Schedule H

Oral, Intramuscular (IM)

• Tablets: 2.5 mg, 5 mg

• Injection: 5 mg/mL ampoule (for IM use)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

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

Used for treatment and prophylaxis of extrapyramidal symptoms induced by antipsychotic medications (typical antipsychotics such as haloperidol, chlorpromazine).

Parameter Recommendation

Starting dose 2.5 mg three times daily

Titration Increase by 2.5 mg/day every 2–3 days based on symptom response and tolerability

Usual maintenance dose 7.5–15 mg/day in 3 divided doses

Maximum dose 20 mg/day (in divided doses)

Clinical Notes:

• Oral route preferred for maintenance therapy

• May be administered with food to reduce gastrointestinal upset

• Adjust dose according to symptom severity and anticholinergic tolerability

• Review need for continued therapy regularly; consider trial withdrawal after 3–6 months of stable antipsychotic dosing

1. Acute Dystonic Reactions (including Oculogyric Crisis)

Emergency treatment of acute dystonic reactions caused by antipsychotic medications or antiemetics (metoclopramide).

Intramuscular Route:

Parameter Recommendation

Starting dose 5–10 mg IM as single dose

Titration May repeat 5 mg IM after 20–30 minutes if response incomplete

Usual maintenance dose Convert to oral maintenance if recurrence likely (2.5–5 mg TID)

Maximum dose 20 mg in first hour (acute situation)

Clinical Notes:

• Relief typically occurs within 15–30 minutes of IM injection

• Always identify and address causative agent

• Consider prophylactic oral anticholinergic if continuing antipsychotic known to cause EPS

• IV route is NOT recommended for procyclidine

1. Idiopathic Parkinson's Disease (Adjunctive Therapy)

Used as adjunct in Parkinson's disease, primarily for tremor-predominant disease in younger patients. Not first-line therapy.

Parameter Recommendation

Starting dose 2.5 mg three times daily

Titration Increase by 2.5 mg every 3–4 days as tolerated

Usual maintenance dose 7.5–15 mg/day in 3 divided doses

Maximum dose 20 mg/day

Clinical Notes:

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

• Consider in younger patients (<65 years) with tremor-predominant disease

• Avoid in elderly patients due to cognitive adverse effects

• Not recommended as monotherapy except in very mild early disease

Secondary Indications — Adults (Off-label)

Not applicable — No established off-label indications documented in standard Indian practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Drug-Induced Acute Dystonic Reactions

Use under paediatric psychiatry or neurology supervision only.

Acute Dystonia — Intramuscular Route (Age ≥5 years):

Parameter Recommendation

Starting dose 0.05–0.1 mg/kg IM (maximum 5 mg per dose)

Titration May repeat once after 20–30 minutes if incomplete response

Usual maintenance dose Not applicable for single acute episode

Maximum dose 5 mg per dose; 10 mg total in acute setting

Maintenance Therapy (if recurrent EPS):

Age Starting Dose Titration Usual Maintenance Maximum Dose

5–12 years 1.25–2.5 mg twice daily Increase by 1.25 mg every 3–4 days 0.04–0.08 mg/kg/day in 2–3 divided doses 10 mg/day

12 years 2.5 mg twice daily As per adult protocol 5–10 mg/day in 2–3 divided doses 15 mg/day

Clinical Notes:

• Oral maintenance rarely required in children; assess need for continued antipsychotic

• Monitor for anticholinergic side effects (dry mouth, blurred vision, constipation, urinary retention)

• Monitor for behavioural changes and cognitive effects

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

Safety Monitoring:

• Vital signs (heart rate, temperature)

• Hydration status

• Cognitive and behavioural assessment

• Bowel and bladder function

Secondary Indications — Paediatrics (Off-label)

Not applicable — No established off-label paediatric indications.

• Known hypersensitivity to procyclidine or any excipient

• Untreated narrow-angle (angle-closure) glaucoma

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

• Myasthenia gravis

• Paralytic ileus or gastrointestinal obstruction

• Toxic megacolon

• Elderly patients — increased sensitivity to anticholinergic effects including confusion, cognitive impairment, falls, constipation, and urinary retention

• Cardiovascular disease — may cause tachycardia; use with caution in arrhythmias

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

• History of seizure disorder — may lower seizure threshold

• Psychiatric disorders — may worsen psychosis, cause hallucinations, or precipitate delirium, especially in elderly

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

• Cognitive impairment or dementia — may worsen confusion

• Gastrointestinal motility disorders — may worsen constipation

• Treated narrow-angle glaucoma — monitor intraocular pressure

• Abrupt discontinuation after prolonged use — may precipitate withdrawal symptoms or worsening of parkinsonism

• Tardive dyskinesia — anticholinergics may mask symptoms initially but may worsen long-term outcome

