Schedule H

Oral

• Tablets: 2 mg, 5 mg

• Oral solution: 2 mg/5 mL (limited availability)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Idiopathic Parkinson's Disease

Used as adjunctive therapy, primarily for tremor-predominant Parkinson's disease. May be used as monotherapy in early mild disease or in combination with levodopa.

Parameter Recommendation

Starting dose 1 mg once daily (with food to reduce GI upset)

Titration Increase by 2 mg every 3–5 days based on response and tolerability

Usual maintenance dose 6–10 mg/day in 3 divided doses

Maximum dose 15 mg/day

Clinical Notes:

• Most effective for tremor; less effective for rigidity and bradykinesia

• Best suited for younger patients (<65 years) with tremor-predominant disease

• Often combined with levodopa preparations

• Avoid in elderly due to cognitive adverse effects

• May take meals with each dose to reduce nausea

1. Drug-Induced Parkinsonism and Extrapyramidal Symptoms (EPS)

Used for treatment of parkinsonism and EPS caused by antipsychotic medications (haloperidol, chlorpromazine, risperidone, etc.) or antiemetics (metoclopramide).

Parameter Recommendation

Starting dose 1–2 mg once daily

Titration Increase by 2 mg every 3–5 days as needed

Usual maintenance dose 5–10 mg/day in 2–3 divided doses

Maximum dose 15 mg/day

Clinical Notes:

• Effective for acute EPS (parkinsonism, akathisia, dystonia)

• Not effective for tardive dyskinesia — may worsen it with chronic use

• Consider discontinuation trial after 3–6 months of stable antipsychotic dosing

• Do not use prophylactically with atypical antipsychotics (lower EPS risk)

1. Post-Encephalitic Parkinsonism

Parameter Recommendation

Starting dose 1 mg once daily

Titration Increase by 2 mg every 3–5 days

Usual maintenance dose 6–10 mg/day in 3 divided doses

Maximum dose 15 mg/day

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Primary Dystonia (generalised, focal, segmental) Starting: 2 mg/day; Titration: increase by 2 mg every 5–7 days; Maintenance: 6–15 mg/day in 3 divided doses; Maximum: 20–30 mg/day in some cases Long-term; chronic treatment OFF-LABEL — Specialist only (Neurology/Movement Disorders). Widely used in Indian neurology practice. Higher doses often required than for Parkinson's. Very slow titration essential to minimise adverse effects. Based on clinical experience and international guidelines.

Cervical Dystonia (torticollis) Starting: 2 mg/day; Maintenance: 6–12 mg/day Long-term OFF-LABEL — Specialist only. Often used as adjunct to botulinum toxin. Based on clinical practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Drug-Induced Extrapyramidal Symptoms

Use under paediatric neurology or psychiatry supervision only. Not first-line treatment.

Age ≥5 years — Weight-based Dosing:

Parameter Recommendation

Starting dose 0.5–1 mg once daily OR 0.1 mg/kg/day in 2–3 divided doses

Titration Increase by 0.5–1 mg every 3–5 days as tolerated

Usual maintenance dose 1–5 mg/day OR 0.1–0.2 mg/kg/day in 2–3 divided doses

Maximum dose 0.5–0.6 mg/kg/day OR 15 mg/day (whichever is lower)

Clinical Notes:

• Oral solution preferred for accurate dosing in younger children

• Administer with meals to reduce GI upset

• Monitor for behavioural changes, cognitive effects, dry mouth, constipation

Minimum Age Statement: Not recommended in children below 5 years of age. Use in children below 5 years only under paediatric neurologist supervision in exceptional circumstances.

Safety Monitoring:

• Behavioural and cognitive assessment

• Vital signs (heart rate, temperature)

• Bowel and bladder function

• Hydration status (especially in hot weather)

• Growth monitoring

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Notes

Childhood Dystonia (primary generalised dystonia, cerebral palsy-related dystonia) ≥3 years Starting: 0.5 mg once daily OR 0.05 mg/kg/day; Titration: increase by 0.5 mg every 3–5 days; Maintenance: 0.2–0.6 mg/kg/day in 3 divided doses; Maximum: 1 mg/kg/day OR 30 mg/day (in severe cases) OFF-LABEL — Paediatric neurologist supervision mandatory. Very slow titration essential. High doses often required for dystonia (higher than for EPS). Used in paediatric neurology centres in India. Monitor closely for cognitive and autonomic effects.

DYT1 Dystonia ≥3 years As above; often requires higher doses OFF-LABEL — Specialist only. May require doses up to 30–40 mg/day in adolescents under specialist supervision.

Trihexyphenidyl is highly lipophilic and primarily hepatically metabolised; renal excretion of unchanged drug is minimal. Not significantly removed by dialysis.

