Adult: As neostigmine methylsulfate: 0.5-2.5 mg via IM or SC inj. Dosing recommendations may vary among countries and individual products (refer to specific product guidelines). Child: As neostigmine methylsulfate: 0.125-1 mg via IM or SC inj. Dosing recommendations may vary among countries and individual products and between countries (refer to specific product guidelines).
Intramuscular, Subcutaneous Myasthenia gravis
Adult: Dosage and frequency of dosing is individualised according to the patient's needs and response. As neostigmine methylsulfate: 1-2.5 mg via IM or SC inj. Usual total daily dose: 5-20 mg. Doses are given at adequate intervals and should be adjusted based on the patient's response. Child: As neostigmine methylsulfate: >1 month to 11 years 0.2-0.5 mg via IM or SC inj; 12-17 years Same as adult dose. Doses are given at adequate intervals and should be adjusted based on the patient's response.
Intravenous Reversal of neuromuscular blockade
Adult: As neostigmine methylsulfate: 0.03-0.07 mg/kg via slow IV inj over 60 seconds. May repeat dose, if needed. Max dose: 0.07 mg/kg or up to a total of 5 mg (whichever is less). Dosage is individualised based on the patient's response and the degree of neuromuscular block. Anticholinergic agents (e.g. atropine or glycopyrronium bromide) should be given concomitantly with each dose; if the patient is experiencing bradycardia, the pulse rate should be increased by administering the anticholinergic agent before the neostigmine dose. Dosing recommendations may vary among individual products and between countries. (refer to specific product guidelines). Child: As neostigmine methylsulfate: 0.05 mg/kg via slow IV inj over 60 seconds, may give a further dose of 0.025 mg if needed. Max dose: 2.5 mg. Dosage is individualised based on the patient's response and the degree of neuromuscular block. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Adult: As neostigmine bromide: 15-30 mg. Dosing frequency may vary based on the patient's response. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product or country guidelines). Child: As neostigmine bromide: 2.5-15 mg. Dosing frequency may vary based on the patient's response. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product or country guidelines).
Oral Myasthenia gravis
Adult: Dosage and frequency of dosing is individualised according to the patient's needs and response. As neostigmine bromide: Initially, 15-30 mg. Usual total daily dose: 75-300 mg. Doses are given at adequate intervals throughout the day when maximum strength is needed (e.g. on rising and before mealtimes); may administer larger portions of the total daily dose at times of greater fatigue. Child: As neostigmine bromide: <6 years Initially, 7.5 mg; ≥6-12 years Initially, 15 mg. Doses are adjusted based on the patient’s response up to a total dailys dose of 15-90 mg.
Contraindications
Peritonitis, mechanical gastrointestinal or urinary tract obstruction.
Special Precautions
Patient with bronchial asthma, cardiovascular disease (e.g. bradycardia, cardiac arrhythmia, CAD, recent acute coronary syndrome, recent MI, hypotension), epilepsy, parkinsonism, hyperthyroidism, peptic ulcer disease, vagotonia. Patient who underwent recent intestinal or bladder surgery. Avoid large doses if with megacolon or decreased gastrointestinal motility. If used for the reversal of neuromuscular blockade, avoid use or use with caution in patients with neuromuscular diseases (e.g. myasthenia gravis, muscular dystrophy). Children and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Bradycardia, dysrhythmias, hypotension (especially with IV use); hypersensitivity reactions (e.g. anaphylaxis, angioedema, bronchospasm, erythema multiforme, facial swelling, flushing, generalized rash, hypotension, peripheral oedema, pyrexia, urticaria); neuromuscular dysfunction (use of high IV doses). Eye disorders: Lacrimation, miosis, nystagmus. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal cramps, excessive salivation, increased peristalsis (may result in involuntary defecation). General disorders and administration site conditions: General weakness. Musculoskeletal and connective tissue disorders: Muscle cramps, muscle spasms, fasciculations, paralysis. Nervous system disorders: Headache, convulsions, slurred speech, loss of consciousness, coma, restlessness, agitation, fear. Renal and urinary disorders: Urinary frequency. Respiratory, thoracic and mediastinal disorders: Tight chest, wheezing, increased bronchial secretion, respiratory depression. Skin and subcutaneous tissue disorders: Skin rash, hyperhidrosis, diaphoresis.
