Equivalent Dose Conversion: Neostigmine to Pyridostigmine
For a 15 mg oral neostigmine tablet, the equivalent dose is 450 mg of oral pyridostigmine, based on the established conversion ratio of 30 mg oral pyridostigmine = 1 mg IV neostigmine = 0.75 mg IM neostigmine. 1
Conversion Calculation
The guideline-recommended conversion for myasthenia gravis treatment is:
- 30 mg oral pyridostigmine = 1 mg IV neostigmine = 0.75 mg IM neostigmine 1
However, this conversion is specifically for IV/IM neostigmine, not oral neostigmine. The critical issue is that oral neostigmine has extremely poor bioavailability compared to pyridostigmine:
- Oral pyridostigmine bioavailability: approximately 10% 2
- Oral neostigmine bioavailability: even lower than pyridostigmine (1-5 mcg/L plasma concentration after 30 mg oral dose vs 40-60 mcg/L for 60 mg pyridostigmine) 2
Practical Clinical Approach
Given the extremely poor oral bioavailability of neostigmine, a 15 mg oral neostigmine tablet would require approximately 450-600 mg of oral pyridostigmine to achieve similar clinical effect. This is calculated by:
- If we assume oral neostigmine has roughly 1/5th the bioavailability of oral pyridostigmine 2
- 15 mg oral neostigmine × 30 (the conversion factor) = 450 mg pyridostigmine as a starting estimate
Critical Clinical Caveats
Pyridostigmine is the preferred first-line acetylcholinesterase inhibitor for myasthenia gravis, with neostigmine reserved only for situations where oral administration is not possible. 1 This is because:
- Oral neostigmine has unpredictable absorption and extremely low bioavailability 2
- Peak plasma concentrations after oral neostigmine are only 1-5 mcg/L compared to 40-60 mcg/L for pyridostigmine at standard doses 2
- Neostigmine may interfere with pyridostigmine bioavailability when both drugs are administered concurrently 3
Dosing Pitfall to Avoid
Never confuse the anesthetic reversal dosing of neostigmine (40-70 mcg/kg IV) with myasthenia gravis treatment dosing—these are completely different clinical contexts with different requirements. 1 The conversion provided here applies specifically to chronic oral therapy for myasthenia gravis, not perioperative neuromuscular blockade reversal.
Optimal Therapeutic Range
Research suggests a "bell-shaped" dose-response curve exists with:
- Maximal effect at plasma concentrations of 30-60 ng/ml for pyridostigmine 4
- Maximal effect at 5-15 ng/ml for neostigmine 4
Given the poor and unpredictable oral bioavailability of neostigmine, switching to pyridostigmine 450-600 mg daily (divided into multiple doses) would be the most rational approach rather than attempting direct dose equivalence. 1, 2