Schedule H

Oral

• Tablets: 5 mg (as distigmine bromide)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Neurogenic Bladder / Detrusor Underactivity (Atonic/Hypotonic Bladder)

Indications include:

• Post-spinal cord injury with flaccid bladder

• Diabetic autonomic neuropathy with bladder atony

• Post-operative urinary retention (non-obstructive)

• Cauda equina syndrome with bladder involvement

Parameter Adult Dosing

Starting dose 5 mg orally once daily (preferably in the morning, 30 minutes before breakfast)

Titration Assess response after 1–2 weeks; dose increase rarely required

Usual maintenance dose 5 mg orally once daily

Maximum dose 10 mg/day (in divided doses); rarely exceeded due to cumulative cholinergic toxicity risk

Clinical Notes:

• Confirm detrusor underactivity with urodynamic studies before initiation

• Measure post-void residual volume at baseline; drug indicated only if significant residual (>100 mL)

• Not indicated for overactive bladder or obstructive uropathy

• Very long half-life (~70 hours) — effects and side effects may be delayed and cumulative

• Assess response after 2–4 weeks; discontinue if ineffective

1. Postoperative Intestinal Atony / Paralytic Ileus (Short-term Use)

Parameter Adult Dosing

Starting dose 5 mg orally once daily

Titration Not applicable for short-term use

Usual maintenance dose 5 mg orally once daily for 3–5 days

Maximum dose 5 mg/day

Clinical Notes:

• Use only after mechanical obstruction is definitively excluded

• Short-term use only (typically 3–7 days post-operatively)

• Monitor for passage of flatus/stool as response marker

• Discontinue once bowel function returns

Secondary Indications — Adults (Off-label)

Indication Dose Duration Evidence Basis Notes

Myasthenia Gravis 5 mg orally once or twice daily Chronic; individualised Historical case series; largely superseded by pyridostigmine OFF-LABEL; Specialist (neurologist) only; Pyridostigmine strongly preferred in India due to shorter half-life and better titratability

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

• NOT RECOMMENDED in paediatric population

Secondary Indications — Paediatrics (Off-label)

• Not applicable

Age Restriction Statement:

• Not recommended below 18 years of age

• Very long half-life and high sensitivity to cholinergic agents in children increases risk of cholinergic crisis

• No established safety or efficacy data in paediatric population

• If absolutely necessary in adolescents, use only under strict specialist (paediatric urologist/neurologist) supervision in tertiary care setting

60 mL/min/1.73m² No adjustment required

30–60 mL/min/1.73m² Reduce to alternate day dosing (5 mg every 48 hours); monitor closely for cholinergic excess

15–29 mL/min/1.73m² Avoid; if essential, 5 mg every 72 hours under specialist supervision

<15 mL/min/1.73m² Contraindicated; high risk of accumulation and cholinergic crisis

Haemodialysis Avoid; not significantly dialysed; risk of severe accumulation

Clinical Note:

• Distigmine is primarily renally excreted

• Long half-life (~70 hours) increases accumulation risk in renal impairment

• Monitor closely for cholinergic symptoms even with dose reduction

• Mechanical gastrointestinal obstruction

• Mechanical urinary tract obstruction (including bladder outlet obstruction from BPH)

• Peritonitis

• Known hypersensitivity to distigmine bromide or other carbamate derivatives

• History of cholinergic crisis

• Bronchial asthma or COPD with significant bronchospasm

• Severe bradycardia (HR <50 bpm)

• Second or third-degree AV block

• Sick sinus syndrome (without pacemaker)

• Concurrent use with depolarising neuromuscular blockers

• Severe renal impairment (eGFR <15 mL/min/1.73m²)

• Benign prostatic hyperplasia (may worsen obstructive symptoms; ensure no significant BOO before use)

• Epilepsy (cholinergic stimulation may lower seizure threshold)

• Recent bowel or bladder surgery

• Peptic ulcer disease (increased gastric acid secretion)

• Cardiac disease, especially coronary artery disease

• Hyperthyroidism

• Parkinsonism

• Concurrent use with other cholinesterase inhibitors

• Moderate renal impairment

• Elderly patients (increased sensitivity)

• Conditions requiring careful bladder assessment before treatment

Parameter Recommendation

Risk category Limited data; not recommended unless clearly necessary

Preferred alternatives Pyridostigmine (shorter half-life, more safety data); intermittent catheterisation for bladder management

When may be used Only if benefit clearly outweighs risk; specialist input mandatory

Monitoring Monitor uterine activity (cholinergic stimulation may affect uterine tone); fetal heart rate monitoring; observe for maternal cholinergic symptoms

Parameter Recommendation

Compatibility Not well studied; generally avoided during lactation

Drug levels in milk Unknown; presumed low but long half-life is a concern

Preferred alternatives Pyridostigmine (better studied); intermittent catheterisation for bladder management

Infant monitoring If use unavoidable: observe for poor feeding, excessive salivation, diarrhoea, muscle weakness, respiratory difficulty

Parameter Recommendation

Starting dose 2.5 mg once daily (half tablet) or 5 mg every alternate day

Titration Slower escalation; assess response after 2 weeks before any dose increase

