title: Worsening pneumonitis due to a pharmacokinetic drug-drug interaction between everolimus and voriconazole in a renal transplant patient.
abstract: OBJECTIVE
  Azole antifungals, prescribed prophylactically to avoid severe infections in immunosuppressed organ transplant recipients, can interact with drug substrates of CYP3A4. We report serious adverse effects due to interaction between orally administered voriconazole and everolimus in a renal transplant recipient.
  
  
  METHODS
  Despite reduction of the dose of everolimus by a third, the blood trough concentration of everolimus increased considerably in a kidney transplant recipient upon oral administration of voriconazole. Everolimus was then discontinued. Pneumonia secondary to pulmonary aspergillosis worsened, possibly due to the excessive immunosuppression.
  
  
  CONCLUSIONS
  Orally administered voriconazole inhibits intestinal and hepatic cytochrome P450-3A4 activity and thereby reduces everolimus metabolism. An 80% decrease in dose or discontinuation of everolimus is required when concomitant voriconazole is introduced. Daily blood monitoring of everolimus is warranted until a steady state of concentrations is reached.
authors.affiliation: Clinical Pharmacy, Bicetre Hospital, AP/HP, Le Kremlin Bicetre, France.
authors.forename: C
authors.initials: C
authors.lastname: Lecefel
authors.forename: P
authors.initials: P
authors.lastname: Eloy
authors.forename: B
authors.initials: B
authors.lastname: Chauvin
authors.forename: B
authors.initials: B
authors.lastname: Wyplosz
authors.forename: V
authors.initials: V
authors.lastname: Amilien
authors.forename: L
authors.initials: L
authors.lastname: Massias
authors.forename: A-M
authors.initials: AM
authors.lastname: Taburet
authors.forename: H
authors.initials: H
authors.lastname: Francois
authors.forename: V
authors.initials: V
authors.lastname: Furlan
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D004347:Drug Interactions; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D009181:Mycoses / Q000276:immunology / Q000517:prevention & control*; D011014:Pneumonia / Q000139:chemically induced*; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D065819:Voriconazole / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D000068338:Everolimus; D065819:Voriconazole; D020123:Sirolimus
keywords: everolimus; interaction; pneumonitis; transplantation; voriconazole