Management of Drug Interaction between Posaconazole and Sirolimus in Patients Who Undergo Hematopoietic Stem Cell Transplant

Study Objective 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). Design Retrospective cohort study. Setting Comprehensive cancer center in the United States....

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Bibliographic Details
Published in:Pharmacotherapy 2015-06, Vol.35 (6), p.578-585
Main Authors: Cho, Eunah, Chan, Holly, Nguyen, Huan (Mark), Shayani, Sepideh, Nakamura, Ryotaro, Pon, Doreen
Format: Article
Language:English
Subjects:
Adult
Aged
Antifungal Agents - adverse effects
cytochrome P450
drug interaction
Drug Interactions
Female
hematopoietic stem cell transplant
Hematopoietic Stem Cell Transplantation
Humans
Immunosuppressive Agents - adverse effects
Immunosuppressive Agents - pharmacokinetics
Male
Middle Aged
Ovarian cancer
p-glycoprotein
posaconazole
Retrospective Studies
sirolimus
Sirolimus - adverse effects
Sirolimus - pharmacokinetics
Stem cells
Triazoles - adverse effects
Young Adult
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Summary:Study Objective 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). Design Retrospective cohort study. Setting Comprehensive cancer center in the United States. Subjects Seventy five allogeneic HSCT patients who received posaconazole oral suspension and oral sirolimus concurrently between 2009 and 2011. Measurements and Main Results 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) and 15 ng/mL (27% vs. 2.6%, p=0.003). Conclusion 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.
ISSN:0277-0008
1875-9114
DOI:10.1002/phar.1600