• Known hypersensitivity to trihexyphenidyl or any excipient

• Untreated narrow-angle (angle-closure) glaucoma

• Urinary retention due to bladder outlet obstruction (e.g., severe benign prostatic hyperplasia with retention)

• Myasthenia gravis

• Paralytic ileus or gastrointestinal obstruction

• Toxic megacolon

• Elderly patients (>65 years) — increased sensitivity to anticholinergic effects including cognitive impairment, confusion, hallucinations, falls, urinary retention

• Prostatic hypertrophy (without complete obstruction) — increased risk of urinary retention

• Cognitive impairment or dementia — may worsen confusion and memory impairment

• History of psychiatric disorders — may exacerbate psychosis; use with caution in schizophrenia patients

• History of seizure disorder — may lower seizure threshold

• Cardiovascular disease — tachycardia may worsen cardiac conditions

• Pyrexia or high ambient temperature — impaired sweating may lead to hyperthermia

• Treated narrow-angle glaucoma — monitor intraocular pressure

• Gastrointestinal motility disorders — may worsen constipation

• Tardive dyskinesia — anticholinergics may mask early symptoms and potentially worsen long-term outcome; do not use to treat TD

• Chronic use with antipsychotics — regularly reassess need; avoid indefinite prophylactic use

• Abrupt discontinuation — may precipitate withdrawal symptoms or worsening of parkinsonism; taper gradually

• Substance abuse potential — euphorigenic properties may lead to misuse

Parameter Recommendation

Safety Category Limited human data; animal studies do not indicate significant teratogenicity; not formally classified in India

Preferred Alternatives For Parkinson's disease: levodopa-based regimens have more safety data; For drug-induced EPS: consider reducing/changing causative antipsychotic

When to Use Only if clearly necessary and benefits outweigh risks; avoid in first trimester if possible

Monitoring Maternal: monitor for anticholinergic toxicity, adequate hydration, constipation; Fetal: standard anomaly screening, growth monitoring

Parameter Recommendation

Breastfeeding Compatibility Use with caution; likely excreted in breast milk (data limited)

Drug Levels in Milk Unknown; expected to be low-moderate based on drug characteristics

Preferred Alternatives If anticholinergic essential, consider procyclidine (similar safety profile); reduce/stop causative antipsychotic if possible

Infant Monitoring Monitor for feeding difficulties, sedation, constipation, irritability, decreased urine output (anticholinergic effects)

Parameter Recommendation

Starting dose 0.5–1 mg once daily (significantly lower than younger adults)

Titration Very slow titration; increase by 0.5–1 mg every 7–10 days

Maximum dose 6–10 mg/day (lower than standard adult maximum; often 6 mg/day sufficient)

Additional Risks Anticholinergic toxicity (confusion, delirium, cognitive impairment, hallucinations); falls risk (dizziness, ataxia); constipation and faecal impaction; urinary retention; hyperthermia in hot weather; paradoxical agitation

Recommendation Avoid in elderly patients (>65 years) with baseline cognitive impairment; use alternative strategies when possible (reduce antipsychotic dose, switch to atypical antipsychotic); if essential, use lowest effective dose with close cognitive monitoring

Note: Trihexyphenidyl is included in Beers Criteria as potentially inappropriate for elderly due to high anticholinergic burden.

Interacting Drug Mechanism/Effect Management

Other anticholinergics (procyclidine, benztropine, orphenadrine, antihistamines with anticholinergic activity, oxybutynin) Additive anticholinergic toxicity (confusion, urinary retention, hyperthermia, paralytic ileus, delirium) Avoid concomitant use of multiple anticholinergics; if essential, use lowest doses and monitor closely

Antipsychotics (haloperidol, chlorpromazine, risperidone) May suppress EPS but masks early symptoms of tardive dyskinesia; chronic use may worsen TD outcome Use anticholinergic only when clearly indicated for EPS; regularly reassess need every 3–6 months; do not use prophylactically with atypical antipsychotics

Potassium chloride (solid oral formulations) Anticholinergic-induced reduced GI motility increases risk of potassium-induced GI ulceration and obstruction Avoid solid oral potassium preparations; use liquid formulations if potassium supplementation needed

MAO inhibitors Enhanced anticholinergic effects Avoid combination or use with extreme caution

Interacting Drug Effect Management

Levodopa Additive antiparkinsonian effect; may improve tremor control; however, may potentiate dyskinesias and psychiatric adverse effects Monitor for dyskinesias; titrate carefully; useful combination for tremor-predominant PD

Tricyclic antidepressants (amitriptyline, imipramine, nortriptyline) Additive anticholinergic effects (dry mouth, constipation, urinary retention, confusion) Use with caution; monitor for enhanced anticholinergic adverse effects; avoid in elderly

Amantadine Additive anticholinergic effects; increased risk of confusion and psychosis, especially in elderly Monitor CNS effects; avoid combination in elderly if possible

