CONTRAINDICATIONS / PRECAUTIONS
General Information
Pyridostigmine is contraindicated in patients with known hypersensitivity anticholinesterase agents.[34253]
Pyridostigmine is for military medical use only as a pretreatment for the exposure to the chemical nerve agent Soman. Do not rely solely on the pretreatment with pyridostigmine and the antidotes, atropine and pralidoxime, to provide complete protection from poisoning by Soman. Primary protection against exposure to chemical nerve agents is the wearing of protective garments. Pyridostigmine alone will not protect against exposure to Soman; the efficacy of pyridostigmine is dependent upon the rapid use of atropine and pralidoxime after Soman exposure. Pyridostigmine must not be taken after exposure to Soman. If pyridostigmine is taken immediately before exposure (e.g., when the attack alarm is given) or at the same time as Soman poisoning, it is not expected to be effective and may exacerbate the effects of sublethal exposure to Soman.[64093]
Bromide hypersensitivity
Use pyridostigmine with caution in patients with known bromide hypersensitivity. Weigh the risks and benefits of pyridostigmine use against the potential for rash or other adverse reactions in these patients.[64093]
Bladder obstruction, GI obstruction, ileus, urinary tract obstruction
Pyridostigmine is contraindicated in mechanical intestinal obstruction (i.e., GI obstruction or ileus) or urinary tract obstruction (i.e., bladder obstruction).[32948] [34253] [64002]
Cholinesterase inhibitor toxicity
Myasthenic crisis may be difficult to distinguish from cholinergic crisis (i.e., cholinesterase inhibitor toxicity) on a symptomatic basis given both states are characterized by increasing or extreme muscle weakness. Differentiation is important since increases in pyridostigmine doses in cholinergic crisis or a refractory or "insensitive" state could have grave consequences; differential diagnosis of the 2 types of crisis may require edrophonium chloride use as well as clinical judgment. In managing the crises, myasthenic crisis suggests the need for more intensive anticholinesterase therapy while cholinergic crisis requires prompt withdrawal of all anticholinergic medications. The immediate use of atropine in cholinergic crisis is also recommended. Use atropine with caution for counteracting adverse effects. Atropine may be used to abolish or obtund gastrointestinal adverse effects or other muscarinic reactions, but by masking signs of cholinesterase inhibitor toxicity, can lead to inadvertent induction of cholinergic crisis.[32948] [64002]
Asthma, bradycardia, cardiac arrhythmias, chronic obstructive pulmonary disease (COPD), glaucoma, hypertension
Use pyridostigmine with caution in patients at increased risk of anticholinergic reactions, including patients with bronchial asthma, chronic obstructive pulmonary disease (COPD), bradycardia, or cardiac arrhythmias as well as patients being treated for hypertension or glaucoma with beta-adrenergic receptor blockers.[32948] [64002]
Neonates
Pyridostigmine injection contains benzyl alcohol as a preservative and is not for use in neonates. Exposure to excessive amounts of benzyl alcohol has been associated with hypotension, metabolic acidosis, and kernicterus in neonates. In this population, a "gasping syndrome" characterized by CNS depression, metabolic acidosis, and gasping respirations has been associated with dosages more than 99 mg/kg/day. However, the minimum amount of benzyl alcohol at which toxicity may occur is unknown, and premature and low-birth-weight neonates may be more likely to develop toxicity.[34253] [52949]
Renal disease
Lower pyridostigmine doses may be required in patients with renal disease; base treatment on titration of drug dosage to effect. Pyridostigmine is mainly excreted unchanged by the kidney.[32948] [64002]
Adrenal insufficiency, electrolyte imbalance
Electrolyte imbalance and diseases which lead to electrolyte imbalance, such as adrenal insufficiency, have been shown to alter neuromuscular blockade. Depending on the nature of the imbalance, either enhancement or inhibition may be expected. Consider the possibility that such circumstances may interfere with the restoration of neuromuscular function when using parenteral pyridostigmine for neuromuscular blockade reversal.[64093]
Requires an experienced clinician
The use of parenteral pyridostigmine for neuromuscular blockade reversal requires an experienced clinician familiar with the use of agents which reverse or antagonize the effects of neuromuscular blocking agents.[34253]
Pregnancy
There are no adequate data on the developmental risk associated with pyridostigmine use during human pregnancy.[63768] Guidelines consider oral pyridostigmine as the first-line treatment of myasthenia gravis during pregnancy. Intravenous pyridostigmine may produce uterine contractions, and its use is not recommended during pregnancy.[61823] Pyridostigmine crosses the placenta. There is a possibility that neonates born to myasthenic mothers can have transient muscle weakness if pyridostigmine is used during pregnancy.[63769]
