Impact of risk‐stratified mycophenolate dosing in heart transplantation

Abstract

Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid, is a highly effective immunosuppressive agent in heart transplant therapy. While the FDA approved dose is 1500 mg twice daily, dosing is often reduced due to dose-dependent adverse effects.However, empiric MMF dose reductions may lead to sub-therapeutic dosing and impair clinical outcomes. Our single center protocolized a risk-stratified approach based on age and weight to dose 500 mg twice daily or 1000 mg twice daily to patients after heart transplantation. This retrospective single-center study analyzed 140 consecutive heart transplant patients who were initiated on our risk-stratified MMF protocol post-transplant. The analysis revealed that the composite rate of biopsy-proven rejection, graft loss, or mortality at 1-year post-transplantation was similar between the two groups. Incidence of neutropenia, thrombocytopenia, infection, cardiac allograft vasculopathy, or acute kidney injury by 1-year also showed similar results between the two groups. Risk-stratification of MMF dosing appears to be a safe and effective strategy after heart transplantation.

Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2 g versus 3 g daily early after heart transplantation

“…Patients were risk‐stratified based on age and weight; patients ≥60 years old or weighing <60 kg received MMF 0.5 g twice daily, whereas patients <60 years old and weighing >60 kg received MMF 1 g twice daily. Their recently published study of 140 HT recipients found no difference in the 1‐year incidence of high‐grade ACR, graft loss, or mortality, as well as 1‐year incidence of neutropenia, thrombocytopenia, or infection between the two dosing cohorts 27 . These data are intriguing; however, the two MMF doses were prescribed to very different patient populations, and, as such, it is impossible to discern if their equivocal outcomes were derived from the MMF dose or from the inherent differences between the groups.…”

“…In the CLEAR study, 26 an initial loading dose of 3 g MMF administered after renal transplant was shown to be correlated with less MPA underexposure and lower rates of early rejection compared to the standard high-grade ACR, graft loss, or mortality, as well as 1-year incidence of neutropenia, thrombocytopenia, or infection between the two dosing cohorts. 27 These data are intriguing; however, the two MMF doses were prescribed to very different patient populations, and, as such, it is impossible to discern if their equivocal outcomes were derived from the MMF dose or from the inherent differences between the groups.…”