阿莫西林-克拉维酸钾的肝毒性反应

Hepatotoxic reactions induced by amoxicillin-clavulanate potassium

阿莫西林-克拉维酸钾为广泛应用的抗生素,其抗菌谱同阿莫西林。已有阿莫西林-克拉维酸钾引起肝炎和胆汁淤积型黄疸的报道,其机制尚不十分清楚,可能和免疫反应与代谢因素有关。其发生率约为0.001%～0.022%,肝毒性反应一般发生在用药后数天至数周(平均8.9d)。临床表现为黄疸、瘙痒、疲劳、恶心、呕吐、肝大、皮疹、腹痛和发热等。血清ALT、AST、碱性磷酸酶、γ-谷氨酰转肽酶水平明显升高(正常值上限的2～10倍)。一般停药后1～8周黄疸消退,4～16周肝功能恢复正常。肝毒性反应的危险因素包括男性(男:女之比约为4:1至2:1),老年,用药时间长及合并用药(尤其是肝毒性药物如对乙酰氨基酚、别嘌醇、红霉素等)。预防措施为:严格掌握适应证,大于65岁男性老年患者不用或慎用,用药时间一般不超过14d,避免多药合用,用药过程中加强监测。

Amoxicillin-clavulanate potassium is a widely used antibiotic and its antimicrobial spectrum is the same as that of amoxicillin.Hepatitis and cholestatic jaundice related to amoxicillin-clavulanate potassium have been reported.The mechanism is unclear,however,it may involve in immune reactions or metabolism factors.The incidence is about 0.001%~0.022%.The time to hepatotoxic reaction onset is several days or weeks（average 8.9 days） after treatment start.Clinical manifestations include jaundice,itching,weakness,nausea,vomiting,hepatomegaly,skin rash,abdominal pain,fever,and so on.The serum ALT,AST,alkaline phosphatase,and γ-GT levels markedly increase（2~10 times the upper limit of normal）.Generally,jaundice subsided within 1 to 8 weeks after the drug discontinuation and liver functions return to within normal range 4 to 16 weeks after the drug stop.The risk factors for hepatotoxic reactions include male（the ratio of males to females is about 4 to 1 or 2 to 1）,advanced age,long-term treatment,and combination therapy（especially hepatotoxic drugs such as acetaminophen,allopurinol,and erythromycin）.Preventive measures are as follows：never use amoxicillin-clavulanate potassium unless there is a good indication;the drug should be avoided or used very carefully in male aged 65 years;the treatment duration should not exceed 14 days;multidrug therapy should be avoided;monitoring should be performed during treatment.