背景：

抗病毒藥物acyclovir 使用時應依照腎功能進行劑量調整，其導致之神經毒性為其一罕見之副作用，已知好發於腎功能不全者，但即使依照現行建議給予劑量調整，仍有發生相關症狀之可能，臨床上要在第一時間鑑別診斷是病毒性腦炎或藥物引起的副作用並不容易，因此acyclovir 之藥物濃度監測或許可作為臨床治療診斷時的輔助工具。

 

案例陳述：

本案例為59 歲女性，身高157 公分，體重57 公斤，病史包含末期腎臟病（接受腹膜透析）、糖尿病、高血壓、血脂異常、甲狀腺功能亢進及貧血。因帶狀疱疹口服acyclovir 800 mg Q12H，服藥第2 天開始出現神經學症狀（口齒不清、定向障礙、步態不穩等），第4 天停藥後仍無明顯改善，並因意識變差，故於第7 天起接受血液透析治療，使得acyclovir 及其代謝物9-Carboxymethoxymethylguanine濃度分別從3.61 μg/mL 及18.82 μg/mL 下降至1.70 μg/mL 及4.06 μg/mL。在此之後又接受兩次血液透析，病人意識及神經學症狀逐漸改善並恢復至完全正常，之後改回腹膜透析，狀況穩定後於第19 天出院。依據Naranjo scale 評估此藥品不良反應為6分，屬於「極有可能」。

 

結論：

使用acyclovir 時應依據適應症及腎功能給予適當劑量，但即使依照建議劑量給藥仍有發生神經毒性之可能，因此用藥期間應密切監測療效與不良反應。當病人接受藥物治療後出現相關神經學症狀時，藥物濃度監測亦可作為一輔助工具，及時幫助鑑別診斷並協助訂定後續治療決策。

 

 

　Acyclovir dosage should be adjusted based on renal function. Neurotoxicity is a rare adverse effect and occurs mostly in patients with renal insufficiency. Furthermore, neurologic symptoms may occur even after dosage adjustment according to current recommendations. Additionally, making a differential diagnosis between viral encephalitis and drug-induced neurotoxicity is difficult. Therefore, therapeutic drug monitoring of acyclovir might be a feasible approach to guide the following management.

　A 59-year-old woman with a medical history of end-stage renal disease, type 2 diabetes mellitus, hypertension, dyslipidemia, hyperthyroidism, and anemia undergoing peritoneal dialysis was prescribed oral acyclovir (800 mg Q12H) for the treatment of herpes zoster infection. She was admitted to the emergency department due to neurologic symptoms, including slurred speech, disorientation, and unstable gait, and she was suspected to have acyclovir toxicity. Because there was no improvement after stopping taking acyclovir, hemodialysis was initiated. After the first session of hemodialysis, serum concentrations of acyclovir and its metabolite 9-Carboxymethoxymethylguanine decreased from 3.61 and 18.82 μg/mL to 1.70 and 4.06 μg/mL, respectively. Her neurologic status returned to baseline gradually, and peritoneal dialysis was resumed after three hemodialysis sessions. On the Naranjo scale, the probability of an adverse drug reaction was 6. 

　Acyclovir dosage should be adjusted promptly in accordance with renal function in patients with renal insufficiency. In addition to therapeutic effects, adverse events should be monitored closely during the treatment period. When neurologic symptoms appear after acyclovir administration, therapeutic drug monitoring could be helpful for making a differential diagnosis to guide future patient management.

 

 

Summited for publication: 2021.4.16; Accepted for publication: 2021.8.17