du-tet-ra-BEN-a-zeen

Therapeutic Classification: antichoreas

Pharmacologic Classification: reversible monoamine depleters

• Chorea due to Huntington's Disease.
• Tardive dyskinesia.

• 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.

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

Absorption: 80% absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Metabolized in liver to two active metabolites (-dihydrotetrabenazine (-HTBZ) and -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.

(plasma concentrations)

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
• Concurrent use of strong CYP2D6 inhibitors (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.

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/IDEATION, tremor.

Drug-Drug:

• Concurrent use of 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; ↓ dose of deutetrabenazine.
• QTc interval prolonging drugs may ↑ risk of QTc interval prolongation.
• Concurrent use with dopamine antagonists or antipsychotics may ↑ risk of neuroleptic malignant syndrome and extrapyramidal disorders.
• Concurrent use of alcohol or other CNS depressants may ↑ risk of CNS depression.

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

Huntington's Disease

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

• Immediate-release tablets: 6 mg; 9 mg; 12 mg;
• Extended-release tablets: 6 mg; 12 mg; 18 mg; 24 mg; 30 mg; 36 mg; 42 mg; 48 mg;

• Assess signs of Huntington's disease (changes in mood, cognition, chorea, rigidity, and functional capacity) periodically during therapy. Re-evaluate need for deutetrabenazine periodically by assessing beneficial effect and side effects; determination may require dose reduction or discontinuation. Underlying chorea may improve over time, decreasing need for deutetrabenazine.
• Monitor closely for new or worsening depression or suicidality. If depression or suicidality occurs, ↓ dose and may initiate or ↑ dose of antidepressants.
• Monitor for signs of neuroleptic malignant syndrome (hyperpyrexia, muscle rigidity, altered mental status, irregular pulse or BP, tachycardia, diaphoresis, cardiac arrhythmia) periodically during therapy. If symptoms occur, discontinue deutetrabenazine and manage symptomatically. If reintroduction of deutetrabenazine is considered, monitor carefully; recurrences of neuroleptic malignant syndrome have occurred.
• Monitor for onset of akathisia (restlessness or desire to keep moving) and parkinsonism (difficulty speaking or swallowing, loss of balance control, pill rolling of hands, mask-like face, shuffling gait, rigidity, tremors). Notify health care professional if these symptoms occur; reduce dose or discontinue therapy.

• Monitor electrolytes and ECG because of risk of QT interval prolongation.

• PO: Administer with food. DNC: Swallow tablet whole; do not crush, break, or chew.
  • Administer extended-release tablet without regard to food.
• If switching from Austedo to Austedo XR, switch to the same total daily dose.
• To switch from tetrabenazine to deutetrabenazine, stop tetrabenazine and administer deutetrabenazine the following day. If patient was taking 12.5–25 mg of tetrabenazine, administer 6 mg deutetrabenazine; if taking 37.5 mg tetrabenazine, give 9 mg deutetrabenazine; if taking 50 mg tetrabenazine, give 12 mg deutetrabenazine; if taking 62.5 mg tetrabenazine, give 15 mg deutetrabenazine; if taking 75 mg tetrabenazine, give 18 mg deutetrabenazine; if taking 87.5 mg tetrabenazine, give 21 mg deutetrabenazine; if taking 100 mg tetrabenazine, give 24 mg deutetrabenazine. Dose adjustments can be made weekly.
• Deutetrabenazine may be stopped without taper. If therapy interrupted >1 wk, retitrate when resuming therapy. If <1 wk since discontinuation, may restart at previous dose.

• Instruct patient to take deutetrabenazine as directed. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
• Advise patient and family 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 professional promptly.
• Advise patient to notify health care professional if signs and symptoms of neuroleptic malignant syndrome, akathisia, or irregular heartbeat occurs.
• 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 professional if side effects occur.
• Advise patient to avoid alcohol or sedating drugs; may increase drowsiness.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

• ↓in chorea due to Huntington's disease.
• Reduced severity of tardive dyskinesia.

Austedo, Austedo XR

NDC Code^*

• 68546- Teva Neuroscience, Inc.
  • 68546-170- Austedo
    • 68546-170-60- 60 TABLET, COATED in 1 BOTTLE (68546-170-60)

• 68546- Teva Neuroscience, Inc.
  • 68546-170- Austedo
    • 68546-170-66- 60 TABLET, COATED in 1 BOTTLE (68546-170-66)

• 68546- Teva Neuroscience, Inc.
  • 68546-171- Austedo
    • 68546-171-60- 60 TABLET, COATED in 1 BOTTLE (68546-171-60)

• 68546- Teva Neuroscience, Inc.
  • 68546-171- Austedo
    • 68546-171-66- 60 TABLET, COATED in 1 BOTTLE (68546-171-66)

• 68546- Teva Neuroscience, Inc.
  • 68546-172- Austedo
    • 68546-172-60- 60 TABLET, COATED in 1 BOTTLE (68546-172-60)

• 68546- Teva Neuroscience, Inc.
  • 68546-172- Austedo
    • 68546-172-66- 60 TABLET, COATED in 1 BOTTLE (68546-172-66)