Drug Interaction Report

GENERALLY AVOID: Anticholinergic agents and other agents with significant anticholinergic activity (e.g., clozapine, class IA antiarrhythmics especially disopyramide) may antagonize the effects of cholinergic skeletal muscle stimulants (e.g., ambenonium, edrophonium, guanidine, neostigmine, pyridostigmine). Although this interaction may be desirable in some situations, such as when atropine is used to treat excessive muscarinic side effects and cholinergic crisis induced by anticholinesterase overdose, unintentional or indiscriminate use of anticholinergic agents in the treatment of myasthenia gravis may exacerbate symptoms. In addition, such use may mask the less serious, gastrointestinal signs of cholinergic overdose and lead to inadvertent induction of cholinergic crisis, which can produce respiratory paralysis and death.

MANAGEMENT: Agents with potent anticholinergic activity should preferably be avoided in patients receiving cholinergic skeletal muscle stimulants. If concurrent use is necessary, patients treated for myasthenia gravis should be monitored for potential exacerbation of symptoms. Caution is advised not only because anticholinergic agents may mask the signs of a cholinergic overdose, but also because increasing muscle weakness associated with disease aggravation may be difficult to distinguish from that due to cholinergic crisis.

MONITOR: Additive cholinergic effects may occur when methacholine is coadministered with cholinesterase inhibitors. Methacholine is a cholinergic agonist that is hydrolyzed by cholinesterases, and concomitant use of cholinesterase inhibitors may decrease methacholine inactivation, thereby increasing the risk of cholinergic toxicity.

MANAGEMENT: Caution is advised when methacholine is coadministered with cholinesterase inhibitors. Patients should be monitored for increased cholinergic effects and potential toxicity.

ADJUST DOSING INTERVAL: Anticholinergics, beta-agonists, and theophylline may inhibit the bronchial airway response to methacholine. Methacholine is a cholinergic agonist that binds muscarinic receptors in bronchial smooth muscle, which leads to bronchoconstriction. Since patients with asthma exhibit greater sensitivity to induced bronchoconstriction than healthy subjects, methacholine is used to diagnose bronchial airway hyperreactivity in the absence of clinically apparent asthma. Bronchodilation caused by anticholinergics, beta-agonists, and theophylline may counteract methacholine-induced bronchoconstriction, possibly leading to diagnostic failure.

MANAGEMENT: Treatment with anticholinergics, beta-agonists, and theophylline should be interrupted before methacholine administration for the following durations:
--Short-acting anticholinergics (e.g., ipratropium): 12 hours
--Long-acting anticholinergics (e.g., tiotropium): At least 168 hours
--Short-acting beta-agonists (e.g., albuterol): 6 hours
--Long-acting beta-agonists (e.g., salmeterol): 36 hours (some authorities recommend 48 hours for ultra-long-acting beta-agonists [e.g., indacaterol, olodaterol, vilanterol])
--Oral theophylline: 12 to 48 hours

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.