pyridostigmine bromide
Mestinon, Regonol

Available forms
Available by prescription only
Injection: 5 mg/ml in 2-ml ampule or 5-ml vial
Syrup: 60 mg/5 ml
Tablets: 60 mg
Tablets (sustained-release): 180 mg

Indications and dosages
 Reversal of the effects of nondepolarizing drugs, curariform antagonist (postoperatively). Adults: 10 to 20 mg I.V. preceded by atropine sulfate 0.6 to 1.2 mg I.V.
 Myasthenia gravis. Adults: 60 to 180 mg P.O. b.i.d. or q.i.d. Usual dose is 600 mg daily, but higher doses may be needed (up to 1,500 mg daily). Give 1/30 of oral dose I.M. or I.V. Adjust dosage based on patient response and tolerance of adverse effects. Sustained-release and regular-release forms are often used together depending on patient’s symptoms.
Children: 7 mg/kg/24 hours P.O. divided into five or six doses.
Neonates of myasthenic mothers: 0.05 to 0.15 mg/kg I.M.

Pharmacodynamics
Muscle stimulant action: Blocks acetylcholine’s hydrolysis by cholinesterase, resulting in acetylcholine accumulation at cholinergic synapses, increasing stimulation of cholinergic receptors at the myoneural junction.

Pharmacokinetics
Absorption: Poorly absorbed from GI tract.
Distribution: Little information available; however, may cross the placental barrier, especially when given in large doses.
Metabolism: Exact metabolic fate unknown. Duration of effect depends on patient’s physical and emotional status and disease severity. Drug hydrolyzed by cholinesterase.
Excretion: Drug and metabolites excreted in urine.

Contraindications and precautions
Contraindicated in patients hypersensitive to anticholinesterases and in those with mechanical obstruction of the intestine or urinary tract. Use cautiously in patients with bronchial asthma, bradycardia, or arrhythmias.

Interactions
Drug-drug. Aminoglycoside antibiotics: Mild but definite nondepolarizing blocking action of these drugs may accentuate neuromuscular block. Monitor patient for pyridostigmine effectiveness.
Corticosteroids: Decreases cholinergic effect of drug; when corticosteroids are stopped, this effect may increase, possibly affecting muscle strength. Monitor patient.
Ganglionic blockers: Decreases blood pressure; decrease is usually preceded by abdominal symptoms. Monitor patient and blood pressure closely.
Magnesium: Antagonizes beneficial effects of pyridostigmine. Monitor patient for pyridostigmine effectiveness.
Procainamide, quinidine: Reverses pyridostigmine’s cholinergic effect on muscle. Monitor patient for pyridostigmine effectiveness.
Succinylcholine: Prolongs respiratory depression from plasma esterase inhibition, delaying succinylcholine hydrolysis. Monitor patient closely.

Adverse reactions
CNS: headache (with high doses), weakness.
CV: bradycardia, hypotension, thrombophlebitis.
EENT: miosis.
GI: abdominal cramps, nausea, vomiting, diarrhea, excessive salivation, increased peristalsis.
Musculoskeletal: muscle cramps, muscle fasciculations.
Respiratory: bronchospasm, bronchoconstriction, increased bronchial secretions.
Skin: rash, diaphoresis.

Effects on lab test results
None reported.

Overdose and treatment
Toxicity may cause nausea, vomiting, diarrhea, blurred vision, miosis, excessive tearing, bronchospasm, increased bronchial secretions, hypotension, incoordination, excessive sweating, muscle weakness, cramps, fasciculations, paralysis, bradycardia or tachycardia, excessive salivation, and restlessness or agitation.
 Support respiration; bronchial suctioning may be performed. Discontinue drug immediately. Atropine may be given to block muscarinic effects; however, it won’t counter skeletal muscle paralysis. Avoid atropine overdose because it may lead to bronchial plug formation.

Special considerations
• If muscle weakness is severe, determine if this effect stems from drug toxicity or exacerbation of myasthenia gravis. A test dose of edrophonium I.V. will aggravate drug-induced weakness but will temporarily relieve weakness that results from the disease.
• Avoid giving large doses to patients with decreased GI motility because toxicity may result once motility has been restored.
• Give drug with food or milk to reduce risk of muscarinic adverse effects.
• Atropine sulfate should always be readily available as an antagonist for the muscarinic effects of pyridostigmine.
• Stop all other cholinergics during drug therapy to avoid additive toxicity.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Because of potential for serious adverse reactions in breast-fed infant, stop either breast-feeding or drug, taking into account importance of drug to mother.
Pediatric patients
• Safety and efficacy haven’t been established.

Patient education
• When drug is used in patient with myasthenia gravis, stress importance of taking drug exactly as ordered, on time, and in evenly spaced doses.
• If patient is taking sustained-release tablets, explain how these work and instruct him to take them at the same time each day; swallow tablets whole rather than crushing them.
• Teach patient how to evaluate muscle strength; instruct him to observe changes in muscle strength and to report muscle cramps, rash, or fatigue.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use