Reversible skeletal disease and high fluoride serum levels in hematologic patients receiving voriconazole

• Published in: Blood Vol. 120; no. 12; pp. 2390 - 2394
• Main Authors: Gerber, Bernhard, Guggenberger, Roman, Fasler, David, Nair, Gayathri, Manz, Markus G., Stussi, Georg, Schanz, Urs
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 20.09.2012; Americain Society of Hematology
• Subjects: Adult; Antifungal Agents - therapeutic use; Biological and medical sciences; Bone Diseases - chemically induced; Bone Diseases - prevention & control; Female; Fluorides - blood; Hematologic and hematopoietic diseases; Hematologic Neoplasms - complications; Hematologic Neoplasms - microbiology; Hematologic Neoplasms - therapy; Humans; Itraconazole - therapeutic use; Medical sciences; Middle Aged; Muscle, Skeletal - physiopathology; Periostitis - chemically induced; Pyrimidines - therapeutic use; Retrospective Studies; Stem Cell Transplantation; Transplantation, Homologous; Triazoles - therapeutic use; Voriconazole; Human; Hematology; Azole derivatives; Voriconazole; Triazole derivatives; Serum; Skeleton
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2012-01-403030

We here investigate the occurrence of fluoride intake-associated alterations in patients with hematologic disease on triazol antifungal medication. Clinical, laboratory, and radiology data of overall 43 patients with hematologic malignancies taking voriconazole (n = 20), posaconazole (n = 8), and itraconazole (n = 4), and a hematologic patient control group (n = 11) are described. Bone pain and radiologic evidence of periostitis were exclusively observed in patients receiving long-term voriconazole. Cessation of treatment led to clinical improvement in all cases. In line with clinical evidence, fluoride serum concentration was elevated in patients receiving voriconazole (median, 156.5 μg/L; interquartile range, 96.8 μg/L; normal < 30 μg/L) but not in the other treatment groups (P < .001 for all comparisons vs voriconazole). We conclude that serum fluoride levels were elevated on average 5-fold above normal levels in hematologic patients receiving voriconazole. Clinically relevant skeletal disease was associated with renal insufficiency and above 10-fold elevated fluoride levels, and was reversible on termination of voriconazole treatment.