Drug Interactions between DDAVP Rhinal Tube and Orphengesic

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: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

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Food may decrease the rate and extent of absorption of desmopressin following oral administration. In 16 healthy, nonsmoking volunteers, administration of a single 400 mcg oral dose of desmopressin concomitantly with a standardized meal (27% fat) resulted in a 52% decrease in the peak plasma concentration (Cmax) of desmopressin and a 43% decrease in systemic exposure (AUC) compared to administration in the fasting state. The Cmax and AUC were still reduced by 46% and 41%, respectively, when desmopressin was administered 1.5 hours after eating. Both feeding regimens prolonged the time to reach peak plasma concentration (Tmax) from 1 hour to 1.5 hours. However, the pharmacodynamic effects of desmopressin were not affected as assessed by urine volume and osmolality for at least 4 hours postdose. The degree of antidiuresis was similar in the absence of food and when the drug was taken with or 1.5 hours after eating. These findings would suggest a fairly minor clinical impact of the interaction in most patients, especially since oral desmopressin is intended for administration at bedtime. Nevertheless, the possibility of food effects should be considered before increasing the dose whenever a diminution of effect is noted. A significant interaction is not expected to occur with the sublingual formulation, since absorption occurs primarily in the oral mucosa, pharynx, and esophagus.

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The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

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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.

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