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.

GENERALLY AVOID: Theoretically, the coadministration with grapefruit juice may increase the plasma concentrations of pimozide. The mechanism is decreased clearance of pimozide due to inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The use of pimozide alone has been associated with dose-dependent prolongation of the QT interval. Although clinical data are lacking, this interaction may result in potentiation of the proarrhythmic effect of pimozide and consequently an increased risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes. In addition, alcohol may potentiate some of the pharmacologic effects of pimozide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: The manufacturer recommends avoiding grapefruit juice (and probably grapefruits) during therapy with pimozide. Patients should also be advised to avoid or limit consumption of alcohol.