Approved August 15, 2008

TETRABENAZINE
(FDA Category 1P)

XENAZINE(R) (Prestwick, Inc) is a monoamine depletor whose exact mechanism is unknown. It depletes monoamine such as dopamine, serotonin, norepinephrine, and histamine from nerve terminals.

DOSING INFORMATION: The initial dose is 12.5 mg orally once daily in the morning. Increase dose in 12.5 mg increments up to a maximum of 100 mg a day, except in CYP2D6 poor metabolizers the maximum daily dose is 50 mg. If a dose of 37.5 mg to 50 mg per day is required, it should be given in divided doses 3 times daily. Maximum recommended single dose is 37.5 mg for CYP2D6 extensive and intermediate metabolizers, and 25 mg for CYP2D6 poor metabolizers.

PHARMACOKINETICS: Peak plasma concentrations of the active metabolites are reached within 90 minutes to 2 hours post-dosing. It is at least 75% absorbed following oral administration. Tetrabenazine undergoes rapid and extensive hepatic metabolism to the primary circulating metabolites, alpha-HTBZ and beta-HTBZ which undergo further metabolism via CYP2D6 to O-dealkylated-HTBZ. Following a single 25-milligram dose, the elimination half-life of tetrabenazine, alpha-HTBZ, and beta-HTBZ were approximately 17.5 hours, 10 and 8 hours, respectively, in patients with mild to moderate chronic hepatic impairment (Child-Pugh score 5 to 9).

CAUTIONS: Serious adverse events include prolonged QT interval, increased risk of depression and suicidal thoughts and behavior (suicidality). Common adverse events include sedation/somnolence, Parkinsonism/bradykinesia, akathisia, insomnia, nausea, dysphagia, and fatigue. Patients who require greater than 50 milligrams/day should be genotyped for CYP2D6.

FDA APPROVED INDICATIONS: Tetrabenazine is indicated for the treatment of chorea associated with Huntington's disease.