伏立康唑与奈玛特韦/利托那韦联用致肝损伤

Liver injury caused by the combination of voriconazole and nirmatrelvir/ritonavir

1例66岁男性肺移植术后患者,长期服用他克莫司、麦考酚钠、泼尼松三联药物抗排斥反应。因患者发生新型冠状病毒和肺部真菌感染,给予奈玛特韦/利托那韦(Paxlovid)抗病毒治疗,2 d后加用伏立康唑抗真菌治疗。加用伏立康唑前患者丙氨酸转氨酶34 U/L,天冬氨酸转氨酶28 U/L。伏立康唑与Paxlovid联用第4天,伏立康唑血药谷浓度16.06 mg/L,丙氨酸转氨酶176 U/L,天冬氨酸转氨酶166 U/L,立即停用伏立康唑,2 d后停用Paxlovid。伏立康唑停药5 d后,患者肝功能恢复正常;9 d后,其血药谷浓度为5.84 mg/L。考虑患者的肝损伤是伏立康唑与Paxlovid联用所致。

A 66‑year‑old male patient who underwent lung transplantation took a combination therapy with tacrolimus,mycophenolate sodium,and prednisone for a long time to resist rejection.Due to the occurrence of novel coronavirus and pulmonary fungal infection,the patient was given antiviral therapy with nirmatrelvir/ritonavir(Pavlovid),followed by antifungal therapy with voriconazole 2 days later.Before voriconazole treatment,the patient′s alanine aminotransferase was 34 U/L,and aspartate aminotransferase was 28 U/L.On the 4th day of the combination of voriconazole and Paxlovid,the patient′s blood trough concentration of voriconazole was 16.06 mg/L,alanine aminotransferase was 176 U/L,and aspartate amino-transferase was 166 U/L.Voriconazole was discontinued immediately and 2 days later,Paxlovid was discontinued.Five days after discontinuation of voriconazole,the patient′s liver function returned to normal;9 days later,blood trough concentration of voriconazole was 5.84 mg/L.It was considered that the patient′s liver injury was caused by the combination of voriconazole and Paxlovid.