Posaconazole Therapeutic Drug Monitoring in the Real‐life Setting: A Single‐Center Experience and Review of the Literature

Gross, Barbara N.; Ihorst, Gabriele; Jung, Manfred; Wäsch, Ralph; Engelhardt, Monika

doi:10.1002/phar.1328

Cited by 36 publications

(32 citation statements)

References 21 publications

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“…9,39 The lowest APL were noted for POS-Liq with the results being similar to those found by Lebeaux et al and others in patients with hematological malignancies. 40–42 The median APL for POS-Tab were tripled compared with POS-Liq, whereas other studies showed mostly a 2-fold increase in APL. 37,38,43–45 Previous studies have found higher ITR APL in patients with acquired immunodeficiency syndrome 46 and lower levels in patients who are neutropenic 47 compared with our results in lung transplant recipients.…”

Section: Discussionmentioning

confidence: 87%

Comparing Azole Plasma Trough Levels in Lung Transplant Recipients: Percentage of Therapeutic Levels and Intrapatient Variability

Stelzer

Weber²,

Ihle

et al. 2017

Therapeutic Drug Monitoring

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Background:This study compared therapeutic azole plasma trough levels (APL) of the azole antimycotics itraconazole (ITR), voriconazole (VOR), and posaconazole (POS) in lung transplant recipients and analyzed the influencing factors. In addition, intrapatient variability for each azole was determined.Methods:From July 2012 to July 2015, 806 APL of ITR, VOR, posaconazole liquid (POS-Liq), and posaconazole tablets (POS-Tab) were measured in 173 patients of the Munich Lung Transplantation Program. Therapeutic APL were defined as follows: ITR, ≥700 ng/mL; VOR, 1000–5500 ng/mL; and POS, ≥700 ng/mL (prophylaxis) and ≥1000 ng/mL (therapy).Results:VOR and POS-Tab reached the highest number of therapeutic APL, whereas POS-Liq showed the lowest percentage (therapy: ITR 50%, VOR 70%, POS-Liq 38%, and POS-Tab 82%; prophylaxis: ITR 62%, VOR 85%, POS-Liq 49%, and POS-Tab 76%). Risk factors for subtherapeutic APL of all azoles were the azole dose (ITR, P < 0.001; VOR, P = 0.002; POS-Liq, P = 0.006) and age over 60 years (ITR, P = 0.003; VOR, P = 0.002; POS-Liq, P = 0.039; POS-Tab, P < 0.001). Cystic fibrosis was a significant risk factor for subtherapeutic APL for VOR and POS-Tab (VOR, P = 0.002; POS-Tab, P = 0.005). Double lung transplantation (LTx) was significantly associated with less therapeutic APL for VOR and POS-Liq (VOR, P = 0.030; POS-Liq, P < 0.001). Concomitant therapy with 80 mg pantoprazole led to significantly fewer therapeutic POS APL as compared to 40 mg (POS-Liq, P = 0.015; POS-Tab, P < 0.001). VOR displayed the greatest intrapatient variability (46%), whereas POS-Tab showed the lowest (32%).Conclusions:Our study showed that VOR and POS-Tab achieve the highest percentage of therapeutic APL in patients with LTx; POS-Tab showed the lowest intrapatient variability. APL are significantly influenced by azole dose, age, cystic fibrosis, type of LTx, and comedication with proton-pump inhibitors. Considering the high number of subtherapeutic APL, therapeutic drug monitoring should be integrated in the post-LTx management.

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Section: Discussionmentioning

confidence: 87%

Comparing Azole Plasma Trough Levels in Lung Transplant Recipients: Percentage of Therapeutic Levels and Intrapatient Variability

Stelzer

Weber²,

Ihle

et al. 2017

Therapeutic Drug Monitoring

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“…Despite the approval of posaconazole for this indication, the oral suspension has limited bioavailability, particularly when decreased oral intake, mucositis, gastrointestinal graft-versus-host disease (GVHD), or diarrhea is present (3). Given that subtherapeutic posaconazole levels may be associated with breakthrough IFIs (4) and decreased likelihood of successful treatment (5), a new delayed-release (DR) tablet formulation with higher oral bioavailability (6) holds promise.…”

mentioning

confidence: 99%

Retrospective Comparison of Posaconazole Levels in Patients Taking the Delayed-Release Tablet versus the Oral Suspension

