Drug Interaction Report

MONITOR: Coadministration with inducers or mixed inducer/inhibitors of certain metabolic pathways may produce clinically meaningful reductions in the plasma concentrations of caspofungin. This assumption is based on results from regression analyses of patient pharmacokinetic data derived from a small number of patients who were administered the drugs efavirenz, nelfinavir, nevirapine, phenytoin, rifampin, dexamethasone, or carbamazepine prior to and/or concurrently with caspofungin. There are no data from formal drug interaction studies to evaluate these regression analyses, and it is not known which metabolic pathway involved in caspofungin clearance may be inducible.

MANAGEMENT: Caspofungin product labeling recommends that during coadministration with efavirenz, nelfinavir, nevirapine, phenytoin, rifampin, dexamethasone or carbamazepine, an increase in the daily dosage to 70 mg (following the usual 70 mg loading dose) should be considered in patients who are not clinically responding. While data are lacking for other drugs that are known to induce hepatic enzymes, the possibility of a similar interaction should be considered.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

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.

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.