title: Voriconazole and sirolimus coadministration after allogeneic hematopoietic stem cell transplantation.
abstract: Sirolimus is increasingly used in transplantation for prevention and treatment of graft-versus-host disease and organ rejection. Voriconazole is contraindicated when used concomitantly with sirolimus because of a substantial increase in sirolimus drug exposure with unadjusted dosing, but voriconazole is also considered the best initial treatment of invasive aspergillosis and other fungal infections. Patients who received voriconazole and sirolimus concomitantly were identified by a review of the medical records of all allogeneic hematopoietic stem cell recipients at our institution from September 1, 2002, to June 1, 2005. Data including baseline characteristics, indications for both drugs, and potential adverse effects were evaluated. Eleven patients received voriconazole and sirolimus concomitantly for a median of 33 days (range, 3-100 days). In 8 patients whose sirolimus dose was initially reduced by 90%, trough sirolimus levels were similar to those obtained before the administration of voriconazole; no obvious significant toxicity from either drug was observed during coadministration. Serious adverse events were observed in 2 patients in whom sirolimus dosing was not adjusted during voriconazole administration. Sirolimus and voriconazole may be safely coadministered if there is an empiric initial 90% sirolimus dose reduction combined with systematic monitoring of trough levels.
authors.affiliation: Division of Infectious Diseases, Brigham & Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA. fmarty@partners.org
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Marty
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Lowry
authors.forename: Corey S
authors.initials: CS
authors.lastname: Cutler
authors.forename: Bonnie J
authors.initials: BJ
authors.lastname: Campbell
authors.forename: Karen
authors.initials: K
authors.lastname: Fiumara
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004347:Drug Interactions; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000139:chemically induced; D007938:Leukemia / Q000276:immunology / Q000601:surgery; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D011183:Postoperative Complications / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D008055:Lipids; D011743:Pyrimidines; D014230:Triazoles; D003404:Creatinine; D065819:Voriconazole; D020123:Sirolimus