Drug Interactions between DDAVP and Trycet

GENERALLY AVOID: Alcohol may have additive CNS- and/or respiratory-depressant effects with propoxyphene. Misuse of propoxyphene, either alone or in combination with other CNS depressants, has been a major cause of drug-related deaths, particularly in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse.

MANAGEMENT: The use of alcohol during propoxyphene therapy should be avoided. Patients should be warned not to exceed the recommended dosage of propoxyphene and to avoid activities requiring mental alertness until they know how these agents affect them.

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GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

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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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