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Neostigmine

Pronunciation: (NEE-oh-STIG-meen)
Class: Anticholinesterase muscle stimulant

Trade Names

Prostigmin
- Tablets 15 mg
- Injection 1:1,000
- Injection 1:2,000
- Injection 1:4,000

Pharmacology

Facilitates myoneural junction impulse transmission by inhibiting acetylcholine destruction by cholinesterase.

Pharmacokinetics

Absorption

Rapid absorption of neostigmine methylsulfate; neostigmine bromide is poorly absorbed from the GI tract. T _max is 30 min (IV) and 1 to 2 h (oral).

Distribution

Neostigmine protein binding is 15% to 25% (serum albumin).

Metabolism

Neostigmine is metabolized in the liver by microsomal enzymes and undergoes hydrolysis by cholinesterase.

Elimination

Neostigmine is eliminated in urine (50% as unchanged). Half-life is 51 to 90 min and plasma half-life is 47 to 60 min (IV); half-life ranges from 42 to 60 min, with a mean half-life of 52 min (oral).

Onset

Onset of IM neostigmine is 20 to 30 min.

Duration

Duration of IM neostigmine is 2.5 to 4 h.

Indications and Usage

Symptomatic control of myasthenia gravis; antidote for nondepolarizing neuromuscular blocking agents after surgery; prevention and treatment of postoperative distention and urinary retention (IV only).

Contraindications

Hypersensitivity to anticholinesterases and bromides; mechanical intestinal or urinary obstruction; peritonitis.

Dosage and Administration

Antidote
Adults

IV 0.5 to 2 mg by slow infusion repeated as needed, preceded by 0.6 to 1.2 mg of atropine sulfate. May be repeated as needed up to total dose of 5 mg.

Myasthenia Gravis
Adults

PO 15 to 375 mg/day; Subcutaneous/IM 1 mL of 1:2,000 solution (0.5 mg); individualize subsequent doses.

Prevention of Postoperative Urinary Distention and Retention
Adults

Subcutaneous / IM 1 mL of 1:4,000 solution (0.25 mg) after surgery; repeat every 4 to 6 h for 2 or 3 days.

Treatment of Postoperative Distention
Adults

Subcutaneous / IM 1 mL of 1:2,000 solution (0.5 mg), as required.

Treatment of Urinary Retention
Adults

Subcutaneous / IM 1 mL of 1:2,000 solution (0.5 mg) after bladder is emptied; continue 0.5 mg injection every 3 h for at least 5 injections.

General Advice

Injection
For IV, subcutaneous, or IM administration. Not for intradermal or intra-arterial administration.
Do not administer if particulate matter or discoloration is noted.
Patients on IV neostigmine can be transferred to the oral form as soon as it can be tolerated.

Tablets
Administer as prescribed. Size of dose (eg, number of tablets) and frequency of administration will be adjusted to provide max relief of myasthenia gravis symptoms.
Administer without regard to meals. Administer with food if GI upset occurs.
Larger portions of the daily dose may be given at times when the patient is more prone to fatigue (eg, afternoons, mealtimes).
Large doses should be avoided in situations where there might be an increased absorption rate from the intestinal tract.
Ensure that parenteral atropine is available for emergency treatment of cholinergic crisis.

Storage/Stability

Store at 59° to 86°F. Keep injection in carton until ready to use and protect from light.

Drug Interactions

Anticholinergic agents (eg, atropine, belladonna)

Intestinal motility may be slowed, increasing neostigmine absorption. Use with caution. Adjust the neostigmine dose as needed.

Beta-blockers (eg, propranolol)

Severe or prolonged bradycardia may occur because of additive pharmacologic effects. Use with caution. Larger dosages of atropine and sympathomimetic pressor agents may be needed to reverse bradycardia and hypotension.

Corticosteroids (eg, corticotropin, hydrocortisone)

The effects of neostigmine may be decreased. In addition, the effects of neostigmine may be increased after corticosteroids are discontinued. Provide mechanical respiratory support if needed.

Drugs that interfere with neuromuscular transmission

May interfere with neuromuscular transmission. Use with caution in myasthenic patients. Monitor the patient and increase the neostigmine dose as needed.

Kanamycin, streptomycin

Neuromuscular blockade may be enhanced. Use these antibiotics in myasthenic patients only when clearly indicated. Closely monitor the patient. Adjust the neostigmine dose as needed.

Local/General anesthetics, antiarrhythmic agents (eg, procainamide)

Use with caution in myasthenic patients; may interfere with neuromuscular transmission. Increase the neostigmine dose as needed.

Quinine

Quinine may antagonize the effects of neostigmine. Avoid using quinine in patients receiving neostigmine for myasthenia gravis.

Succinylcholine

Neuromuscular blockade produced by succinylcholine may be prolonged. Avoid this combination in the presence of a depolarizing (phase 1) type of neuromuscular blockade. Use with caution if a nondepolarizing (phase 2) type of blockade is present. Provide mechanical respiratory support as needed.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Arrhythmia (AV block, bradycardia, nodal rhythm, tachycardia); cardiac arrest; hypotension; nonspecific ECG changes; syncope.

CNS

Convulsions; dizziness; drowsiness; dysarthria; dysphonia; headache; loss of consciousness.

Dermatologic

Diaphoresis; flushing; rash; urticaria.

EENT

Miosis; vision changes.

GI

Bowel cramps; diarrhea; emesis; flatulence; increased peristalsis; nausea; salivation; vomiting.

Genitourinary

Urinary frequency.

Respiratory

Dyspnea; increased oral, pharyngeal, and bronchial secretions; respiratory arrest, respiratory depression, and bronchospasm (IV).

Musculoskeletal

Arthralgia; muscle cramps and spasms.

Miscellaneous

Allergy and anaphylaxis; fasciculations; weakness.

Precautions

Monitor

Frequently assess muscle strength and function in patient with myasthenia gravis or patient recovering from nondepolarizing neuromuscular blocking agent.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hypersensitivity

Anaphylaxis may occur. Have atropine and antishock medications available.

Special Risk Patients

Use with caution in patients with bradycardia, bronchial asthma, cardiac arrhythmias, epilepsy, hyperthyroidism, peptic ulcer, recent coronary occlusion, or vagotonia.

Anticholinesterase insensitivity

May develop.

Overdosage

Symptoms

Abdominal cramps, anxiety, diarrhea, excessive salivation, miosis, panic attacks, progressive muscle weakness leading to paralysis and death, sweating, urinary urgency.

Patient Information

Advise patient or caregiver that injection will be prepared and administered by a health care provider in a medical setting.
Advise patient that dose and frequency of administration may be adjusted to achieve max benefit.
Advise patient to take prescribed oral dose without regard to meals, but to take with food if stomach upset occurs.
Advise patient with myasthenia gravis to keep a diary of medication administration times and times when muscle weakness or other symptoms occur. This log will help the health care provider adjust the dose and dosing interval to establish the most effective dose and times of administration.
Instruct patient to contact health care provider immediately if any of the following occur: difficulty breathing, dizziness, fainting, severe abdominal pain, slow or irregular heart rate, vomiting, worsening muscle weakness.
Advise patient that diarrhea, increased salivation, nausea, and sweating are common adverse reactions and to notify health care provider if any occur and are bothersome.