Deutetrabenazine

Indications

Deutetrabenazine is used for: Indicated for chorea associated with Huntington disease, Tardive Dyskinesia

Adult Dose

Chorea Indicated for chorea associated with Huntington disease Dose is determined individually for each patient based on reduction of chorea and tolerability Initial dose when not being switched from tetrabenazine: 6 mg PO qDay May increased dose at weekly intervals in increments of 6 mg/day; not to exceed 48 mg/day Administer doses >12 mg/day in 2 divided doses Tardive Dyskinesia Indicated for treatment of tardive dyskinesia (TD) Dose is determined individually for each patient based on reduction of TD and tolerability Initial dose when not being switched from tetrabenazine: 6 mg PO BID May increased dose at weekly intervals in increments of 6 mg/day; not to exceed 48 mg/day Hepatic impairment Contraindicated Effect of hepatic impairment on the pharmacokinetics of deutetrabenazine and its primary metabolites has not been studied In a clinical study conducted with tetrabenazine, a closely related VMAT2 inhibitor, there was a large increase in exposure to tetrabenazine and its active metabolites The clinical significance of this increased exposure has not been assessed, but because of concerns for a greater risk for serious adverse reactions, it is contraindicated

Child Dose

Renal Dose

Administration

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

Contra Indications

Patients with Huntington disease who are suicidal, or in patients with untreated or inadequately treated depression Hepatic impairment Coadministration with MAOIs; deutetrabenazine should not be used in combination with an MAOI or within 14 days of discontinuing an MAOI Coadministration with reserpine; at least 20 days should elapse after stopping reserpine before initiating deutetrabenazine Coadministration with tetrabenazine or valbenazine

Precautions

Huntington disease is a progressive disorder characterized by changes in mood, cognition, chorea, rigidity, and functional capacity over time; VMAT2 inhibitors, including deutetrabenazine, may cause a worsening in mood, cognition, rigidity, and functional capacity; periodically reevaluate the need for deutetrabenazine by assessing effect on chorea and adverse effects Patients with Huntington disease are at increased risk for depression and suicidality; deutetrabenazine may increase this risk. May increase the risk of akathisia, agitation, and restlessness in patients with Huntington’s disease and tardive dyskinesia; reduce dose or discontinue if this occurs Sedation/somnolence reported; may impair patient’s ability to drive or operate complex machinery

Pregnancy-Lactation

Pregnancy There are no adequate data on the developmental risk in pregnant women Animal studies Administration of deutetrabenazine to rats during organogenesis produced no clear adverse effect on embryofetal development However, administration of tetrabenazine to rats throughout pregnancy and lactation resulted in an increase in stillbirths and postnatal offspring mortality Lactation Unknown if distributed in human breast milk Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Interactions

Coadministration with dopamine antagonists or antipsychotics may increase risk for parkinsonism, NMS, and akathisia Coadministration with alcohol and other sedating drugs may worsen somnolence associated with deutetrabenazine

Side Effects

Side effects of Deutetrabenazine : >10% Somnolence (11%) 1-10% Diarrhea (9%) Dry mouth (9%) Fatigue (9%) Urinary tract infection (7%) Insomnia (7%) Anxiety (4%) Constipation (4%) Contusion (4%) Dizziness (4%) Akathisia, agitation, or restlessness (4%) Depression in patients with Huntington’s disease (4%) Suicidal ideation in patients with Huntington’s disease (2%) Parkinsonism in patients with Huntington’s disease

Mode of Action

Oral vesicular monoamine transporter-2 (VMAT-2) inhibitor; 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