Breast-feeding
Pyridostigmine is excreted in human milk.[49432] Previous American Academy of Pediatrics recommendations considered pyridostigmine to be generally compatible with breast-feeding.[27500] Based on the amount of pyridostigmine detected in breast milk of 2 nursing mothers, the estimated amount of pyridostigmine per kg of body weight of a nursing infant would be 0.1% or less of the maternal dose. Pyridostigmine milk concentrations ranged from 13 to 24 ng/mL at various times during dosing intervals on days 5 and 35 postpartum in a mother taking oral pyridostigmine 3 mg/kg per day (60 mg three times daily). Pyridostigmine concentrations ranged from the lower limit of detection (2 to 5 ng/mL) to 5 ng/mL during a dosage interval when the same mother received 2mg/kg per day (40 mg 3 times daily) at 102 days postpartum. In a second mother receiving 5 mg/kg per day (60 mg 5 times daily), pyridostigmine concentrations were 25 ng/mL at the time of a dose, and 22 ng/mL 2.5 hours after the dose at 60 days postpartum. No adverse effects occurred in the infants.[49432] Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for pyridostigmine and any potential adverse effects on the breast-fed infant from pyridostigmine or the underlying maternal condition.[63768]
DRUG INTERACTIONS
Ambenonium Chloride: (Major) Other cholinesterase inhibitors can produce additive pharmacodynamic effects if used concomitantly with ambenonium chloride. Because ambenonium has a more prolonged action than other antimyasthenic drugs, simultaneous administration with other cholinergics is contraindicated except under strict medical supervision. The overlap in duration of action of several drugs complicates dosage schedules. Therefore, when a patient is to be given ambenonium, suspend the administration of all other cholinergics until the patient has been stabilized. In most instances, the myasthenic symptoms are effectively controlled by ambenonium use alone.
Amifampridine: (Moderate) Coaministration of amifampridine and pyridostigmine may increase the risk for adverse reactions due to additive cholinergic effects. Monitor patients closely for new or worsening side effects such as headache, visual disturbances, watery eyes, excessive sweating, shortness of breath, nausea, vomiting, diarrhea, bradycardia, loss of bladder control, confusion, or tremors.
Amikacin: (Moderate) Aminoglycosides have been associated with neuromuscular blockade when used as an abdominal irrigant intraoperatively. Although the risk of neuromuscular blockade is remote with parenteral aminoglycoside therapy, these antibiotics should be used cautiously in myasthenic patients. This represents a pharmacodynamic interaction with cholinesterase inhibitors when used to treat myasthenia gravis, rather than a pharmacokinetic interaction.
Aminoglycosides: (Moderate) Aminoglycosides have been associated with neuromuscular blockade when used as an abdominal irrigant intraoperatively. Although the risk of neuromuscular blockade is remote with parenteral aminoglycoside therapy, these antibiotics should be used cautiously in myasthenic patients. This represents a pharmacodynamic interaction with cholinesterase inhibitors when used to treat myasthenia gravis, rather than a pharmacokinetic interaction.
Amitriptyline: (Moderate) Tricyclic antidepressants may antagonize some of the effects of parasympathomimetics, such as pyridostigmine, due to their anticholinergic activity.
Amitriptyline; Chlordiazepoxide: (Moderate) Tricyclic antidepressants may antagonize some of the effects of parasympathomimetics, such as pyridostigmine, due to their anticholinergic activity.
Amoxapine: (Major) Amoxapine may antagonize some of the effects of parasympathomimetics. However, bethanechol has occasionally been used therapeutically to offset some of the adverse antimuscarinic effects of cyclic antidepressants. Due to their anticholinergic actions, some cyclic antidepressants, such as amoxapine, may potentially antagonize the therapeutic actions of pyridostigmine. Consider alternatives if concurrent therapy is needed.
Articaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Atropine: (Major) Coadministration of atropine and pyridostigmine bromide may produce a mutually antagonistic effect.
Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Coadministration of atropine and pyridostigmine bromide may produce a mutually antagonistic effect. (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of hyoscyamine.
Atropine; Difenoxin: (Major) Coadministration of atropine and pyridostigmine bromide may produce a mutually antagonistic effect.
