Reactions 1680, p219 - 2 Dec 2017 Increased voriconazole level: case report A 78-year old man had an increased level of voriconazole following meropenem and voriconazole interaction. The man, who was newly diagnosed with high risk prostate cancer, was hospitalised for open prostatectomy and his postoperative course was complicated by right heart failure, intra-abdominal haematoma and ischemia of large parts of the colon requiring subtotal colectomy and ileostomy, progressive renal impairment requiring dialysis and multiple bacterial and fungal infections including bacteremia with multidrug- resistant Klebsiella pneumoniae, systemic fungal infection with Candida glabrata, infections with Enterococcus faecium, Pseudomonas aeruginosa and Aspergillus fumigatus. He received treatment with IV voriconazole, meropenem and their combination [route and dosage not stated] at numerous times, for multiple infections. His voriconazole concentration was noted using a high-performance liquid chromatography assay throughout the anti fungal treatment phases, which showed that voriconazole dose requirements rapidly and substantially decreased to approximately one third whenever meropenem was co-administered. These findings indicated that meropenem considerably impairs voriconazole clearance. As he had not received any cytochrome P450 (CYP) mediated co-medications which are known to interact with voriconazole and meropenem therapy, a novel drug interaction between voriconazole and meropenem was suspected. He received various co-medications and none of the drug had interfered with CYP isoenzymes. From the in vitro and in vivo studies it was concluded that the metabolic ratio of voriconazole decreased whenever co-administered with meropenem and quickly recovered upon discontinuation of meropenem, which suggested impairment of voriconazole metabolism by meropenem. Author comment: "We repeatedly observed a substantial concentration-dependent interaction between meropenem and voriconazole in a patient on high-dose meropenem and in vitro confirmed the suspected inhibitor action of meropenem on CYP3A4 and CYP2C19, the key enzymes involved in voriconazole metabolism." Mahmoudi M, et al. Substantial impairment of voriconazole clearance by high-dose meropenem in a patient with renal failure. Clinical Infectious Diseases 65: 1033-1036, No. 6, 15 Sep 2017. Available from: URL: http://doi.org/10.1093/cid/ cix443 - Germany 803284125 0114-9954/17/1680-0001/$14.95 Adis © 2017 Springer International Publishing AG. All rights reserved Reactions 2 Dec 2017 No. 1680
Reactions Weekly – Springer Journals
Published: Dec 2, 2017
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