Neos-R

Approved Indications:

• Reversal of Non-Depolarizing Neuromuscular Blockade
  Used to reverse residual effects of non-depolarizing neuromuscular blocking agents (e.g., rocuronium, vecuronium, pancuronium) at the conclusion of surgery under general anesthesia.
• Myasthenia Gravis (Symptomatic Management)
  Indicated for improving muscle strength in patients with myasthenia gravis through enhanced neuromuscular transmission.
• Postoperative Urinary Retention
  Utilized to promote detrusor muscle contraction in patients with postoperative non-obstructive urinary retention.
• Paralytic Ileus (Non-Obstructive Postoperative Intestinal Atony)
  Employed to stimulate gastrointestinal motility in cases of paralytic ileus following surgery.

Clinically Accepted Off-Label Use:

• Diagnostic Aid in Myasthenia Gravis
  Occasionally used in diagnostic protocols for evaluating suspected cases of myasthenia gravis alongside edrophonium.

Routes:

• Intravenous (IV), Intramuscular (IM), Subcutaneous (SC)

Adults:

• Reversal of Neuromuscular Blockade:
  • 0.03–0.07 mg/kg IV slowly (over ≥1 minute)
  • Administer with atropine (0.6–1.2 mg IV) or glycopyrrolate to offset muscarinic side effects
  • Maximum total dose: 5 mg
• Myasthenia Gravis:
  • 0.5–2.5 mg IM or SC every 2–3 hours as needed
  • Titrate dose to clinical response
• Postoperative Urinary Retention or Paralytic Ileus:
  • 0.25–0.5 mg SC or IM every 4–6 hours
  • Maximum single dose: 2 mg
  • Discontinue if no response after 5 doses

Pediatrics:

• Reversal of Neuromuscular Blockade:
  • 0.025–0.08 mg/kg IV slowly
  • Co-administer atropine 0.02 mg/kg IV
• Myasthenia Gravis:
  • 0.01–0.04 mg/kg SC or IM every 2–4 hours based on response

Elderly:

• Similar adult dosage; monitor closely for bradycardia and hypersensitivity.

Renal Impairment:

• Use cautiously; reduce dose if needed due to reduced clearance.

Hepatic Impairment:

• No specific adjustment required, but monitor for heightened cholinergic effects.

Neostigmine Methylsulfate is a reversible inhibitor of acetylcholinesterase, the enzyme responsible for hydrolyzing acetylcholine at neuromuscular junctions. By inhibiting this enzyme, it increases acetylcholine concentration at nicotinic and muscarinic receptors. This facilitates transmission of nerve impulses across neuromuscular junctions, improving skeletal muscle contractility in conditions like myasthenia gravis and reversing the muscle paralysis induced by non-depolarizing neuromuscular blockers. Its peripheral cholinergic effects also enhance smooth muscle activity in the gastrointestinal and urinary tracts.

• Absorption:
  Poor oral absorption; well absorbed via parenteral routes (IV, IM, SC).
• Distribution:
  • Volume of distribution: ~0.2–1.4 L/kg
  • Does not cross the blood-brain barrier (quaternary ammonium compound)
• Onset:
  • IV: within 1–20 minutes
  • IM: 10–30 minutes
• Peak Effect:
  • IV: 7–30 minutes
• Duration of Action:
  2.5 to 4 hours (dose- and route-dependent)
• Metabolism:
  Partially metabolized by plasma esterases and liver enzymes.
• Elimination:
  • 40–70% excreted unchanged via the kidneys
  • Half-life: 50–90 minutes (prolonged in renal impairment)

Pregnancy:

• FDA Category C
  Animal studies have shown adverse fetal effects. No adequate studies in humans. Use only if clearly needed. May stimulate uterine contractions.

Lactation:

• May be excreted in small amounts into breast milk.
  Caution advised; observe nursing infant for signs of cholinergic effects (e.g., drooling, loose stools, irritability).

• Cholinesterase Inhibitor
• Subclass: Peripheral anticholinesterase agent
• Category: Neuromuscular blockade reversal agent; parasympathomimetic

• Hypersensitivity to neostigmine or excipients
• Mechanical gastrointestinal or urinary tract obstruction
• Peritonitis
• Known hypersensitivity to anticholinesterase agents
• Recent gastrointestinal surgery where increased peristalsis may be harmful

• Bradycardia & Heart Block:
  Can cause significant bradycardia; always co-administer with atropine or glycopyrrolate when used IV.
• Cholinergic Crisis:
  Overdosage may lead to a crisis characterized by excessive muscarinic and nicotinic stimulation: salivation, muscle twitching, weakness, respiratory paralysis. Requires emergency atropine treatment.
• Respiratory Compromise:
  Use cautiously in patients with asthma or chronic bronchitis due to risk of bronchospasm and increased secretions.
• Renal Impairment:
  Use cautiously; dosage adjustments may be necessary.
• Seizure Disorders:
  May increase risk of seizures in predisposed patients.

Common:

• Nausea, vomiting, diarrhea
• Abdominal cramps
• Excessive salivation
• Sweating
• Bradycardia
• Hypotension
• Muscle twitching or cramps

Less Common:

• Dizziness, blurred vision
• Bronchospasm
• Urinary urgency
• Lacrimation

Serious:

• Cholinergic crisis
• Respiratory paralysis
• Severe bradycardia or asystole
• Anaphylaxis (rare)

Onset & Severity:

• Onset of side effects is rapid, especially with IV administration. Most are dose-related and reversible with anticholinergic agents.

• Non-depolarizing Neuromuscular Blockers (e.g., rocuronium):
  Neostigmine reverses their effects (intended therapeutic interaction).
• Depolarizing Neuromuscular Blockers (e.g., succinylcholine):
  May prolong paralysis; avoid concurrent use.
• Anticholinergic Agents (e.g., atropine, glycopyrrolate):
  Co-administered to block muscarinic effects.
• Beta-blockers, digoxin:
  Increased risk of bradycardia
• Corticosteroids:
  May antagonize the effects in myasthenia gravis
• No known significant CYP450 interactions

• Neuromuscular Monitoring:
  ASA and international anesthesiology societies recommend quantitative monitoring when using neostigmine for reversal, ensuring adequate recovery before extubation.
• Sugammadex vs. Neostigmine:
  In facilities where sugammadex is unavailable or unaffordable, neostigmine remains the preferred reversal agent for most non-depolarizing neuromuscular blockers.
• Bangladesh Availability:
  Verified on Medex.com.bd. Available in 0.5 mg/mL and 2.5 mg/mL ampoules under brand names such as Neostigmin®, Myostigmin®, and others.

• Temperature:
  Store at 20°C to 25°C (68°F to 77°F)
• Humidity & Light:
  Protect from light and excess moisture. Keep in original container until use.
• Handling Instructions:
• Do not freeze
• Discard if solution is cloudy, colored, or contains particles
• Use ampoule immediately after opening
• Refrigeration:
  Not required under normal conditions