Atropine; Diphenoxylate: (Major) Coadministration of atropine and pyridostigmine bromide may produce a mutually antagonistic effect.
Atropine; Edrophonium: (Major) Coadministration of atropine and pyridostigmine bromide may produce a mutually antagonistic effect. (Major) Edrophonium and pyridostigmine are both parasympathomimetics. Coadministration results in additive effects and should be done cautiously.
Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Coadministration of atropine and pyridostigmine bromide may produce a mutually antagonistic effect. (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of hyoscyamine. (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of scopolamine.
Azelastine; Fluticasone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Bacitracin: (Moderate) Parenteral administration of high doses of certain antibiotics such as bacitracin may intensify or produce neuromuscular block through their own pharmacologic actions. If unexpected prolongation of neuromuscular block or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect.
Beclomethasone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of hyoscyamine.
Benztropine: (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of benztropine. Benztropine might also antagonize some of the effects of the parasympathomimetics.
Betamethasone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Parenteral administration of high doses of certain antibiotics such as tetracyclines may intensify or produce neuromuscular block through their own pharmacologic actions. If unexpected prolongation of neuromuscular block or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Parenteral administration of high doses of certain antibiotics such as tetracyclines may intensify or produce neuromuscular block through their own pharmacologic actions. If unexpected prolongation of neuromuscular block or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect.
Budesonide: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Budesonide; Formoterol: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Bupivacaine Liposomal: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Bupivacaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Bupivacaine; Lidocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Chloroprocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Cholinergic agonists: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Ciclesonide: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Clomipramine: (Moderate) Tricyclic antidepressants may antagonize some of the effects of parasympathomimetics, such as pyridostigmine, due to their anticholinergic activity.
Cocaine: (Major) cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine's effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued. Additionally, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis.
Colistimethate, Colistin, Polymyxin E: (Moderate) Parenteral administration of high doses of certain antibiotics such as colistimethate sodium may intensify or produce neuromuscular blockade through their own pharmacologic actions. If unexpected prolongation of neuromuscular blockade or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Corticosteroids: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Corticotropin, ACTH: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Cortisone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Deflazacort: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Demeclocycline: (Moderate) Parenteral administration of high doses of certain antibiotics such as tetracyclines may intensify or produce neuromuscular block through their own pharmacologic actions. If unexpected prolongation of neuromuscular block or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect.
Desipramine: (Moderate) Tricyclic antidepressants may antagonize some of the effects of parasympathomimetics, such as pyridostigmine, due to their anticholinergic activity.
Dexamethasone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Dextromethorphan; Quinidine: (Moderate) Quinidine can potentiate the effects of depolarizing and nondepolarizing neuromuscular blockers. Recurrent paralysis may occur if quinidine injection is administered during recovery from use of nondepolarizing muscle relaxants. Consider the possible effect from quinidine when administering anticholinesterase agents such as pyridostigmine to antagonize neuromuscular blockade induced by nondepolarizing muscle relaxants
Dicyclomine: (Major) The muscarinic actions of pyridoostigmine can antagonize the antimuscarinic actions of dicyclomine and vice-versa.
Digoxin: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may be increased when given with other medications known to cause bradycardia such as digoxin. In one study involving multiple doses of galantamine at 24 mg/day with digoxin at a dose of 0.375 mg/day, there was no effect on the pharmacokinetics of digoxin, except one healthy subject was hospitalized due to second and third degree heart block and bradycardia.
Disopyramide: (Moderate) Disopyramide possesses anticholinergic properties. Disopyramide should not be used in patients with myasthenia gravis because the anticholinergic properties of the drug could precipitate a myasthenic crisis. It is unclear if disopyramide can interfere with the cholinomimetic activity of pyridostigmine.
Doxepin: (Moderate) Tricyclic antidepressants may antagonize some of the effects of parasympathomimetics, such as pyridostigmine, due to their anticholinergic activity.
Doxycycline: (Moderate) Parenteral administration of high doses of certain antibiotics such as tetracyclines may intensify or produce neuromuscular block through their own pharmacologic actions. If unexpected prolongation of neuromuscular block or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect.
Edrophonium: (Major) Edrophonium and pyridostigmine are both parasympathomimetics. Coadministration results in additive effects and should be done cautiously.
