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Factors influencing posaconazole plasmatic concentrations in patients presenting with acute myeloid leukemia
P-Y Desplanques1, R Burlacu2, V Poinsignon3
1Service de pharmacie clinique, Institut Gustave-Roussy, 94805 Villejuif cedex, France.
Purpose:
The effectiveness of posaconazole (PSZ) prophylaxis on invasive fungal infections, in patients presenting with acute myeloid leukemia (AML), seems to be correlated to its blood plasma concentration. Our goal was to identify the risk factors for underdosing.
Patients And Methods:
We retrospectively reviewed the records of patients treated for AML treated with PSZ, during a 2-year period. Assays<500ng/mL were considered as under dosed.
Results:
Fifty-nine assays (43 patients) were performed during induction (n=22) or consolidation (n=37) chemotherapy. PSZ treatment was initiated within a median of 3 days before neutropenia with a first assay performed at 8 days (3-28). The median PSZ blood plasma concentration was 375ng/mL (<200-1900). Forty-one (69%) treatment were maintained until the end of neutropenia. One patient presented with candidemia, 9 with possible invasive aspergillosis, without any significant association with underdosing. The univariate analysis showed that co-administration of proton pump inhibitors (PPIs) (P=0.01) and cause of hospitalization (induction chemotherapy vs consolidation, P=0.008) were associated with underdosing, contrary to feeding difficulties (P=0.07) and digestive disorders (P=0.5). The multivariate analysis confirmed the impact of PPI use (P=0.01) and the cause of hospitalization (P=0.003).
Conclusion:
This study highlights the major impact of PPI administration on PSZ blood plasma levels and stresses the risk of non-effective prophylaxis during induction treatment of AML.
Insights
Proton pump inhibitors (PPIs) and hospitalization type significantly increase the risk of underdosing posaconazole (PSZ) in acute myeloid leukemia (AML) patients, potentially reducing the effectiveness of antifungal prophylaxis.
Area of Science:
- Pharmacology
- Hematology
- Infectious Diseases
Background:
- Posaconazole (PSZ) prophylaxis effectiveness in acute myeloid leukemia (AML) patients correlates with blood plasma concentration.
- Identifying risk factors for PSZ underdosing is crucial for optimizing antifungal prophylaxis.
Purpose of the Study:
- To identify risk factors associated with suboptimal posaconazole (PSZ) blood plasma concentrations in patients with acute myeloid leukemia (AML).
Main Methods:
- Retrospective review of patient records for AML treated with PSZ over a 2-year period.
- Defined underdosing as PSZ assays <500 ng/mL.
- Analyzed univariate and multivariate associations of factors like PPI use and hospitalization type with underdosing.
Main Results:
- Median PSZ concentration was 375 ng/mL, with 69% of treatments maintained through neutropenia.
- Univariate analysis revealed PPI co-administration (P=0.01) and hospitalization cause (induction vs. consolidation, P=0.008) as significant risk factors for underdosing.
- Multivariate analysis confirmed PPI use (P=0.01) and hospitalization cause (P=0.003) as independent predictors of underdosing.
Conclusions:
- Proton pump inhibitor (PPI) administration significantly impacts posaconazole (PSZ) blood plasma levels.
- Underdosing of PSZ poses a risk for ineffective antifungal prophylaxis, particularly during induction treatment for AML.
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