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 (Ref). 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 (Ref).
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 (Ref).
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 (Ref).
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) (Ref).
Discontinuation of therapy: Avoid abrupt discontinuation except in the case of severe adverse drug reaction (eg, cholinergic crisis) (Ref). For patients with stable myasthenia gravis (eg, stabilized on chronic immunosuppression), may reduce daily pyridostigmine dose gradually by ~30 mg per week (Ref).
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 (Ref).
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 (Ref).
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.
Refer to adult dosing.
(For additional information see "Pyridostigmine: Pediatric drug information")
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 (Ref). 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 (Ref).
Myasthenia gravis, autoimmune (juvenile): Limited data available: Note: Pyridostigmine usually considered part of initial treatment for most patients (Ref). 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 (Ref); 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 (Ref).
IM, IV: 0.05 to 0.15 mg/kg/dose; maximum dose: 10 mg/dose (Ref).
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 (Ref).
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 (Ref) and a 2-year-old receiving vincristine for a cervical synovial sarcoma (Ref).
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.
Acetylcholinesterase inhibitors, including pyridostigmine, have been associated with cardiac effects, including bradycardia, atrioventricular block, and syncope (Ref).
Mechanism: Related to the mechanism of action; increased cholinergic stimulation of the parasympathetic nervous system results in reduced automaticity of the sinus node leading to bradycardia (Ref).
Onset: Varied; bradycardia occurred within 4 minutes of IV administration (administered in combination with atropine) (Ref) and within 120 minutes of oral administration (Ref).
Risk factors:
• Administration without concomitant anticholinergic agent (eg, atropine, glycopyrrolate) for neuromuscular blockade reversal (Ref)
• Patients with preexisting conduction defects without a functioning pacemaker (Ref)
• Concomitant risk factors for bradyarrhythmias (eg, electrolyte abnormalities, infection, hypothyroidism) (Ref)
• Concomitant use of cardiac glycosides (eg, digoxin) (Ref)
• Older patients (Ref)
Gastrointestinal effects including abdominal cramps, diarrhea, increased peristalsis, nausea, sialorrhea, and vomiting have been reported with pyridostigmine and may lead to dose reduction or discontinuation (Ref).
Mechanism: Related to the mechanism of action; increased cholinergic activity increases smooth muscle contraction, peristalsis, and sphincter relaxation in the GI tract (Ref).
Onset: Rapid; in one study, abdominal discomfort and sialorrhea were reported within 120 minutes of oral administration (Ref).
Risk factors:
• Doses >450 to 600 mg/day (Ref)
• Dose titration (Ref)
• Older age (Ref)
• History of dysphagia (Ref)
Respiratory effects, including increased bronchial secretions and bronchoconstriction, have been reported with pyridostigmine (Ref).
Mechanism: Related to the mechanism of action; increased cholinergic activity increases bronchial smooth muscle constriction and bronchial secretions (Ref).
Onset: Rapid; a reduction in FEV1 (-1.6% from baseline) occurred within 14 minutes of IV administration (administered in combination with atropine) (Ref); a reduction in FVC (-4.3% of predicted from baseline) occurred within 2 hours following oral administration (Ref).
Risk factors:
• History of asthma or obstructive lung disease (Ref)
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Frequency not defined:
Gastrointestinal: Increased peristalsis, vomiting
Nervous system: Asthenia
Neuromuscular & skeletal: Fasciculations
Ophthalmic: Miosis
Postmarketing:
Cardiovascular: Atrioventricular block (Chaucer 2018), bradycardia (Fogdall 1973), syncope (Arsura 1987), thrombophlebitis (IV)
Dermatologic: Diaphoresis (Maggi 2011), skin rash (Maggi 2011)
Gastrointestinal: Abdominal cramps (Remijn-Nelissen 2022), bloating (Kanjwal 2011), diarrhea (Remijn-Nelissen 2022), flatulence (Remijn-Nelissen 2022), nausea (Kanjwal 2011), sialorrhea (Maggi 2011)
Genitourinary: Urinary urgency (Remijn-Nelissen 2022)
Hypersensitivity: Hypersensitivity reaction (Castellano 1998)
Nervous system: Tingling of extremities (fingers and toes) (Maggi 2011)
Neuromuscular & skeletal: Muscle cramps (Remijn-Nelissen 2022), muscle twitching (Remijn-Nelissen 2022)
Respiratory: Bronchoconstriction (Feldt-Rasmussen 1985), increased bronchial secretions (Maggi 2011)
Hypersensitivity to pyridostigmine, anticholinesterase agents, or any component of the formulation; mechanical intestinal or urinary obstruction
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:
• 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.
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.
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
Solution (Mestinon Oral)
60 mg/5 mL (per mL): $4.16
Solution (pyRIDostigmine Bromide Oral)
60 mg/5 mL (per mL): $2.83 - $3.24
Solution (Regonol Intravenous)
10 mg/2 mL (per mL): $16.04
Tablet, controlled release (Mestinon Oral)
180 mg (per each): $45.99
Tablet, controlled release (pyRIDostigmine Bromide ER Oral)
180 mg (per each): $24.81 - $24.83
Tablets (Mestinon Oral)
60 mg (per each): $24.25
Tablets (pyRIDostigmine Bromide Oral)
30 mg (per each): $8.70
60 mg (per each): $0.15 - $1.61
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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: 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 (Ref).
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
Myasthenia gravis (oral only): Treatment of symptoms associated with myasthenia gravis.
Reversal of nondepolarizing neuromuscular blocking agents (injection only): Reversal agent or antagonist of nondepolarizing neuromuscular blocking agents.
Disopyramide-induced anticholinergic adverse effects; Postural orthostatic tachycardia syndrome
PyRIDostigmine may be confused with PHYSostigmine, pyridoxine
Regonol may be confused with Reglan, Renagel
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.
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
Chlorprothixene: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Chlorprothixene. Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Chlorprothixene. Risk C: Monitor therapy
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
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. 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).
Pyridostigmine is present in breast milk (Hardell 1982).
Information is available from two mothers using pyridostigmine for myasthenia gravis throughout pregnancy and postpartum. Maternal doses ranged from 120 mg to 300 mg/day and sampling occurred from 5 to 102 days after delivery. Milk concentrations averaged ≤0.1% of the weight-adjusted maternal dose (n=2); infant plasma concentrations were less than the limit of quantification (<2 ng/mL; n=1) (Hardell 1982).
Disease exacerbations may occur in breastfeeding women with poorly controlled myasthenia gravis due to fatigue associated with breastfeeding. Babies born to women with myasthenia gravis may have feeding difficulties due to transient myasthenia gravis of the newborn (Norwood 2014). Breastfed infants should be monitored for fatigue associated with transient neonatal myasthenia gravis (Varner 2013); however, current guidelines note that breastfeeding is acceptable in women taking pyridostigmine for myasthenia gravis (Norwood 2014).
ECG, blood pressure, and heart rate especially when administered IV; cholinergic reactions (eg, nausea, vomiting, diarrhea, increased salivation) especially when administered IV; consult individual institutional policies and procedures.
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).
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