Neostigmine Methylsulphate is indicated for:

• Symptomatic management of myasthenia gravis when oral therapy is not feasible.
• Prevention and treatment of postoperative abdominal distension and urinary retention, after excluding mechanical obstruction.
• Reversal of the effects of non-depolarizing neuromuscular blocking agents (such as tubocurarine, metocurine, gallamine, or pancuronium) following surgery.

Neostigmine Methylsulphate Injection is an anticholinesterase medication supplied as a sterile, non-pyrogenic solution in Water for Injection. It is suitable for administration via intramuscular (IM), intravenous (IV), or subcutaneous (SC) routes. Neostigmine functions as a parasympathomimetic agent and acts as a reversible inhibitor of cholinesterase. It blocks acetylcholinesterase, the enzyme responsible for breaking down acetylcholine, thereby increasing the amount of acetylcholine available at synaptic junctions. This enhanced availability leads to greater stimulation of both nicotinic and muscarinic receptors, which are essential for muscle contraction. Neostigmine does not cross the blood-brain barrier.

Antagonist to Nondepolarising Neuromuscular Blockade:

• Adults: A single dose of Neostigmine Methylsulfate injection 2 to 3 mg with atropine sulphate 0.6–1.2 mg by slow IV injection over 1 minute. The recommended ratio of atropine to Neostigmine Methylsulfate injection is 1:2 to 1:3. The maximum recommended dose of Neostigmine Methylsulfate injection in adults is 5 mg.
• Children: The suggested dose in children is 0.05 mg/kg/dose and atropine sulphate 0.02 mg/kg/dose by slow IV injection. Maximum recommended dose of Neostigmine Methylsulfate injection in children is 2.5 mg.

Myasthenia Gravis:

• Adults: 1 mg to 2.5 mg given IM or SC at intervals throughout the day when greater strength may be needed (e.g. mornings and before meals), given a total daily dose of 5 to 20 mg. Duration of action of a single dose is 2 to 4 hours.
• Neonates: 0.05–0.25 mg IM every 2–4 hours, half an hour before feeding. Treatment is not usually required beyond 8 weeks of age. Because the condition is usually self limiting the daily dosage should gradually be reduced until the medicine can be withdrawn.
• When large doses of Neostigmine Methylsulfate injection are given to myasthenic patients, atropine sulphate may be required to counteract the muscarinic side effects.

Urinary Retention:

• Prophylaxis: 0.25 mg SC or IM before or immediately after the operation, repeated every 4 to 6 hours for 2–3 days.
• Treatment: 0.5 mg SC or IM and apply warmth to lower abdomen. After patient has voided continue 0.5 mg SC or IM every 3 hours for at least 5 injections. If there has been no urinary response within one hour of the first dose, the patient should be catheterised.

Neostigmine Methylsulfate injection does not counteract and may prolong the Phase I blockade produced by depolarizing muscle relaxants such as succinylcholine or decamethonium. Certain antibiotics, including neomycin, streptomycin, and kanamycin, possess mild nondepolarizing neuromuscular blocking effects, which can enhance neuromuscular blockade.

These antibiotics should be used in patients with myasthenia gravis only when necessary, with careful adjustment of anticholinesterase dosage. Local and general anesthetics, antiarrhythmic drugs, and other agents that interfere with neuromuscular transmission should be used cautiously, as dosage adjustments of Neostigmine Methylsulfate may be required.

Neostigmine Methylsulfate injection is contraindicated in patients with known hypersensitivity to the drug. It is also contraindicated in patients with peritonitis or mechanical obstruction of the gastrointestinal or urinary tract.

Adverse reactions, particularly in cases of overdose, may include:

• Cardiovascular: Bradycardia, arrhythmias, hypotension, cardiac arrest, syncope.
• Central Nervous System: Headache, dizziness, seizures, unconsciousness, coma, drowsiness, restlessness, ataxia, slurred speech, agitation, anxiety.
• Gastrointestinal: Nausea, vomiting, diarrhea, flatulence, abdominal cramps, increased bowel movements, involuntary defecation.
• Genitourinary: Urinary urgency or involuntary urination.
• Musculoskeletal: Muscle cramps, fasciculations, weakness, paralysis.
• Respiratory: Increased secretions, dyspnea, bronchospasm, respiratory depression, respiratory failure, chest tightness, wheezing.
• Allergic: Hypersensitivity reactions including anaphylaxis.
• Skin: Rash, urticaria.
• Others: Excessive sweating, salivation, miosis, visual disturbances, nystagmus, tearing.

Pregnancy Category C: There are no adequate and well-controlled studies in animals or pregnant women. It is unknown whether Neostigmine Methylsulfate can cause fetal harm or affect fertility. It should be used during pregnancy only if clearly necessary.

Non-teratogenic Effects: Anticholinesterase agents may cause uterine contractions and may induce premature labor when administered intravenously near term.

Lactation: It is not known whether Neostigmine Methylsulfate is excreted in human milk. Due to the potential for serious adverse effects in nursing infants, a decision should be made to either discontinue breastfeeding or stop the drug, considering its importance to the mother.

Neostigmine Methylsulfate should be used cautiously in patients with epilepsy, bronchial asthma, bradycardia, recent myocardial infarction, vagotonia, hyperthyroidism, cardiac arrhythmias, or peptic ulcer disease. When high doses are administered, atropine sulfate may be given beforehand or simultaneously. Separate syringes should be used for each drug. Emergency medications, including atropine and antishock agents, should always be readily available due to the risk of hypersensitivity.

Overdose may result in a cholinergic crisis, characterized by severe muscle weakness. It may be difficult to distinguish from a myasthenic crisis, which is due to worsening of the underlying disease. Cholinergic crisis can lead to respiratory paralysis and death, whereas myasthenic crisis causes profound muscle weakness. Differentiation between the two is critical and can be made using edrophonium testing along with clinical evaluation.

Anticholinesterase agents; drugs used in myasthenia gravis

Store at controlled room temperature, protected from light. Discard any unused portion after opening.