Tetraben

Tetrabenazine is indicated for the treatment of chorea associated with Huntington’s disease.

Prolongation of the QTc interval has been observed at doses of 50 mg. In rats, it has been observed that tetrabenazine or its metabolites bind to melanin-containing tissues such as the eyes and skin. After a single oral dose of radiolabeled tetrabenazine, radioactivity was still detected in eye and fur at 21 days post dosing.

Tetrabenazine is a reversible human vesicular monoamine transporter type 2 inhibitor (Ki = 100 nM). It acts within the basal ganglia and promotes depletion of monoamine neurotransmitters serotonin, norepinephrine, and dopamine from stores. It also decreases uptake into synaptic vesicles. Dopamine is required for fine motor movement, so the inhibition of its transmission is efficacious for hyperkinetic movement. Tetrabenazine exhibits weak in vitro binding affinity at the dopamine D2 receptor (Ki = 2100 nM).

Tetrabenazine should not be given with or within 14 days of discontinuation of MAOI therapy. Blocks action of reserpine. Decreases effects of levodopa and worsen parkinsonism. Increased risk of extrapyramidal side effects when given with amantadine, metoclopramide, antipsychotics.

The following serious adverse reactions are Depression, Suicidality Akathisia, restlessness, and agitation, Parkinsonism, Dysphagia, Sedation and somnolence

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Tetrabenazine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: It is not known whether Tetrabenazine or its metabolites are excreted in human milk. Since many drugs are excreted into human milk and because of the potential for serious adverse reactions in nursing infants from Tetrabenazine, a decision should be made whether to discontinue nursing or to discontinue Tetrabenazine, taking into account the importance of the drug to the mother.

May exacerbate symptoms of parkinsonism. Caution to be exercised when driving or performing skilled tasks. Pregnancy.

Pediatric Use: The safety and efficacy of Tetrabenazine in pediatric patients have not been established.

Geriatric Use: The pharmacokinetics of Tetrabenazine and its primary metabolites have not been formally studied in geriatric subjects.

Hepatic Impairment: Because the safety and efficacy of the increased exposure to Tetrabenazine and other circulating metabolites are unknown, it is not possible to adjust the dosage of Tetrabenazine in hepatic impairment to ensure safe use. The use of Tetrabenazine in patients with hepatic impairment is contraindicated

Atypical neuroleptic drugs

Three episodes of overdose occurred in the open-label trials performed in support of registration. Eight cases of overdose with Tetrabenazine have been reported in the literature. The dose of Tetrabenazine in these patients ranged from 100 mg to 1g. Adverse reactions associated with Tetrabenazine 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.