Deutetrabenazine is a vesicular monoamine transporter 2 (VMAT2) inhibitor used for the treatment of:

• Chorea associated with Huntington’s disease
• Tardive dyskinesia in adult patients

The exact mechanism of action of deutetrabenazine in reducing chorea is not fully understood. However, it is believed to work by reversibly decreasing monoamines such as dopamine, serotonin, norepinephrine, and histamine from nerve endings. Its active metabolites, α-dihydrotetrabenazine and β-dihydrotetrabenazine, act as reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). This leads to reduced uptake of monoamines into synaptic vesicles and ultimately depletion of monoamine storage in nerve terminals.

Patients not presently receiving Tetrabenazine:

Chorea associated with Huntington’s disease

• Initial dose: 6 mg/day
• Maintenance dose: 6 mg-48 mg/day
• Maximum dose: 48 mg/day

Tardive dyskinesia

• Initial dose: 12 mg/day
• Maintenance dose: 12 mg-48 mg/day
• Maximum dose: 48 mg/day

Titrate up at weekly intervals by 6 mg per day to a tolerated dose that reduces chorea, up to a maximum recommended daily dosage of 48 mg (24 mg twice daily). Administer total daily dosages of 12 mg or above in two divided doses and administer with foods.

Patients receiving Tetrabenazine: If switching patients from tetrabenazine, discontinue tetrabenazine and initiate deutetrabenazine the following day. The recommended initial dosing regimen of deutetrabenazine in patients switching from tetrabenazine to deutetrabenazine is shown in below chart:

After patients are switched to deutetrabenazine, the dose may be adjusted at weekly intervals.

Concomitant use of strong CYP2D6 inhibitors increases exposure to deutetrabenazine; therefore the maximum recommended dose is 36 mg per day (18 mg twice daily). Alcohol and other sedating drugs may cause additive effects such as increased sedation and somnolence.

Deutetrabenazine is contraindicated in patients with suicidal ideation, untreated or inadequately treated depression, hepatic impairment, and in patients taking MAO inhibitors, reserpine, or tetrabenazine.

The most common adverse effects (>8%) include somnolence, diarrhea, dry mouth, and fatigue.

There are no adequate data regarding the risk of deutetrabenazine during pregnancy. It is also unknown whether the drug or its metabolites are present in human breast milk or its effects on the breastfed infant and milk production.

Patients may develop Neuroleptic Malignant Syndrome (in which case deutetrabenazine should be discontinued). Other possible effects include akathisia, agitation, restlessness, Parkinsonism (dose reduction or discontinuation may be required), and sedation/somnolence.

Use in children: Safety and efficacy have not been established in infants and children.
Hepatic & renal impairment: No clinical studies are available regarding pharmacokinetics in these patients.
Poor CYP2D6 metabolizers: Maximum dose is 36 mg per day (18 mg twice daily).

Overdose may cause acute dystonia, oculogyric crisis, nausea, vomiting, sweating, sedation, hypotension, confusion, diarrhea, hallucinations, flushing, and tremor.

Store below 30°C, protected from light and moisture. Keep out of reach of children.