Differential profiles of adverse events associated with mycophenolate mofetil between adult and pediatric renal transplant patients

Mycophenolate mofetil (MMF), an immunosuppressive drug, is extensively used after renal transplantation.1 MMF is used in combination with other immunosuppressant medications, mainly with the calcineurin inhibitors cyclosporine and tacrolimus.2 MMF is also used in the treatment of autoimmune and chronic inflammatory diseases.3 Early clinical trials have shown that MMF reduces acute rejection in renal transplant patients by 20% to 40% compared with azathioprine, and reduces graft loss and chronic allograft dysfunction.4–7 However, MMF has been reported to be associated with a high incidence of adverse events.8–10 In the clinical setting, dose reduction or discontinuation of MMF is often required to alleviate adverse events. This results in an unnecessarily increased risk of acute rejection11 and poor long-term graft survival.12 Recently, there has been growing opinion that detailed evaluation of information gained through pharmacovigilance activity is important for all drugs to ensure their safe use.13,14 Pharmacovigilance practices can improve the quality of information, which is provided to medical staff and patients in a timely manner, thereby reducing the overall risk to patients. Drugs are approved for clinical use on the basis of showing a satisfactory balance of benefits and risks. However, the safety profile of drugs can change over time because their use expands with the patients’ characteristics and the number of patients exposed. In Japan, the “Risk Management Plan Guidance”15 issued in 2012, describes the basic ideas needed to develop a drug risk management plan, including safety considerations, a drug safety monitoring plan, and a risk minimization plan based on the International Conference on Harmonization E2E guidelines (2004).16 This study aimed to obtain a comprehensive, nationwide overview of adverse events associated with MMF in patients with a renal transplantation using an adverse drug events database in Japan composed of voluntarily submitted reports.