1 INDICATIONS AND USAGE Neostigmine Methylsulfate Injection, a cholinesterase inhibitor, is indicated for reversal of the effects of nondepolarizing neuromuscular blocking agents (NMBA) after surgery.

Neostigmine Methylsulfate, a cholinesterase inhibitor, is indicated for reversal of the effects of nondepolarizing neuromuscular blocking agents (NMBA) after surgery ( 1 ).

6 ADVERSE REACTIONS The most common adverse reactions include bradycardia and nausea and vomiting.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trial 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.

The following serious adverse reactions are described below and elsewhere in the labeling: Bradycardia [ see Warnings and Precautions ( 5.1 ) ] Cardiovascular Complications [ see Warnings and Precautions ( 5.2 ) ] Hypersensitivity (Anaphylaxis) [ see Warnings and Precautions ( 5.3 ) ] Adverse reactions to neostigmine methylsulfate are most often attributable to exaggerated pharmacological effects, in particular, at muscarinic receptor sites.

The use of an anticholinergic agent, e.g., atropine sulfate or glycopyrrolate, may prevent or mitigate these reactions.

Quantitative adverse event data are available from trials of neostigmine methylsulfate in which 200 adult patients were exposed to the product.

Adverse reactions that occurred with an overall frequency of 1% or greater included the following: Allergic: Allergic reactions and anaphylaxis.

Neurological: Dizziness, syncope, weakness, convulsions, loss of consciousness, drowsiness, headache, dysarthria, miosis and visual changes.

Cardiovascular: Cardiac arrhythmias including bradycardia, tachycardia, atrioventricular block and nodal rhythm, as well as cardiac arrest, and hypotension.

Respiratory: Increased oral, pharyngeal and bronchial secretions, dyspnea, respiratory depression, oxygen desaturation, respiratory arrest and bronchospasm.

Dermatologic: Diaphoresis, flushing, rash, pruritus, and urticaria.

Gastrointestinal: Dry mouth, nausea, emesis, flatulence and increased peristalsis.

Genitourinary: Increased urinary frequency.

Musculoskeletal: Muscle cramps and spasm, arthralgia.

Psychiatric: Insomnia General: Incision site complication, pharyngolaryngeal pain, procedural complication, procedural pain 6.2 Post-Marketing Experience The following adverse reactions have been identified during parenteral use of neostigmine methylsulfate.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Allergic Disorders: Allergic reactions, anaphylaxis Nervous System Disorders: Convulsions, drowsiness, dysarthria, fasciculation, loss of consciousness, miosis, visual changes Cardiovascular Disorders: Cardiac arrest, cardiac arrhythmias (A-V block, nodal rhythm), hypotension, nonspecific EKG changes, syncope Respiratory, Thoracic and Mediastinal Disorders: Bronchospasm; increased oral, pharyngeal and bronchial secretions; respiratory arrest; respiratory depression Skin and Subcutaneous Tissue Disorders: Rash, urticaria diaphoresis, flushing Gastrointestinal Disorders: Bowel cramps, diarrhea, flatulence, increased peristalsis Renal and Urinary Disorders: Urinary frequency Musculoskeletal and Connective Tissue Disorders: Arthralgia, muscle cramps, spasms, weakness