Tetrabenazine (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- TETRABENAZINE
- XENAZINE
Boxed Warning
Tetrabenazine tablets can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Anyone considering the use of tetrabenazine tablets 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’s disease. Tetrabenazine tablets are contraindicated in patients who are actively suicidal, and in patients with untreated or inadequately treated depression [see Contraindications (4), ].
Indications and Usage
Tetrabenazine tablets are indicated for the treatment of chorea associated with Huntington’s disease.
Contraindications
Tetrabenazine tablets are contraindicated in patients: •Who are actively suicidal, or in patients with untreated or inadequately treated depression [see Warnings and Precautions (5.1)]. •With hepatic impairment [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)]. •Taking monoamine oxidase inhibitors (MAOIs). Tetrabenazine tablets should not be used in combination with an MAOI, or within a minimum of 14 days of discontinuing therapy with an MAOI [see Drug Interactions (7.3)]. •Taking reserpine. At least 20 days should elapse after stopping reserpine before starting tetrabenazine tablets [see Drug Interactions (7.2)]. •Taking deutetrabenazine or valbenazine [see Drug Interactions (7.7)].
Adverse Reactions
The following serious adverse reactions are described below and elsewhere in the labeling: •Depression and Suicidality [see Warnings and Precautions (5.1)] •Neuroleptic Malignant Syndrome (NMS) [see Warnings and Precautions (5.4)] •Akathisia, Restlessness, and Agitation [see Warnings and Precautions (5.5)] •Parkinsonism [see Warnings and Precautions (5.6)] •Sedation and Somnolence [see Warnings and Precautions (5.7)] •QTc Prolongation [see Warnings and Precautions (5.8)] •Hypotension and Orthostatic Hypotension [see Warnings and Precautions (5.9)] •Hyperprolactinemia [see Warnings and Precautions (5.10)] •Binding to Melanin-Containing Tissues [see Warnings and Precautions (5.11)]
Mechanism of Action
The precise mechanism by which tetrabenazine tablets exert its anti-chorea effects is unknown but is believed to be related to its effect as a reversible depletor of monoamines (such as dopamine, serotonin, norepinephrine, and histamine) from nerve terminals. Tetrabenazine reversibly inhibits the human vesicular monoamine transporter type 2 (VMAT2) (Ki ≈ 100 nM), resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores. Human VMAT2 is also inhibited by dihydrotetrabenazine (HTBZ), a mixture of α-HTBZ and β-HTBZ. α- and β-HTBZ, major circulating metabolites in humans, exhibit high in vitro binding affinity to bovine VMAT2. Tetrabenazine exhibits weak in vitro binding affinity at the dopamine D2 receptor (Ki = 2100 nM).
Overdosage
Three episodes of overdose occurred in the open-label trials performed in support of registration. Eight cases of overdose with tetrabenazine tablets have been reported in the literature. The dose of tetrabenazine tablets in these patients ranged from 100 mg to 1 g. Adverse reactions associated with tetrabenazine tablets overdose include acute dystonia, oculogyric crisis, nausea and vomiting, sweating, sedation, hypotension, confusion, diarrhea, hallucinations, rubor, and tremor. Treatment should consist of those general measures employed in the management of overdosage with any CNS-active drug. General supportive and symptomatic measures are recommended. Cardiac rhythm and vital signs should be monitored. In managing overdosage, the possibility of multiple drug involvement should always be considered. The physician should consider contacting a poison control center on the treatment of any overdose.