用sirolimus需要注意什么？

Sirolimus has received more and more attention in solid organ transplantation due to its low nephrotoxicity, anti-tumor, and anti-proliferation characteristics. Kidney transplant patients can also benefit from this drug. However, during the actual treatment process, there are some things that patients still need to pay attention to:

1. Increase the chance of infection and may cause lymphoma

Immunosuppression with sirolimus may increase susceptibility to infection and may increase the chance of developing lymphoma and other malignancies, especially skin cancer. In Trials 1 and 2, lymphoma and lymphoid hyperplasia occurred in 0.7% to 3.2% of patients in the sirolimus-treated group, compared with 0.6% to 0.8% in the azathioprine and placebo control groups. Oversuppression of the immune system also increases susceptibility to infections, including opportunistic infections such as tuberculosis, fatal infections, and sepsis. Sirolimus should only be used by physicians experienced with immunosuppressive therapy and treating solid organ transplant patients. Patients receiving this drug should be treated in a facility with appropriate laboratory and ancillary medical facilities and personnel. Physicians responsible for maintenance therapy should have complete information necessary for patient follow-up.

2. Liver transplantation - increased mortality, loss of graft function and hepatic artery thrombosis (HAT)

The safety and effectiveness of sirolimus as an immunosuppressant in liver or lung transplant patients have not been established and, therefore, its use in these patients is not recommended.

3. Interactions with strong inhibitors and inducers of CYP3A4 and/or P-gp

Coadministration of sirolimus with strong inhibitors of CYP3A4 and/or P-gp (e.g. ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin and clarithromycin) or strong inducers of CYP3A4 and/or P-gp (e.g. rifampicin and rifabutin) is not recommended. Sirolimus is extensively metabolized in the intestinal wall and liver by the CYP3A4 isoenzyme. Inhibitors of CYP3A4 can slow down the metabolism of sirolimus and increase the plasma concentration of sirolimus. Inducers of CYP3A4 accelerate the metabolism of sirolimus and reduce the plasma concentration of sirolimus.