The bioavailability of
ketoconazole is reduced by
omeprazole (AUC reduced by about 80%) and rabeprazole (bioavailability reduced by 30%). Other
proton pump inhibitors are expected to behave similarly. Omeprazole also markedly reduces the absorption of
itraconazole capsules (AUC decreased by 65%), but not the oral solution. Posaconazole absorption is predicted to be reduced by
proton pump inhibitors. Omeprazole levels may be increased by
ketoconazole (and therefore possibly itraconazole), and markedly increased by
fluconazole and
voriconazole. Voriconazole may more than double the levels of esomeprazole.
An increase in the antifungal dose has been suggested to overcome this interaction, as has giving
ketoconazole or
itraconazole with an acidic drink such as cola, which increases its bioavailability. The manufacturers of
posaconazole advise avoiding concurrent use. Fluconazole and oral
itraconazole solution appear to be unaffected, and they may therefore be alternatives. However, as
fluconazole significantly increases
omeprazole levels, a dose adjustment may be required with long-term treatment. Voriconazole does not require a dose adjustment when given with
omeprazole. However, the manufacturers of
voriconazole recommend halving the dose of
omeprazole, but this is probably only necessary with higher doses. The dose of esomeprazole will only need adjusting in those taking
voriconazole if the esomeprazole dose is very high (e.g. 240 mg).