Drug Interactions between metoclopramide and Synalgos-DC

MONITOR: By diminishing gastrointestinal motility, narcotic analgesics may antagonize the pharmacologic effects of gastrointestinal prokinetic agents. In addition, concomitant use may increase central nervous system effects such as sedation, dizziness, confusion, and mental depression.

MONITOR: Gastrointestinal prokinetic agents may alter the absorption characteristics of some controlled release narcotic analgesic preparations. In a study of 20 patients undergoing surgery, peak plasma concentration (Cmax) of morphine was reached more quickly in patients who received a 20 mg dose of sustained-release morphine with 20 mg metoclopramide compared to patients who received morphine alone, although the actual Cmax and systemic exposure (AUC) were not significantly altered. Both the degree and the rate of onset of sedation were also increased in the metoclopramide group, which may have been partially due to additive pharmacodynamic effects of the drugs. During chronic administration, however, the clinical relevance of this interaction may be diminished due to tolerance.

MANAGEMENT: The potential for reduced efficacy of gastrokinetic agents should be considered during coadministration with opioid analgesics. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their doctor if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Coadministration with metoclopramide may enhance the rate and extent of absorption of drugs that are mainly absorbed in the small intestine, such as paracetamol, aspirin, and tetracycline. The proposed mechanism is a metoclopramide-mediated increase in gastric emptying. Clinical and laboratory monitoring should be considered and the dose adjusted as appropriate. The clinical significance of this interaction is unknown.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.