Tetrabenazine

What it is and how it works

Mechanism of Action The precise mechanism by which tetrabenazine tablets exert its anti-chorea effects is unknown but is believed to be related to its effect as a reversible depletor of monoamines (such as dopamine, serotonin, norepinephrine, and histamine) from nerve terminals. Tetrabenazine reversibly inhibits the human vesicular monoamine transporter type 2 (VMAT2) (K i ≈ 100 nM), resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores. Human VMAT2 is also inhibited by dihydrotetrabenazine (HTBZ), a mixture of α-HTBZ and β-HTBZ. α- and β-HTBZ, major circulating metabolites in humans, exhibit high in vitro binding affinity to bovine VMAT2.

Mechanism class: Vesicular Monoamine Transporter 2 Inhibitors

Indications

Tetrabenazine tablets are indicated for the treatment of chorea associated with Huntington's disease. Tetrabenazine tablets are a vesicular monoamine transporter 2 (VMAT) inhibitor indicated for the treatment of chorea associated with Huntington's disease.

Dosage and administration (summary)

• Individualization of dose with careful weekly titration is required. The 1 st week's starting dose is 12.5 mg daily; 2 nd week, 25 mg (12.5 mg twice daily); then slowly titrate at weekly intervals by 12.5 mg to a tolerated dose that reduces chorea. ( 2.1 , 2.2 ) • Doses of 37.5 mg and up to 50 mg/day should be administered in three divided doses per day with a maximum recommended single dose not to exceed 25 mg. • Patients requiring doses above 50 mg/day should be genotyped for the drug metabolizing enzyme CYP2D6 to determine if the patient is a poor metabolizer (PM) or an extensive metabolizer (EM).

Contraindications

Tetrabenazine tablets are contraindicated in patients: • Who are actively suicidal, or in patients with untreated or inadequately treated depression . • With hepatic impairment . • Taking monoamine oxidase inhibitors (MAOIs). Tetrabenazine tablets should not be used in combination with an MAOI, or within a minimum of 14 days of discontinuing therapy with an MAOI . • Taking reserpine. At least 20 days should elapse after stopping reserpine before starting tetrabenazine tablets .

Warnings and precautions

• Periodically reevaluate the benefit and potential for adverse effects such as worsening mood, cognition, rigidity, and functional capacity. • 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.

Pregnancy

Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of tetrabenazine tablets in pregnant women. Administration of tetrabenazine to rats throughout pregnancy and lactation resulted in an increase in stillbirths and postnatal offspring mortality.

Storage and supply

Storage Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) .

Source: Tetrabenazine (Tetrabenazine) — US FDA prescribing information, 2019-11-29, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.