Tetrabenazine is indicated for the treatment of chorea associated with Huntington's disease,

Atypical neuroleptic drugs

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).

General Dosing Considerations: The chronic daily dose of Tetrabenazine used to treat chorea associated with Huntington's disease (HD) is determined individually for each patient. When first prescribed, Tetrabenazine therapy should be titrated slowly over several weeks to identify a dose of XENAXINE that reduces chorea and is tolerated. Tetrabenazine can be administered without regard to food. Individualization Of Dose: Dosing Recommendations Up to 50 mg per day: The starting dose should be 12.5 mg per day given once in the morning. After one week, the dose should be increased to 25 mg per day given as 12.5 mg twice a day. Tetrabenazine should be titrated up slowly at weekly intervals by 12.5 mg daily, to allow the identification of a tolerated dose that reduces chorea. If a dose of 37.5 to 50 mg per day is needed, it should be given in a three times a day regimen. The maximum recommended single dose is 25 mg. If adverse reactions such as akathisia, restlessness, parkinsonism, depression, insomnia, anxiety or sedation occur, titration should be stopped and the dose should be reduced. If the adverse reaction does not resolve, consideration should be given to withdrawing Tetrabenazine treatment or initiating other specific treatment (e.g., antidepressants).Dosing Recommendations Above 50 mg per day: Patients who require doses of Tetrabenazine greater than 50 mg per day should be first tested and genotyped to determine if they are poor metabolizers (PMs) or extensive metabolizers (EMs) by their ability to express the drug metabolizing enzyme, CYP2D6. The dose of Tetrabenazine should then be individualized accordingly to their status as PMs or EMs Extensive and Intermediate CYP2D6 Metabolizers: Genotyped patients who are identified as extensive (EMs) or intermediate metabolizers (IMs) of CYP2D6, who need doses of Tetrabenazine above 50 mg per day, should be titrated up slowly at weekly intervals by 12.5 mg daily, to allow the identification of a tolerated dose that reduces chorea. Doses above 50 mg per day should be given in a three times a day regimen. The maximum recommended daily dose is 100 mg and the maximum recommended single dose is 37.5 mg. If adverse reactions such as akathisia, parkinsonism, depression, insomnia, anxiety or sedation occur, titration should be stopped and the dose should be reduced. If the adverse reaction does not resolve, consideration should be given to withdrawing Tetrabenazine treatment or initiating other specific treatment (e.g., antidepressants)

With medicine: Strong CYP2D6 Inhibitors: A reduction in Tetrabenazine dose may be necessary when adding a strong CYP2D6 inhibitor (e.g., fluoxetine, paroxetine, quinidine) in patients maintained on a stable dose of Tetrabenazine. Reserpine: Reserpine binds irreversibly to VMAT2, and the duration of its effect is several days. At least 20 days should elapse after stopping reserpine before starting Tetrabenazine, Tetrabenazine and Reserpine should not be used concomitantly. With food & others: No interaction with food, can be taken with or without food.

Tetrabenazine is contraindicated in: Actively suicidal, or who have depression which is untreated or undertreated Hepatic impairment. Concurrent use of monoamine oxidase inhibitors (MAOIs) or reserpine. Concurrent use of deutetrabenazine or valbenazine.

Common: Most common adverse reactions (>10% and at least 5% greater than placebo) were-Sedation/somnolence, fatigue, insomnia, depression, akathisia, anxiety/anxiety aggravated & nausea.Rare: Suicidal thoughts, neuroleptic malignant syndrome, a reaction characterized by fever, muscle rigidity and confusion & pneumonia.

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.

The benefit and potential for adverse effects such as worsening mood, cognition, rigidity, and functional capacity should be periodically re-evaluated. The maximum daily dose should not exceed 50 mg/day and the maximum single dose should not exceed 25 mg if administered in conjunction with a strong CYP2D6 inhibitor (e,g., fluoxetine, paroxetine). In case of Neuroleptic Malignant Syndrome, the treatment should be discontinued. The dose should be reduced or discontinued if patient experience restlessness, agitation, akathisia and parkinsonism, The treatment may impair patient's ability to drive or operate complex machinery, Tetrabenzine is not recommended in combination with other drugs that prolong QTc.

Signs and symptoms of overdosage of Tetrabenazine may include drowsiness, sweating and hypothermia.

Store in a cool & dry place. protect from light & moisture. Keep all medicines out of the reach of the children.

Atypical neuroleptic drugs

Tetrabenazine is a drug formerly used as an antipsychotic but now used primarily in the symptomatic treatment of various hyperkinetic disorders, It is a vesicular monoamine transporter-2 (VMAT-2) inhibitor that used as symptomatic treatment of chorea associated with Huntington's disease.

There are no adequate data on the developmental risk associated with the use of Tetrabenazine in pregnant women. There are no data on the presence of tetrabenazine or its metabolites in human milk.