Deutetrabenazine

Deutetrabenazine is an oral VMAT2 inhibitor that decreases uptake of monoamines (eg, dopamine, serotonin, norepinephrine, histamine) into synaptic vesicles and depletes monoamine stores from nerve terminals. The precise mechanism by which deutetrabenazine exerts its antichorea effects is unknown, but is believed to be related to its effect on reversible depletion of monoamines from nerve terminals. The major circulating metabolites of deutetrabenazine are reversible inhibitors of VMAT2, resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.

• Chorea associated with Huntington's disease
• Tardive dyskinesia in adults

The precise mechanism by which deutetrabenazine exerts its antichorea effects is unknown but is believed to be related to its effect as a reversible depletor of monoamines from nerve terminals. The major circulating metabolites of deutetrabenazine are reversible inhibitors of VMAT2, resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.

Deutetrabenazine inhibits VMAT2, reducing monoamine uptake into synaptic vesicles and depleting monoamine stores from nerve terminals, which helps reduce chorea and tardive dyskinesia symptoms.

Huntington disease (Chorea) - not switching from tetrabenazine: Initial 6 mg once daily; increase by 6 mg/day weekly; max 48 mg/day (doses >12 mg in 2 divided doses).
Tardive Dyskinesia - not switching from tetrabenazine: Initial 6 mg twice daily; increase by 6 mg/day weekly; max 48 mg/day.
Strong CYP2D6 inhibitors: Maximum 36 mg/day (18 mg twice daily).

Administer with food. Swallow tablet whole; do not chew, crush, or break.

If you miss a dose of Deutetrabenazine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose. Do not double the dose.

Common (>8%): Somnolence (11%), diarrhea (9%), dry mouth (9%), fatigue (9%).
Other (1-10%): UTI (7%), insomnia (7%), anxiety (4%), constipation (4%), contusion (4%), dizziness (4%), akathisia/agitation/restlessness (4%), depression in Huntington's (4%), suicidal ideation (2%), parkinsonism.

Huntington disease patients are at increased risk for suicidality; deutetrabenazine may increase this risk. Risk of akathisia, agitation, restlessness. Sedation/somnolence may impair driving or operating machinery. Periodically reevaluate need for treatment by assessing effect on chorea and adverse effects.

Suicidal or untreated/inadequately treated depression; hepatic impairment; coadministration with MAOIs or within 14 days of discontinuing MAOI; within 20 days of stopping reserpine; coadministration with tetrabenazine or valbenazine.

Dopamine antagonists or antipsychotics: May increase risk for parkinsonism, NMS, and akathisia.
Alcohol and other sedating drugs: May worsen somnolence.
Strong CYP2D6 inhibitors: Maximum 36 mg/day.

Administer with food. Caution is advised when consuming alcohol (may worsen somnolence).

There are no adequate data on the developmental risk in pregnant women. Animal studies produced no clear adverse effect on embryofetal development.

Unknown if distributed in human breast milk. Consider developmental and health benefits of breastfeeding along with the mother's clinical need.

Safety and effectiveness in infants and children have not been established.

No specific dosage adjustment is necessary for elderly patients.

Hepatic impairment: Not studied; contraindicated.
Renal impairment: Not studied.
Poor CYP2D6 metabolizers: Maximum 36 mg/day (18 mg twice daily).

Adverse reactions with overdose: acute dystonia, oculogyric crisis, nausea and vomiting, sweating, sedation, hypotension, confusion, diarrhea, hallucinations, rubor, and tremor.

Keep below 30°C temperature, away from light & moisture. Keep out of reach of children.

Deutetrabenazine