Drug Interaction Report

GENERALLY AVOID: Coadministration with potent 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 ketoconazole (400 mg). The half-life increased from 5 hours to 8 hours. Likewise, erythromycin (1000 mg) increased eletriptan Cmax by 2-fold and AUC by nearly 4-fold, while half-life increased from about 5 hours to 7 hours. 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. Alternatively, other 5-HT1 receptor agonists that are not metabolized by CYP450 3A4 may be considered, such as frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan.

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.