Abstract
Posaconazole (PCZ) is frequently used for prophylaxis against invasive fungal infections (IFI) in patients undergoing induction chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Posaconazole is commercially available as an oral suspension (PCZ-susp) and as a delayed-release tablet (PCZ-tab). Differences in absorption and bioavailability between these formulations may result in variability in serum posaconazole concentrations. The primary objective of this retrospective analysis was to compare attainment of goal serum posaconazole steady state concentrations (Css) ≥ 700 ng/ml in patients with AML/MDS undergoing induction chemotherapy receiving PCZ-susp 600–800 mg per day (N = 118) versus PCZ-Tablet 300 mg twice daily for one day, followed by 300 mg daily (N = 64). Sixty-two patients (97%) in the PCZ-tab group compared to 20 patients (17%) in the PCZ-susp group achieved goal Css (P < 0.0001). Median posaconazole serum Css was 1,665 ng/ml (522–3,830 mg/ml) in the PCZ-tab group versus 390 ng/ml (51–1,870 ng/ml) in the PCZ-susp group (P < 0.0001). There was no difference in hepatotoxicity, QTc prolongation, or breakthrough IFI. Patients receiving PCZ-tab were significantly more likely to achieve goal Css and demonstrated higher Css versus patients receiving PCZ-susp. Prospective studies are needed to assess the potential correlation of serum concentrations with efficacy and toxicity.
Highlights
Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing induction chemotherapy are severely immunocompromised and at risk of developing invasive fungal infections (IFI)
In the PCZ-tab group 97% (n = 62) achieved goal serum concentrations ≥ 700 ng/ml, while only 17% (n = 20) reached goal concentrations in the PCZ-susp (P < 0.0001)
We examined the influence of specific factors within each formulation
Summary
Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing induction chemotherapy are severely immunocompromised and at risk of developing invasive fungal infections (IFI). Posaconazole (PCZ) has the widest spectrum of antifungal activity among the triazole drug class and has demonstrated superiority versus fluconazole in the prevention of IFI in patients with AML or high-grade MDS undergoing induction chemotherapy and in patients with graft-versus-host disease (GVHD) receiving immunosuppression [1, 2]. This formulation does not require food intake or a fatty meal to improve absorption and does not seem to be affected by use of acid suppressing agents [10,11,12,13]. These factors are especially important, considering the patient population being treated. Most patients receiving intensive chemotherapy and/or having GVHD are likely to have poor oral intake and be receiving stress ulcer prophylaxis
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