Pyridostigmine

Mestinon (pyridostigmine) is useful in the treatment of myasthenia gravis.

No information provided.

The side effects of Mestinon (pyridostigmine) are most commonly related to overdosage and generally are of two varieties, muscarinic and nicotinic. Among those in the former group are nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, miosis and diaphoresis. Nicotinic side effects are comprised chiefly of muscle cramps, fasciculation and weakness. Muscarinic side effects can usually be counteracted by atropine, but for reasons shown in the preceding section the expedient is not without danger. As with any compound containing the bromide radical, a skin rash may be seen in an occasional patient. Such reactions usually subside promptly upon discontinuance of the medication.

Read the entire FDA prescribing information for Mestinon (Pyridostigmine)

You should not use pyridostigmine if you you have a bladder or bowel obstruction.

Pyridostigmine bromide tablets, USP are an orally active cholinesterase inhibitor. Chemically, Pyridostigmine bromide is 3-hydroxy-1-methylpyridinium bromide dimethylcarbamate. Its structural formula is:

Pyridostigmine bromide, USP is a white or almost white crystalline, deliquescent powder. It is very soluble in water and in alcohol, slightly soluble in hexane, practically insoluble in ether.

Each Pyridostigmine bromide tablet, USP intended for oral administration contains 60 mg of Pyridostigmine bromide, USP. In addition, each tablet contains the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, low substituted hydroxypropyl cellulose, silicon dioxide and stearic acid.

Pyridostigmine bromide tablets, USP is available as

Conventional Tablets - each containing 60 mg Pyridostigmine bromide.

Dosage: The size and frequency of the dosage must be adjusted to the needs of the individual patient.

Conventional Tablets - The average dose is ten 60 mg tablets, spaced to provide maximum relief when maximum strength is needed. In severe cases as many as 25 tablets a day may be required, while in mild cases one to six tablets a day may suffice.

Note: For information on a diagnostic test for myasthenia gravis, and for the evaluation and stabilization of therapy, please see product literature on Tensilon®# (edrophonium chloride).

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.

Myasthenia gravis:

Oral: Highly individualized dosing ranges:

Immediate-release: 60 to 1,500 mg/day, usually 600 mg/day divided into 5 to 6 doses, spaced to provide maximum relief

Sustained release: 180 to 540 mg once or twice daily (doses separated by at least 6 hours); Note: It may be necessary to use immediate-release therapy in conjunction with sustained-release therapy.

IM, IV (off-label use): To supplement during labor and postpartum, during myasthenic crisis, or when oral therapy is impractical: ~1/30th of oral dose; observe patient closely for cholinergic reactions. IM route preferred due to significant complications (eg, cardiac arrest) observed with the IV route (Maggi 2011; Varner 2013). May also administer as a continuous infusion for myasthenic crisis.

Continuous infusion: IV: 1 to 2 mg/hour with gradual titration in increments of 0.5 to 1 mg/hour, up to a maximum rate of 4 mg/hour (Berrouschot 1997; Saltis 1993)

Reversal of nondepolarizing muscle relaxants: IV: 0.1 to 0.25 mg/kg/dose (onset to peak effect is dose-dependent; return of twitch height to 90% of control occurs within ~6 minutes; full recovery usually occurs within 15 to 30 minutes)

Note: The monitoring of muscle twitch response to peripheral nerve stimulation is advised; administer pyridostigmine after spontaneous recovery of neuromuscular function has begun. Atropine sulfate or glycopyrrolate I.V. 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).

Soman nerve gas exposure, pretreatment (military use): Note: Do not administer pyridostigmine after Soman exposure; if taken immediately before exposure (eg, when gas attack alarm is given) or at the same time, it is not expected to be effective and may exacerbate the effects of a sub-lethal exposure to Soman.

Oral: 30 mg every 8 hours beginning several hours prior to exposure; discontinue at first sign of Soman exposure, then immediately begin atropine and pralidoxime.

Myasthenia gravis (off-label use):

Note: Limited data available; dosage should be adjusted such that larger doses administered prior to time of greatest fatigue.

Oral: Immediate release: 1 mg/kg/dose every 4 to 6 hours; maximum daily dose: 7 mg/kg/day divided in 5 to 6 doses; (Usual daily dose: 600 mg/day; doses as high as 1,500 mg/day have been used) (Andrews 1998; Maggi 2011)

IM, IV: 0.05 to 0.15 mg/kg/dose (maximum dose: 10 mg) (Kleigman 2007). IM route preferred due to significant complications (eg, cardiac arrest) observed with the IV route (Maggi 2011).

Do not crush extended release tablet. For myasthenic crisis (off-label use), may administer IM, slow IV push, or as a continuous infusion (Maggi 2011; Saltis 1993).

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, decreased heart rate, 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% (Limited to important or life-threatening): Fecal incontinence, loss of consciousness, pallor (postsyncopal), stiffness (arms or upper torso), thrombophlebitis, urinary incontinence

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 COPD.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Bromide sensitivity: Use with caution in patients with bromide sensitivity.

• Pediatrics: Injection not indicated for use in neonates; may contain benzyl alcohol which has been associated with "gasping syndrome" in neonates.

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 muscle relaxants: Inadequate reversal induced by nondepolarizing muscle relaxants 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.

• Military use: Only for pretreatment for exposure to Soman; discontinue pyridostigmine at the first sign of Soman exposure (do not administer pyridostigmine after Soman exposure); atropine and pralidoxime must be administered after Soman exposure (pyridostigmine pretreatment offers no benefit against Soman unless atropine and pralidoxime are administered once symptoms of poisoning appear). Use in conjunction with protective garments, including gas mask, hood and overgarments.