Drug Interaction Report

ADJUST DOSE: 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: The manufacturer of caspofungin states 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.

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.