deutetrabenazine

Contraindicated in:

Hepatic impairment;
Concurrent use of MAO inhibitors, tetrabenazine, or valbenazine;
Patients who are suicidal or have untreated or inadequately treated depression;
Congenital long QT syndrome or cardiac arrhythmias.

Use Cautiously in:

History of/propensity for depression, psychiatric illness, or suicidality;
Poor CYP2D6 metabolizers; initial dose ↓ required;
Bradycardia, hypokalemia, hypomagnesemia, or concurrent use of QT-interval prolonging drugs;
History of breast cancer;
OB: Use during pregnancy only when potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only when potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: QTc interval prolongation

Endo: hyperprolactinemia

GI: constipation, diarrhea, dry mouth

GU: urinary tract infection

MS: bradykinesia

Neuro: akathisia, sedation/somnolence, agitation, anxiety,

depression

, dizziness, fatigue, gait disturbances, insomnia, NEUROLEPTIC MALIGNANT SYNDROME, parkinsonism, restlessness, SUICIDAL THOUGHTS/BEHAVIOR, tremor

Interactions ⬆ ⬇

Drug-drug:

MAO inhibitors↑ risk of serious adverse reactions and are contraindicated; wait ≥14 days after discontinuing to initiate deutetrabenazine.
Concurrent use of tetrabenazine or valbenazine is contraindicated.
Strong CYP2D6 inhibitors, including bupropion, fluoxetine, paroxetine, and quinidine, may ↑ levels and risk of toxicity; ↓ dose of deutetrabenazine.
QTc interval prolonging drugs may ↑ risk of QTc interval prolongation.
Dopamine antagonists or antipsychotics may ↑ risk of neuroleptic malignant syndrome and extrapyramidal disorders.
Alcohol or other CNS depressants may ↑ risk of CNS depression.

Availability ⬆ ⬇

(Generic available)

Immediate-release tablets (Austedo): 6 mg; 9 mg; 12 mg
Extended-release tablets (Austedo XR): 6 mg; 12 mg; 18 mg; 24 mg; 30 mg; 36 mg; 42 mg; 48 mg

Route/Dosage ⬆ ⬇

When switching between immediate-release and extended-release formulations, use same total daily dose.

Huntington Disease

PO (Adults ): Immediate-release tablets: 6 mg twice daily; may ↑ dose by 6 mg/day at weekly intervals (max dose = 48 mg/day) based on tolerability to ↓ chorea. Extended-release tablets: 12 mg once daily; may ↑ dose by 6 mg/day at weekly intervals (max dose = 48 mg/day) based on tolerability to ↓ chorea. Concurrent use of strong CYP2D6 inhibitors or poor CYP2D6 metabolizers: Do not exceed dose of 36 mg/day.

Tardive Dyskinesia

PO (Adults ): Immediate-release tablets: 6 mg twice daily; may ↑ dose by 6 mg/day at weekly intervals (max dose = 48 mg/day) based on tolerability to ↓ tardive dyskinesia. Extended-release tablets: 12 mg once daily; may ↑ dose by 6 mg/day at weekly intervals (max dose = 48 mg/day) based on tolerability to ↓ tardive dyskinesia. Concurrent use of strong CYP2D6 inhibitors or poor CYP2D6 metabolizers: Do not exceed dose of 36 mg/day.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Its major metabolites act as reversible inhibitors of the vesicle monoamine transporter type 2 (VMAT-2), resulting in decreased reuptake of monoamines (including serotonin, norepinephrine, and dopamine) into vesicles in presynaptic neurons and depletion of monoamine stores.

Therapeutic effects:

Decreased chorea due to Huntington Disease.
Reduced severity of tardive dyskinesia.

Classifications ⬆ ⬇

Therapeutic Classification: antichoreas

Pharmacologic Classification: reversible monoamine depleters

Pharmacokinetics ⬆ ⬇

Absorption: ≥80% absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Metabolized in liver to two active metabolites (α-dihydrotetrabenazine (α-HTBZ) and β-HTBZ), which are subsequently metabolized primarily via CYP2D6 (and to lesser extent by CYP1A2 and CYP3A4/5) to several minor metabolites (the CYP2D6 enzyme system exhibits genetic polymorphism; 7% of population may be poor metabolizers and may have significantly ↑ concentrations and an ↑ risk of adverse effects). Primarily excreted in the urine as metabolites.

Half-Life: 9–10 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	3–4 hr	12 hr
PO-XR	unknown	3 hr	24 hr

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy. Instruct patient to take as directed.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Advise patient and caregiver to monitor for changes, especially sudden changes in mood, behaviors, thoughts, or feelings. If new or worse feelings of sadness; crying spells; lack of interest in friends or activities; sleeping a lot more or less; feelings of unimportance, guilt, hopelessness, or helplessness; irritability or aggression; more or less hunger; difficulty paying attention; or thoughts of self-harm or suicide occur, notify health care provider promptly.
Advise patient to notify health care provider if signs and symptoms of neuroleptic malignant syndrome, akathisia, or irregular heartbeat occur.
Advise patient to avoid driving and other activities requiring alertness until response to medication is known.
Inform patient of potential side effects and instruct patient to notify health care provider if side effects occur.
Advise patient to avoid alcohol or sedating drugs; may ↑ drowsiness.
Inform patients not to be concerned if they occasionally notice something that looks like a tablet shell in their stool when taking Austedo XR.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

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Indications ⬇

Contraind./Precautions ⬆ ⬇