Ketoconazole Esomeprazole

Clinically important, potentially hazardous interactions with chlorpheniramine, clarithromycin, efavirenz, esomeprazole, imatinib, indinavir, ketoconazole, nelfinavir, nilutamide, ritonavir... 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, atazanavir, carbamazepine, chlorpheniramine, cimetidine, clarithromycin, clorazepate, CNS depressants, darunavir, delavirdine, dexamethasone, efavirenz, erythromycin, esomeprazole, fluconazole, fluoxetine, fosamprenavir, grapefruit juice, griseofulvin, imatinib, indinavir, itraconazole, ivermectin, ketoconazole, lopinavir, nelfinavir, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, ritonavir, roxithromycin, saquinavir, St John s wort, telithromycin, tipranavir... 

The bioavailability of ketoconazole is reduced by both omeprazole and rabeprazole. Other proton pump inhibitors are expected to behave similarly. Omeprazole also markedly reduces the absorption of itraconazole capsules, but not the oral solution. Proton pump inhibitors are predicted to reduce the bioavailability of posaconazole. The bioavailabilities of fluconazole and voriconazole are not significantly affected by omeprazole. Esomeprazole levels may also be Increased by voriconazole.Omeprazole levels are Increased by ketoconazole, and markedly increased by fluconazole and voriconazole. 

Based on data for omeprazole (see below), and the known acid-lowering effect of esomeprazole, the manufacturers predict that esomeprazole might reduce the absorption of itraconazole and ketoconazole, which depend on a low pH for optimal dissolution and absorption. Voriconazole may more than double the levels of esomeprazole. ... 

Fluconazole and voriconazole almost certainly cause a rise in omeprazole and esomeprazole levels by inhibiting their metabolism by the cytochrome P450 isoenzymes CYP2C19 and CYP3A4. As esomeprazole is an inhibitor of and also a substrate for CYP2C19, it is likely to have the same effect as omeprazole. Ketoconazole only inhibits CYP3A4 and therefore causes a less marked rise in omeprazole levels. Itraconazole would be expected to interact similarly to ketoconazole. 

Tan AR, Gibbon DG, Stein MN, Lindquist D, Edenfield JW, Martin JC, et al. Effects of ketoconazole and esomeprazole on the pharmacokinetics of pazopanib in patients with solid tumors. Cancer Chemother Pharmacol 2013 71(6) 1635-43. 

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