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standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Medication Safety Issues
Sound-alike/look-alike issues:
Pyridostigmine may be confused with physostigmine
Mestinon® may be confused with Metatensin®
Regonol® may be confused with Reglan®, Renagel®
Pronunciation
(peer id oh STIG meen)
U.S. Brand Names
Index Terms
Generic Available
Yes: Tablet
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Symptomatic treatment of myasthenia gravis; antagonism of nondepolarizing neuromuscular blockers
Military use: Pretreatment for Soman nerve gas exposure
Pregnancy Risk Factor
B
Pregnancy Considerations
Safety has not been established for use during pregnancy. The potential benefit to the mother should outweigh the potential risk to the fetus. When pyridostigmine is needed in myasthenic mothers, giving dose parenterally 1 hour before completion of the second stage of labor may facilitate delivery and protect the neonate during the immediate postnatal state.
Lactation
Enters breast milk/compatible
Breast-Feeding Considerations
Neonates of myasthenia gravis mothers may have difficulty in sucking and swallowing (as well as breathing). Neonatal pyridostigmine may be indicated by symptoms (confirmed by edrophonium test).
Contraindications
Hypersensitivity to pyridostigmine, bromides, or any component of the formulation; GI or GU obstruction
Warnings/Precautions
Boxed warnings:
• Regonol® injection: See “Dosage form specific issues” below.
Concerns related to adverse effects:
• Anticholinesterase insensitivity: For brief or prolonged periods, anticholinesterase insensitivity can develop.
• Cholinergic effects: Discontinue if symptoms of excess cholinergic activity (eg, salivation, sweating, urinary incontinence); overdosage may result in cholinergic crisis, which must be distinguished from myasthenic crisis.
• Hypersensitivity reactions: Have atropine and epinephrine ready to treat hypersensitivity reactions.
Disease-related concerns:
• Asthma or bronchospastic disease: Use with extreme caution in patients with asthma or bronchospastic disease.
• Cardiovascular disease: Use with caution in patients with bradycardia or cardiac arrhythmias.
• GI disease: Use with caution in patients with GI disease, including peptic ulcer disease.
• Hyperthyroidism: Use with caution in patients with hyperthyroidism.
• Myasthenia gravis: Adequate facilities should be available for cardiopulmonary resuscitation when testing and adjusting dose for myasthenia gravis.
• Seizure disorder: Use with caution in patients with a history of seizure disorder.
Dosage form specific issues:
• Regonol® injection: Contains 1% benzyl alcohol as the preservative; not intended for use in newborns. [U.S. Boxed Warning]: Must be administered by trained personnel.
Adverse Reactions
Frequency not defined.
Cardiovascular: Arrhythmias (especially bradycardia), AV block, cardiac arrest, decreased carbon monoxide, flushing, hypotension, nodal rhythm, nonspecific ECG changes, syncope, tachycardia
Central nervous system: Convulsions, dizziness, drowsiness, dysphonia, headache, loss of consciousness
Dermatologic: Skin rash, thrombophlebitis (I.V.), urticaria
Gastrointestinal: Abdominal pain, diarrhea, dysphagia, flatulence, hyperperistalsis, nausea, salivation, stomach cramps, vomiting
Genitourinary: Urinary urgency
Neuromuscular & skeletal: Arthralgia, dysarthria, fasciculations, muscle cramps, myalgia, spasms, weakness
Ocular: Amblyopia, lacrimation, small pupils
Respiratory: Bronchial secretions increased, bronchiolar constriction, bronchospasm, dyspnea, laryngospasm, respiratory arrest, respiratory depression, respiratory muscle paralysis
Miscellaneous: Allergic reactions, anaphylaxis, diaphoresis increased
Drug Interactions
Beta-Blockers: Acetylcholinesterase Inhibitors may enhance the bradycardic effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Cholinergic Agonists: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Cholinergic Agonists. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy
Ginkgo Biloba: May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Methocarbamol: May diminish the therapeutic effect of Pyridostigmine. Risk C: Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Acetylcholinesterase Inhibitors may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Succinylcholine: Acetylcholinesterase Inhibitors may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
Storage
Injection: Protect from light.
Tablet:
30 mg: Store under refrigeration at 2°C to 8°C (36°F to 46°F). Protect from light. Stable at room temperature for up to 3 months.
Mestinon®: Store at 25°C (77°F). Protect from moisture.
Compatibility
Y-site administration: Compatible: Heparin, hydrocortisone sodium succinate, potassium chloride, vitamin B complex with C.
Compatibility in syringe: Compatible: Glycopyrrolate.
Mechanism of Action
Inhibits destruction of acetylcholine by acetylcholinesterase which facilitates transmission of impulses across myoneural junction
Pharmacodynamics/Kinetics
Onset of action: Oral, I.M.: 15-30 minutes; I.V. injection: 2-5 minutes
Duration: Oral: Up to 6-8 hours (due to slow absorption); I.V.: 2-3 hours
Absorption: Oral: Very poor
Distribution: 19 ± 12 L
Metabolism: Hepatic
Bioavailability: 10% to 20%
Half-life elimination: 1-2 hours; Renal failure: ?6 hours
Excretion: Urine (80% to 90% as unchanged drug)
Dosage
Myasthenia gravis:
Oral:
Children: 7 mg/kg/24 hours divided into 5-6 doses
Adults: Highly individualized dosing ranges: 60-1500 mg/day, usually 600 mg/day divided into 5-6 doses, spaced to provide maximum relief
Sustained release formulation: Highly individualized dosing ranges: 180-540 mg once or twice daily (doses separated by at least 6 hours); Note: Most clinicians reserve sustained release dosage form for bedtime dose only.
