title: High prevalence of potential drug interactions affecting mycophenolic acid pharmacokinetics in nonmyeloablative hematopoietic stem cell transplant recipients.
abstract: OBJECTIVE
  Mycophenolic acid (MPA) exposure is associated with clinical outcomes in hematopoietic cell transplant (HCT) recipients. Various drug interaction studies, predominantly in healthy volunteers or solid organ transplant recipients, have identified medications which impact MPA pharmacokinetics. Recipients of nonmyeloablative HCT, however, have an increased burden of comorbidities, potentially increasing the number of concomitant medications and potential drug interactions (PDI) affecting MPA exposure. Thus, we sought to be the first to characterize these PDI in nonmyeloablative HCT recipients.
  
  
  METHODS
  We compiled PDI affecting MPA pharmacokinetics and characterized the prevalence of PDI in nonmyeloablative HCT recipients. A comprehensive literature evaluation of four databases and PubMed was conducted to identify medications with PDI affecting MPA pharmacokinetics. Subsequently, a retrospective medication review was conducted to characterize the cumulative PDI burden, defined as the number of PDI for an individual patient over the first 21 days after allogeneic graft infusion, in 84 nonmyeloablative HCT recipients.
  
  
  RESULTS
  Of the 187 concomitant medications, 11 (5.9%) had a PDI affecting MPA pharmacokinetics. 87% of 84 patients had one PDI, with a median cumulative PDI burden of 2 (range 0 - 4). The most common PDI, in descending order, were cyclosporine, omeprazole and pantoprazole.
  
  
  CONCLUSIONS
  Only a minority of medications (5.9%) have a PDI affecting MPA pharmacokinetics. However, the majority of nonmyeloablative HCT recipients had a PDI, with cyclosporine and the proton pump inhibitors being the most common. A better understanding of PDI and their management should lead to safer medication regimens for nonmyeloablative HCT recipients.
authors.forename: Alenka
authors.initials: A
authors.lastname: Jaklič
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Collins
authors.forename: Aleš
authors.initials: A
authors.lastname: Mrhar
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Sorror
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Meagan J
authors.initials: MJ
authors.lastname: Bemer
authors.forename: Igor
authors.initials: I
authors.lastname: Locatelli
authors.forename: Jeannine S
authors.initials: JS
authors.lastname: McCune
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D004347:Drug Interactions; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000493:pharmacokinetics*; D015995:Prevalence
chemical_list: D009173:Mycophenolic Acid