Etomidate: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Fludrocortisone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Flunisolide: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Fluticasone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Fluticasone; Salmeterol: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Fluticasone; Umeclidinium; Vilanterol: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Fluticasone; Vilanterol: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Formoterol; Mometasone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Fospropofol: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Gentamicin: (Moderate) Aminoglycosides have been associated with neuromuscular blockade when used as an abdominal irrigant intraoperatively. Although the risk of neuromuscular blockade is remote with parenteral aminoglycoside therapy, these antibiotics should be used cautiously in myasthenic patients. This represents a pharmacodynamic interaction with cholinesterase inhibitors when used to treat myasthenia gravis, rather than a pharmacokinetic interaction.
Glycopyrrolate: (Minor) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
Glycopyrrolate; Formoterol: (Minor) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
Halogenated Anesthetics: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Hetastarch; Dextrose; Electrolytes: (Moderate) Magnesium salts may enhance the neuromuscular blockade and may interfere with the restoration of neuromuscular function. Consider the possibility of enhanced neuromuscular blockade from magnesium salts during pyridostigmine administration.
Homatropine; Hydrocodone: (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of homatropine.
Hydrocortisone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Hyoscyamine: (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of hyoscyamine.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of hyoscyamine.
Imipramine: (Moderate) Tricyclic antidepressants may antagonize some of the effects of parasympathomimetics, such as pyridostigmine, due to their anticholinergic activity.
Indacaterol; Glycopyrrolate: (Minor) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
Kanamycin: (Moderate) Aminoglycosides have been associated with neuromuscular blockade when used as an abdominal irrigant intraoperatively. Although the risk of neuromuscular blockade is remote with parenteral aminoglycoside therapy, these antibiotics should be used cautiously in myasthenic patients. This represents a pharmacodynamic interaction with cholinesterase inhibitors when used to treat myasthenia gravis, rather than a pharmacokinetic interaction.
Ketamine: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Levobupivacaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Lidocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Magnesium Salts: (Moderate) Magnesium salts may enhance the neuromuscular blockade and may interfere with the restoration of neuromuscular function. Consider the possibility of enhanced neuromuscular blockade from magnesium salts during pyridostigmine administration.
Magnesium: (Moderate) Magnesium salts may enhance the neuromuscular blockade and may interfere with the restoration of neuromuscular function. Consider the possibility of enhanced neuromuscular blockade from magnesium salts during pyridostigmine administration.
Maprotiline: (Major) Maprotiline may antagonize some of the effects of pyridostigmine.
Mepivacaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Mepivacaine; Levonordefrin: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of hyoscyamine.
Methocarbamol: (Moderate) Methocarbamol may inhibit the effect of cholinesterase inhibitors. Methocarbamol also has sedative properties that may interfere with cognition. Therefore, methocarbamol should be used with caution in patients receiving cholinesterase inhibitors.
Methscopolamine: (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of methscopolamine.
Methylprednisolone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Minocycline: (Moderate) Parenteral administration of high doses of certain antibiotics such as tetracyclines may intensify or produce neuromuscular block through their own pharmacologic actions. If unexpected prolongation of neuromuscular block or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect.
Mometasone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Neostigmine: (Major) Neostigmine and pyridostigmine are both parasympathomimetics. Coadministration results in additive effects and should be done cautiously.
Neuromuscular blockers: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
Nonsteroidal antiinflammatory drugs: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Nortriptyline: (Moderate) Tricyclic antidepressants may antagonize some of the effects of parasympathomimetics, such as pyridostigmine, due to their anticholinergic activity.
Omadacycline: (Moderate) Parenteral administration of high doses of certain antibiotics such as tetracyclines may intensify or produce neuromuscular block through their own pharmacologic actions. If unexpected prolongation of neuromuscular block or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect.
Oxybutynin: (Moderate) Oxybutynin is an antimuscarinic; the muscarinic actions of pyridostigmine could be antagonized when used concomitantly with oxybutynin.
Paromomycin: (Moderate) Aminoglycosides have been associated with neuromuscular blockade when used as an abdominal irrigant intraoperatively. Although the risk of neuromuscular blockade is remote with parenteral aminoglycoside therapy, these antibiotics should be used cautiously in myasthenic patients. This represents a pharmacodynamic interaction with cholinesterase inhibitors when used to treat myasthenia gravis, rather than a pharmacokinetic interaction.
Perphenazine; Amitriptyline: (Moderate) Tricyclic antidepressants may antagonize some of the effects of parasympathomimetics, such as pyridostigmine, due to their anticholinergic activity.
Physostigmine: (Major) Pyridostigmine and physostigmine are both parasympathomimetics. Coadministration results in additive effects and should be done cautiously.
