Pericardial Effusion Coincident With Sirolimus Therapy: A Review of Wyeth's Safety Database

Abstract

Sirolimus is an immunosuppressive agent approved for prophylaxis of acute rejection in renal transplant patients aged 13 years or older. A retrospective review of pericardial effusion coincident with sirolimus therapy was conducted from key clinical trials and spontaneous reporting sources. A significantly higher rate of pericardial effusion occurred with sirolimus versus azathioprine treatment in a cardiac transplantation trial (28.6% versus 9.3%, respectively). Cases of pericardial effusion were also observed in the sirolimus treatment arms of three de novo renal transplant studies (rates 0.5 to 1.9%). Although most of the pericardial effusions occurred in cardiac transplantation, sirolimus is not approved for this use. As of January 31, 2007, the Wyeth safety database (which includes clinical trial data and spontaneous reports) contained reports of pericardial effusion in 56 sirolimus-treated patients, 31 of whom required pericardial drainage. These data suggest that pericardial effusion should be considered in the differential diagnosis of a clinical deterioration in posttransplant patients treated with sirolimus. The adverse reaction of pericardial effusion has been added to product labeling.

Everolimus: an update on the mechanism of action, pharmacokinetics and recent clinical trials

“…Cases of pericardial effusion were also observed in the SRL treatment arms of three de novo renal transplant studies (rates 0.5 -1.9%) [81] . As of 31 January 2007, the Wyeth safety database (which includes clinical trial data and spontaneous reports) contained reports of pericardial effusion in 56 SRL-treated patients, 31 of whom required pericardial drainage [81] .…”

“…A significantly higher rate of pericardial effusion occurred with SRL versus azathioprine treatment in a cardiac transplantation trial (28.6 versus 9.3%, respectively) [81] . Cases of pericardial effusion were also observed in the SRL treatment arms of three de novo renal transplant studies (rates 0.5 -1.9%) [81] .…”

Everolimus: efficacy and safety in cardiac transplantation

“…Frequency of pericardial effusions following cardiac transplant are threefold greater in sirolimus treated patients often requiring interventions such as drainage with or without sirolimus dose reductions [40,70,71]. Cases of pericardial tamponade have been described following the initiation of sirolimus both in de novo cardiac and late conversion heart transplant patients as well as non-cardiac transplants patients [70,72]. The prevalence of effusions, pleural and pericardial, is similar between MMF and everolimus treated patients suggesting that this side effect may be PSI specific with greater frequency seen in sirolimus versus everolimus treated patients [73].…”

Sirolimus‐associated pericardial effusion with cardiac tamponade and interstitial pneumonitis in a hematopoietic stem cell transplant recipient

“…It is widely used for the prevention of graft rejection among solid organ transplant (SOT) patients . A diverse spectrum of sirolimus‐associated adverse effects has been reported in SOT patients, including peripheral edema, hyperlipidemia, proteinuria, impaired wound healing, lymphocele formation, pericardial effusion, and interstitial pneumonitis . However, sirolimus‐associated life‐threatening toxicities are underreported among hematopoietic stem cell transplant (HSCT) patients despite its increasing use in prevention and treatment of graft‐versus‐host disease (GVHD) in allogeneic HSCT patients .…”