neostigmine (Rx)

Frequency Not Defined

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 (predominantly with parenteral dosage form)

Respiratory: Increased oral, pharyngeal and bronchial secretions, and dyspnea; respiratory depression, respiratory arrest and bronchospasm have been reported following the use of the injectable form

Dermatologic: Rash and urticaria

Gastrointestinal: Nausea, emesis, flatulence, and increased peristalsis and salivation

Genitourinary: Urinary frequency

Musculoskeletal: Muscle cramps and spasms, arthralgia

Miscellaneous: Diaphoresis, flushing and weakness

Contraindications

Hypersensitivity, previous history of reaction to bromides

Peritonitis or mechanical GI or urinary tract obstruction

Cautions

To lessen risk of bradycardia, administer glycopyrrolate or atropine sulfate prior to therapy

Caution in epilepsy, bronchial asthma, bradycardia, recent coronary occlusion, vagotonia, hyperthyroidism, cardiac arrhythmias, peptic ulcer

In patients with certain cardiovascular conditions such as coronary artery disease, cardiac arrhythmias or recent acute coronary syndrome, risk of blood pressure and heart rate complications may be increased; risk of these complications may also be increased in patients with myasthenia gravis; standard antagonism with anticholinergics (eg, atropine) is generally successful to mitigate risk of cardiovascular complications

Neonates; because of self-limiting nature of myasthenia gravis, reduce daily dosage gradually released until drug can be withdrawn

Avoid large doses in situations where there might be an increased absorption rate from the intestinal tract; caution when coadministered with anticholinergic drugs because of decreased GI motility

Differentiate between myasthenic crisis and cholinergic crisis caused by overdosage of neostigmine; both conditions result in extreme muscle weakness but require radically different treatment

Large doses administered when neuromuscular blockade is minimal can produce neuromuscular dysfunction; the dose should be reduced if recovery from neuromuscular blockade is nearly complete

Anticholinesterase insensitivity can develop

If excess cholinergic symptoms develop, discontinue therapy

Atropine and epinephrine must be available to treat a hypersensitivity reaction

Not recomended for use in patients with vagotonia

May prolong the phase 1 block of depolarizing muscle relaxants

Pregnancy

There are no adequate or well-controlled studies in pregnant women; not known whether neostigmine can cause fetal harm or affect reproductive capacity; should administer only if clearly needed

Anticholinesterase drugs, including neostigmine, may cause uterine irritability and induce premature labor when administered to pregnant women near term

Animal data

• No adverse effects were noted in rats or rabbits treated with human equivalent doses of neostigmine methylsulfate doses up to 8.1 and 13 mcg/kg/day, respectively, during organogenesis (0.1 to 0.2 times the maximum recommended human dose of 5 mg/60 kg person/day based on body surface area comparisons)

Lactation

The drug has not been studied in lactating women; not known whether neostigmine methylsulfate is present in human milk, or has effects on milk production or breastfed child; the developmental and health benefits of breastfeeding should be considered along with mother’s need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Competitive inhibitor of cholinesterase resulting in decreased hydrolysis of acetylcholine by cholinesterase; by reducing the breakdown of acetylcholine, neostigmine increases acetylcholine in the synaptic cleft which competes for the same binding site as nondepolarizing neuromuscular blocking agents, and reverses the neuromuscular blockade

Absorption

Bioavailability: 1-2% (PO); general PO:IV equivalence ~15 mg neostigmine bromide PO is equivalent to 0.5 mg neostigmine methylsulfate parenteral

Onset: 1-20 min (IV); 20-30 min (IM)

Duration: 2.5-4 hr (IM); 1-2 hr (IV)

Peak plasma time: 30 min (IM); 1-2 hr (PO)

Distribution

Protein bound: 15-25% to albumin (PO)

Metabolism

Liver microsomal enzymes and hydrolysis by cholinesterase enzymes

Elimination

Half-Life: 47-60 min (IV); 51-90 min (IM); 42-60 min (PO)

Excretion: 50% urine

IV Incompatibilities: none specified

IV Administration: slow IV injection