Deutetrabenazine (3 brand names, 2 dosage forms, 1 route)
Available dosage forms: TABLET, TABLET, EXTENDED RELEASE.
Routes of administration: ORAL.
Brand Names
- AUSTEDO
- AUSTEDO XR
- DEUTETRABENAZINE
Boxed Warning
AUSTEDO XR and AUSTEDO can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Anyone considering the use of AUSTEDO XR or AUSTEDO must balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior. Patients, their caregivers, and families should be informed of the risk of depression and suicidality and should be instructed to report behaviors of concern promptly to the treating physician. Particular caution should be exercised in treating patients with a history of depression or prior suicide attempts or ideation, which are increased in frequency in Huntington’s disease. AUSTEDO XR and AUSTEDO are contraindicated in patients who are suicidal, and in patients with untreated or inadequately treated depression [see Contraindications (4) and Warnings and Precautions (5.1 )].
Indications and Usage
AUSTEDO XR® and AUSTEDO® are indicated in adults for the treatment of: chorea associated with Huntington’s disease [see Clinical Studies (14.1)] tardive dyskinesia [see Clinical Studies (14.2)]
Contraindications
AUSTEDO XR and AUSTEDO are contraindicated in patients: With Huntington’s disease who are suicidal, or have untreated or inadequately treated depression [see Warnings and Precautions (5.1)]. With hepatic impairment [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)]. Taking reserpine. At least 20 days should elapse after stopping reserpine before starting AUSTEDO XR or AUSTEDO [see Drug Interactions (7.2 )]. Taking monoamine oxidase inhibitors (MAOIs). AUSTEDO XR and AUSTEDO should not be used in combination with an MAOI, or within 14 days of discontinuing therapy with an MAOI [see Drug Interactions (7.3 )]. Taking tetrabenazine or valbenazine [see Drug Interactions (7.6)].
Adverse Reactions
The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Depression and Suicidality in Patients with Huntington’s disease [see Warnings and Precautions (5.1)] QTc Prolongation [see Warnings and Precautions (5.3)] Neuroleptic Malignant Syndrome (NMS) [see Warnings and Precautions (5.4)] Akathisia, Agitation, and Restlessness [see Warnings and Precautions (5.5)] Parkinsonism [see Warnings and Precautions (5.6)] Sedation and Somnolence [see Warnings and Precautions (5.7)] Hyperprolactinemia [see Warnings and Precautions (5.8)] Binding to Melanin-Containing Tissues [see Warnings and Precautions (5.9)]
Mechanism of Action
The precise mechanism by which deutetrabenazine exerts its effects in the treatment of tardive dyskinesia and chorea in patients with Huntington’s disease 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. The major circulating metabolites (α-dihydrotetrabenazine [HTBZ] and β-HTBZ) of deutetrabenazine, are reversible inhibitors of VMAT2, resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
Overdosage
Overdoses ranging from 100 mg to 1 g have been reported in the literature with tetrabenazine, a closely related VMAT2 inhibitor. The following adverse reactions occurred with overdosing: acute dystonia, oculogyric crisis, nausea and vomiting, sweating, sedation, hypotension, confusion, diarrhea, hallucinations, rubor, and tremor. Treatment should consist of those general measures employed in the management of overdosage with any central nervous system-active drug. General supportive and symptomatic measures are recommended. Cardiac rhythm and vital signs should be monitored. In managing overdosage, the possibility of multiple drug involvement should always be considered. The physician should consider contacting a poison control center on the treatment of any overdose. Telephone numbers for certified poison control centers are listed on the American Association of Poison Control Centers website www.aapcc.org.