Ajuben

A. Approved Indications

• Chorea associated with Huntington’s Disease (HD):
• Reduces involuntary movements in adult patients with Huntington’s disease.
• Tardive Dyskinesia (TD):
• Treatment of tardive dyskinesia in adults, including those with schizophrenia, schizoaffective disorder, or mood disorders.

B. Clinically Accepted Off-Label Uses

• Tourette Syndrome (TS):
• Investigational use in reducing motor and vocal tics in pediatric and adult populations.
• Tic Disorders and Other Hyperkinetic Movement Disorders:
• May be used off-label in selected refractory cases.

A. Adults

• Chorea of Huntington’s Disease:
• Starting dose: 6 mg once daily.
• Titration: Increase in increments of 6 mg/day at weekly intervals.
• Maximum dose: 48 mg/day, administered in two divided doses.
• Tardive Dyskinesia:
• Starting dose: 6 mg twice daily.
• Titration: Increase by 6 mg/day at weekly intervals based on response and tolerability.
• Maximum dose: 48 mg/day (24 mg twice daily).
• Dosage with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine):
• Maximum dose: 36 mg/day.

B. Pediatric Use

• Safety and efficacy not established in patients <18 years.

C. Elderly

• Use standard adult dosing with caution due to potential increased sensitivity to adverse CNS effects.

D. Renal Impairment

• Use with caution in severe renal impairment (CrCl <30 mL/min); no specific dose recommendations.

E. Hepatic Impairment

• Moderate to severe hepatic impairment (Child-Pugh B or C):
• Contraindicated due to increased exposure and risk of adverse effects.

Route of Administration: Oral

Duration of Use: Long-term use is appropriate with regular monitoring of efficacy and side effects.

Deutetrabenazine is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor. VMAT2 is responsible for transporting monoamines (especially dopamine) into synaptic vesicles. By reversibly inhibiting VMAT2, deutetrabenazine reduces presynaptic dopamine storage and release into the synaptic cleft. This leads to decreased dopaminergic transmission in the basal ganglia, reducing hyperkinetic movement disorders like chorea and tardive dyskinesia. The drug is a deuterated form of tetrabenazine, which improves metabolic stability and prolongs half-life, allowing for more stable plasma levels and potentially fewer side effects.

• Absorption:
• Oral bioavailability is good; not significantly affected by food.
• Tmax: ~4–8 hours for active metabolites.
• Distribution:
• Volume of distribution: ~500 L
• Plasma protein binding: ~82–85%
• Metabolism:
• Extensively metabolized via carbonyl reductase to active metabolites (α-HTBZ and β-HTBZ).
• These are then metabolized via CYP2D6.
• Elimination:
• Half-life: ~9–10 hours for active metabolites
• Excretion: Primarily via urine (75%), minor amounts in feces

• Pregnancy:
• No FDA pregnancy category under current labeling system.
• Use only if benefits outweigh risks. Animal data are limited, and no well-controlled human studies exist.
• Lactation:
• Unknown if excreted in human milk.
• Due to the potential for serious adverse effects (e.g., sedation, movement disorders), caution is advised if used during breastfeeding.

• Primary Class: VMAT2 Inhibitor
• Subclass: Central nervous system dopamine-depleting agent
• Generation: Deuterated analog of tetrabenazine (improved pharmacokinetics)

• Known hypersensitivity to deutetrabenazine or any formulation component
• Suicidal ideation or untreated depression
• Hepatic impairment (moderate to severe)
• Concomitant use with MAO inhibitors or within 14 days of stopping an MAOI
• Use with reserpine or tetrabenazine (within 20 days)

• Depression and Suicide Risk:
• Risk increased in Huntington’s disease patients; monitor closely for mood changes and suicidal thoughts.
• QT Prolongation:
• Caution in patients with known QT prolongation or using other QT-prolonging agents.
• Neuroleptic Malignant Syndrome (NMS):
• Rare but serious; discontinue immediately if symptoms arise.
• Parkinsonism and Sedation:
• Dopamine-depleting effects can worsen or mimic Parkinson’s disease. Monitor motor function.
• CYP2D6 Poor Metabolizers:
• Dose adjustment required due to altered metabolism.
• Akathisia and Restlessness:
• Dose reduction or discontinuation may be required if symptoms occur.

Common (≥5%):

• CNS: Somnolence, fatigue, dizziness
• Psychiatric: Anxiety, insomnia, depression (especially in HD patients)
• GI: Diarrhea, dry mouth
• Musculoskeletal: Falls, gait disturbance

Less Common (1–5%):

• Akathisia
• QT interval prolongation
• Urinary tract infections

Serious or Rare (<1%):

• Suicidal ideation or behavior
• Neuroleptic malignant syndrome
• Severe hypotension
• Bradycardia
• Parkinsonism

• Strong CYP2D6 inhibitors (e.g., fluoxetine, paroxetine, quinidine):
• May increase exposure to active metabolites; max dose = 36 mg/day
• MAO Inhibitors:
• Contraindicated due to increased risk of neurotoxicity and hypertensive crises
• Reserpine or Tetrabenazine:
• Additive dopamine depletion; avoid use within 20 days.
• QT-prolonging drugs (e.g., amiodarone, sotalol):
• Use cautiously due to potential additive QT prolongation.
• Alcohol and CNS depressants:
• May enhance sedation and cognitive impairment.

• FDA Updates (2023):
• Added warnings about dose adjustments with CYP2D6 inhibitors and extended monitoring for mood-related changes.
• AAN Guidelines (2024):
• Deutetrabenazine is now a preferred treatment for tardive dyskinesia in adults due to better tolerability compared to tetrabenazine.
• Ongoing Trials (2025):
• Evaluating deutetrabenazine for Tourette syndrome and pediatric movement disorders.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Humidity: Protect from moisture; store in a dry place
• Light Protection: Keep in original container to protect from light exposure
• Handling Instructions:
• Do not split, crush, or chew tablets
• Keep tightly closed
• Discard unused tablets after expiry date
• Keep out of reach of children