Plazomicin: (Moderate) Aminoglycosides have been associated with neuromuscular blockade when used as an abdominal irrigant intraoperatively. Although the risk of neuromuscular blockade is remote with parenteral aminoglycoside therapy, these antibiotics should be used cautiously in myasthenic patients. This represents a pharmacodynamic interaction with cholinesterase inhibitors when used to treat myasthenia gravis, rather than a pharmacokinetic interaction.
Polymyxin B: (Moderate) Parenteral administration of high systemic doses of certain antibiotics, such as Polymyxin B, may intensify or produce neuromuscular block or paralysis through its pharmacologic actions. If Polymyxin B or other newly introduced antibiotics are used in conjunction with nondepolarizing neuromuscular blocking drugs during surgery, unexpected prolongation of neuromuscular block or resistance to its reversal should be considered a possibility.
Polymyxins: (Moderate) Parenteral administration of high doses of certain antibiotics such as colistimethate sodium may intensify or produce neuromuscular blockade through their own pharmacologic actions. If unexpected prolongation of neuromuscular blockade or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Prednisolone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Prednisone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Prilocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Prilocaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Procainamide: (Major) Procainamide may antagonize the effects of cholinesterase inhibitors such as pyridostigmine in the treatment of myasthenia gravis. Isolated case reports describe worsening symptoms shortly after procainamide is added however, this interaction may be due more to procainamide's local anesthetic properties than its anticholinergic properties.
Procaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Propantheline: (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of propantheline.
Propofol: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Protriptyline: (Moderate) Tricyclic antidepressants may antagonize some of the effects of parasympathomimetics, such as pyridostigmine, due to their anticholinergic activity.
Quinidine: (Moderate) Quinidine can potentiate the effects of depolarizing and nondepolarizing neuromuscular blockers. Recurrent paralysis may occur if quinidine injection is administered during recovery from use of nondepolarizing muscle relaxants. Consider the possible effect from quinidine when administering anticholinesterase agents such as pyridostigmine to antagonize neuromuscular blockade induced by nondepolarizing muscle relaxants
Quinine: (Major) The actions of quinine on skeletal muscle are pharmacologically opposite to those of cholinesterase inhibitors. Therefore, quinine may interfere with the actions of cholinesterase inhibitors in treating such conditions as myasthenia gravis. This represents a pharmacodynamic interaction with cholinesterase inhibitors rather than a pharmacokinetic interaction.
Sarecycline: (Moderate) Parenteral administration of high doses of certain antibiotics such as tetracyclines may intensify or produce neuromuscular block through their own pharmacologic actions. If unexpected prolongation of neuromuscular block or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect.
Scopolamine: (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of scopolamine.
Streptomycin: (Moderate) Aminoglycosides have been associated with neuromuscular blockade when used as an abdominal irrigant intraoperatively. Although the risk of neuromuscular blockade is remote with parenteral aminoglycoside therapy, these antibiotics should be used cautiously in myasthenic patients. This represents a pharmacodynamic interaction with cholinesterase inhibitors when used to treat myasthenia gravis, rather than a pharmacokinetic interaction.
Tetracaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Tetracycline: (Moderate) Parenteral administration of high doses of certain antibiotics such as tetracyclines may intensify or produce neuromuscular block through their own pharmacologic actions. If unexpected prolongation of neuromuscular block or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect.
Tetracyclines: (Moderate) Parenteral administration of high doses of certain antibiotics such as tetracyclines may intensify or produce neuromuscular block through their own pharmacologic actions. If unexpected prolongation of neuromuscular block or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect.
Tobramycin: (Moderate) Aminoglycosides have been associated with neuromuscular blockade when used as an abdominal irrigant intraoperatively. Although the risk of neuromuscular blockade is remote with parenteral aminoglycoside therapy, these antibiotics should be used cautiously in myasthenic patients. This represents a pharmacodynamic interaction with cholinesterase inhibitors when used to treat myasthenia gravis, rather than a pharmacokinetic interaction.
Triamcinolone: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
Tricyclic antidepressants: (Moderate) Tricyclic antidepressants may antagonize some of the effects of parasympathomimetics, such as pyridostigmine, due to their anticholinergic activity.
Trihexyphenidyl: (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of trihexyphenidyl.
Trimipramine: (Moderate) Tricyclic antidepressants may antagonize some of the effects of parasympathomimetics, such as pyridostigmine, due to their anticholinergic activity.