Deutetrabenazine

Indications

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

Adult Dose

Chorea Oral 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 once daily 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

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

Increases the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease Balance risks of depression and suicidality with the clinical need for treatment of chorea when considering the use of Deutetrabenazine Inform patients, caregivers and families of the risk of depression and suicidality and instruct to report behaviors of concern promptly to the treating physician Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation Deutetrabenazine is contraindicated in patients who are suicidal, and in patients with untreated or inadequately treated depression QT Prolongation: May cause an increase in QT interval. Avoid use in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval Neuroleptic Malignant Syndrome (NMS): Discontinue if this occurs Akathisia, agitation, restlessness, and parkinsonism: Reduce dose or discontinue if this occurs Sedation/somnolence: May impair the patient’s ability to drive or operate complex machinery Monitoring Parameters Monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior Monitor for manifestations of NMS (eg, hyperpyrexia, muscle rigidity, altered mental status, autonomic instability, increased creatinine phosphokinase, myoglobinuria, rhabdomyolysis, acute renal failure)

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 Contraindicated (12) isocarboxazid linezolid mavorixafor methylene blue phenelzine rasagiline safinamide selegiline selegiline transdermal tetrabenazine tranylcypromine valbenazine Serious (20) acrivastine adagrasib benzhydrocodone/acetaminophen buprenorphine buccal buprenorphine subdermal implant buprenorphine transdermal buprenorphine, long-acting injection givosiran iobenguane I 131 metoclopramide intranasal oliceridine olopatadine intranasal opicapone reserpine ropeginterferon alfa 2b safinamide sodium oxybate thalidomide tolcapone zuranolone

Adverse 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

Mechanism 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