Evaluation of potential interactions between mycophenolic acid derivatives and proton pump inhibitors.
OBJECTIVE
To evaluate the incidence of gastrointestinal (GI) complications in solid organ transplant (SOT) recipients, impact of the complications on transplant outcomes, and the potential interactions between mycophenolic acid (MPA) derivatives and proton pump inhibitors (PPIs).


METHODS
An unrestricted literature search (1980-January 2012) was performed with MEDLINE and EMBASE using the following key words: drug-drug interaction, enteric-coated mycophenolic acid, GI complications, mycophenolate mofetil, solid organ transplant, and proton pump inhibitor, including individual agents within the class. Abstracts from scientific meetings were also evaluated. Additionally, reference citations from identified publications were reviewed.


METHODS
Relevant English-language, original research articles and review articles were evaluated if they focused on any of the topics identified in the search or included substantial content addressing GI complications in SOT recipients or drug interactions.


RESULTS
GI complications are frequent among SOT recipients, with some studies showing prevalence rates as high as 70%. Transplant outcomes among renal transplant recipients are significantly impacted by GI complications, especially in patients requiring immunosuppressant dosage reductions or premature discontinuation. To this end, PPI use among patients receiving transplants is common. Recent data demonstrate that PPIs significantly reduce the overall exposure to MPA after oral administration of mycophenolate mofetil. Similar studies show this interaction does not exist between PPIs and enteric-coated mycophenolic acid (EC-MPA). Unfortunately, most of the available data evaluating this interaction are pharmacokinetic analyses that do not investigate the clinical impact of this interaction.


CONCLUSIONS
A significant interaction exists between PPIs and mycophenolate mofetil secondary to reduced dissolution of mycophenolate mofetil in higher pH environments. EC-MPA is not absorbed in the stomach; therefore, low intragastric acidity does not impact EC-MPA and bioavailability is maintained with this formulation during PPI coadministration. The clinical impact of this interaction is unknown, yet one can theorize that reduced exposure to MPA in SOT recipients can increase the risk of allograft rejection and/or failure.
Department of Transplant Surgery, Brigham and Women's Hospital, Boston, MA, USA. sgabardi@partners.org
Steven
S
Gabardi
Ali
A
Olyaei
D004347:Drug Interactions; D005767:Gastrointestinal Diseases / Q000209:etiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009173:Mycophenolic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016377:Organ Transplantation; D054328:Proton Pump Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D054328:Proton Pump Inhibitors; D009173:Mycophenolic Acid