Neostigmine methylsulfate

BLOXIVERZ, is a cholinesterase inhibitor, indicated for the reversal of the effects of non-depolarizing neuromuscular blocking agents after surgery.

Neostigmine methylsulfate is a competitive cholinesterase inhibitor. By reducing the breakdown of acetylcholine, neostigmine methylsulfate induces an increase in acetylcholine in the synaptic cleft which competes for the same binding site as nondepolarizing neuromuscular blocking agents, and reverses the neuromuscular blockade.

• Should be administered by trained healthcare providers. • Peripheral nerve stimulator and monitoring for twitch responses should be used to determine when BLOXIVERZ should be initiated and if additional doses are needed o 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 o 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 BLOXIVERZ 2.1.

BLOXIVERZ 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. • Hypersensitivity to neostigmine. • Peritonitis or mechanical obstruction of the intestinal or urinary tract

• Bradycardia: Atropine or glycopyrrolate should be administered prior to BLOXIVERZ to lessen risk of bradycardia. • Serious Reactions with Coexisting Conditions: Use with caution in patients with, coronary artery disease, cardiac arrhythmias, recent acute coronary syndrome or myasthenia gravis. • Neuromuscular Dysfunction: Can occur if large doses of BLOXIVERZ are administered when neuromuscular blockade is minimal, reduce dose if recovery from neuromuscular blockade is nearly complete.

Most common adverse reactions during treatment: bradycardia, nausea and vomiting.

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 BLOXIVERZ with other drugs which may alter the activity of metabolizing enzymes or transporters.

Store in carton until time of use.