Is it safe to switch from 360mg of pyridostigmine (Mestinon) to 60mg of neostigmine (Prostigmin) orally?

Safety of Switching from Oral Pyridostigmine to Oral Neostigmine

This switch is not recommended and potentially unsafe due to lack of established oral neostigmine dosing equivalencies, significant pharmacokinetic differences, and potential drug interactions that could compromise myasthenia gravis control. 1, 2

Critical Problems with This Proposed Switch

Lack of Oral Neostigmine Formulation

• Neostigmine is not routinely available or approved as an oral tablet formulation for chronic myasthenia gravis management 3
• The standard formulation is neostigmine bromide for injection, not oral tablets 4
• When oral administration is needed in palliative care, neostigmine has been used subcutaneously as a continuous infusion rather than as oral tablets 3

Pharmacokinetic Incompatibility

• The conversion ratio you're proposing (360mg pyridostigmine to 60mg neostigmine orally) has no established evidence base 1, 2
• Plasma concentration studies show maximal therapeutic effect occurs at 30-60 ng/ml for pyridostigmine versus 5-15 ng/ml for neostigmine, suggesting approximately 6-fold difference in potency at the receptor level 2
• However, this does not translate to a simple 6:1 oral dosing ratio due to different bioavailability profiles 1, 2

Drug Interaction Concerns

• Neostigmine may interfere with pyridostigmine bioavailability when both drugs are administered, though the mechanism for oral neostigmine specifically is unclear 1
• In myasthenic patients receiving both drugs orally, the expected relationship between dose and plasma concentration (AUC) was lost, suggesting unpredictable pharmacokinetics 1

Established Conversion Guidelines (IV Context Only)

The only established conversion is for intravenous/intramuscular administration in anesthesia settings:

• 30 mg oral pyridostigmine corresponds to 1 mg IV neostigmine or 0.75 mg IM neostigmine 4
• This 30:1 ratio applies only to parenteral neostigmine, not oral formulations 4

Clinical Management Recommendations

If Oral Administration is Compromised

• Continue pyridostigmine via nasogastric tube if enteral access is available 3
• Consider neostigmine as a continuous subcutaneous infusion (not oral tablets) if enteral route is impossible 3
• Typical subcutaneous neostigmine dosing requires careful titration under specialist supervision 3

If Switching is Absolutely Necessary

• This must be done under direct neurologist supervision with frequent clinical monitoring 4
• Start with conservative dosing and titrate based on clinical response, not theoretical conversions 2
• Monitor for cholinergic side effects (increased salivation, lacrimation, diarrhea, urinary urgency, sweating, bradycardia) which are common with both agents 4, 5
• Assess for myasthenic crisis indicators: respiratory muscle weakness, bulbar symptoms, dysphagia 4

Monitoring Parameters

• Pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) 4
• Clinical assessment of muscle strength, particularly bulbar and respiratory muscles 4
• Watch for paradoxical worsening, as inadequate dosing can precipitate myasthenic crisis 4, 3

Why Pyridostigmine Remains Standard

• Pyridostigmine is the most commonly used and evidence-based oral anticholinesterase for chronic myasthenia gravis management 5
• Standard dosing is well-established: starting at 30 mg PO three times daily, gradually increasing to maximum 120 mg four times daily 4
• In orthostatic hypotension (another indication), pyridostigmine 30-60 mg three times daily is preferred because it causes less supine hypertension than other sympathomimetics 4

Critical Pitfall to Avoid

Abrupt withdrawal or inadequate replacement of anticholinesterase therapy can trigger myasthenic crisis, which may be mistaken for disease progression or other acute deterioration 3. Any medication change must ensure continuous adequate cholinergic support.