Neostigmine Methylsulfate and Succinylcholine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Neostigmine Methylsulfate
Succinylcholine
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased neuromuscular blockade
Interaction Deep Dive
A number of case reports have demonstrated prolonged neuromuscular blockade from succinylcholine with anticholinesterases (neostigmine, physostigmine, edrophonium, and pyridostigmine). These drugs are more likely to prolong the desensitizing blockade in patients with partial pseudocholinesterase deficiency, or patients receiving succinylcholine infusions or frequent succinylcholine boluses728.
Why it happens (mechanism)
Decreased succinylcholine metabolism
Literature reports
4 reports — tap to read
a) Neostigmine can inhibit plasma cholinesterase activity, with the degree of inhibition dependent upon the dose. In normal patients, administration of neostigmine within 1.5 hours of succinylcholine 1 to 1.5 milligrams/kilogram can prolong the duration of neuromuscular blockage to 35 to 180 minutes 1. Prolonged apnea was also reported in patients heterozygous for atypical plasma cholinesterase when they were administered physostigmine and succinylcholine 2. Prolonged neuromuscular blockade lasting up to six hours was noted in chronic renal failure patients who were administered succinylcholine and pyridostigmine 3.
b) The mean duration of effect of a bolus of succinylcholine was prolonged about two-fold by pyridostigmine and neostigmine, but not edrophonium. Plasma cholinesterase activities were reduced in those receiving these drugs. However, the changes in duration of action did not correlate with changes in cholinesterase activity. These data suggest that other mechanisms in addition to cholinesterase inhibition may contribute to this drug interaction 4.
c) Administration of pyridostigmine two hours after a patient had received succinylcholine was reported to result in prolonged succinylcholine-induced paralysis. An 82 year-old male with no evidence of hepatic disease or pseudocholinesterase activity received a total dose of pyridostigmine 30 mg over 15 minutes which resulted in prolongation (3 hours) of succinylcholine-induced paralysis. The patient subsequently recovered with no recurrence of muscle weakness and the effects were attributed to residual anticholinesterase effects of pyridostigmine 5.
d) A 29 year-old white male ingested an estimated 6 grams of amitriptyline. The patient received physostigmine 0.4 mg intravenously and later received 100 mg of succinylcholine to facilitate intubation prior to gastric lavage. The patient required ventilatory assistance for 45 minutes following the succinylcholine administration 6.
Common questions
Can I take Neostigmine Methylsulfate and Succinylcholine together?
Increased neuromuscular blockade Always confirm with your pharmacist or prescriber before making any change.
How serious is the Neostigmine Methylsulfate and Succinylcholine interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Neostigmine Methylsulfate or Succinylcholine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (8)
- Viby-Mogensen J: Interaction of other drugs with muscle relaxants. Semin Anesth 1985; 4:52-64.
- Kopman AF, Strachovsky G, & Lichtenstein L: Prolonged response to succinylcholine following physostigmine. Anesthesiology 1978; 49:142-143. PubMed
- Bishop MJ & Hornbein TF: Prolonged effect of succinylcholine after neostigmine and pyridostigmine administration in patients with renal failure. Anesthesiology 1983; 58:384-386. DOI
- Fleming NW, Macres S, Antognini JF, et al: Neuromuscular blocking action of suxamethonium after antagonism of vecuronium by edrophonium, pyridostigmine or neostigmine. Br J Anaesth 1996; 77:492-495. PubMed
- Bentz EW & Stoelting RK: Prolonged response to succinylcholine following pancuronium reversal with pyridostigmine. Anesthesiology 1976; 44:258-260. DOI
- Manoguerra AS & Steiner RW: Prolonged neuromuscular blockade after administration of physostigmine and succinylcholine. Clin Toxicol 1981; 18:803-805. PubMed
- Sunew KY & Hicks RG: Effects of neostigmine and pyridostigmine on duration of succinylcholine action and pseudocholinesterase activity. Anesthesiology 1978; 49:188-191. PubMed
- Baraka A: Suxamethonium-neostigmine interaction in patients with normal or atypical cholinesterase. Br J Anaesth 1977; 49:479-484. DOI
Keep reading about Neostigmine Methylsulfate
Keep reading about Succinylcholine
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