毒理性
氟伐他汀治疗与1%至5%的患者出现轻度、无症状且通常是暂时的血清转氨酶升高有关，但在超过3倍ULN的水平上大约为1%。在大规模前瞻性监测研究的总结分析中，ALT升高超过正常范围的患者高达5%；氟伐他汀治疗的患者中ALT水平超过正常上限3倍（ULN）的发生率为1.1%，而安慰剂接受者为0.3%。这些升高更常见于较高剂量的氟伐他汀。大多数这些升高是自限性的，不需要调整剂量。氟伐他汀是最常与血清转氨酶升高和症状性肝损伤最高发生率相关的他汀类药物，然而，明显的、临床上可见的氟伐他汀引起的肝损伤仍然相当罕见，估计在使用期间每10,000人年发生1.7例。在报告的少数病例中，临床损伤的发作通常在1到4个月内，损伤模式通常是胆汁淤积性或混合性。皮疹、发热和嗜酸性粒细胞增多不常见。至少有一例具有自身免疫特征的病例已被描述。大多数病例在发病后几个月内解决。
Fluvastatin therapy is associated with mild, asymptomatic and usually transient serum aminotransferase elevations in 1% to 5% of patients but in levels above 3 times ULN is approximately 1%. In summary analyses of large scale studies with prospective monitoring, ALT elevations above normal occurred in up to 5% of patients; ALT levels of above 3 times the upper limit of normal (ULN) occurred in 1.1% of fluvastatin treated versus 0.3% of placebo recipients. These elevations were more common with higher doses of fluvastatin. Most of these elevations were self-limited and did not require dose modification. Fluvastatin is the statin most commonly associated with serum aminotransferase elevations and the highest rates of symptomatic liver injury, yet frank, clinically apparent hepatic injury from fluvastatin is still quite rare estimated to occur in 1.7 per 10,000 person years of use. In the few cases that have been reported, the onset of clinical injury has been within 1 to 4 months, the pattern of injury is typically cholestatic or mixed. Rash, fever and eosinophilia are uncommon. At least one case with features of autoimmunity has been described. Most cases resolve within a few months of onset.
来源:LiverTox
