Schedule H

Oral, Intramuscular, Intravenous

• Tablets: 60 mg (as pyridostigmine bromide)

• Sustained-release tablets: 180 mg

• Injection: 1 mg/mL (2 mL ampoule), 5 mg/mL (1 mL ampoule) — as pyridostigmine bromide

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Myasthenia Gravis (Symptomatic Treatment)

Oral Therapy:

Parameter Adult Dosing

Starting dose 60 mg orally TID (total 180 mg/day)

Titration Increase by 60 mg/day every 48–72 hours based on clinical response and tolerability

Usual maintenance dose 60–120 mg orally every 4–6 hours (total 300–600 mg/day in divided doses)

Maximum dose 720 mg/day (rarely exceeded; higher doses increase cholinergic toxicity risk)

Sustained-Release Formulation:

Parameter Dosing

Starting dose 180 mg orally once daily at bedtime

Titration May increase to 180 mg twice daily based on response

Usual maintenance dose 180–360 mg/day

Maximum dose 540 mg/day

Clinical Notes:

• Sustained-release tablets are useful for nocturnal and early morning symptoms

• Do not crush or chew sustained-release formulation

• Not suitable for myasthenic crisis management

• Individualise dosing based on muscle strength assessment

Parenteral Therapy (when oral administration not feasible):

Parameter Dosing

Starting dose 2 mg IM or slow IV

Titration Repeat every 2–3 hours based on clinical response

Usual maintenance dose 2–5 mg IM/IV every 2–4 hours

Maximum dose 30 mg/day parenterally

Clinical Notes:

• Parenteral dose is approximately 1/30th of oral dose due to increased bioavailability

• IV administration must be slow (over 1–2 minutes) with cardiac monitoring

• Reserve for NPO patients, perioperative period, or crisis situations

• Transition to oral therapy as soon as feasible

1. Reversal of Non-depolarising Neuromuscular Blockade

Parameter Dosing

Starting dose 0.1–0.25 mg/kg IV (usual: 10–20 mg)

Titration Not applicable (single dose)

Usual maintenance dose Not applicable

Maximum dose 0.25 mg/kg or 20 mg

Anticholinergic Co-administration (mandatory):

• Atropine: 0.6–1.2 mg IV (given before or with pyridostigmine), OR

• Glycopyrrolate: 0.2–0.4 mg IV

Clinical Notes:

• Administer only after evidence of spontaneous recovery (TOF twitch response present)

• Neostigmine is generally preferred for reversal in Indian practice due to faster onset

• Pyridostigmine has slower onset (10–15 minutes) but longer duration

• Monitor for at least 60 minutes post-administration

Secondary Indications — Adults (Off-label)

Indication Dose Duration Evidence Basis Notes

Orthostatic hypotension / Neurogenic hypotension 30–60 mg orally BID–TID Chronic; individualised Specialist practice; supportive clinical studies OFF-LABEL; Specialist (neurologist/cardiologist) supervision required; often combined with fludrocortisone or midodrine

Postural orthostatic tachycardia syndrome (POTS) 30 mg orally BID–TID, titrate up to 60 mg TID Chronic Limited evidence; specialist practice OFF-LABEL; Specialist only; monitor heart rate response

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Juvenile Myasthenia Gravis

Neonates (transient neonatal MG) 1–2 mg/kg/day orally in 4–6 divided doses Titrate based on feeding ability and respiratory effort 1–2 mg/kg/day 5 mg/kg/day

Infants–5 years 1 mg/kg/dose orally every 4–6 hours Increase by 0.5 mg/kg/dose every 2–3 days 1–2 mg/kg/dose every 4–6 hours 7 mg/kg/day

6–12 years 15–30 mg orally every 4–6 hours Increase by 15 mg/dose every 48–72 hours 30–60 mg every 4–6 hours 7 mg/kg/day or 360 mg/day

12 years Adult dosing protocol As per adult titration As per adult maintenance As per adult maximum

Parenteral Dosing:

All paediatric ages 0.05–0.15 mg/kg/dose IM or slow IV every 4–6 hours

Clinical Notes:

• Mandatory paediatric neurologist supervision

• Neonatal myasthenia is usually transient (2–4 weeks); taper as clinically indicated

• Monitor for cholinergic symptoms: excessive salivation, diarrhoea, bradycardia, muscle fasciculations

