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Pyridostigmine Bromide

Pronunciation

Class: Parasympathomimetic (Cholinergic) Agents
VA Class: AU300
CAS Number: 101-26-8
Brands: Mestinon, Regonol

Warning(s)

  • Military Use for Soman Poisoning Prophylaxis
  • Use of pyridostigmine alone is not protective against soman effects.111 Efficacy depends on rapid use of nerve agent antidotes (i.e., atropine and pralidoxime) following nerve agent exposure.111

  • Protective garments (e.g., masks, hoods, overgarments) specifically designed for protection from chemical nerve agents are the primary means of protection against nerve agent exposure; do not rely solely on pretreatment with pyridostigmine, atropine, and pralidoxime to provide complete protection.111

  • Do not administer pyridostigmine after soman exposure.111 Discontinue at first sign of nerve agent poisoning; may exacerbate effects of a sublethal exposure.111

  • Experience of Health Care Personnel
  • Pyridostigmine should be administered by IV injection only by adequately trained individuals familiar with the drug’s actions, characteristics, and risks.124

Introduction

Reversible anticholinesterase agent.a 123 124 111

Uses for Pyridostigmine Bromide

Myasthenia Gravis

Symptomatic management of myasthenia gravis to improve muscle strength.a 123

Not effective in patients resistant to anticholinesterase drugs.a

Has been used parenterally (IV or IM) for symptomatic treatment of acute exacerbations of myasthenia gravis or when oral therapy was impractical.a However, the injectable preparation that was used for this indication no longer is commercially available in the US; the parenteral injection currently commercially available in the US does not include this use in its prescribing information.124

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Surgery

Postoperative reversal of the effects of nondepolarizing neuromuscular blocking agents (e.g., gallamine, metocurine, tubocurarine [all no longer commercially available in the US], pancuronium).a 124

Not effective and should not be used for reversal of depolarizing neuromuscular blocking agents (e.g., succinylcholine, decamethonium).a

Chemical Warfare Agent Poisoning

Preexposure prophylaxis against lethal effects of soman nerve agent poisoning in military combat personnel.111 116

Used in conjunction with standard treatment of nerve agent poisoning (i.e., atropine and pralidoxime chloride) and other protective measures (e.g., masks, hoods, overgarments).111

Discontinue use at first indication of nerve agent poisoning.111 Not for use after exposure to soman; not expected to be effective after such exposure and may exacerbate effects of sublethal exposure.111 (See Military Use for Soman Poisoning Prophylaxis in Boxed Warning.)

Pyridostigmine Bromide Dosage and Administration

General

Myasthenia Gravis

  • Dosage, route, and frequency of administration depend on the requirements and clinical response of the patient.a Carefully individualize dosage according to individual requirements and response and minimize adverse effects by precise dosage adjustment.a

  • Dosage requirements may vary from day to day, according to remissions and exacerbations of the disease and the physical and emotional stress suffered by the patient.a

  • Treat mild exacerbations by increasing dosage under medical supervision as long as increase produces symptomatic improvement.a

  • Once stabilized on pyridostigmine, may teach patients how to recognize adverse muscarinic effects and self-modify dosage or take atropine, if necessary.a

  • Complete restoration of muscle strength is rare; do not attempt to relieve all symptoms by increasing dosage above maximum response level.a

  • Individual muscle groups respond differently to the same dose; may produce weakness in one while increasing strength in another.a Measure vital capacity whenever increasing dosage to ensure good respiratory function.a Have adequate facilities for CPR, cardiac monitoring, endotracheal intubation, and respiratory assistance available during dosage adjustment.a

Postoperative Reversal of Nondepolarizing Neuromuscular Blocking Agent Effects

  • Administer IV only by adequately trained individuals familiar with the actions, characteristics, and risks of pyridostigmine.124

  • Always have atropine and medications to treat shock readily available in case of hypersensitivity reaction.124

  • Give atropine sulfate or glycopyrrolate immediately prior to or concurrently with pyridostigmine when reversing the actions of nondepolarizing neuromuscular blocking agents to minimize pyridostigmine's adverse effects (e.g., excessive secretions, bradycardia).124

  • Monitor muscle twitch response to peripheral nerve stimulation; administer pyridostigmine after spontaneous recovery of neuromuscular function begins.124 Satisfactory reversal is evident by adequate voluntary respiration, respiratory measurements, and use of a peripheral nerve stimulator device.124

  • Patient must be well ventilated; maintain patent airway and manual or mechanical ventilation until complete recovery of normal respiration is assured.124 Recurrence of paralysis unlikely after satisfactory reversal attained.124

Chemical Warfare Agent Poisoning

  • Administer orally prior to an expected exposure to soman (i.e., when under the threat of a nerve agent attack).111 Do not take after exposure to soman.111

  • If taken immediately before or at the same time as soman poisoning, pyridostigmine is not likely to be effective and may exacerbate the effects of a sublethal exposure.111

Administration

Administer orally or by very slow IV injection.a Also has been administered by IM injection,a 125 but manufacturer of currently available injectable preparation states that this injection is for IV injection only.124

Oral Administration

Administer orally, adjusting frequency and timing of administration according to individual response.a

Oral solution may be useful for children and patients who have difficulty swallowing or who require precise dosage adjustments not possible with tablets.a 123 g

Some clinicians recommend that extended-release tablets be used only at bedtime for patients who are very weak upon awakening.a May use extended-release tablets concurrently with conventional tablets or syrup to achieve optimum control.123

NG Tube

May administer oral solution through nasogastric tube.a

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by very slow IV injection.a (See General under Dosage and Administration.)

Dosage

Pediatric Patients

Myasthenia Gravis
Oral

Neonates: 5 mg every 4–6 hours.a 125 Gradually reduce daily dosage until drug can be withdrawn.a (See Pediatric Use under Cautions.)

Children: 7 mg/kg daily administered in 5–6 divided doses.a 125 (See Pediatric Use under Cautions.)

IV or IM

Neonates: 0.05–0.15 mg/kg (maximum single IV or IM dose of 10 mg) every 4–6 hours.a 125 Gradually reduce daily dosage until drug can be withdrawn.a (See Pediatric Use under Cautions.)

Children: 0.05–0.15 mg/kg (maximum single IV or IM dose of 10 mg) every 4–6 hours.125

Adults

Myasthenia Gravis
Oral

Initially, 60 mg 3 times daily or dosage smaller than that required to produce maximum strength.a May gradually increase as needed at intervals ≥48 hours.a

Adjust dosage of conventional tablets or syrup for treatment of myasthenia gravis so larger doses are taken at times of greatest fatigue (e.g., 30–45 minutes before meals to assist patients who have difficulty eating).a 123

Usual daily maintenance dosage is 60–1500 mg (average 600 mg).a 123

Extended-release tablets: 180–540 mg 1–2 times daily (with ≥6 hours between doses).a 123 However, some clinicians recommend use of extended-release tablets only at bedtime for patients who are very weak upon awakening.a

Oral dosage changes may take several days to produce results.a When a further increase in dosage produces no corresponding increase in muscle strength, reduce dosage to the previous level.a

Dosage requirements may vary from day to day.a

Oral dosage requirements are approximately 30 times parenteral dosage requirements.a

IV or IM

Give 1/30 usual oral dose.a

Observe closely for cholinergic reactions.a

Surgery
Reversal of Nondepolarizing Neuromuscular Blocking Agent Effects
IV

0.1–0.25 mg/kg.124 Give concurrently with or immediately after 0.6–1.2 mg IV atropine sulfate a 124 or an equipotent dose of glycopyrrolate.124

Full recovery usually occurs within 15 minutes but may require ≥30 minutes.124

Additional doses of pyridostigmine not recommended if reversal is inadequate; instead, manage with manual or mechanical ventilation until adequate recovery occurs.124

Chemical Warfare Agent Poisoning
Preexposure Prophylaxis for Soman Poisoning
Oral

30 mg every 8 hours beginning several hours prior to anticipated exposure.111

Discontinue at first sign of nerve agent poisoning; immediately treat with atropine and pralidoxime.111

Effects of use for >14 consecutive days not established; evaluate continuation of prophylaxis based on likelihood of exposure to soman.111

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.111 a 123 124

Renal Impairment

Lower dosages may be required; carefully titrate dosage.a 123

Geriatric Patients

Careful dosage selection recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.111

Pregnant Women

Myasthenia Gravis

Labor and Delivery: An IM or slow IV injection of 1/30 the usual oral dose has been administered 1 hour before completion of the second stage of labor.a

Cautions for Pyridostigmine Bromide

Contraindications

  • Known hypersensitivity to anticholinesterase agents.111 a 124

  • Mechanical obstruction of the intestinal or urinary tract.a 111 123 124

Warnings/Precautions

Warnings

Cholinergic Crisis

Overdosage may result in cholinergic crisisa 123 (e.g., excessive salivation and sweating, miosis, nausea, vomiting, diarrhea, bradycardia or tachycardia, hypotension or hypertension, confusion, seizures, coma, severe muscle weakness, paralysis);a may result in death.123 If overdosage occurs, maintain adequate respiration and give IV atropine.a

Myasthenic crisis due to increased disease severity also causes extreme muscle weakness; symptomatic differentiation from cholinergic crisis may be difficult.a 123 Time to onset of symptoms approximately 1 hour after dose suggests overdosage, while ≥3 hours after dose suggests underdosage or resistance is the more likely diagnosis.a May require use of edrophonium chloride for the differential diagnosis.a 123

If severe cholinergic reaction occurs, discontinue pyridostigmine immediately and institute appropriate therapy as indicated (e.g., atropine, medications to treat shock).a 124

Excessive IV doses may produce depolarization block when administered at doses above therapeutic range to reverse nondepolarizing neuromuscular blocking agent effects.124 Therapeutic index (ratio of reversal dose to blocking dose) is approximately 1:6.124

Concomitant Diseases

Use with caution in patients with bronchial asthma, COPD, bradycardia, or cardiac arrhythmias.a 124 111

Preexposure Prophylaxis for Soman Poisoning

Do not administer pyridostigmine after soman exposure.111 Discontinue at first sign of nerve agent poisoning; may exacerbate effects of a sublethal soman exposure.111 (See Boxed Warning.)

Military personnel experiencing severe adverse effects (e.g., difficulty breathing, severe dizziness, loss of consciousness) associated with pyridostigmine use should temporarily discontinue the drug and immediately seek medical care.111

Sensitivity Reactions

Bromide Sensitivity

Use caution in patients with known bromide sensitivity.111

May cause skin rash, which usually disappears when pyridostigmine bromide is discontinued.a 111 123 124

General Precautions

Electrolyte Imbalance

Conditions resulting in electrolyte imbalance (e.g., adrenocortical insufficiency) may alter neuromuscular blockade (enhance or inhibit) and interfere with postoperative restoration of neuromuscular function by pyridostigmine.124

Specific Populations

Pregnancy

Category C (injection, oral solution, and tablets [except 30-mg tablets for military use]).124 Risk of uterine irritability and induction of premature labor if anticholinesterase agents are given IV near term.a

Category B (30-mg tablets for military use only).111

Lactation

Not known whether pyridostigmine is distributed into milk.111 Caution advised if used in nursing women.111

Pediatric Use

Safety and efficacy not established.109 111 124

Pyridostigmine bromide injection contains 1% benzyl alcohol.124 Manufacturer does not recommend use in neonates;124 AAP states that the presence of small amounts of this preservative in a commercially available injection should not proscribe its use when indicated in neonates.103 Consider combined daily intake of benzyl alcohol from all sources.124

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.111

Substantially eliminated by the kidneys; may be useful to monitor renal function since geriatric patients are more likely to have decreased renal function.111

Renal Impairment

Use with caution.111 Clearance may be decreased; dosage adjustments necessary in renal disease. (See Renal Impairment under Dosage and Administration.)109 111

Common Adverse Effects

Diarrhea,111 abdominal pain or cramps,111 116 dysmenorrhea,111 increased flatus,116 nausea,116 urinary urgency and frequency.116

Interactions for Pyridostigmine Bromide

Specific Drugs

Drug

Interaction

Comments

4-Aminopyridine (not commercially available in the US)

Possible delayed onset of IV pyridostigmine124

Aminoglycosides (e.g., gentamicin, kanamycin, neomycin, streptomycin)

Possible prolongation of neuromuscular blockade or resistance to reversal if used in conjunction with nondepolarizing neuromuscular blocking agents124

Use cautiously, if at all111

Anesthetics, local or general

Interfere with neuromuscular transmissiona

Use cautiously, if at alla

Antiarrhythmic agents

Interfere with neuromuscular transmissiona

Use cautiously, if at alla

Atropine

Antagonizes muscarinic effects of pyridostigminea 111

Interaction used to therapeutic advantage to counteract muscarinic symptoms of pyridostigmine toxicity; however,111 atropine also may mask manifestations of pyridostigmine overdose and prevent early detection of cholinergic crisisa 123

Bacitracin

Possible prolongation of neuromuscular blockade or resistance to reversal if used in conjunction with nondepolarizing neuromuscular blocking agents124

β-Adrenergic blocking agents

Possible additive bradycardiae

Possible inhibition of pyridostigmine efficacy in myasthenia gravise

Use concomitantly with caution; 111 effects on patients with borderline heart failure or AV conduction disturbances not determined118

Dexpanthenol

Converted to pantothenic acid in vivo; possible additive effects due to increased acetylcholine productiona 111

Magnesium salts

Possible enhanced neuromuscular blockade124

Consider possibility of interference with restoration of neuromuscular function by pyridostigmine124

Mefloquine

Possible additive GI effects111

Possible additive effects on atrial rate111

Miotics, topical (e.g., physostigmine)

Possible additive effects; may cause or exacerbate problems with night visiona 111

Neuromuscular blocking agents, depolarizing (e.g., succinylcholine)

Possible enhanced and/or prolonged neuromuscular blockade111 a

Do not use for reversal of depolarizing neuromuscular blockadea

Use caution in soldiers who received pyridostigmine if depolarizing agent administered during surgery111 117

Neuromuscular blocking agents, nondepolarizing (e.g., tubocurarine, metocurine, gallamine [all no longer commercially available in the US], pancuronium)

Antagonism of nondepolarizing muscle relaxant effectsa

Interaction used to therapeutic advantage to reverse muscle relaxation induced by neuromuscular blocking agents after surgerya

May need to increase dosage of nondepolarizing agent in soldiers who received pyridostigmine111

Opiate agonists

Possible exacerbation of pyridostigmine-induced bradycardia111

Polymyxins (e.g., colistin, polymyxin B, sodium colistimethate)

Possible prolongation of neuromuscular blockade or resistance to reversal if used in conjunction with nondepolarizing neuromuscular blocking agents124

Quinidine

Recurrent paralysis may occur if used in conjunction with nondepolarizing neuromuscular blocking agents124

Tetracyclines

Possible prolongation of neuromuscular blockade or resistance to reversal if used in conjunction with nondepolarizing neuromuscular blocking agents124

Pyridostigmine Bromide Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from GI tract following oral administration;a bioavailability is 10–20%.101 111 115

Peak plasma concentrations occur 2.2 hours after oral ingestion of a 30-mg dose as conventional tablet.111

Extended-release tablets reportedly release one-third of total dose immediately, then remainder over 8–12 hours; however, release may be erratic and unpredictable.a

Onset

Following oral administration in patients with myasthenia gravis, 30–45 minutes.a

Following IV injection in patients with myasthenia gravis, muscle strength increased in 2–5 minutes.a

When used for postoperative reversal of nondepolarizing neuromuscular blocking agent effects, time to peak effect is dose-dependent; with 0.25-mg/kg dosage, return of twitch height to 90% of control occurs within about 6 minutes.124 At lower dosages, full recovery usually occurs within 15 minutes; may require ≥30 minutes in some patients.124

Duration

Duration of effects varies in patients with myasthenia gravis.a Effects generally persist for 3–6 hours for conventional oral tablets, about 8–12 hours for extended-release tablets, and about 2–3 hours for IV injection.a

Distribution

Extent

Distributed into most tissues, except brain, intestinal wall, fat, and thymus.a

Crosses the placenta;a not known whether distributed into milk.a 111

Elimination

Metabolism

Metabolized via hydrolysis by cholinesterases and by microsomal enzymes in the liver.a 111

Elimination Route

Excreted in urine, principally as unchanged drug (80–90%).100 101 102

Half-life

Conventional oral tablets: 3 hours.100 101 102 110 111

IV: 1.05–1.86 hours.100 101 102 110

Special Populations

Patients with severe myasthenia gravis metabolize and excrete pyridostigmine faster than patients with milder forms of the disease.a

Anephric patients: Half-life 6.3 hours;102 clearance decreased by 75%.111

Geriatric patients (71–85 years of age): Plasma clearance decreased 30%, but half-life is unchanged.111

No information available on pyridostigmine pharmacokinetics in patients with hepatic impairment.111

Stability

Storage

Oral

Conventional 60-mg Tablets and Extended-release Tablets

25°C (may be exposed to 15–30°C).123

Do not store in moist environments (e.g., bathrooms, kitchens).g Hygroscopic; tablets may become mottled, but this does not affect potency.a 123 g

Conventional 30-mg Tablets for Military Use

2–8°C; protect from light.111 Discard unrefrigerated unit-dose packages after 3 months.111

Oral Solution

25°C (may be exposed to 15–30°C).123 Protect from light.a

Parenteral

Injection

25°C (may be exposed to 15–30°C). Protect from light.124 124

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Drug Compatibility

Y-Site CompatibilityHID

Compatible

Heparin sodium

Hydrocortisone sodium succinate

Potassium chloride

Vitamin B complex with C

Compatibility in SyringeHID

Compatible

Glycopyrrolate

Actions

  • Analog of neostigmine, but pyridostigmine may have a longer duration of action and fewer adverse GI effects.a 123 124

  • Reversibly inhibits acetylcholinesterase, thereby prolonging and exaggerating the effects of acetylcholine.111 117 118 120 121 a Has direct cholinomimetic effect on skeletal muscle.a

  • Produces generalized cholinergic responses including miosis, bradycardia, increased tonus of intestinal musculature, constriction of bronchi and ureters, and stimulation of secretion by salivary and sweat glands.a

  • At sufficiently high dosage, directly blocks action at autonomic ganglia, causes CNS stimulation followed by CNS depression and, ultimately, depolarization block.a

  • Blocks nerve agent soman from access to acetylcholinesterase active sites, protecting the enzyme from irreversible inhibition.111 117

Advice to Patients

  • Patients with myasthenia gravis: importance of carefully following prescribed dosage instructions.g Importance of recording response to each dosage, especially when initiating therapy or during times of disease instability, to assist clinician with prescribing dosage adjustments.g

  • Advise military personnel to take pyridostigmine as directed by chain of command for preexposure prophylaxis for possible soman poisoning; advise not to take pyridostigmine immediately before (when attack alarm is given), during, or after exposure to soman.111 f Importance of discontinuing pyridostigmine and following instructions provided in pyridostigmine patient information for treatment (e.g., atropine, pralidoxime) if soman poisoning occurs.f

  • Military personnel: Importance of discarding 30-mg tablets 3 months after date of issue.f

  • Advise military personnel that pyridostigmine alone is not protective against soman poisoning; the primary means of protection against nerve agent exposure is wearing protective garments (e.g., masks, hoods, overgarments) designed for this use.111 f

  • Advise military personnel that if they experience serious adverse effects (e.g., difficulty breathing, severe dizziness, loss of consciousness), to temporarily discontinue the drug and immediately seek medical care.111

  • Importance of informing clinician of any allergy to bromide or anticholinesterase drugs.f

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.a f

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Pyridostigmine bromide 30-mg tablets are for military use only.111

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Pyridostigmine Bromide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

60 mg/5 mL

Mestinon Syrup (with alcohol 5%)

Valeant

Tablets

60 mg*

Mestinon (scored)

Valeant

Pyridostigmine Bromide Tablets

Global, Sandoz

Tablets, extended-release

180 mg

Mestinon Timespan (scored)

Valeant

Parenteral

Injection

5 mg/mL

Regonol (with benzyl alcohol)

Sandoz

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Mestinon 180MG Controlled-release Tablets (VALEANT): 30/$127.99 or 90/$365.97

Mestinon 60MG/5ML Syrup (VALEANT): 240/$95.99 or 480/$179.96

Mestinon 60MG Tablets (VALEANT): 30/$97.00 or 90/$260.47

Pyridostigmine Bromide 60MG Tablets (GLOBAL PHARMACEUTICAL CORP): 30/$21.99 or 90/$49.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 2, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

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101. Aquilonius SM, Hartvig P. Clinical pharmacokinetics of cholinesterase inhibitors. Clin Pharmacokinet. 1986; 11:236-49. [IDIS 217475] [PubMed 3524957]

102. Cronnelly R, Stanski DR, Miller RD et al. Pyridostigmine kinetics with and without renal function. Clin Pharmacol Ther. (IDIS 124818)

103. American Academy of Pediatrics Committee on Fetus and Newborn and Committee on Drugs. Benzyl alcohol: toxic agent in neonatal units. Pediatrics. 1983; 72:356-8. [IDIS 175725] [PubMed 6889041]

104. Anon. Benzyl alcohol may be toxic to newborns. FDA Drug Bull. 1982; 12(2):10-1. [PubMed 7188569]

105. Centers for Disease Control. Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982; 31:290-1. [IDIS 150868] [PubMed 6810084]

106. Gershanik J, Boecler B, Ensley H et al. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982; 307:1384-8. [IDIS 160823] [PubMed 7133084]

107. Menon PA, Thach BT, Smith CH et al. Benzyl alcohol toxicity in a neonatal intensive care unit: incidence, symptomatology, and mortality. Am J Perinatol. 1984; 1:288-92. [PubMed 6440575]

108. Anderson CW, Ng KJ, Andresen B et al. Benzyl alcohol poisoning in a premature newborn infant. Am J Obstet Gynecol. 1984; 148:344-6. [IDIS 181207] [PubMed 6695984]

109. ICN Pharmaceuticals. Mestinon (pyridostigmine bormide) syrup, tablets and timespan caplets prescribing information (dated Aug 2000). In: Physician’s Desk Refence electronic library. From PDR web site.

110. Breyer-Pfaff U, Maier U, Brinkmann AM et al. Pyridostigmine kinetics in healthy subjects and patients with myasthenia gravis. Clin Pharmacol Ther. 1985; 37:495-501. [IDIS 200487] [PubMed 3987173]

111. Defense Supply Center. Pyridostigmine bromide tablets prescribing information. Philadelphia, PA; 2003 Feb.

112. Agency for Toxic Substances and Disease Registry. Medical Management Guidelines for Nerve Agents: Tabun (GA); Sarin (GB); Soman (GD); and VX. From the CDC website. Accessed Nov 12, 2001.

113. DeLorenzo RA. Exposed: signs, symptoms & EMS management of nerve-agent poisoning. J Emerg Med Serv JEMS. 2001; 26:48-57. [PubMed 11409202]

114. In Ellenhorn MJ, Schonwald S, Ordog G, Wasserberger J, eds. Ellenhorn’s medical toxicology: diagnosis and treatment of human poisoning. 2nd ed. Baltimore: Williams & Wilkins; 1997:1267-90.

115. Marino MT, Schuster BG, Brueckner RP et al. Population pharmacokinetics and pharmacodynamics of pyridostigmine bromide for prophylaxis against nerve agents in humans. J Clin Pharmacol. 1998; 38:227-35. [IDIS 403655] [PubMed 9549661]

116. Keeler JR, Hurst CG, Dunn MA. Pyridostigmine used as a nerve agent pretreatment under wartime conditions. JAMA. 1991; 266:693-5. [IDIS 283899] [PubMed 2072481]

117. Pellegrini JE. The effect of oral pyridostigmine bromide nerve agent prophylaxis on return of twitch height in persons receiving succinylcholine. Milit Med. 2000; 165:252-5.

118. Arad M, Roth A, Zelinger J et al. Safety of pyridostigmine in hypertensive patients receiving beta blockers. Am J Cardiol. 1992; 69:518-22. [IDIS 291776] [PubMed 1346558]

119. Schumm WR, Reppert EJ, Jurich AP et al. Pyridostigmine bromide and the long-term subjective health status of a sample of over 700 male reserve component gulf war era veterans. Psychol Rep. 2002; 90:707-21. [PubMed 12090498]

120. Gouge SF, Daniels D, Smith CE. Exacerbation of asthma after pyridostigmine during Operation Desert Storm. Milit Med. 1994; 159:108-11.

121. In Goldfrank LR, Flomenbaum NE, Lewin NA, Howland MA, Hoffman RS, Nelson LS, eds. Goldfrank’s Toxicologic Emergencies. 7th ed. New York: McGraw-Hill; 2002:1527-51.

122. Leikin JB, Thomas RG, Walter FG et al. A review of nerve agent exposure for critical care physicians. Crit Care Med. 2002; 30:2346-54. [IDIS 490747] [PubMed 12394966]

123. Valeant Pharmaceuticals International. Mestinon (pyridostigmine bromide) syrup, tablets, and Timespan tablets prescribing information. Costa Mesa, CA; 2005 Jul. From the DailyMed website. Accessed Jun 28, 2007.

124. Sandoz Inc. Regonol (pyridostigmine bromide) injection prescribing information. Broomfield, CO; 2005 Mar.

125. Gunn VL, Nechyba C, eds. The Harriet Lane handbook: a manual for pediatric house officers. 16th ed. Philadelphia, PA: Mosby; 2002:827.

a. AHFS drug information 2007. McEvoy GK, ed. Pyridostigmine bromide. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1249-52.

e. Stockley IH, editor. Stockley's drug interactions. 6th edition. Chicago, IL: Pharmaceutical Press; 2002.

f. Defense Supply Center. Pyridostigmine bromide tablets patient information. Philadelphia, PA; 2003 Feb.

g. Valeant Pharmaceuticals International. Mestinon(pyridostigmine bromide) syrup, tablets, and Timespan tablets product information. From the Valeant website. Accessed Jun 28, 2007.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1433-4.

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