INDICATIONS AND USAGE Neostigmine Methylsulfate Injection is indicated for: the symptomatic control of myasthenia gravis when oral therapy is impractical. the prevention and treatment of postoperative distention and urinary retention after mechanical obstruction has been excluded. reversal of effects of nondepolarizing neuromuscular blocking agents (e.g., tubocura- rine, metocurine, gallamine or pancuronium) after surgery.
CLINICAL PHARMACOLOGY Neostigmine inhibits the hydrolysis of acetylcholine by competing with acetylcholine for attachment to acetylcholinesterase at sites of cholinergic transmission. It enhances cholinergic action by facilitating the transmission of impulses across neuromuscular junctions. It also has a direct cholinomimetic effect on skeletal muscle and possibly on autonomic ganglion cells and neurons of the central nervous system. Neostigmine undergoes hydrolysis by cholinesterase and is also metabolized by microsomal enzymes in the liver. Protein binding to human serum albumin ranges from 15 to 25 percent. Following intramuscular administration, neostigmine is rapidly absorbed and eliminated. In a study of five patients with myastheniagravis, peak plasma levels were observed at 30 minutes and the half-life ranged from 51 to 90 minutes. Approximately 80 percent of the drug was eliminated in urine within 24 hours; approximately 50 percent as the unchanged drug and 30 percent as metabolites. Following intravenous administration, plasma half-life ranges from 47 to 60 minutes have been reported with a mean half-life of 53 minutes. The clinical effects of neostigmine usually begin within 20 to 30 minutes after intramuscular injection and last from 2.5 to 4 hours.
DOSAGE AND ADMINISTRATION Symptomatic control of myasthenia gravis: One mL of the 1:2000 solution (0.5 mg) subcutaneously or intramuscularly. Subsequent doses should be based on the individual patient's response. Prevention of postoperative distention and urinary retention: 0.25 mg subcutaneously or intramuscularly as soon as possible after operation; repeat every 4 to 6 hours for two or three days. Treatment of postoperative distention: One mL of 1:2000 solution (0.5.mg) subcutaneously or intramuscularly, as required. Treatment of urinary retention : One mL of the 1:2000 solution (0.5. mg) subcutaneously or intramuscularly. If urination does not occur within an hour, the patient should be catheterized. After the patient has voided, or the bladder has been emptied, continue the 0.5 mg injections every three hours for at least 5 injections. Reversal of Effects on Nondepolarizing Neuromuscular Blocking Agents : When Neostig-mine Methylsulfate Injection is administered intravenously, it is recommended that atropine sulfate (0.6 to 1.2 mg) also be given intravenously using separate syringes. Some authorities have recommended that the atropine be injected several minutes before the neostigmine rather than concomitantly. The usual dose is 0.5 to 2 mg Neostigmine Methylsulfate Injection given by slow intravenous injection, repeated as required. Only in exceptional cases should the total dose of neostigmine exceed 5 mg, it is recommended that the patient be well ventilated and a patent airway maintained until complete recovery of normal respiration is assured. The optimum time for administration of the drug is during hyperventilation when the carbon dioxide level of the blood is low. It should never be administered in the presence of high concentrations of halothane or cyclopro- pane. In cardiac cases and severely ill patients, it is advisable to titrate the exact dose of neostigmine required, using a peripheral nerve stimulator device. In the presence of bradycardia, the…
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ADVERSE REACTIONS Side effects are generally due to an exaggeration of pharmacological effects of which salivation and fasciculation are the most common. Bowel cramps and diarrhea may also occur. The following additional adverse reactions have been reported following the use of neostigmine methylsulfate. Allergic: Allergic reactions and anaphylaxis. Neurologic: Dizziness, convulsions, loss of consciousness, drowsiness, headache, dysarthria, miosis and visual changes. Cardiovascular: Cardiac arrhythmias (including bradycardia, tachycardia, A-V block and nodal rhythm) and nonspecific EKG changes have been reported, as well as cardiac arrest, syncope and hypotension. These have been predominantly noted following the use of the injectable form of neostigmine. Respiratory: Increased oral, pharyngeal and bronchial secretions, dyspnea, respiratory depression, respiratory arrest and bronchospasm. Dermatologic: Rash and urticaria. Gastrointestinal: Nausea, emesis, flatulence and increased peristalsis. Genitourinary: Urinary frequency. Musculoskeletal: Muscle cramps and spasms, arthralgia Miscellaneous: Diaphoresis, flushing and weakness.
CONTRAINDICATIONS 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 intestinal or urinary tract.
Drug Interactions Neostigmine does not antagonize, and may in fact prolong, the Phase I block of depolariz- ing muscle relaxants such as succinylcholine or decamethonium. Certain antibiotics, especially neomycin, streptomycin and kanamycin, have a mild but definite nondepolarizing blocking action which may accentuate neuromuscular block. These antibiotics should be used in the myasthenic patient only where definitely indicated, and then careful adjustment should be made of the anticholinesterase dosage. Local and some general anesthetics, antiarrhythmic agents and other drugs that interfere with neuromuscular transmission should be used cautiously, if at all, in patients with myasthenia gravis; the dose of neostigmine may have to be increased accordingly.
WARNINGS Neostigmine should be used with caution in patients with epilepsy, bronchial asthma, bradycardia, recent coronary occlusion, vagotonia, hyperthyroidism, cardiac arrhythmias or peptic ulcer. When large doses of neostigmine are administered, the prior or simultaneous injection of atropine sulfate may be advisable. Separate syringes should be used for the neostigmine and atropine. Because of the possibility of hypersensitivity in an occasional patient, atropine and antishock medication should always be readily available.