Drug Interaction Report

MONITOR: Theoretically, anticholinergic agents and other agents with significant anticholinergic activity (e.g., antihistamines, antispasmodics, neuroleptics, phenothiazines, skeletal muscle relaxants, tricyclic antidepressants, class IA antiarrhythmics especially disopyramide) may antagonize the effects of topically administered cholinergic agents such as acetylcholine, carbachol, demecarium, echothiophate, isoflurophate, physostigmine, and pilocarpine. The proposed mechanism involves opposing pharmacodynamic action on muscarinic receptor sites in ocular tissue. 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.

MANAGEMENT: Patients receiving long-term therapy with anticholinergic agents should be monitored for potentially diminished therapeutic (miotic) response to ophthalmic cholinergic therapy, and dosages adjusted as necessary.

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.