Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of delavirdine, which is primarily metabolized by the isoenzyme. In seven HIV-infected subjects, administration of delavirdine (400 mg three times a day for 30 days) in combination with the potent CYP450 3A4 inducer rifampin (600 mg once daily on days 16 thru 30) decreased mean delavirdine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by approximately 92%, 97% and 100%, respectively, compared to administration of delavirdine alone. Oral clearance of delavirdine also increased by nearly 27-fold in the presence of rifampin. When delavirdine (400 mg three times a day for 30 days) was given with rifabutin (300 mg once daily on days 16 thru 30) in seven HIV-positive subjects, mean delavirdine Cmax, AUC and Cmin decreased by about 75%, 84% and 95%, respectively, and oral clearance increased by approximately 5-fold. Likewise, population pharmacokinetic data from efficacy studies showed that delavirdine Cmin was reduced by approximately 90% in patients (n=8) treated with various dosages of phenytoin, phenobarbital, and/or carbamazepine who were given delavirdine 300 to 400 mg three times a day.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, caution is advised when delavirdine is used with CYP450 3A4 inducers. Pharmacologic response to the antiretroviral regimen should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the antiretroviral dosage(s) adjusted as necessary.

ADJUST DOSING INTERVAL: Administration with food may increase the oral bioavailability of rifapentine and reduce the incidence of gastrointestinal adverse events. Administration with a high fat meal typically increases rifapentine's maximum concentration (Cmax) and systemic exposure (AUC) by approximately 40% to 50% over that observed when rifapentine is administered under fasting conditions. Rifapentine is often prescribed in combination with isoniazid. When single doses of rifapentine (900 mg) and isoniazid (900 mg) were administered with a low fat, high carbohydrate breakfast, the Cmax and AUC of rifapentine increased by 47% and 51%, respectively. On the other hand, isoniazid's Cmax and AUC decreased by 46% and 23%, respectively.

MANAGEMENT: Products containing oral rifapentine as the sole ingredient recommend administration with a meal to increase bioavailability and reduce the occurrence of gastrointestinal upset, nausea, and/or vomiting. Consultation of product labeling for combination products and/or relevant guidelines may be helpful if rifapentine is combined with a medication that is typically taken on an empty stomach.