Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of eletriptan, which is primarily metabolized by the isoenzyme. According to the product labeling, eletriptan peak plasma concentration (Cmax) and systemic exposure (AUC) increased by nearly 3-fold and 6-fold, respectively, during coadministration with the potent inhibitor ketoconazole (400 mg). Likewise, erythromycin (1000 mg) increased eletriptan Cmax by 2-fold and AUC by nearly 4-fold. The half-life of eletriptan increased from about 5 hours to 8 hours with ketoconazole and 7 hours with erythromycin. Verapamil (480 mg), a moderate CYP450 3A4 inhibitor, increased eletriptan Cmax by 2.2-fold and AUC by 2.7-fold, while fluconazole (100 mg), a relatively weak inhibitor, increased eletriptan Cmax by 1.4-fold and AUC by 2-fold. Clinically, this interaction may result in increased risk of vasospastic reactions associated with the use of 5-HT1 receptor agonists, such as coronary artery vasospasm, peripheral vascular ischemia, and colonic ischemia.

MANAGEMENT: Eletriptan should not be used within at least 72 hours of treatment with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, nefazodone, delavirdine, most protease inhibitors, and ketolide and certain macrolide antibiotics. The manufacturer makes no specific recommendations for use with less potent inhibitors, but caution is appropriate. Patients should have vital signs monitored regularly and advised to notify their physician if they experience signs and symptoms of vasospasm such as numbness, tingling, or cyanosis in the extremities; muscle pains; weakness; or chest pain or tightness. Alternatively, other 5-HT1 receptor agonists that are not metabolized by CYP450 3A4 may be considered, such as frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan.

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.