Parameter Recommendation

Safety Category Limited human data; animal studies do not indicate direct 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; Fetal: standard anomaly screening, growth monitoring

Parameter Recommendation

Breastfeeding Compatibility Use with caution; excretion in human milk unknown but expected (low-moderate based on drug characteristics)

Drug Levels in Milk Unknown; probably low

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

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

Parameter Recommendation

Starting dose 1.25 mg twice daily (significantly lower than younger adults)

Titration Very slow titration; increase by 1.25 mg every 5–7 days

Maximum dose 10 mg/day (lower than standard adult maximum)

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

Recommendation Avoid in elderly if possible; use alternative strategies (reduce antipsychotic dose, switch to atypical antipsychotic with lower EPS risk); if essential, use lowest effective dose with close monitoring

Interacting Drug Mechanism/Effect Management

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

Antipsychotics (haloperidol, chlorpromazine, risperidone) May mask early symptoms of tardive dyskinesia; anticholinergics may reduce antipsychotic efficacy in some cases Use anticholinergic only when clearly indicated for EPS; regularly reassess need; do not use prophylactically with atypical antipsychotics

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

Interacting Drug Effect Management

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

Tricyclic antidepressants (amitriptyline, imipramine) Additive anticholinergic effects Use with caution; monitor for enhanced anticholinergic adverse effects

Amantadine Additive anticholinergic effects Monitor for increased CNS effects and anticholinergic toxicity

Levodopa May have additive antiparkinsonian effect; may also worsen psychiatric symptoms Monitor for dyskinesias and psychiatric adverse effects

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

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

Alcohol Additive CNS depression Advise avoidance or strict moderation

• Dry mouth (very common)

• Blurred vision, mydriasis

• Constipation

• Urinary hesitancy or retention

• Dizziness

• Drowsiness or mild sedation

• Tachycardia, palpitations

• Nausea

• Nervousness, anxiety

• Memory impairment

• Reduced sweating

Adverse Effect Clinical Significance

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

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

Paralytic ileus Severe constipation with abdominal distension; discontinue immediately

Hyperthermia Due to impaired sweating; risk increases in hot environment or with fever; may be life-threatening

Urinary retention (acute) May require catheterisation; discontinue drug

Seizures Rare; may lower seizure threshold

Dependence and withdrawal Chronic use may lead to psychological dependence; abrupt discontinuation may cause withdrawal symptoms (anxiety, insomnia, movement disorder worsening)

Baseline:

• Mental status and cognitive assessment (especially elderly)

• Intraocular pressure assessment if glaucoma risk

• Prostate symptoms assessment in males

• Bowel habit documentation

• Heart rate

• Assessment of indication (is anticholinergic truly necessary?)

After Initiation/Dose Change:

• Monitor for anticholinergic adverse effects within 1–2 weeks

• Mental status assessment (confusion, memory)

• Heart rate

• Bowel and bladder function

• Response to treatment (improvement in EPS/parkinsonism symptoms)

Long-term:

• Periodic cognitive assessment (especially in elderly)

• 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 by anticholinergic)

• Dental health (dry mouth increases caries risk)

• Kemadrin® (Abbott) — 5 mg tablets; 5 mg/mL injection

• Pacitane® (Abbott) — 2.5 mg, 5 mg tablets

• Procyclidine (generic formulations)

Note: Availability may vary by region; injection formulation may have limited availability outside tertiary care settings.

• Not included in NLEM 2022

• Not under NPPA price control

• Available in government psychiatric hospitals

• Price variation between brands and regions

• Avoid routine prophylaxis: Do not prescribe procyclidine prophylactically with all antipsychotics; use only when EPS develops or when using high-potency typical antipsychotics in high-risk patients

• Prefer atypical antipsychotics: When possible, use atypical antipsychotics (risperidone at lower doses, olanzapine, quetiapine) which have lower EPS risk, reducing need for anticholinergics

• Elderly caution: Procyclidine is poorly tolerated in elderly patients; anticholinergic burden leads to cognitive decline, falls, and delirium; consider antipsychotic dose reduction or switch as alternative

• Regular review: Reassess need for anticholinergic every 3–6 months; many patients can discontinue after initial antipsychotic stabilisation

• Acute dystonia response: IM procyclidine provides rapid relief of acute dystonic reactions; always identify and address causative medication

• Tardive dyskinesia awareness: Anticholinergics may mask early tardive dyskinesia and potentially worsen long-term outcome; do not use to treat TD

procyclidine; anticholinergic; extrapyramidal symptoms; EPS; drug-induced parkinsonism; acute dystonia; antipsychotic side effects; psychiatry; movement disorders; elderly-caution

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• API Textbook of Medicine

• AIIMS Drug Formulary

• AIIMS Psychiatry and Neurology Protocols

• ICMR Schizophrenia Management Guidelines

• IAP Drug Formulary (paediatric dosing reference)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine