Myasthenic syndrome; congenital: Limited data available: Therapeutic response dependent upon inherited genetic variation and resultant type of myasthenic syndrome; pyridostigmine use should be under the supervision of a specialist experienced in the diagnosis and management of congenital myasthenic syndromes; some syndromes may be worsened by pyridostigmine therapy (eg, slow-channel myasthenic syndrome) and pyridostigmine use should be avoided (Ciafaloni 2019; Kliegman 2020; Lorenzoni 2012). Dosage should be individualized based on patient response.
Oral: Immediate release: 1 mg/kg/dose every 4 hours; maximum daily dose: 7 mg/kg/day divided in 5 to 6 doses (Lorenzoni 2012).
Myasthenic syndromes, congenital: Limited data available:
Note: Therapeutic response dependent upon inherited genetic variation and resultant type of myasthenic syndrome; pyridostigmine use should be under the supervision of a specialist experienced in the diagnosis and management of congenital myasthenic syndromes; some syndromes may be worsened by pyridostigmine therapy (eg, slow-channel myasthenic syndrome) and pyridostigmine use should be avoided (Ciafaloni 2019; Kliegman 2020). Dosage should be individualized based on patient response.
Infants, Children, and Adolescents: Oral: Immediate release: 1 mg/kg/dose every 4 hours; usual range: 4 to 5 mg/kg/day in 4 to 6 divided doses; maximum daily dose: 7 mg/kg/day divided in 5 to 6 doses (Kliegman 2020; Lorenzoni 2012).
Myasthenia gravis, autoimmune (juvenile): Limited data available: Note: Pyridostigmine usually considered part of initial treatment for most patients (MGFA [Sanders 2016]). Dosage should be adjusted such that larger doses administered prior to time of greatest fatigue.
Infants, Children, and Adolescents:
Oral: Immediate release: 0.5 to 1 mg/kg/dose every 4 to 6 hours; usual maximum single dose: 60 mg/dose; maximum daily dose: 7 mg/kg/day in divided doses (Kliegman 2020); in adults, therapeutic effects usually observed at total daily doses <960 mg/day divided into 4 to 8 doses; in some pediatric patients, doses as high as 1,500 mg/day have been reported (Andrews 1998; Kliegman 2020; Maggi 2011).
IM, IV: 0.05 to 0.15 mg/kg/dose; maximum dose: 10 mg/dose (Gal 2007).
Reversal of nondepolarizing neuromuscular blocker: Limited data available: Note: Pyridostigmine rarely used; other agents (eg, neostigmine, sugammadex) have routine place in therapy. Administer atropine or glycopyrrolate immediately prior to minimize side effects.
Infants, Children, and Adolescents: IM, IV: 0.1 to 0.25 mg/kg/dose (Gal 2007).
Vincristine-induced neurotoxicity: Very limited data available; efficacy results variable: Children ≥2 years and Adolescents: Oral: Immediate release: 3 mg/kg/day divided in 2 doses, in combination with pyridoxine for 3 weeks; dosing based on a case series of 4 children (age: 2 to 13 years) receiving vincristine for treatment of acute lymphoblastic leukemia (Akbayram 2010) and a 2-year-old receiving vincristine for a cervical synovial sarcoma (Müller 2004).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments are provided in the manufacturer's labeling; however, lower doses may be required due to prolonged elimination; dosage titration should be based on drug effects.
There are no dosage adjustments are provided in the manufacturer's labeling.
(For additional information see "Pyridostigmine: Drug information")
Myasthenia gravis:
Note: Recommendations provided are general guidelines only; dosing should be highly individualized, taking into account symptom severity and tolerance of side effects.
Immediate release: Oral: Initial: 30 to 60 mg 3 times daily; may increase in increments of 30 mg/dose every 2 to 3 days based on response and tolerability to 60 to 120 mg every 3 to 4 hours while awake (Bird 2022; Farmakidis 2018). Usual total daily dose: ≤960 mg/day divided into 4 to 8 doses (each dose administered no sooner than every 3 hours while awake); total daily doses higher than 450 to 600 mg/day may be associated with increased side effects (Bird 2022; Maggi 2011).
Sustained release (alternative formulation):
Note: It may be necessary to use IR therapy in conjunction with sustained-release therapy.
Oral: 180 to 360 mg once daily at bedtime (Maggi 2011; Sieb 2010).
IM, IV (off-label):
Note: For use when oral therapy is impractical. IM route preferred due to significant complications (eg, cardiac arrest) observed with IV route (Maggi 2011; Varner 2013).
IM, IV: One-thirtieth of oral dose; may repeat every 3 to 4 hours (example: patient’s maintenance oral dose is 60 mg oral pyridostigmine; may administer 2 mg IM/IV) (Maggi 2011; Varner 2013).
Discontinuation of therapy: Avoid abrupt discontinuation except in the case of severe adverse drug reaction (eg, cholinergic crisis) (Maggi 2011). For patients with stable myasthenia gravis (eg, stabilized on chronic immunosuppression), may reduce daily pyridostigmine dose gradually by ~30 mg per week (Farrugia 2020).
Postural orthostatic tachycardia syndrome (off-label use):
Immediate release: Oral: Initial: 30 mg twice daily; may increase dose at intervals of 1 to 2 weeks to 30 to 60 mg up to 3 times daily (CCS [Raj 2020]; Kanjwal 2011).
Reversal of nondepolarizing neuromuscular blocking agents:
Note: Monitor muscle twitch response to peripheral nerve stimulation; administer pyridostigmine after spontaneous recovery of neuromuscular function has begun. Atropine sulfate or glycopyrrolate IV should be administered immediately prior to or simultaneously with pyridostigmine to minimize side effects. Inadequate reversal is possible; manage by manual or mechanical ventilation until recovery is judged adequate (additional doses are not recommended).
IV: 0.1 to 0.25 mg/kg/dose.
Disopyramide-induced anticholinergic adverse effects (off-label use): Oral: Sustained release: 90 to 180 mg every 12 hours or as needed (Sherrid 2013; Sherrid 2016; Teichman 1987).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. However, lower initial doses may be required due to prolonged elimination in renal impairment.
There are no dosage adjustments provided in the manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as bromide:
Regonol: 10 mg/2 mL (2 mL) [contains benzyl alcohol]
Solution, Oral, as bromide:
Mestinon: 60 mg/5 mL (473 mL) [contains alcohol, usp, fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye), sodium benzoate; raspberry flavor]
Generic: 60 mg/5 mL (5 mL, 473 mL)
Tablet, Oral, as bromide:
Mestinon: 60 mg [scored]
Generic: 30 mg, 60 mg
Tablet Extended Release, Oral, as bromide:
Mestinon: 180 mg [scored]
Generic: 180 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as bromide:
Mestinon: 60 mg
Generic: 60 mg
Tablet Extended Release, Oral, as bromide:
Mestinon SR: 180 mg
Oral: Swallow sustained release tablets whole, do not chew or crush
Parenteral: May administer IM or as a direct IV slowly over 2-4 minutes; patients receiving large parenteral doses should be pretreated with atropine
Oral: Do not crush ER tablet.
Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. ER tablets should be swallowed whole. Do not break, crush, or chew. IR tablet, oral solution, syrup, and injectable formulations are available.
If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, selection of IR pyridostigmine formulations should be strongly considered in those with severe myasthenia gravis symptoms or when using for nerve gas exposure prophylaxis.
IV: Administer as slow IV push (Saltis 1993).
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); protect from moisture.
Oral: Mestinon: Treatment of myasthenia gravis (FDA approved in adults); has also been used for treatment of vincristine-induced neurotoxicity and congenital myasthenic syndrome.
Parenteral: Regonol: Reversal agent for effects of nondepolarizing neuromuscular blocking agents (FDA approved in adults); has also been used for treatment of myasthenia gravis.
Pyridostigmine may be confused with physostigmine
Regonol may be confused with Reglan, Renagel
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Central nervous system: Twitching (3%), hyperesthesia (2%)
Dermatologic: Xeroderma (2%)
Gastrointestinal: Abdominal pain (7%), diarrhea (7%)
Genitourinary: Dysmenorrhea (5%), urinary frequency (2%)
Neuromuscular & skeletal: Myalgia (2%), neck pain (2%)
Ophthalmic: Amblyopia (2%)
Respiratory: Epistaxis (2%)
Frequency not defined:
Cardiovascular: Bradycardia (transient), chest tightness, increased blood pressure
Central nervous system: Confusion, depressed mood, disturbed sleep, drowsiness, headache, hypertonia, lack of concentration, lethargy, localized warm feeling, numbness of tongue, tingling of extremities, vertigo
Dermatologic: Alopecia, diaphoresis, skin rash
Gastrointestinal: Abdominal cramps, bloating, borborygmi, flatulence, increased peristalsis, nausea, salivation, vomiting
Hypersensitivity: Hypersensitivity reaction
Neuromuscular & skeletal: Fasciculations, muscle cramps, weakness
Ophthalmic: Eye pain, lacrimation, miosis, visual disturbance
Respiratory: Acute bronchitis (exacerbation), exacerbation of asthma, increased bronchial secretions
<1%, postmarketing, and/or case reports: Fecal incontinence, loss of consciousness, pallor (postsyncopal), stiffness (arms or upper torso), thrombophlebitis, urinary incontinence
Hypersensitivity to pyridostigmine, anticholinesterase agents, or any component of the formulation; mechanical intestinal or urinary obstruction
Documentation of allergenic cross-reactivity for anticholinergic muscle stimulants is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Concerns related to adverse effects:
• Cholinergic effects: Symptoms of excess cholinergic activity may occur (eg, salivation, sweating, urinary incontinence). Overdosage may result in cholinergic crisis (eg, muscle weakness), which must be distinguished from myasthenic crisis; discontinue immediately in the presence of cholinergic crisis.
• Hypersensitivity reactions: May occur; have atropine and epinephrine ready to treat hypersensitivity reactions.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with bradycardia or other cardiac arrhythmias.
