Schedule H

Oral

• Tablets: 6 mg, 9 mg, 12 mg

• Note: Limited availability — may require import through specialty channels; verify current CDSCO status before prescribing

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Chorea Associated with Huntington's Disease — Specialist Only

Parameter Recommendation

Starting dose 6 mg twice daily

Titration Increase by 6 mg/day at weekly intervals based on response and tolerability

Usual maintenance dose 24–48 mg/day in two divided doses

Maximum dose 48 mg/day

Clinical Notes:

• Initiate only under neurologist supervision

• Reduce dose or discontinue if intolerable somnolence, parkinsonism, or suicidal ideation develops

• Screen for depression at each visit

• Administer with food

1. Tardive Dyskinesia — Specialist Only

Parameter Recommendation

Starting dose 6 mg twice daily (12 mg/day total)

Titration Increase by 6 mg/day at weekly intervals

Usual maintenance dose 24–36 mg/day in two divided doses

Maximum dose 48 mg/day

Clinical Notes:

• Psychiatric supervision recommended

• Evaluate therapeutic response after 8–12 weeks

• Consider gradual tapering if symptoms adequately controlled

• Reassess need for continued therapy every 3–6 months

Secondary Indications – Adults Only (Off-label, if any)

NOT ESTABLISHED in Indian clinical practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

NOT RECOMMENDED in children and adolescents (<18 years)

Age Group Recommendation

<18 years Not approved; safety and efficacy not established

Safety Notes:

• No paediatric dosing data available from Indian or international sources

• Use only in exceptional circumstances under specialist paediatric neurologist supervision with documented informed consent

• If used: close monitoring for depression, suicidality, and extrapyramidal symptoms required

Secondary Indications – Paediatrics (Off-label, if any)

Not applicable

• Active suicidal ideation or behaviour

• Untreated or inadequately treated depression

• Concurrent use with reserpine (wait ≥20 days after stopping reserpine)

• Concurrent use with tetrabenazine

• Concurrent or recent use of monoamine oxidase inhibitors (within 14 days)

• Known hypersensitivity to deutetrabenazine or tetrabenazine

• History of depression or suicide attempts — requires close psychiatric monitoring

• Parkinson's disease or parkinsonism — may worsen motor symptoms

• Known QT prolongation or concurrent use of QT-prolonging medications

• Hepatic impairment — increased accumulation risk

• Concurrent CNS depressants — additive sedation

• Occupations requiring mental alertness — sedating effects

• Dysphagia or aspiration risk — especially in Huntington's disease patients

Aspect Information

Overall safety Limited human data; animal studies suggest potential developmental risk

Recommendation Avoid unless benefit clearly outweighs risk; specialist supervision mandatory

Preferred alternatives Not established for chorea/tardive dyskinesia; consider atypical antipsychotics with better pregnancy data if movement disorder management essential

Monitoring Fetal growth surveillance; neonatal observation for extrapyramidal symptoms or sedation if exposed near term

Aspect Information

Compatibility Not recommended; avoid breastfeeding during treatment

Excretion in milk Unknown; likely excreted based on lipophilicity

Preferred alternatives Consider formula feeding if deutetrabenazine essential

Infant monitoring If breastfeeding unavoidable: observe for sedation, poor feeding, failure to thrive, developmental milestones

• Starting dose: 6 mg once daily

• Titration: Slow — increase at 2-week intervals rather than weekly

• Use lowest effective dose

• Additional risks:

• Enhanced somnolence and sedation

• Increased fall risk due to gait instability

• Greater susceptibility to parkinsonism

• Closer monitoring for depression and cognitive changes required

Drug/Class Mechanism Clinical Action

MAO inhibitors (phenelzine, tranylcypromine, selegiline) Risk of hypertensive crisis, serotonin syndrome Contraindicated — allow 14-day washout

Reserpine Cumulative dopamine depletion, severe CNS depression Contraindicated — wait ≥20 days after stopping reserpine

