他克莫司制剂临床换用的安全性考虑

他克莫司是一种强效的免疫抑制剂,但治疗指数窄,个体变异大,剂量或者浓度的微小改变就有可能导致不良反应甚至治疗失败。目前,生物等效性研究的常规可接受范围、研究人群及考察指标等并不完全适用于他克莫司等治疗指数狭窄药物,导致批准上市的他克莫司仿制药与原研药可能不具有临床上的治疗等效性。因此临床治疗中随意换用他克莫司制剂存在一定的风险,需要临床医生谨慎决策。

Safety consideration on the conversion of tacrolimus formulations

Tacrolimus is a powerful immunosuppresant and is characterized by narrow therapeutic window and considerable individual variability of pharmacokinetics features.Small changes in the tacrolimus dose or concentration in blood may lead to adverse effect even the failure of therapy.However,the required range、study population and test parameters of bioequivalence study are not suitable for narrow therapeutic index drug such as tacrolimus.Therefore,these generic tacrolimus formulations may not be therapeutic equivalent to progarf and the conversion to different tacrolimus formulations must be undertaken with caution.