title: Significant sirolimus and dronedarone interaction in a kidney transplant recipient.
abstract: OBJECTIVE
  To report the potential clinically significant pharmacokinetic interaction between sirolimus and dronedarone.
  
  
  METHODS
  A 67-year-old man status post-kidney transplant in 2004 was maintained on an immunosuppressive regimen consisting of sirolimus, mycophenolate mofetil, and prednisone. He had been maintained for more than 1 year on a stable dose of sirolimus (5 mg/day), with concentrations ranging between 5 and 13.5 ng/mL. The patient was admitted to the hospital with a complaint of bloody diarrhea; shortly after admission, he developed atrial fibrillation for which dronedarone 400 mg twice daily was initiated. Sirolimus concentrations obtained 3 days after initiation of dronedarone revealed a trough concentration that was increased by more than 3-fold (38.6 ng/mL) from his baseline trough concentration. After sirolimus was held for 6 days, the trough concentration was 7.8 ng/mL. The dosage was reduced to 1 mg/day; there was no need for further adjustment.
  
  
  CONCLUSIONS
  While the potential for an interaction between sirolimus and dronedarone is listed in the package insert of dronedarone, there are no documented reports of this interaction in the peer-reviewed literature. Since sirolimus is a narrow therapeutic index medication, information about the severity and magnitude of the interaction with dronedarone may help clinicians avoid therapeutic misadventures when this combination is employed. Our case clearly demonstrates a significant pharmacokinetic interaction between sirolimus and dronedarone. The Horn Drug Interaction Probability Scale indicates that the occurrence of an interaction between sirolimus and dronedarone in our case is probable.
  
  
  CONCLUSIONS
  Due to the potential for sirolimus toxicity and excessive immunosuppression, the concurrent use of dronedarone and sirolimus should be avoided when possible. If concurrent administration cannot be avoided, we suggest close monitoring and a 50-75% dose reduction of sirolimus prior to dronedarone initiation.
authors.affiliation: Solid Organ Transplant, Department of Pharmacy, Yale-New Haven Hospital, New Haven, CT 06510, USA. eric.tichy@ynhh.org
authors.forename: Eric M
authors.initials: EM
authors.lastname: Tichy
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Medwid
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mills
authors.forename: Richard N
authors.initials: RN
authors.lastname: Formica
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kulkarni
mesh_terms: D000368:Aged; D000638:Amiodarone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D000077764:Dronedarone; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D020123:Sirolimus / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000889:Anti-Arrhythmia Agents; D007166:Immunosuppressive Agents; D000077764:Dronedarone; D000638:Amiodarone; D020123:Sirolimus