伏立康唑与埃索美拉唑联用致乙肝肝硬化并肺部侵袭性真菌感染患者横纹肌溶解症

Voriconazole Coadministration with Esomeprazole Induced Hepatitis B Liver Cirrhosis Combining Pulmonary Invasive Fungal Infection Patient Rhabdomyolysis

"伏立康唑"目前被认为是治疗侵袭性真菌感染应用较多的抗真菌药物,但由于其具有潜在的较多的药物相互作用及药代动力学个体间差异较大,使其在临床使用过程中问题重重。1例54 a男性患者因乙肝肝硬化(活动期、失代偿期)并自发性腹膜炎入院治疗,常规性给予"埃索美拉唑、拉米夫定、呋塞米、前列地尔、多烯磷脂酰胆碱、美罗培南、白蛋白"等抑酸、抗病毒、利尿、改善肝功能、护肝、抗感染、补充白蛋白等治疗。住院第3日可疑肺部侵袭性真菌感染,首先给予"氟康唑"经验性抗真菌治疗,3 d后根据药敏实验结果及患者经济状况改为"伏立康唑(针剂4 d,口服12 d)"治疗。肝功能有好转迹象,但住院第21日患者开始出现全身不适、乏力,轻度胸闷、气促,呕吐症状,怀疑与使用"伏立康唑"或"拉米夫定"有关,次日停用。住院第23日相关检查结果示横纹肌溶解症伴肝功能衰竭。经"小剂量补碱、丙种球蛋白封闭抗体及提高免疫力、甲强龙抗炎、血液透析等"对症治疗1周,患者肌酶进行性下降,但之后出现血钾、肌酐、尿素氮进行性升高,尿量进行性减少,最终导致急性肾功能衰竭,肺部感染加重,自动出院。推测:原因为"埃索美拉唑"的肝药酶CYP2C19抑制作用引起"伏立康唑"血药浓度升高从而加重"伏立康唑"的肝药酶抑制作用及药物性肝损害,并因"伏立康唑"的肝药酶CYP2C19抑制作用降低"埃索美拉唑"的代谢,从而造成二者在体内蓄积,最终导致肝肾衰竭、药物性横纹肌溶解症。

Voriconazole is thought to be the major antifungal agents for the treatment of invasive fungal infection（IFI）.But for its latent drug-drug interactions as well as the pharmacokinetics between inter-individual variation makes its clinical application be problematic.This case describes a 54 a man who was admitted with hepatitis B liver cirrhosis combining spontaneous peritonitis.He was administered with ＂esomeprazole,lamivudine,furosemide,alprostadil,polyene phosphatidylcholine,meropenem,human albumin＂ routinely for symptomatic treatment.On the 3th day of admission,he was suspected of pulmonary invasive fungal infection.Fluconazole was prescribed for empirical treatment and was switched to voriconazole according to the results of drug sensitivity test and the patient＇s economic status from the 6th day of admission.His liver function showed some improvement,but on the 21th day of admission he appeared general malaise,asthenia,slightly shortness of breath,＂voriconazole＂ and ＂lamivudine＂ was suspected and suspended on the next day.On the 23th day of admission,coherence check showed rhabdomyolysis and liver failure.By supplying small dose of alkali,blocking antibodies and improving immunity with immunoglobulin,anti-inflammation,hemodialysis for 1 week＇s treatment,his blood creatase progressively dropped,but his blood Potassium,creatinine,urea nitrogen progressively stepped-up,urine volume progressively decreased,finally induced Acute Kidney Failure,aggravated pulmonary infection,he was discharged from hospital voluntarily.We presume it is esomeprazole＇s inhibition of CYP2C19 that elevated the blood concentration of voriconazole and aggratated its liver enzyme inhibition and drug induced liver injury,and voriconazole＇s liver enzyme inhibition that decreased the metabolism of esomeprazole,accordingly resulting in accumulation of voriconazole and esomeprazole,liver and renal failure as well as drug induced rhabdomyolysis.