Drug Interaction Report

GENERALLY AVOID: Metoclopramide may antagonize the pharmacologic effects of amantadine in the treatment of Parkinson's disease and drug-induced extrapyramidal reactions. Animal data suggest that amantadine may possess direct and indirect effects on dopamine neurons, and more recent studies have demonstrated that amantadine is a weak, noncompetitive NMDA (N-methyl-D-aspartate) receptor antagonist. In contrast, metoclopramide exhibits central antidopaminergic effects and augments NMDA activity. Adverse effects of metoclopramide include pseudoparkinsonism and extrapyramidal reactions, which are consistent with its pharmacologic effects. Conversely, amantadine may antagonize the actions of metoclopramide on the gastrointestinal tract due to its anticholinergic effects.

MANAGEMENT: Patients receiving amantadine for Parkinson's disease or drug-induced extrapyramidal reactions should generally avoid antidopaminergic agents including metoclopramide. If these agents have been administered together chronically, amantadine dosing should not be abruptly reduced or discontinued due to the potential to precipitate a parkinsonian crisis, delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, slurred speech, and rarely, neuroleptic malignant syndrome. In patients receiving amantadine for influenza A prophylaxis or treatment, the possibility of diminished efficacy of metoclopramide should be considered during coadministration.

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.