Work

Effectiveness and Safety of New Posaconazole Formulations in Patients With Hematologic Malignancy Receiving Antifungal Prophylaxis

Year: 2016

Type: article

Abstract: Background. Posaconazole (PCZ) is commonly used as prophylaxis against invasive fungal infections (IFI) in patients with hematologic malignancy (HM). The tablet and intravenous (IV) formulations of PCZ result in higher serum concentrations compared to the suspension, raising concern that toxicity may be more common. The purpose of this study was to evaluate the pharmacokinetics and toxicity associated with new formulations of PCZ in patients with HM. Methods. This is a retrospective cohort of all patients with HM at M. D. Anderson Cancer Center who received >3 days of tablet or IV PCZ from January 2014 to January 2016 for IFI prophylaxis. Clinical and toxicity information were collected and correlated with serum PCZ levels, when available. Rates of IFI, defined according to EORTC/MSG criteria, were also assessed. Hepatotoxicity was assessed using standard NCI grading scales, with grade 3/4 hepatotoxicity considered to be significant. Only the first inpatient prophylaxis episode was considered for patients with multiple admissions. Results. A total of 343 patients (mean age 80 ± 20 y; 57% male) were included. Eleven (3%) received IV PCZ and 99% received 300 mg of PCZ daily. Sixty-two percent of patients had acute myeloid leukemia, 20% had received prior hematopoietic stem cell transplantation, and 79% had active malignancy. Seventy-six patients (22%) had a PCZ serum level obtained with a median value of 1380 ng/mL (interquartile range: 864 – 1860). Thirteen (17%) had levels >2000ng/mL. Significant elevations in ALT, alkaline phosphatase, or total bilirubin were uncommon during prophylaxis, occurring in 5% of patients. Seventy-nine patients (23%) had electrocardiograms (EKGs) performed before and during PCZ prophylaxis, with a mean increase in the corrected QT interval of 14 ± 35 msec (range: −88 to 105). One case of Torsades de Pointes occurred; the patient responded to standard treatment. Proven/probable IFI occurred in 5 (1%) patients. Toxicity and IFI did not correlate with serum PCZ levels. Conclusion. The tablet and IV formulations of PCZ appear safe and effective for prophylaxis against IFI in patients with HM. PCZ serum levels do not appear to correlate with effectiveness or toxicity in this cohort. Prospective studies to define the cost-effectiveness of PCZ therapeutic drug monitoring targets may be useful. Disclosures. S. L. Aitken, Astellas: Scientific Advisor, Consulting fee F. P. Tverdek, Astellas: Scientific Advisor, Consulting fee D. P. Kontoyiannis, *: Advisory board, Research grant Pfizer: Grant Investigator, Research support Gilead: Invited lecture, Speaker honorarium Astellas: Consultant, Research support and Speaker honorarium F2G: Consultant, Consulting fee T2Biosystems: Invited lecture, Speaker honorarium Mylan Inc: Invited lecture, Speaker honorarium

Source: Open Forum Infectious Diseases

DOI: 10.1093/ofid/ofw172.1319

Authors: Samuel L. Aitken, Sang Taek Heo, Frank P. Tverdek, Bruno P. Granwehr, Dimitrios P. Kontoyiannis

Institutions: The University of Texas MD Anderson Cancer Center, Jeju National University Hospital, Jeju National University

Language: English

Topic: Antifungal resistance and susceptibility

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,053