XENAZINE (tetrabenazine)

AbsorptionFollowing oral administration of tetrabenazine, the extent of absorption is at least 75%. After single oral doses ranging from 12.5 to 50 mg, plasma concentrations of tetrabenazine are generally below the limit of detection because of the rapid and extensive hepatic metabolism of tetrabenazine by carbonyl reductase to the active metabolites α-HTBZ and β-HTBZ. α-HTBZ and β-HTBZ are metabolized principally by CYP2D6. Peak plasma concentrations (C max ) of α-HTBZ and β-HTBZ are reached w...

Study 1The efficacy of XENAZINE as a treatment for the chorea of Huntington’s disease was established primarily in a randomized, double-blind, placebo-controlled multi-center trial (Study 1) conducted in ambulatory patients with a diagnosis of HD. The diagnosis of HD was based on family history, neurological exam, and genetic testing. Treatment duration was 12 weeks, including a 7-week dose titration period and a 5-week maintenance period followed by a 1-week washout. XENAZINE was started at a dose of 12.5 mg/day, followed by upward titration at weekly intervals, in 12.5 mg increments until s...

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 Orthosta...

XENAZINE is 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). XENAZINE should not be used in combination with an MAOI, or within a minimum of 14 day...

Periodically reevaluate the benefit and potential for adverse effects such as worsening mood, cognition, rigidity, and functional capacity. ( 5.2 ) Do 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). (5.3, 7.1 ) Neuroleptic Malignant Syndrome (NMS): Discontinue if this occurs. ( 5.4 , 7.6 ) Restlessness, agitation, akathisia and parkinsonism: Reduce dose or discontinue if occurs....

7 DRUG INTERACTIONS 7.1 Strong CYP2D6 Inhibitors In vitro studies indicate that α-HTBZ and β-HTBZ are substrates for CYP2D6. Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine) markedly increase exposure to these metabolites. A reduction in XENAZINE dose may be necessary when adding a strong CYP2D6 inhibitor (e.g., fluoxetine, paroxetine, quinidine) in patients maintained on a stabl...