• Respiratory monitoring essential, especially in neonates and infants

• Dose requirements may vary significantly between patients

1. Reversal of Non-depolarising Neuromuscular Blockade

Parameter Paediatric Dosing

Starting dose 0.1–0.25 mg/kg IV

Titration Not applicable

Usual maintenance dose Not applicable

Maximum dose 0.25 mg/kg

Anticholinergic Co-administration:

• Atropine: 0.02 mg/kg IV, OR

• Glycopyrrolate: 0.01 mg/kg IV

Clinical Notes:

• Paediatric anaesthesiologist supervision mandatory

• Neostigmine generally preferred for paediatric reversal

Secondary Indications — Paediatrics (Off-label)

Indication Notes

Orthostatic hypotension / POTS NOT RECOMMENDED in children; insufficient safety and efficacy data

Age Restriction Statement:

• Use in neonates only for confirmed transient neonatal myasthenia under paediatric neurology supervision

• Not recommended below 1 year of age for any indication other than neonatal MG, except under strict specialist guidance

60 mL/min/1.73m² No adjustment required

30–60 mL/min/1.73m² Reduce dose by 25%; monitor for accumulation

15–29 mL/min/1.73m² Reduce dose by 50%; extend dosing intervals; close monitoring

<15 mL/min/1.73m² Use with extreme caution; start with 25% of normal dose; specialist supervision

Haemodialysis Not significantly dialysed; dose after dialysis session; start with 30 mg once or twice daily

Peritoneal dialysis Limited data; use lowest effective dose with close monitoring

Clinical Note:

• Pyridostigmine and its metabolites are primarily renally excreted

• Monitor closely for signs of cholinergic excess in renal impairment

• Mechanical gastrointestinal obstruction

• Mechanical urinary tract obstruction

• Peritonitis

• Known hypersensitivity to pyridostigmine or bromide salts

• Concurrent use with depolarising neuromuscular blockers (e.g., suxamethonium) unless block has fully dissipated

• Bronchial asthma or COPD (risk of bronchospasm and increased secretions)

• Bradyarrhythmias or heart block

• Recent myocardial infarction

• Peptic ulcer disease (increased gastric acid secretion)

• Epilepsy

• Parkinsonism

• Hyperthyroidism

• Vagotonia

• Concurrent beta-blocker or digoxin therapy

• Renal impairment (reduced elimination)

• Elderly patients (increased sensitivity)

• Risk of cholinergic crisis with overdosage — requires clinical differentiation from myasthenic crisis

Parameter Recommendation

Risk category Generally considered safe; extensive clinical experience in pregnant MG patients

Preferred alternatives Pyridostigmine is the preferred anticholinesterase during pregnancy

When may be used Throughout pregnancy when indicated for MG; benefit clearly outweighs risk

Monitoring Use minimum effective dose; fetal heart rate monitoring in third trimester; observe neonate for transient myasthenia, hypotonia, or respiratory difficulty; IV route only if essential

Parameter Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Low (poor oral bioavailability limits infant systemic exposure)

Preferred alternatives Pyridostigmine is acceptable; no need to discontinue breastfeeding

Infant monitoring Observe for excessive salivation, loose stools, feeding difficulties, irritability (all unlikely at therapeutic maternal doses)

Parameter Recommendation

Starting dose 30 mg orally BID or TID

Titration Slower titration with longer intervals (every 72–96 hours)

Special risks Increased sensitivity to cholinergic effects; higher risk of bradycardia, hypotension, syncope, falls; often have reduced renal function; GI side effects more pronounced

Monitoring Assess renal function before dosing; heart rate monitoring; watch for signs of accumulation

Interacting Drug Effect Recommendation

Depolarising muscle relaxants (suxamethonium) Prolongs Phase I block Avoid concurrent use; ensure complete dissipation of suxamethonium effect

Beta-blockers (propranolol, metoprolol) Additive bradycardia and hypotension Avoid combination if possible; if essential, continuous ECG monitoring required

Quinidine Antagonises pyridostigmine effect; may worsen MG Avoid if possible

Aminoglycoside antibiotics (gentamicin, amikacin) Impair neuromuscular transmission; may precipitate MG crisis Avoid in MG patients; if unavoidable, close respiratory monitoring

Anticholinergics (atropine, glycopyrrolate) Block muscarinic effects Required for reversal use; may reduce GI side effects in MG therapy (use judiciously)

Interacting Drug Effect Recommendation

Corticosteroids Initial transient worsening of MG (first 1–2 weeks) when starting steroids Monitor closely; initiate steroids cautiously; may need temporary pyridostigmine dose increase

