Drug Interaction Report

MONITOR: Coadministration with drugs that possess significant anticholinergic activity may potentiate the antimotility effect of loperamide. An isolated case report describes an incident of fatal gastroenteritis during concomitant treatment with clozapine and loperamide. A 36-year-old man who had been treated with clozapine 500 mg/day and was previously in good health died after taking a total of 6 mg of loperamide during an outbreak of intestinal disease in a Finnish hospital. The patient received no other medications. The authors theorized that the anticholinergic effect of clozapine in combination with the antimotility effect of loperamide may have led to toxic megacolon. However, causality has not been determined.

MANAGEMENT: Until further information is available, loperamide should be used with caution in combination with drugs that possess significant anticholinergic activity (e.g., antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; class IA antiarrhythmics especially disopyramide). Ambulatory patients should also be made aware of the possibility of additive CNS effects (e.g., drowsiness, dizziness, lightheadedness, confusion) and counseled to avoid activities requiring mental alertness until they know how these agents affect them.

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GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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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.

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