Voriconazole Omeprazole

OMEPRAZOLE VORICONAZOLE Possible T efficacy and adverse effects of both drugs 1. Inhibition of voriconazole metabolism via CYP2C19 and CYP3A4 2. Inhibition of metabolism of omeprazole 1. No dose adjustment of voriconazole recommended 2. Half omeprazole dose... 

Drugs that may inhibit cytochrome P450 metabolism of other drugs include amiodarone, androgens, atazanavir, chloramphenicol, cimetidine, ciprofloxacin, clarithromycin, cyclosporine, delavirdine, diltiazem, diphenhydramine, disulfiram, enoxacin, erythromycin, fluconazole, fluoxetine, fluvoxamine, furanocoumarins (substances in grapefruit juice), indinavir, isoniazid, itraconazole, ketoconazole, metronidazole, mexile-tine, miconazole, nefazodone, omeprazole, paroxetine, propoxyphene, quinidine, ritonavir, sulfamethizole, verapamil, voriconazole, zafirlukast, and zileuton. 

CYP2C19. Studies have shown that PXR and CAR regulate hepatic CYP2C19 expression in vitro [21, 22], The metabolism and plasma levels of the CYP2C19 substrates omeprazole [74] and voriconazole [129] are affected by the PXR agonists St. John s wort and rifampin, demonstrating that this enzyme is inducible in vivo. 

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. ... 

Voriconazole. A study in 18 healthy subjects found that omeprazole 40 mg daily for 7 days increased the maximum plasma levels and AUC of voriconazole by 15 and 41%, respectively. Food was prohibited within one hour before and after each dose."... 

However, voriconazole 200 mg twice daily increased the maximum plasma levels and AUC of omeprazole 40 mg once daily by about twofold and fourfold respectively. ... 

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. 

The interaction between voriconazole and omeprazole is established but no adjustment to the dose of voriconazole is required. The clinical importance of the marked rise in serum omeprazole levels caused by voriconazole is not established, but the manufacturers recommend that the omeprazole dose be halved, although the US manufacturers restrict this to patients taking omeprazole 40 mg or more. The increase in levels of esomeprazole by voriconazole does not routinely require a dose adjustment of esomeprazole However, patients taking esomeprazole in doses of more than 240 mg daily (e.g. for Zollinger-Ellison syndrome) may require a dose adjustment. ... 

Wood N, Tan K, Purkins L, Layton G, Hamlin J, Kleinermans D, Nichols D. Effect of omeprazole on the steady-state phE acokinetics of voriconazole. BrJ Clin Pharmacol (2003) 56, 56-61. 

Antiulcer agents Omeprazole (Wang et al. 2004a) Antifungals Voriconazole (Rengelshausen et al. 2005) (increase of plasma levels with single St. John s wort dose, decrease after continued use)... 

Fexofenadine Imatinib Irinotecan Loperamide Methadone Midazolam Nefazodone Nevirapine Omeprazole Paroxetine oral contraceptives Phenprocoumon Setraline Simvastine Tacrolimus Theophylline Tolbutamide Voriconazole Warfarin... 

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