Monitor blood pressure, ECG, and heart rate (particularly with IV use).
Overdosage
Symptoms: Cholinergic crisis (nausea, vomiting, diarrhoea, excessive salivation, sweating, increased bronchial secretions, miosis, bradycardia or tachycardia, bronchospasm, cardiospasm, incoordination, muscle cramps, fasciculation, paralysis); CNS symptoms including agitation, fear, or restlessness (excessive high doses); cardiac arrest, respiratory paralysis and pulmonary oedema (may lead to death). Patient with myasthenia gravis: Mild fasciculation and adverse parasympathomimetic effects (may also be absent). Management: Maintain adequate respiration. May perform tracheostomy, bronchial aspiration and postural drainage, if necessary. Administer atropine sulfate via IV or IM, may administer additional doses every 5-30 minutes as required to control muscarinic symptoms.
Drug Interactions
May increase the risk of adverse effects with corticosteroids (e.g. methylprednisolone). May prolong the effect of depolarising muscle relaxants (e.g. suxamethonium). Decreased effects of non-depolarising muscle relaxants (e.g. gallamine, pancuronium, tubocurarine). Therapeutic effect may be reduced with anticholinergic agents (e.g. atropine). Increased bradycardic effects with β-blockers. Drugs with neuromuscular blocking activity (e.g. aminoglycosides, clindamycin, colistin, cyclopropane, halogenated inhalational anaesthesia) may antagonise the effects of neostigmine. Reduced efficacy with quinine, chloroquine, hydroxychloroquine, lithium, procainamide, propafenone and quinidine.
Action
Description: Mechanism of Action: Neostigmine, a quaternary ammonium compound, reversibly inhibits the hydrolysis of acetylcholine by competing with acetylcholine in binding to acetylcholinesterase. This leads to the accumulation of acetylcholine at cholinergic synapses, thus prolonging and intensifying its physiological actions. Additionally, it also has a direct cholinomimetic effect on skeletal muscle and possibly on autonomic ganglion cells and neurons of the CNS. Onset: Peristaltic activity: 2-4 hours (oral); 10-30 minutes (parenteral). Duration: 2.5-4 hours (IM). Pharmacokinetics: Absorption: Poorly absorbed from the gastrointestinal tract. Time to peak plasma concentration: 1-2 hours (oral). Distribution: Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 0.12-1.4 L/kg (IV). Plasma protein binding: 15-25%, mainly to albumin. Metabolism: Metabolised in the liver partly via hydrolysis of the ester linkage by cholinesterases. Excretion: Via urine (80%; 50% as unchanged drug, 15% as 3-hydroxyphenyltrimethylammonium). Elimination half-life: 42-60 minutes (oral); 24-113 minutes (IV); 51-90 minutes (IM).
Chemical Structure
Neostigmine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4456, Neostigmine. https://pubchem.ncbi.nlm.nih.gov/compound/Neostigmine. Accessed Feb. 23, 2024.
N07AA01 - neostigmine ; Belongs to the class of anticholinesterase. Used as parasympathomimetics.
References
Anon. Neostigmine (Pediatric and Neonatal Lexi-Drugs). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 21/02/2024.Anon. Neostigmine. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 29/08/2023.Anon. Neostigmine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 29/08/2023.Bloxiverz Methylsulfate Injection (Exela Pharma Sciences, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 29/08/2023.Buckingham R (ed). Neostigmine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 29/08/2023.Joint Formulary Committee. Neostigmine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 29/08/2023.Max Health Ltd. Neostigmine Methylsulfate Injection, Solution for Injection, 2.5 mg/mL data sheet 26 August 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 29/08/2023.Neostigmine Bromide Tablets (Alliance Pharmaceuticals Limited). MHRA. https://products.mhra.gov.uk. Accessed 29/08/2023.Neostigmine Methylsulfate Injection BP 2.5 mg in 1 mL (Hameln Pharma Limited). MHRA. https://products.mhra.gov.uk. Accessed 29/08/2023.Neostigmine. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 21/02/2024.Paediatric Formulary Committee. Neostigmine. BNF for Children [online]. London. BMJ Group, Pharmaceutical Press, and RCPCH Publications. https://www.medicinescomplete.com. Accessed 21/02/2024.Setisin Injection (Duopharma [M] Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 29/08/2023.
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