Management of drug interaction between posaconazole and sirolimus in patients who undergo hematopoietic stem cell transplant
| Autor: | Huan Mark Nguyen, Holly Chan, Sepideh Shayani, Eunah Cho, Doreen Pon, Ryotaro Nakamura |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Posaconazole medicine.medical_specialty Antifungal Agents Pharmacology Gastroenterology Young Adult Internal medicine medicine Humans Pharmacology (medical) In patient Drug Interactions cardiovascular diseases Aged Retrospective Studies Sirolimus business.industry Hematopoietic Stem Cell Transplantation Hematopoietic stem cell Cancer Retrospective cohort study Drug interaction Middle Aged Triazoles equipment and supplies medicine.disease surgical procedures operative medicine.anatomical_structure Allogeneic hsct cardiovascular system Female business Immunosuppressive Agents medicine.drug |
| Zdroj: | Pharmacotherapy. 35(6) |
| ISSN: | 1875-9114 |
| Popis: | To determine an appropriate empiric oral sirolimus dose adjustment when given concurrently with posaconazole oral suspension in patients who undergo hematopoietic stem cell transplant (HSCT).Retrospective cohort study.Comprehensive cancer center in the United States.Seventy five allogeneic HSCT patients who received posaconazole oral suspension and oral sirolimus concurrently between 2009 and 2011.Sirolimus concentrations were recorded at baseline and for up to 28 days after posaconazole initiation. The sirolimus concentration/dose (C/D) ratio was determined for each sirolimus concentration obtained. Following analysis of patient data and based on the initial empiric sirolimus dose reduction, patients were stratified into two groups: ≥50% sirolimus dose reduction (Group 1) and50% sirolimus dose reduction (Group 2). The mean sirolimus C/D ratio was 2.29 ng/mL/mg prior to posaconzole initiation. Coadministration of posaconazole and sirolimus resulted in an increase in the steady state sirolimus C/D ratio to 6.24 ng/mL/mg, which occurred approximately 17-20 days after initiation of posaconazole. The mean maximum sirolimus concentration was significantly higher in Group 2 compared to Group 1 (12.64 ng/mL vs. 9.24 ng/mL, p=0.001). Significantly more patients in Group 2 than Group 1 experienced at least one sirolimus concentration15 ng/mL (27% vs. 2.6%, p=0.003).Coadministration of posaconazole oral suspension with oral sirolimus increases the sirolimus C/D ratio by approximately 2.7-fold in HSCT patients. An initial empiric oral sirolimus dose reduction between 50% and 65% may be recommended for most clinically stable patients with close sirolimus concentration monitoring for at least 3 weeks following posaconazole initiation. |
| Databáze: | OpenAIRE |
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