Sedating antihistamines (diphenhydramine, promethazine, chlorpheniramine) Additive sedation and anticholinergic effects Avoid combination; if unavoidable, use lowest doses

Opioid analgesics Additive constipation, sedation, and urinary retention Monitor bowel function; consider prophylactic laxatives

Clozapine, quetiapine Monitor for worsening psychosis; additive anticholinergic burden Use with caution; monitor mental status closely

Acetylcholinesterase inhibitors (donepezil, rivastigmine) Pharmacological antagonism; reduced efficacy of cholinesterase inhibitor Avoid concurrent use in dementia patients; if essential, use minimal anticholinergic dose

Alcohol Additive CNS depression Advise avoidance or strict moderation

• Dry mouth (very common)

• Blurred vision, mydriasis

• Constipation

• Urinary hesitancy or retention

• Dizziness

• Nausea

• Drowsiness or sedation

• Tachycardia, palpitations

• Nervousness, anxiety

• Memory impairment, difficulty concentrating

• Reduced sweating

Adverse Effect Clinical Significance

Acute angle-closure glaucoma Ophthalmic emergency; presents with severe eye pain, headache, visual disturbance, nausea, halos around lights; requires immediate ophthalmology referral

Anticholinergic psychosis/delirium Especially in elderly or with high doses; presents with confusion, agitation, visual hallucinations, disorientation; discontinue and provide supportive care

Paralytic ileus Severe constipation with abdominal distension; potentially life-threatening; discontinue immediately

Hyperthermia/heat stroke Due to impaired sweating; risk increases in hot environment; may be life-threatening especially in elderly

Urinary retention (acute) May require catheterisation; discontinue drug

Seizures Rare; may lower seizure threshold; more likely at high doses

Dependence and abuse Euphorigenic properties may lead to psychological dependence and misuse; taper gradually when discontinuing

Withdrawal syndrome Anxiety, insomnia, nausea, movement disorder worsening on abrupt discontinuation

Baseline:

• Mental status and cognitive assessment (especially in patients >65 years)

• Intraocular pressure measurement if glaucoma risk factors present

• Prostate symptom assessment in males

• Bowel habit documentation

• Heart rate

• Assessment of indication (is anticholinergic truly necessary?)

After Initiation/Dose Change:

• Mental status assessment (confusion, memory, hallucinations) at 1–2 weeks

• Anticholinergic adverse effects review (dry mouth, constipation, urinary symptoms)

• Heart rate

• Response to treatment (improvement in tremor/EPS)

Long-term:

• Periodic cognitive assessment (especially in elderly) — every 6 months

• Reassessment of continued need every 3–6 months

• Trial drug withdrawal after 3–6 months of stable antipsychotic dosing (for drug-induced EPS)

• Monitor for emergence of tardive dyskinesia (which may be masked)

• Dental health (dry mouth increases caries risk)

• Bowel function

• Pacitane® (Abbott) — 2 mg tablets

• Benzhexol® (Various) — 2 mg, 5 mg tablets

• Trihex® (Intas) — 2 mg tablets

• Parbenz® — 2 mg tablets

• Hexol® — 2 mg tablets

• Parkin® — 2 mg tablets

Fixed-Dose Combinations (use with caution):

Note: Oral solution availability is limited; may need to be sourced from specific suppliers.

• Not included in NLEM 2022

• Not under NPPA price control

• Available in government psychiatric and neurology hospitals

• Price variation between brands and regions

• Tremor-specific efficacy: Trihexyphenidyl primarily targets tremor in Parkinson's disease; it is minimally effective for rigidity and bradykinesia — do not expect improvement in these features

• Age restriction: Best reserved for patients <65 years; avoid in elderly due to high risk of cognitive impairment, delirium, falls, and other anticholinergic toxicity

• EPS vs tardive dyskinesia: Trihexyphenidyl treats drug-induced EPS (parkinsonism, acute dystonia, akathisia) but does NOT treat tardive dyskinesia — may actually worsen TD with chronic use; differentiate carefully before prescribing

• Periodic reassessment: Do not prescribe indefinitely for EPS; attempt trial discontinuation every 3–6 months when antipsychotic dose is stable

• Dystonia dosing: Higher doses are often required for dystonia (up to 20–30 mg/day in adults) compared to EPS/Parkinson's; very slow titration over weeks to months is essential

• Abuse potential: Trihexyphenidyl has euphorigenic properties and potential for misuse; monitor for dose escalation without clinical need and exercise caution in patients with substance use history

trihexyphenidyl; anticholinergic; Parkinson's disease; extrapyramidal symptoms; EPS; drug-induced parkinsonism; dystonia; tremor; movement disorders; elderly-caution; abuse-potential

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• API Textbook of Medicine

• AIIMS Neurology Practice Guidelines

• ICMR Guidelines on Antipsychotic-Induced Side Effects

• IAP Textbook of Paediatrics

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Indian Movement Disorder Society practice recommendations