Itraconazole Fexofenadine

Drug-drug interactions involving fexofenadine have been reported which includes not only interactions with concomitant chugs, but also those with fruit juices. Concomitant use of itraconazole (303), verapamil (304), and ritonavir (305) increased the area under the curve of the plasma concentration (AUC) and peak plasma concentration (Cmax) of fexofenadine following oral administration, but did not affect the elimination half-life. Itraconazole and verapamil did not affect the renal clearance of fexofenadine, while the effect of ritonavir on the renal clearance was not examined. Considering the absence of the effect on the renal clearance, these interactions will include the inhibition of intestinal... 

Uno T, Shimizu M, Sugawara K, et al. Lack of dose-dependent effects of itraconazole on the pharmacokinetic interaction with fexofenadine. Drug Metab Dispos 2006 34 1875-1879. 

Abacavir Adinazolam 5-Aminosalicylic acid Atorvastatin Avitriptan Bromazepam Bumetanide Celecoxib CGP 43371 Clodronate Cyclosporin Danazol Didanosine Erythromycin Fexofenadine Furosemide Ganciclovir Halofantrine Inidnavir Itraconazole Levofloxacin Methotrexate Nifedipine Pravastatin Rifabutin Stavudine Tacrine... 

In a single dose study, administration of itraconazole 200 mg one hour prior to fexofenadine 180 mg increased the AUC of fexofenadine 2.3-fold, and 3-fold in two groups of subjects of different genotypes for the gene encoding P-glycoprotein. Itraconazole pretreatment increased the effect of fexofenadine on histamine-induced wheal and flare reaction. ... 

In vitro studies have shown that ketoconazole inhibits the metabolism of astemizole. Ketoconazole, and to a lesser extent itraconazole and miconazole, also appear to reduce the metabolism of terfenadine by inhibition of the cytochrome P450 isoenzyme CYP3A. " High serum levels of astemizole and terfenadine (but not its metabolites) block cardiac potassium channels leading to prolongation of the QT interval, which may precipitate the development of torsade de pointes arrhythmia (see Table 15.2 , (p.583)). The risk of cardiac arrhythmias with other non-sedating antihistamines appears to be non-existent or very much lower (see Table 15.2 , (p.583)), so any pharmacokinetic interactions do not result in clinically relevant cardiac toxicity. In fact, studies have shown that desloratadine at nine times the recommended dose, fexofenadine in overdose, and mizolastine at four times the recommended dose do not affect the QT interval. However, some questions remain about loratadine and ebastine. Additionally, some studies have reported that ketoconazole alone is associated with a small increase in QT interval, and at least one case of torsade de pointes has been reported for ketoconazole alone. Therefore the cardiac effects of ketoconazole may be additive with those of the antihistamines, and this may be important for ebastine and loratadine. 

---