Tetrabenazine Additive VMAT2 inhibition Contraindicated

Strong CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine, bupropion) Increased deutetrabenazine exposure Maximum total daily dose: 36 mg

QT-prolonging drugs (haloperidol, methadone, amiodarone, ondansetron) Additive QT prolongation risk Avoid combination or monitor ECG closely

Drug/Class Interaction Clinical Action

CNS depressants (benzodiazepines, opioids, alcohol) Additive sedation Use cautiously; monitor for excessive drowsiness

Antidepressants (SSRIs, SNRIs) Increased psychiatric side effects; some are CYP2D6 inhibitors Monitor mood; consider dose adjustment

Anticholinergics Worsening of cognitive or motor function Minimise concurrent use

Rifampicin CYP3A4 induction may reduce efficacy Monitor therapeutic response; may need dose increase

Macrolides (erythromycin, clarithromycin) CYP3A4 inhibition may increase levels Monitor for excessive sedation

Digoxin Potential P-glycoprotein interaction Monitor digoxin levels

• Somnolence, sedation

• Fatigue

• Diarrhoea

• Dry mouth

• Nausea

• Insomnia

• Akathisia

• Anxiety

• Dizziness

Adverse Effect Clinical Action

Suicidal ideation or worsening depression Immediate psychiatric evaluation; consider discontinuation

Neuroleptic malignant syndrome (rare) Discontinue immediately; hospitalisation required

Severe extrapyramidal symptoms (dystonia, parkinsonism) Reduce dose or discontinue

QT prolongation / Torsades de pointes (rare) Discontinue; cardiology consultation; correct electrolytes

Dysphagia with aspiration pneumonia Discontinue or reduce dose; supportive management

Phase Parameters Frequency

Baseline Psychiatric assessment (depression, suicidality), ECG (if cardiac risk factors), hepatic function, movement disorder severity scoring (UHDRS for chorea, AIMS for tardive dyskinesia) Before initiation

During titration Mood assessment, sedation, extrapyramidal symptoms, response to treatment Weekly

Long-term Depression screening, movement disorder assessment, ECG if on other QT-prolonging drugs, hepatic function Every 3–6 months

Discontinuation Gradual taper recommended; monitor for symptom rebound As clinically indicated

• Austedo® (Teva Pharmaceuticals) — limited availability; may require import

Note: No fixed-dose combinations approved with deutetrabenazine

• Not included in NLEM

• Not under NPPA price control

• Availability limited to specialty neurology centres and private import channels

1. Deutetrabenazine versus tetrabenazine — Deutetrabenazine offers smoother plasma levels due to slower hepatic metabolism, resulting in reduced peak-related sedation and potentially better tolerability.

1. Mandatory psychiatric screening — Depression and suicidality must be actively assessed at baseline and every visit, regardless of psychiatric history.

1. Gradual titration is essential — Rapid dose escalation significantly increases risk of sedation, parkinsonism, and psychiatric adverse effects.

1. CYP2D6 inhibitor interaction — When co-administered with strong CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine), cap total daily dose at 36 mg to prevent toxicity.

1. Periodic reassessment in tardive dyskinesia — Re-evaluate therapeutic need every 3–6 months; some patients may achieve sustained remission allowing dose reduction or discontinuation.

1. Avoid in patients with significant QT prolongation risk — Especially when multiple QT-prolonging medications are used concurrently; obtain baseline ECG in at-risk patients.

Deutetrabenazine; VMAT2 inhibitor; chorea; Huntington disease; tardive dyskinesia; movement disorders; depression risk; CYP2D6 interaction; QT prolongation; specialist-only

RxIndia v1.0 — 28 May 2025

• CDSCO database (availability verification required)

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• API Textbook of Medicine — Huntington's disease chapter

• AIIMS Neurology specialist practice protocols

• US FDA prescribing information (reference for formulation and pharmacokinetic data)