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 direct-acting cholinergic agents such as bethanechol, carbachol, cevimeline, and pilocarpine. This interaction is sometimes desirable and is the basis for using atropine in the treatment of excessive muscarinic side effects and cholinergic crisis induced by cholinergic overdose. Conversely, cholinergic agents may also counteract the pharmacologic effects of anticholinergic agents and other agents that rely partially on their anticholinergic activity for therapeutic effects (e.g., some antiparkinsonian and antiemetic/antivertigo agents). The mechanism of interaction involves opposing pharmacodynamic action on muscarinic receptor sites.

MANAGEMENT: It may be appropriate to avoid concomitant use of anticholinergic agents and cholinergic agents, depending on the needs of the patient. If concurrent use is necessary, the patient should be monitored for reduced pharmacologic effects of both drugs.

The consumption of grapefruit juice may be associated with increased plasma concentrations of darifenacin. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown.