Neostigmine

Neostigmine methylsulfate injection is a cholinesterase inhibitor indicated for the reversal of the effects of non-depolarizing neuromuscular blocking agents after surgery. Neostigmine methylsulfate injection, a cholinesterase inhibitor, is indicated for the reversal of the effects of non-depolarizing neuromuscular blocking agents (NMBAs) after surgery (1) .

• Should be administered by trained healthcare providers • Peripheral nerve stimulator and monitoring for twitch responses should be used to determine when neostigmine methylsulfate injection should be initiated and if additional doses are needed • For reversal of NMBAs with shorter half-lives, when first twitch response is substantially greater than 10% of baseline, or when a second twitch is present: 0.03 mg/kg by intravenous route • For reversal of NMBAs with longer half-lives or when first twitch response is close to 10% of baseline: 0.07 mg/kg by intravenous route • Maximum total dosage is 0.07 mg/kg or up to a total of 5 mg (whichever is less) • An anticholinergic agent, e.g., atropine sulfate or glycopyrrolate, should be administered prior to or concomitantly with neostigmine methylsulfate injection 2.1
• Important Dosage Information Neostigmine methylsulfate injection should be administered by trained healthcare providers familiar with the use, actions, characteristics, and complications of neuromuscular blocking agents (NMBA) and neuromuscular block reversal agents
• Doses of neostigmine methylsulfate injection should be individualized, and a peripheral nerve stimulator should be used to determine the time of initiation of neostigmine methylsulfate injection and should be used to determine the need for additional doses
• Neostigmine methylsulfate injection is for intravenous use only and should be injected slowly over a period of at least 1 minute. …

Neostigmine methylsulfate injection is available as • Injection: 0.5 mg/mL, 5 mg of neostigmine methylsulfate in 10 mL multiple- dose vials • Injection: 1 mg/mL, 10 mg of neostigmine methylsulfate in 10 mL multiple-dose vials Injection: 0.5 mg/mL and 1 mg/mL in 10 mL multiple-dose vials (3)

• Neostigmine methylsulfate injection is approved for the reversal of the effects of non-depolarizing neuromuscular blocking agents after surgery
• In pediatric patients of all ages
• Recovery of neuromuscular activity occurs more rapidly with smaller doses of cholinesterase inhibitors in infants and children than in adults
• However, infants and small children may be at greater risk of complications from incomplete reversal of neuromuscular blockade due to decreased respiratory reserve. …

Because elderly patients are more likely to have decreased renal function, neostigmine methylsulfate injection should be used with caution and monitored for a longer period in elderly patients. The duration of action of neostigmine methylsulfate is prolonged in the elderly; however, elderly patients also experience slower spontaneous recovery from neuromuscular blocking agents. …

Neostigmine methylsulfate injection is contraindicated in patients with: • known hypersensitivity to neostigmine methylsulfate (known hypersensitivity reactions have included urticaria, angioedema, erythema multiforme, generalized rash, facial swelling, peripheral edema, pyrexia, flushing, hypotension, bronchospasm, bradycardia and anaphylaxis). • peritonitis or mechanical obstruction of the intestinal or urinary tract. …

The pharmacokinetic interaction between neostigmine methylsulfate and other drugs has not been studied. Neostigmine methylsulfate is metabolized by microsomal enzymes in the liver. Use with caution when using neostigmine methylsulfate injection with other drugs which may alter the activity of metabolizing enzymes or transporters.

• Bradycardia: Atropine or glycopyrrolate should be administered prior to neostigmine methylsulfate injection to lessen risk of bradycardia. ( 5.1 ) • Serious Reactions with Coexisting Conditions: Use with caution in patients with, coronary artery disease, cardiac arrhythmias, recent acute coronary syndrome or myasthenia gravis. ( 5.2 ) • Neuromuscular Dysfunction: Can occur if large doses of neostigmine methylsulfate injection are administered when neuromuscular blockade is minimal; reduce dose if recovery from neuromuscular blockade is nearly complete. ( 5.4 ) 5.1. Bradycardia Neostigmine has been associated with bradycardia. …

Most common adverse reactions during treatment: bradycardia, nausea and vomiting ( 6) To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy's Laboratories Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions to neostigmine methylsulfate are most often attributable to exaggerated pharmacological effects, in particular, at muscarinic receptor sites. …

8.1 Pregnancy Risk Summary There are no adequate or well-controlled studies of neostigmine methylsulfate injection in pregnant women. It is not known whether neostigmine methylsulfate injection can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. The incidence of malformations in human pregnancies has not been established for neostigmine as the data are limited. …

Muscarinic symptoms (nausea, vomiting, diarrhea, sweating, increased bronchial and salivary secretions, and bradycardia) may appear with overdosage of neostigmine methylsulfate injection (cholinergic crisis), but may be managed by the use of additional atropine or glycopyrrolate. The possibility of iatrogenic overdose can be lessened by carefully monitoring the muscle twitch response to peripheral nerve stimulation. Should overdosage occur, ventilation should be supported by artificial means until the adequacy of spontaneous respiration is assured, and cardiac function should be monitored. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.