Resolution of sirolimus-induced pneumonitis after conversion to everolimus

Background. Sirolimus-induced pneumonitis usually requires the complete cessation of sirolimus. Herein we have reported five cases of recovery from sirolimus pneumonitis after conversion from sirolimus to everolimus. Patients. All five cases were comparable with regard to their clinical conditions. The ages were between 46 and 64 years. They had received kidney transplants 3 to 18 years earlier. In four cases, the reason for sirolimus therapy was toxicity due to calcineurin inhibitors on a transplant biopsy; three of the patients also displayed malignant tumors: renal cell carcinoma, spinocellular carcinoma, or melanoma. Their serum creatinine levels were elevated between 150 and 350 mu mol/L. In all five cases, bronchoscopy disclosed lymphocytic pneumonitis and bronchiolitis obliterans. The immunosuppressive co-medications were prednisolone in three, azathioprine in one, and mycophenolate mofetil in four cases. The previous sirolimus dose was 1 to 4 mg/day, with sirolimus trough levels between 5 and 12 ng/mL. The patients were switched to everolimus at doses between 1 X 0.25 and 2 X 0.75 mg/day to achieve trough concentrations between 3 and 8 ng/mL. Pulmonary symptoms and radiological findings resolved completely within I to 4 weeks. Conclusion. Everolimus is more hydrophilic by virtue of differing from sirolimus by one hydroxyl group. Sirolimus-induced pneumonitis improved after conversion to everolimus.