I.M., slow I.V. push:
Children: 0.05-0.15 mg/kg/dose
Adults: To supplement oral dosage pre- and postoperatively during labor and postpartum, during myasthenic crisis, or when oral therapy is impractical: ~1/30th of oral dose; observe patient closely for cholinergic reactions
or
I.V. infusion: Initial: 2 mg/hour with gradual titration in increments of 0.5-1 mg/hour, up to a maximum rate of 4 mg/hour
Reversal of nondepolarizing muscle relaxants: Note: Atropine sulfate (0.6-1.2 mg) I.V. immediately prior to pyridostigmine to minimize side effects: I.V.:
Children: Dosing range: 0.1-0.25 mg/kg/dose*
Adults: 0.1-0.25 mg/kg/dose; 10-20 mg is usually sufficient*
*Full recovery usually occurs ?15 minutes, but ?30 minutes may be required
Pretreatment for Soman nerve gas exposure (military use): Oral: Adults: 30 mg every 8 hours beginning several hours prior to exposure; discontinue at first sign of nerve agent exposure, then begin atropine and pralidoxime
Dosage adjustment in renal dysfunction: Lower dosages may be required due to prolonged elimination; no specific recommendations have been published
Administration: Oral
Do not crush sustained release tablet.
Administration: I.V. Detail
pH: 5
Monitoring Parameters
Observe for cholinergic reactions, particularly when administered I.V.
Test Interactions
Increased aminotransferase [ALT/AST] (S), increased amylase (S)
Patient Education
This drug will not cure myasthenia gravis, but may help reduce symptoms. Use as directed; do not increase dose or discontinue without consulting prescriber. Take extended release tablets at bedtime; do not chew or crush extended release tablets. Maintain adequate hydration unless instructed to restrict fluid intake. May cause dizziness, drowsiness, or hypotension (rise slowly from sitting or lying position and use caution when driving or climbing stairs); vomiting or loss of appetite (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); or diarrhea. Report persistent abdominal discomfort; significantly increased salivation, sweating, tearing, or urination; flushed skin; chest pain or palpitations; acute headache; unresolved diarrhea; excessive fatigue, insomnia, dizziness, or depression; increased muscle, joint, or body pain; vision changes or blurred vision; or shortness of breath or wheezing.
Geriatric Considerations
Many elderly may have pulmonary or cardiovascular diseases which will require cautious use of pyridostigmine.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: For reversal of neuromuscular blockade, atropine or glycopyrrolate must be administered with pyridostigmine to minimize its cholinergic effects. For patients with myasthenia gravis, extended release products may be preferred at bedtime for patients who are very weak upon rising in the morning.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Dysphagia.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May rarely cause dysphoria or drowsiness
Mental Health: Effects on Psychiatric Treatment
None reported; but mouth watering is common and may be additive to the sialorrhea associated with clozapine therapy
Nursing: Physical Assessment/Monitoring
When used to reverse neuromuscular block (anesthesia or excessive acetylcholine), monitor patient safety until full return of neuromuscular functioning. Assess bladder and sphincter adequacy prior to administering medication. Monitor therapeutic effectiveness and adverse reactions (eg, cholinergic crisis). Assess knowledge/teach patient appropriate use (self-injections, oral), interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as bromide:
Regonol®: 5 mg/mL (2 mL) [contains benzyl alcohol]
Syrup, as bromide:
Mestinon®: 60 mg/5 mL (480 mL) [raspberry flavor; contains alcohol 5%, sodium benzoate]
Tablet, as bromide: 60 mg
Mestinon®: 60 mg
Tablet, sustained release, as bromide:
Mestinon® Timespan®: 180 mg
Pricing: U.S. (www.drugstore.com)
Syrup (Mestinon)
60 mg/5 mL (240): $74.98
Tablet, controlled release (Mestinon)
180 mg (30): $94.99
Tablets (Mestinon)
60 mg (30): $61.49
Tablets (Pyridostigmine Bromide)
60 mg (30): $17.99
References
Dunn MA and Sidell FR, “Progress in Medical Defense Against Nerve Agents,” JAMA, 1989, 262(5):649-52.
Keeler JR, Hurst CG, and Dunn MA, “Pyridostigmine Used as a Nerve Agent Pretreatment Under Wartime Conditions,” JAMA, 1991, 266(5):693-5.
Saltis LM, Martin BR, Traeger SM, et al, “Continuous Infusion of Pyridostigmine in the Management of Myasthenic Crisis,” Crit Care Med,1993, 21(6):938-40.
Sidell FR and Borak J, “Chemical Warfare Agents: II. Nerve Agents,” Ann Emerg Med, 1992, 21(7):865-71.
International Brand Names
Lexi-Comp.com
Last full review/revision July 2009
Content last modified July 2009
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