Switching from Posaconazole (POSA) Suspension to Tablets in Patients with Hematologic Malignancy Results in Increased Serum Levels but no Hepatotoxicity
Background: POSA suspension has been used effectively as prophylaxis and as salvage treatment of invasive fungal infections despite concerns of poor bioavailability. Recent studies suggest that the absorption of the new formulation of POSA tablet is minimally affected by food and they attain higher-average concentrations than the suspension in healthy subjects, and are well tolerated. As there are no published data in patients who received sequential POSA suspension and tablets, we reviewed our early experience in order to determine POSA serum level differences and to identify any association between drug exposure and hepatotoxicity.
Methods: We identified patients with hematologic cancer who switched from POSA suspension (400mg twice or 200mg 4 times a day) to tablet (300mg once daily) and had serum level drawn (December 2013-January 2014) in our cancer center. We calculated a median level for each patient when there was more than one level. Hepatotoxicity was defined as CTCAE (Common Terminology Criteria for Adverse Events, Version 4.0) grade 3 or higher. Electronic medical records were retrospectively reviewed for basic demographic, clinical and laboratory data.
Results: We identified 12 such patients. Twenty-one POSA suspension serum levels and 30 tablet levels were included. Target levels for prophylaxis (>700 ng/ml) and treatment (>1,000 ng/ml) were reached in 29 of 30 levels (97%) and 25 of 30 (83%) in patients receiving POSA tablets immediately prior to the time the level was drawn, but in only 12 of 21 (57%) and 5 of 21 (24%) in suspension (Figure 1A). Median POSA concentrations in the tablet group were higher (1910 ng/ml) than those in the suspension (748 ng/ml) group, and was significantly increased in patients who switched from suspension to tablet (P<0.01) (Figure 1B). In 9 patients who had baseline normal liver function, mild asymptomatic increases in liver enzymes (5 patients) were observed after 7 days of treatment and all returned to normal in three weeks without discontinuation. Elevated liver enzymes are unlikely to be associated with drug exposure.
Conclusion: Switching from POSA suspension to tablets in patients with hematologic cancer results in increased serum level but no clinically relevant hepatotoxicity.
D. S. Jung,
F. Ponce, None
Y. Zhu, None
D. Kontoyiannis, Pfizer, Astellas Pharma US, Gilead, and Merck & Co.,Inc: Research support, Research support