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。
Liver injury caused by the combination of voriconazole and nirmatrelvir/ritonavir
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.
Antiviral agentsAntifungal agentsChemical and drug induced liver injuryVoriconazoleDrug interactionsLung transplantationRitonavirNirmatrelvir
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