毒理性
急性肝性卟啉病是罕见的，且givosiran的关键试验是在相对较少的患者中进行的，因此可能无法完全了解其全部的肝毒性。尽管如此，在注册控制试验中，服用givosiran的患者中有13%出现了血清转氨酶升高，而服用安慰剂的患者中只有2%，但升高到超过正常上限5倍的情况非常罕见。报告有一名患者因转氨酶升高而停用givosiran治疗，但没有患者出现血清胆红素同时升高或提示肝炎的症状。因此，givosiran尚未与急性肝炎或黄疸的病例相关联，但其临床使用有限。
The acute hepatic porphyrias are rare, and the pivotal trials of givosiran were conducted in rather small numbers of patients, so the full spectrum of hepatotoxicity may not be fully known. Nevertheless, in the registration controlled trials, serum aminotransferase elevations arose in 13% of givosiran- versus 2% of placebo-recipients, but rose to levels above 5 times the upper limit of normal only rarely. One patient was reported as discontinuing givosiran therapy because of aminotransferase elevations, but no patient developed concurrent elevations in serum bilirubin or symptoms suggestive of hepatitis. Thus, givosiran has not been linked to instances of acute hepatitis or jaundice, but it has had limited clinical use.
来源:LiverTox
