Zhang Long-Guang, Ma Xue-Juan, Li Xiang-Yang
Department of Nephrology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
Front Nephrol. 2024 Aug 2;4:1413496. doi: 10.3389/fneph.2024.1413496. eCollection 2024.
A 71-year-old man with a 20-year history of grade 3 hypertension experienced kidney dysfunction 2 years earlier. His serum creatinine (SCr) at the time was 140 μmol/L [with estimated glomerular filtration rate (eGFR) of 43.9 ml/min per 1.73m], for which he received irbesartan since. At initial presentation, the spot urine dipstick protein was 1+, with an albumin-to-creatinine ratio of 230 mg/g (0-30) and normal urine sediments. The SCr was 176 μmol/L (eGFR = 32.8 ml/min per 1.73m). The hemoglobulin (Hb) level decreased from 102 to 96 g/L despite oral ferrous succinate 100 mg twice daily starting 2 months ago. Roxadustat (ROXA) 50 mg (body weight, 70 kg) three times weekly was then prescribed. Unfortunately, the patient mistakenly took the drug at 50 mg three times a day (i.e., 1,050 mg instead of the intended 150 mg per week), which was 3.5 times the recommended starting dose for non-dialysis-dependent chronic kidney disease (CKD) patients (100 mg three times weekly for body weight >60 kg) and two times the highest drug manual-recommended weekly dose (2.5 mg/kg three times weekly) approved in the country. When the attending nephrologist discovered the misuse 1 month later, the patient reported no apparent discomfort, and his home blood pressure was in the range 110-130/60-80 mmHg. Repeat blood tests showed that the Hb increased from 96 to 163 g/L and the SCr from 199 to 201 μmol/L in a month. The serum alanine transaminase (ALT) remained within the normal range (from 12 U/L at baseline to 20 U/L), while the serum total and indirect bilirubin levels were slightly elevated. ROXA was withheld immediately. In 30 days, the serum bilirubin returned to baseline, but the Hb decreased from 163 to 140 g/L, and then to 108 g/L after 3 months. On the other hand, the SCr increased from 179 to 203 μmol/L. At 9 months after the initial dosing, when the SCr increased to 256 μmol/L and the Hb decreased to 94 g/L again, ROXA 50 mg three times weekly was reinitiated uneventfully. Herein, by introducing a case who erroneously consumed twice the highest recommended dose of ROXA for a month, but had apparently no obvious discomfort or unfavorable consequence, we attempt to provide a brief overview of the mechanism of action, characteristics, drug metabolism, and side effect profile associated with this agent.
一名患有3级高血压20年的71岁男性在2年前出现肾功能不全。当时他的血清肌酐（SCr）为140μmol/L[估算肾小球滤过率（eGFR）为43.9ml/（min·1.73m²）]，此后他开始服用厄贝沙坦。初次就诊时，尿试纸条蛋白为1+，白蛋白与肌酐比值为230mg/g（0 - 30）且尿沉渣正常。SCr为176μmol/L（eGFR = 32.8ml/（min·1.73m²））。尽管2个月前开始每日口服两次100mg琥珀酸亚铁，但血红蛋白（Hb）水平从102g/L降至96g/L。随后开具了罗沙司他（ROXA），体重70kg，每周三次，每次50mg。不幸的是，患者误将药物服用为每日三次，每次50mg（即每周1050mg，而非非透析依赖型慢性肾脏病（CKD）患者推荐的起始剂量150mg/周，该患者体重>60kg，推荐起始剂量为每周三次，每次100mg），这是国家批准的药物说明书中最高推荐每周剂量（每周三次，2.5mg/kg）的两倍。1个月后主治肾病医生发现用药错误时，患者表示无明显不适，其家庭自测血压在110 - 130/60 - 80mmHg范围内。复查血液检查显示，1个月内Hb从96g/L升至163g/L，SCr从199μmol/L升至201μmol/L。血清丙氨酸转氨酶（ALT）仍在正常范围内（从基线时的12U/L升至20U/L），而血清总胆红素和间接胆红素水平略有升高。立即停用ROXA。30天时，血清胆红素恢复至基线，但Hb从163g/L降至140g/L，3个月后降至108g/L。另一方面，SCr从179μmol/L升至203μmol/L。初次给药9个月后，当SCr升至256μmol/L且Hb再次降至94g/L时，再次顺利重新开始每周三次，每次服用ROXA 50mg。在此，通过介绍一名误服两倍最高推荐剂量ROXA达1个月但显然无明显不适或不良后果的病例，我们试图简要概述该药物的作用机制、特点、药物代谢及副作用情况。