• Glaucoma: Use with caution; additive effect with antiglaucoma drugs may cause or exacerbate problems with night vision.
• Renal impairment: Use with caution in patients with renal impairment; initial lower doses may be needed; titrate to effect.
• Respiratory disease: Use with extreme caution in patients with asthma, bronchospastic disease, or chronic obstructive pulmonary disease.
Special populations:
• Bromide sensitivity: Use with caution in patients with bromide sensitivity.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Injection: Must be administered by trained personnel; use of peripheral nerve stimulation to monitor neuromuscular function recovery and continuous patient observation until recovery of normal respiration is recommended. To counteract anticholinergic effects, use of glycopyrrolate or atropine sulfate simultaneously with or prior to administration is recommended. May contain benzyl alcohol which has been associated with "gasping syndrome" in neonates.
• Oral: Adequate facilities should be available for cardiopulmonary resuscitation when testing and adjusting dose for myasthenia gravis.
Other warnings/precautions:
• Inadequate reversal of nondepolarizing neuromuscular blocking agents: Inadequate reversal induced by nondepolarizing neuromuscular blocking agents is possible; manage with manual or mechanical ventilation until recovery is adequate (additional doses not recommended). Failure to produce prompt (within 30 minutes) reversal of neuromuscular blockade may occur in the presence of extreme debilitation, carcinomatosis, or with concomitant use of certain broad-spectrum antibiotics, or anesthetic agents and other drugs which enhance neuromuscular blockade or cause respiratory depression.
Neonates of myasthenic mothers may have transient difficulties in swallowing, sucking, and breathing; use of pyridostigmine may be of benefit; use edrophonium test to assess neonate with these symptoms.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
Amifampridine: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Amifampridine. Amifampridine side effects may also be increased. Amifampridine may enhance the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Risk C: Monitor therapy
Anticholinergic Agents: Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Benoxinate: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Benoxinate. Specifically, the effects of benoxinate may be prolonged. Risk C: Monitor therapy
Beta-Blockers: Acetylcholinesterase Inhibitors may enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification
Cholinergic Agonists: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Cholinergic Agonists. Specifically, cholinergic effects may be enhanced or increased. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy
Dipyridamole: May diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Kanamycin: Pyridostigmine may diminish the therapeutic effect of Kanamycin. Risk C: Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. 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
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Succinylcholine: Acetylcholinesterase Inhibitors may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Pyridostigmine may cross the placenta (Buckley 1968).
Oral pyridostigmine is the agent of choice for treating myasthenia gravis during pregnancy; the IV route may cause uterine contractions and is not recommended (Sanders 2016). Use should be continued during labor (Norwood 2014). Transient neonatal myasthenia gravis may occur in neonates due to placental transfer of maternal antibodies (Norwood 2014; Sanders 2016).
In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey 2003).
Muscle strength, heart rate, respiration; vital capacity; observe for cholinergic reactions, particularly when administered IV
Inhibits destruction of acetylcholine by acetylcholinesterase which facilitates transmission of impulses across neuromuscular junction
Onset of action:
Recovery from vincristine neurotoxicity: Onset of action: 1 to 2 weeks (Akbayram 2010).
Myasthenia gravis: Oral: Within 30 minutes (Maggi 2011); IM: 15 to 30 minutes; IV: Within 2 to 5 minutes.
Reversal of nondepolarizing neuromuscular blocking agents: IV: Return of twitch height to 90% of control occurs within ~6 minutes following administration of 0.25 mg/kg dose; at lower doses, full recovery usually occurs within 15 to 30 minutes.
Duration: Oral: 3 to 4 hours in the daytime (Maggi 2011); IM, IV: 2 to 3 hours.
Absorption: Oral: Very poor.
Distribution: Vd: 0.53 to 1.76 L/kg (Aquilonius 1986).
Protein binding: None (Aquilonius 1986).
Metabolism: Hepatic and at tissue site by cholinesterases.
Bioavailability: 10% to 20% (Aquilonius 1986).
Half-life elimination:
Oral: 1 to 2 hours; renal failure: ~6 hours (Aquilonius 1986).
IV: ~1.5 hours (Aquilonius 1980).
Time to peak, plasma: Oral: 1 to 2 hours (Aquilonius 1986).
Excretion: Urine (80% to 90% as unchanged drug) (Aquilonius 1986).
Solution (Mestinon Oral)
60 mg/5 mL (per mL): $3.81
Solution (Pyridostigmine Bromide Oral)
60 mg/5 mL (per mL): $2.83
Solution (Regonol Intravenous)
10 mg/2 mL (per mL): $16.04
Tablet, controlled release (Mestinon Oral)
180 mg (per each): $42.13
Tablet, controlled release (Pyridostigmine Bromide ER Oral)
180 mg (per each): $24.81 - $24.83
Tablets (Mestinon Oral)
60 mg (per each): $22.21
Tablets (Pyridostigmine Bromide Oral)
30 mg (per each): $8.70
60 mg (per each): $0.15 - $1.61
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