the risk of toxicity; ↓ initial dose of tetrabenazine.
Concurrent use with neuroleptic drugs or dopamine antagonists, including haloperidol, chlorpromazine, risperidone, and olanzapine, may ↑ risk of QT interval prolongation, neuroleptic malignant syndrome, and extrapyramidal disorders.
Concurrent use of alcohol or other CNS depressants may ↑ risk of CNS depression.

Route/Dosage ⬆ ⬇

PO (Adults ): 12.5 mg/day for one wk initially, ↑ by 12.5 weekly up to 37.5–50 mg/day in 3 divided doses; Concurrent use of strong CYP2D6 inhibitors or poor CYP2D6 metabolizers: start with initial dose of 6.25 mg, titrate carefully.

Availability ⬆ ⬇

(Generic available)

Tablets: 12.5 mg; 25 mg

Assessment ⬆ ⬇

Assess signs of Huntington's disease (changes in mood, cognition, chorea, rigidity, and functional capacity) periodically during therapy. Re-evaluate need for tetrabenazine periodically by assessing beneficial effect and side effects; determination may require dose reduction or discontinuation. Underlying chorea may improve over time, decreasing need for tetrabenazine.
Monitor closely for new or worsening depression or suicidality. If depression or suicidality occurs, ↓ dose and may initiate or ↑ dose of antidepressants.
Monitor for signs of neuroleptic malignant syndrome (hyperpyrexia, muscle rigidity, altered mental status, irregular pulse or BP, tachycardia, diaphoresis, cardiac arrhythmia) periodically during therapy. If symptoms occur, discontinue tetrabenazine and manage symptomatically. If reintroduction of tetrabenazine is considered, monitor carefully; recurrences of neuroleptic malignant syndrome have occurred.
Monitor patient for onset of akathisia (restlessness or desire to keep moving) and parkinsonian (difficulty speaking or swallowing, loss of balance control, pill rolling of hands, mask-like face, shuffling gait, rigidity, tremors). Notify health care professional if these symptoms occur; reduction in dose or discontinuation may be necessary.
Assess BP sitting and standing. May cause orthostatic hypotension.

Lab Test Considerations:

Test for the CYP2D6 gene in patients requiring doses of >50 mg/day to determine if they are poor, intermediate, or extensive metabolizers. Limit dose to 50 mg in patients who are poor metabolizers.

Implementation ⬆ ⬇

Dose should be titrated slowly and individualized.
PO: May be administered without regard to food.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take tetrabenazine as directed. Do not take more or stop taking tetrabenazine without consulting health care professional. Dose adjustment may take several wk. Discuss procedure for missed doses with health care professional before beginning therapy; do not double doses. If a dose is missed or medication discontinued, involuntary movements will return or worsen in 12–18 hr. If tetrabenazine is stopped for more than 5 days, consult health care professional before taking another dose; lower dose may be required. Advise patient to read Medication Guide before starting and with each Rx refill in case of changes.
Advise patient and family to monitor for changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. If new or worse feelings of sadness or crying spells; lack of interest in friends or activities; sleeping a lot more or less; feelings of unimportance, guilt, hopelessness, or helplessness; irritability or aggression; feeling more or less hungry; having difficulty paying attention; or thoughts of hurting self or ending life occur, notify health care professional promptly.
Causes sedation. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
Advise patient to avoid alcohol and other CNS depressants during therapy; ↑ sedation.
Inform patient of potential side effects and instruct to notify health care professional if side effects occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Rep: Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