Durani

Tosh

Barreto

et al. 2015

Antimicrob Agents Chemother

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While posaconazole prophylaxis decreases the risk of invasive fungal infection compared to fluconazole, low bioavailability of the oral-suspension formulation limits its efficacy. A new delayed-release tablet formulation demonstrated an improved pharmacokinetic profile in healthy volunteers. However, serum levels for the two formulations have not been compared in clinical practice. This study compared achievement of therapeutic posaconazole levels in patients taking the delayed-release tablet to those taking the oral suspension. This retrospective cohort study included 93 patients initiated on posaconazole between 2012 and 2014 and had at least one serum posaconazole level measured. The primary measure was the proportion of patients achieving an initial therapeutic level (>700 ng/ml). An initial therapeutic posaconazole level was seen in 29 of 32 (91%) patients receiving tablets and 37 of 61 (61%) patients receiving suspension (P ‫؍‬ 0.003). Among patients with a steady-state level measured 5 to 14 days after initiation, a therapeutic level was observed in 18 of 20 (90%) patients receiving tablets and 25 of 43 (58%) patients receiving suspension (P ‫؍‬ 0.01). In these patients, the median posaconazole level of the tablet cohort (1655 ng/ml) was twice that of the suspension cohort (798 ng/ml) (P ‫؍‬ 0.004). In this cohort study, the improved bioavailability of delayed-release posaconazole tablets translates into a significantly higher proportion of patients achieving therapeutic serum levels than in the cohort receiving the oral suspension. The results of this study strongly support the use of delayed-release tablets over suspension in patients at risk for invasive fungal infection. Despite the approval of posaconazole for this indication, the oral suspension has limited bioavailability, particularly when decreased oral intake, mucositis, gastrointestinal graft-versus-host disease (GVHD), or diarrhea is present (3). Given that subtherapeutic posaconazole levels may be associated with breakthrough IFIs (4) and decreased likelihood of successful treatment (5), a new delayed-release (DR) tablet formulation with higher oral bioavailability (6) holds promise. In fact, a phase 3 trial reports that over 99% of patients with hematologic malignancies receiving DR tablets achieved levels of Ͼ500 ng/ml (7). Aside from a crossover study of 12 leukemia patients (8), clinical practice data comparing serum concentrations of the two posaconazole formulations have not been reported.The primary objective of this study was to compare steadystate levels of serum posaconazole in patients taking DR posaconazole tablets to those taking oral suspension to determine if the pharmacokinetic advantage of DR tablets observed in healthy volunteers and clinical trials translates to a higher rate of therapeutic serum concentrations in clinical practice. MATERIALS AND METHODSStudy population. This study was approved by the institutional review board at Mayo Clinic. All patients who were initiated on posaconazole and had a serum posaconazole leve...

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“…Una de las dificultades que presenta PSC es que su farmacocinética se ve afectada por varios factores: la dieta, medicamentos, alteraciones gastrointestinales, mucositis, frecuencia de las dosis y estado prandial, lo que se refleja en su biodisponibilidad 6 . Esto determina un especial desafío en la profilaxis y/o tratamiento de la IFI en niños, siendo necesario aumentar el conocimiento relacionado al uso de este medicamento y las CPs alcanzadas en la población pediátrica, que tiene una farmacocinética más compleja asociada a la maduración de sus sistemas hepáticos y renales que alteran las CPs de los medicamentos [2][3][4][5][6] .…”

Section: Resultsunclassified

Farmacocinética de posaconazol en la profilaxis y tratamiento de la infección fúngica invasora en niños inmunocomprometidos en un hospital pediátrico

Valenzuela

García

Barraza

et al. 2018

Rev. chil. infectol.

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Posaconazole Therapeutic Drug Monitoring in the Real‐life Setting: A Single‐Center Experience and Review of the Literature

Abstract: Therapeutic drug monitoring of posaconazole is an important tool of therapy optimization because oral posaconazole suspension shows unreliable absorption rates and exposure.

Cited by 36 publications

References 21 publications

Comparing Azole Plasma Trough Levels in Lung Transplant Recipients: Percentage of Therapeutic Levels and Intrapatient Variability

Comparing Azole Plasma Trough Levels in Lung Transplant Recipients: Percentage of Therapeutic Levels and Intrapatient Variability

Retrospective Comparison of Posaconazole Levels in Patients Taking the Delayed-Release Tablet versus the Oral Suspension

Farmacocinética de posaconazol en la profilaxis y tratamiento de la infección fúngica invasora en niños inmunocomprometidos en un hospital pediátrico

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