Correlation of Pain and Fluoride Concentration in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Voriconazole.

Supportive care guidelines recommend antimold prophylaxis in hematopoietic stem cell transplant (HSCT) recipients deemed to have high risk for invasive fungal infection, leading to long-term use of voriconazole after allogeneic HSCT in patients who remain immunocompromised. Voriconazole has been associated with periostitis, exostoses, and fluoride excess in patients after solid organ transplantation, HSCT, and leukemia therapy. The aims of this study were to describe the frequency and clinical presentation of patients presenting with pain and fluoride excess among allogeneic HSCT patients taking voriconazole, to identify when a plasma fluoride concentration was measured with respect to voriconazole initiation and onset of pain, and to describe the outcomes of patients with fluoride excess in the setting of HSCT. A retrospective review was conducted of all adult allogeneic HSCT patients receiving voriconazole at Mayo Clinic in Rochester, Minnesota, between January 1, 2009 and July 31, 2012. Of 242 patients included, 32 had plasma fluoride measured to explore the etiology of musculoskeletal pain. In 31 patients with fluoride measurement while on voriconazole, 29 (93.5%) had elevated levels. The median plasma fluoride was 11.1 µmol/L (range, 2.4 to 24.7). The median duration of voriconazole was 163 days (range, 2 to 1327). The median time to fluoride measurement was 128 days after voriconazole initiation (range, 28 to 692). At 1 year after the start of voriconazole after HSCT, 15.3% of patients had developed pain associated with voriconazole use and 35.7% developed pain while on voriconazole after 2 years. Of the patients with an elevated fluoride level, 22 discontinued voriconazole; pain resolved or improved in 15, stabilized in 3, and worsened in 4 patients. Ten patients continued voriconazole; pain resolved or improved in 7, was attributable to alternative causes in 2, and undefined in 1. Serum creatinine, estimated glomerular filtration rate, alkaline phosphatase, and voriconazole concentration did not predict for fluoride excess and associated pain. Periostitis due to fluoride excess is a common adverse effect of voriconazole that should be considered in patients presenting with pain and is often reversible after drug discontinuation. Alternative antifungal agents with a lower risk for fluoride excess should be considered in patients receiving voriconazole who develop fluoride excess and pain.

A patient-centered approach to the development and pilot of a warfarin pharmacogenomics patient education tool for health professionals.

OBJECTIVE: To describe an exploratory project to develop and pilot a novel patient educational tool that explains the concept of pharmacogenomics and its impact on warfarin dosing that can be utilized by health professionals providing patient counseling. METHODS: A pharmacogenomics educational tool prototype was developed by an interdisciplinary team. During the pilot of the tool, focus group methodology was used to elicit input from patients based upon their perspectives and experiences with warfarin. Focus group sessions were audio-recorded and transcribed, and the data was analyzed through consensus coding in NVivo. RESULTS: The focus group participants were generally unfamiliar with the concept of pharmacogenomics but were receptive to the information. They thought the patient education tool was informative and would provide the most benefit to patients newly initiated on warfarin therapy. CONCLUSIONS: Preliminary results from this exploratory project suggest that implementation and further feasibility testing of this pharmacogenomics patient education tool should be performed in a population of newly initiated patients taking warfarin.