Immunosuppression With Sirolimus After Solid Organ Transplantation in Children

Marcia L. Buck, Pharm.D., FCCP

Pediatr Pharm. 2006;12(2) 

In This Article

Adverse Reactions

The most frequently reported adverse effects associated with sirolimus include hypertension (39-49% of adult patients in clinical trials), hyperlipidemia (38-57%), diarrhea (32-42%), anemia (27-37%), fever (23-34%), thrombocytopenia (13-30%), hypokalemia (11-21%), leukopenia (9-15%), rash (10-20%), and leukopenia (9-15%). In most cases, these adverse effects are dose or concentration-dependent.[2,3] A similar adverse effect profile has been described in pediatric studies.[4,15]

As with any immunosuppressive agent, the use of sirolimus places patients at increased risk for infection and the development of lymphoma. Other rare adverse reactions with sirolimus include anaphylaxis and other hypersensitivity reactions. Interstitial lung disease has been reported in both adult and pediatric patients treated with sirolimus. Some of these cases have resulted in patient death. In addition, bronchial anastomotic dehiscence, usually fatal, has been reported in adult lung transplant patients receiving sirolimus.[2,3,17]

Concomitant use of sirolimus and calcineurin inhibitors may also increase the likelihood for adverse effects. Close monitoring is needed for patients receiving these combinations, with adjustment and/or or discontinuation of one of the drugs if necessary. Adult patients receiving sirolimus in combination with tacrolimus after liver transplantation have been found to be at greater risk for hepatic artery thrombosis, graft loss, and death.[2,3]

Although the incidence of nephrotoxicity with sirolimus appears to be less than that reported with calcineurin inhibitors, it remains a significant concern, particularly when these agents are used in combination[2,3] Butani reported proteinuria in 12 of 13 children receiving sirolimus after renal transplantation.[18] The mean interval to presentation was 1 month, with an increase in the urine protein to creatinine ratio (Up/c) of 1.1 to 3.9 within 5 months of starting therapy. Angiotensin receptor blockers were effective in reducing the Up/c to a mean of 2.2 at follow-up.


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