indication

For the symptomatical treatment of hyperkinetic movement disorder.

mechanism of action

Tetrabenazine works mainly as a VMAT-inhibitor and as such promotes the early metabolic degradation of the neurotransmitter dopamine. Dopamine is required for fine motor movement, so the inhibition of its transmission can lessen the effects of any hyperkinetic movement.

biotransformation

CYP2D6 mediated hepatic metabolism.

route of elimination

After oral administration, tetrabenazine is extensively hepatically metabolized, and the metabolites are primarily renally eliminated. In a mass balance study in 6 healthy volunteers, approximately 75% of the dose was excreted in the urine and fecal recovery accounted for approximately 7-16% of the dose. Urinary excretion of α-HTBZ or β-HTBZ (the major metabolites)accounted for less than 10% of the administered dose.

drug interactions

Acetophenazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Aripiprazole: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Chlorpromazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Clozapine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Cocaine: CYP2D6 Inhibitors (Strong) such as cocaine may increase the serum concentration of tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Patients receiving a strong inhibitor of CYP2D6 together with tetrabenazine should not exceed 50mg of tetrabenazine. Also, patients already taking tetrabenazine prior to starting a strong CYP2D6 inhibitor should have their tetrabenazine dose reduced by 50% upon initiation of the strong CYP2D6 inhibitor.

Droperidol: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Flupenthixol: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Fluphenazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Furazolidone: Tetrabenazine may increase the adverse/toxic effects of Furazolidine. Concomitant therapy is contraindicated.

Haloperidol: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Isocarboxazid: Tetrabenazine may increase the adverse/toxic effects of Isocarboxazid. Concomitant therapy is contraindicated.

Levodopa: Tetrabenazine may cause Parkinsonian symptoms and neutralize the effect of Levodopa.

Linezolid: Tetrabenazine may increase the adverse/toxic effects of Linezolid. Concomitant therapy is contraindicated.

Loxapine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Mesoridazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Moclobemide: Tetrabenazine may increase the adverse/toxic effects of Moclobemide. Concomitant therapy is contraindicated.

Molindone: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Olanzapine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Paliperidone: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Perphenazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Phenelzine: Tetrabenazine may increase the adverse/toxic effects of Phenelzine. Concomitant therapy is contraindicated.

Pimozide: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Procarbazine: Tetrabenazine may increase the adverse/toxic effects of Procarbazine. Concomitant therapy is contraindicated.

Prochlorperazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Quetiapine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Rasagiline: Tetrabenazine may increase the adverse/toxic effects of Rasagiline. Concomitant therapy is contraindicated.

Reserpine: Reserpine may increase the adverse/toxic effects of Tetrabenazine. Concomitant therapy is contraindicated.

Risperidone: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Selegiline: Tetrabenazine may increase the adverse/toxic effects of Selegiline. Concomitant therapy is contraindicated.

Tacrolimus: May cause additive QTc-prolonging effects. Concomitant therapy should be avoided.

Telithromycin: Telithromycin may increase the QTc-prolonging effect of Tetrabenazine. Concomitant therapy should be avoided.

Terbinafine: Terbinafine may reduce the metabolism and clearance of Tetrabenazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Tetrabenazine if Terbinafine is initiated, discontinued or dose changed.

Thioridazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Thiothixene: Additive QTc prolongation may occur. QTc prolongation can lead to Torsade de Pointes (TdP). Concomitant therapy should be avoided.

Toremifene: May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.

Tranylcypromine: Tetrabenazine may increase the adverse/toxic effects of Tranylcypromine. Concomitant therapy is contraindicated.

Trifluoperazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Trimipramine: May cause additive QTc-prolonging effects. Concomitant therapy should be avoided.

Triprolidine: The CNS depressants, Triprolidine and Tetrabenazine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Voriconazole: Additive QTc prolongation may occur. Concomitant therapy should be avoided.

Vorinostat: Additive QTc prolongation may occur. Concomitant therapy should be avoided.

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.

Zuclopenthixol: Additive QTc prolongation may occur. QTc prolongation can lead to Torsade de Pointes (TdP). Concomitant therapy should be avoided.