Investigating barriers to immunosuppressant medication adherence in renal transplant patients.

AIM: Immunosuppressant medication non-adherence can result in allograft rejection and loss. The aim of this study was to investigate the prevalence of non-adherence and barriers to adherence with immunosuppressant medications, in an adult renal transplant cohort. METHODS: Kidney transplant recipients completed a self-report survey consisting of five validated questionnaires (Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS), Beliefs about Medicines Questionnaire, Immunosuppressant Therapy Barrier Scale, Brief-Illness Perception Questionnaire, and Multidimensional Health Locus of Control Scale), and provided sociodemographic information. Adherence was categorised according to BAASIS, with adherence barriers compared between the groups. RESULTS: One hundred and sixty-one patients in total completed the survey. Eighty-six participants (55%) were categorised as non-adherent, with 45% delaying doses, and 25% skipping doses. Non-adherent patients were more likely to forget doses (P = 0.005), and more likely to skip doses when their daily routine changed (P < 0.001) or when short of money (P = 0.03). Additionally, non-adherent patients had less self-reported understanding about their graft than adherent patients (P = 0.008). Adherence was not associated with a patient's medicine beliefs or perception of locus of control. CONCLUSION: Over half the patients self-reported non-adherence. The main modifiable barriers leading to non-adherence were forgetfulness and skipped doses. Personalised interventions focused on habit forming may improve adherence in this population.

Therapeutic monitoring of mycophenolate in transplantation: is it justified?

Mycophenolate mofetil (MMF) is the preferred antimetabolite in solid organ transplantation. It is a prodrug that undergoes pre-systemic metabolism to mycophenolic acid (MPA), the active drug moiety. MMF is typically administered as a fixed dose without routine monitoring of MPA concentrations. However, a role for therapeutic drug monitoring (TDM) of MPA has been suggested based on the drug's narrow therapeutic window and considerable between-subject variability. Dose-normalized MPA area under the concentration-time curve (AUC) has been observed to vary >/=10-fold. Some of this variability may be accounted for by patient variability in renal and liver function, serum albumin and haemoglobin levels, body mass, concomitant medication exposure and genetic polymorphisms in enzymes responsible for drug metabolism and transport, but much is unexplained. Widespread adoption of MPA TDM has been limited by the impracticality of full 0 to 12 hour AUC measurement (AUC(0-12)), poor correlation between pre-dose MPA concentration and AUC(0-12), ongoing questions regarding the utility of free versus total MPA measurements and lack of evidence correlating MPA exposure with clinical outcomes. Two recent randomized studies evaluating the role of MPA TDM in renal transplant recipients have reported conflicting results. Promising areas of ongoing study include use of Bayesian forecasting to predict MPA dosage and measurement of inosine monophosphate dehydrogenase activity. This review provides an overview of the pharmacokinetics of MMF in solid organ transplantation, and discusses the benefits and limitations of MPA monitoring. Areas that require additional research are identified.