Tetrabenazine

Indications

Tetrabenazine is used for: Movement disorders, Moderate to severe tardive dyskinesia

Adult Dose

Oral Huntington Disease Indicated for treatment of chorea associated with Huntington’s disease Adult: Individualize and slowly titrate dosage over several weeks to identify a dose that reduces chorea and is well tolerated Total daily dose up to 50 mg/day 12.5 mg PO qDay initially; after 1 week, the dose should be increased to 12.5 mg q12hr Maintenance: Titrate slowly by weekly intervals of 12.5 mg/day to identify dose that reduces chorea and is tolerated If daily dose is 37.5 to 50 mg/day, administer in divided doses q8hr Elderly: Initially 12.5 mg daily, increased gradually. Total Daily dose >50 mg/day If >50 mg/day is required, test and genotype to determine if poor or extensive metabolizers of CYP2D6; not to exceed 100 mg/day or 37.5 mg/dose Moderate to severe tardive dyskinesia Adult: Initially 12.5 mg daily increased gradually according to response. Hepatic impairment Contraindicated; it is not possible to adjust the dose to ensure safe use

Child Dose

Safety and efficacy not established

Renal Dose

Administration

May be taken with or without food.

Contra Indications

Hypersensitivity. Lactation. Hepatic impairment. Patients who are actively suicidal, or who have untreated or inadequately treated depression.

Precautions

May exacerbate symptoms of parkinsonism. Caution to be exercised when driving or performing skilled tasks. Pregnancy. Increased risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Monitor for emergence or worsening of depression, suicidality, or unusual changes in behavior. Caution in patients with a history of depression or prior suicide attempts or ideation.

Pregnancy-Lactation

Pregnancy There are no adequate data on the developmental risk associated with therapy in pregnant women; administration of tetrabenazine to rats throughout pregnancy and lactation resulted in an increase in stillbirths and postnatal offspring mortality Lactation There are no data on presence of tetrabenazine or metabolites in human milk, effects on breastfed infant, or on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and potential adverse effects on breastfed infant or underlying maternal condition

Interactions

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.

Adverse Effects

Side effects of Tetrabenazine : >10% Sedation/somnolence (31%), Fatigue (22%), Insomnia (22%), Depression (19%), Akathisia (19%), Extrapyramidal event (15%), Anxiety (15%), Nausea (13%) 1-10% Irritability (9%), Bruising (6%), Vomiting (6%), Decreased appetite (4%), Dysuria (4%), Obsessive reaction (4%), Imbalance (9%), Parkinsonism/bradykinesia (9%), Dizziness (4%), Dysarthria (4%), Unsteady gait (4%), Headache (4%) Frequency Not Defined QTc prolongation, Neuroleptic malignant syndrome, Orthostatic Hypotension, Restlessness and agitation, Dysphagia, Depression and suicidality Potentially Fatal: Neuroleptic malignant syndrome (NMS).

Mechanism of Action

Reversibly inhibits human vesicular monoamine transporter type 2 (VMAT2), resulting in decreased uptake of monoamines (eg, dopamine, serotonin, norepinephrine, histamine) into synaptic vesicles and depletion of monoamine stores from nerve terminals This effect is similar to reserpine, but with less peripheral activity and is shorter-acting