奈玛特韦/利托那韦与他克莫司联用致他克莫司血药谷浓度升高

Increase of trough concentration of tacrolimus induced by combination of nirmatrelvir/ritonavir and tacrolimus

1例55岁男性患者肺移植术后口服他克莫司(早2.5 mg、晚2 mg)6个月用以抗排斥反应,他克莫司血药谷浓度维持在8.0~10.0μg/L。因感染新型冠状病毒接受抗病毒治疗(奈玛特韦/利托那韦300 mg/100 mg口服、2次/d,共用药5 d),此间患者继续抗排斥反应治疗。接受抗病毒治疗第2天,患者他克莫司血药谷浓度升高至>40.0μg/L,考虑为奈玛特韦/利托那韦与他克莫司相互作用所致,停用他克莫司,继续抗病毒治疗。停用他克莫司8 d且停用奈玛特韦/利托那韦3 d后,患者他克莫司血药谷浓度降至25.7μg/L;减量服用他克莫司3 d,该药血药谷浓度为8.3μg/L;按原剂量和频次恢复服用他克莫司13 d,该药血药谷浓度为9.2μg/L。此后患者的他克莫司血药谷浓度未再出现异常。

A 55‑year‑old male patient was treated with tacrolimus(2.5 mg in the morning and 2 mg at night)for 6 months after lung transplantation to prevent rejection.The blood trough concentration of tacrolimus was stable at 8.0-10.0μg/L.The patient received antiviral treatment due to corona virus disease 2019(nirmatrelvir/ritonavir 300 mg/100 mg twice daily orally for a total of 5 days).During the antiviral treatment,the patient continued the anti‑rejection treatment.On the second day of antiviral treatment,the patient′s blood trough concentration of tacrolimus increased to>40.0μg/L,which was considered to be caused by the interaction between nirmatrelvir/ritonavir and tacrolimus.Tacrolimus was withdrawn and antiviral therapy was continued.After discontinuation of tacrolimus for 8 days and nirmatrelvir/ritonavir for 3 days,the blood trough concentration of tacrolimus decreased to 25.7μg/L.After re-giving tacrolimus at reducing dosage for 3 days,the blood trough concentration of tacrolimus was 8.3μg/L.After 13 days of resuming administration of tacrolimus at the original dose and frequency,the patient′s blood trough concentration of tacrolimus was 9.2μg/L.Since then,the blood trough concentration of tacrolimus in the patient was not abnormal again.