Magnesium sulphate Potentiates neuromuscular blockade Use with caution; avoid high-dose magnesium in MG patients

Other cholinesterase inhibitors (neostigmine, donepezil) Additive cholinergic toxicity Avoid concurrent use; if switching agents, allow washout period

Clindamycin, Polymyxins, Tetracyclines May impair neuromuscular transmission Monitor muscle strength; avoid if possible in MG

Lithium May impair neuromuscular transmission Monitor muscle strength if concurrent use necessary

Procainamide May worsen MG Avoid in MG patients

• Nausea and vomiting

• Abdominal cramps

• Diarrhoea

• Increased salivation

• Sweating

• Lacrimation

• Miosis

• Muscle fasciculations and cramps

• Urinary frequency

• Bradycardia (mild)

• Increased bronchial secretions

Adverse Effect Clinical Action

Cholinergic crisis (worsening muscle weakness, excessive secretions, respiratory failure, bradycardia, hypotension) Discontinue immediately; IV atropine 1–2 mg; ventilatory support; ICU admission; differentiate from myasthenic crisis

Severe bradycardia / Heart block Discontinue; IV atropine; cardiac monitoring

Bronchospasm Discontinue; bronchodilators; atropine if needed

Seizures (rare, with overdose) Discontinue; standard seizure management

Hypersensitivity reactions (bromism with chronic use) Discontinue; supportive care

Phase Parameters

Baseline Muscle strength assessment (quantitative MG score); respiratory function (FVC, NIF); heart rate and ECG if cardiovascular risk factors; renal function

During titration Daily assessment of muscle strength; monitor for signs of under-dosing (ptosis, diplopia, dysphagia, weakness) vs over-dosing (fasciculations, excessive secretions, diarrhoea, cramps)

Long-term (chronic therapy) Periodic FVC and respiratory assessment; muscle strength scoring; renal function (every 6–12 months); weight monitoring; symptom diary review

During crisis or dose changes Frequent clinical assessment; differentiate myasthenic from cholinergic crisis; respiratory monitoring

Brand name Manufacturer Formulation

Mestinon Bausch Health (Valeant) Tablets 60 mg

Distinon Astra Zeneca Tablets 60 mg

Pyrimine Sun Pharma Tablets 60 mg

Myestin Cadila Tablets 60 mg

Gravitor Torrent Tablets 60 mg

Regaste Generic Tablets 60 mg

Generic Various Tablets 60 mg; Injection

Notes:

• Sustained release 180 mg tablets may have limited availability; often need to be sourced from specific distributors

• No fixed-dose combinations available

• Not under NPPA price ceiling as of current NLEM

• Available in both government and private sector

• Prices vary significantly by brand and region

1. Differentiate myasthenic from cholinergic crisis — Worsening weakness may indicate either under-dosing (myasthenic crisis) or over-dosing (cholinergic crisis); look for muscarinic signs (SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis) to identify cholinergic crisis; edrophonium test may help differentiate in supervised settings.

1. Pyridostigmine preferred over neostigmine for chronic MG — Longer duration of action (3–6 hours vs 2–3 hours), fewer GI side effects, and more stable symptom control make pyridostigmine the first-line oral anticholinesterase.

1. Sustained-release formulation for nocturnal symptoms — Use 180 mg SR at bedtime to prevent morning weakness and difficulty swallowing medications; not for acute symptom control.

1. Avoid abrupt withdrawal — May precipitate myasthenic crisis; always taper slowly if discontinuation needed.

1. Aminoglycosides are dangerous in MG — These antibiotics impair neuromuscular transmission and can precipitate crisis; use alternative antibiotics whenever possible.

1. Parenteral dosing is not equivalent to oral — Parenteral dose is approximately 1/30th of oral dose; careful conversion required when switching routes.

pyridostigmine; myasthenia gravis; cholinesterase inhibitor; anticholinesterase; neurology; neuromuscular junction; pregnancy-safe; lactation-compatible; renal-caution; specialist-drug; NLEM India

RxIndia v1.0 — 01 Feb 2026

• CDSCO product inserts and approval database

• Indian Pharmacopoeia / NFI

• NLEM India 2022

• API Textbook of Medicine, 11th Edition — Myasthenia Gravis chapter

• AIIMS Neurology Department protocols

• IAP Guidelines — Paediatric neuromuscular disorders

• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th Edition

• Harrison's Principles of Internal Medicine — Myasthenia Gravis

• PGIMER and CMC Vellore hospital formularies

• Indian Academy of Neurology practice recommendations