Blood Concentration of Voriconazole in Patients with Ultrarapid Metabolism Increased by Combination of Voriconazole and Omeprazole

doi:10.19803/j.1672-8629.2020.08.10

Abstract

Abstract: Objective To explore the role of voriconazole combined with omeprazole sodium in increasing the blood concentration of voriconazole and enhancing antifungal efficacy in patients with CYP2C19 ultrarapid metabolism. Methods The clinical data on three patients who had voriconazole-associated gene CYP2C19 with ultrarapid metabolizing invasive pulmonary mycosis was analyzed. The treatment with voriconazole was designed and adjusted based on monitoring results of blood concentrations. Results Two of the three patients were diagnosed with pulmonary mycosis based on clinical symptoms, signs, and sputum culture, suggesting fungal infection (one case with Aspergillus and one case with Candida tropicalis) combined with pulmonary CT changes. The third case was a patient with degree IV myelosuppression after chemotherapy, who had agranulocytosis and fever and needed to be treated with an empirical antifungal therapy due to the poor efficacy of a standardized anti-infective therapy. All the three patients had voriconazole-associated gene CYP2C19 with ultrarapid metabolism. The initial antifungal treatment with voriconazole was not effective (the clinical symptoms were not improved, and the blood concentration was not up to the standard). The treatment plan was adjusted by increasing the single dose of voriconazole and by combining voriconazole with omeprazole sodium so that the antifungal effect was significantly improved (the blood concentration of voriconazole increased and reached the standard, and the symptoms of infection were significantly improved), and the patients were cured. Conclusion When an antifungal therapy with voriconazole is used in patients with CYP2C19 ultrarapid metabolism, the blood concentration of voriconazole can be greatly increased via the competition and inhibitory effect of omeprazole on voriconazole metabolism enzymes. This approach can not only improve the antifungal effect of voriconazole, but also eliminate the risk of adverse reactions caused by excessive drug adjustment. It provides a new idea for clinical individualized treatment of voriconazole.

Key words: voriconazole, omeprazole sodium, drug interaction, blood concentration monitoring, drug metabolizing enzyme

CLC Number:

R994.11

LIAN Yufei, LIU Hongtao, REN Bingnan, ZHAO Haijing, WANG Yanze, ZHANG Yue, TIAN Dongdong, CAO Gexi, YUE Yuanyuan, YAN Li. Blood Concentration of Voriconazole in Patients with Ultrarapid Metabolism Increased by Combination of Voriconazole and Omeprazole[J]. Chinese Journal of Pharmacovigilance, 2020, 17(8): 496-501.

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