Special risks Increased sensitivity to cholinergic effects; higher risk of bradycardia, hypotension, falls, confusion, urinary incontinence; often have reduced renal function

Monitoring Baseline ECG; heart rate monitoring; renal function assessment; close observation for cholinergic excess

Interacting Drug Effect Recommendation

Other cholinesterase inhibitors (neostigmine, pyridostigmine, rivastigmine, donepezil) Additive cholinergic toxicity; high risk of cholinergic crisis Avoid combination absolutely

Depolarising muscle relaxants (suxamethonium) Prolonged paralysis due to enzymatic competition Avoid; allow adequate washout (>1 week) before surgery requiring suxamethonium

Beta-blockers Additive bradycardia; risk of severe bradycardia or heart block Avoid combination if possible; if essential, continuous cardiac monitoring

Anticholinergic agents (oxybutynin, tolterodine, solifenacin) Pharmacological antagonism; negates therapeutic effect Avoid concurrent use; defeats purpose of therapy

Digoxin Additive bradycardia Use with caution; monitor heart rate and ECG

Interacting Drug Effect Recommendation

Aminoglycoside antibiotics May impair neuromuscular transmission; additive weakness Monitor muscle strength; use alternative antibiotics if possible

Corticosteroids May blunt parasympathomimetic response Monitor therapeutic efficacy

Antipsychotics (especially those with anticholinergic effects) May counteract distigmine action Monitor response; may need to reconsider therapy

Magnesium salts May potentiate neuromuscular blockade Use with caution

Procainamide, Quinidine May antagonise cholinergic effects Monitor therapeutic response

• Abdominal cramps

• Nausea

• Diarrhoea

• Increased salivation

• Sweating

• Urinary urgency or incontinence

• Muscle cramps

• Lacrimation

• Miosis

• Bradycardia (mild)

Adverse Effect Clinical Action

Cholinergic crisis (severe bradycardia, bronchospasm, hypotension, excessive secretions, muscle weakness, respiratory failure) Discontinue immediately; IV atropine 1–2 mg (repeat as needed); supportive care; ICU admission; effects may persist for days due to long half-life

Severe bradycardia / AV block Discontinue; IV atropine; cardiac monitoring; consider temporary pacing if severe

Bronchospasm Discontinue; bronchodilators; atropine if needed

Paralytic ileus (if used despite obstruction) Discontinue; surgical consultation

Hypersensitivity reactions Discontinue; supportive care

Important Note:

• Due to the very long half-life (~70 hours), serious adverse effects may persist for several days even after drug discontinuation

• Repeated atropine doses may be needed

Phase Parameters

Baseline ECG (especially if cardiac history); renal function (serum creatinine, eGFR); post-void residual urine volume (bladder scan/USG); urodynamic studies to confirm detrusor underactivity

After initiation (Week 1–2) Watch for signs of cholinergic excess (excessive salivation, sweating, abdominal cramps, bradycardia, diarrhoea); heart rate monitoring

Week 2–4 Assess therapeutic response (voiding pattern, residual volume); if no improvement, consider discontinuation

Long-term Periodic post-void residual measurement; renal function (every 6–12 months); symptom assessment; ECG if on concurrent cardiac medications

Brand Name Manufacturer Formulation

Ubretid Takeda/Sun Pharma Tablets 5 mg

Notes:

• Limited brand availability in India

• May need to source from specific distributors

• No fixed-dose combinations available

• Not listed under NLEM 2022

• Not under NPPA price control

• Availability may be inconsistent; may need advance ordering

• Available primarily in private sector

1. Confirm detrusor underactivity before prescribing — Always perform urodynamic studies or at minimum measure post-void residual; distigmine is contraindicated in overactive bladder or obstructive conditions.

1. Beware the long half-life — Distigmine has an exceptionally long half-life (~70 hours); side effects may appear days after initiation and persist for days after discontinuation. Counsel patients and monitor accordingly.

1. Not first-line for myasthenia gravis — Pyridostigmine is strongly preferred in MG due to shorter half-life allowing better symptom control and easier dose adjustment.

1. Once-daily dosing is usually sufficient — Due to long duration of action, once-daily morning dosing is standard; avoid dose escalation without adequate observation period (at least 1–2 weeks).

1. Atropine is the antidote — For cholinergic crisis, IV atropine is life-saving; multiple doses may be needed due to distigmine's prolonged effect.

1. Reassess at 4 weeks — If no improvement in bladder function after 4 weeks of therapy, discontinue and consider alternative management strategies.

distigmine; neurogenic bladder; detrusor underactivity; cholinesterase inhibitor; long-acting anticholinesterase; urinary retention; atonic bladder; renal-caution; elderly-caution; cholinergic-crisis; urology

RxIndia v1.0 — 01 Feb 2026

• CDSCO product information

• Indian Pharmacopoeia / National Formulary of India

• API Textbook of Medicine — Neurogenic bladder management

• AIIMS Pharmacology and Urology Department protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Indian Urological Association practice recommendations