Apixaban 是一種選擇性、可逆性的凝血因子Xa 抑制劑，不會對血小板凝集反應產生直接的影響，但會間接地抑制由凝血酶所引發的血小板凝集反應，用於降低心房顫動患者中風和全身栓塞的風險。除了dabigatran 外，所有 direct oral anticoagulants (DOACs) 都在肝臟代謝，2013 年歐洲指南建議使用DOACs 應每年監測肝功能。
Apixaban 主要通過CYP3A4 和P-glycoprotein 在肝臟中代謝，強的CYP3A4 抑制劑可導致apixaban 血中濃度升高，而CYP3A4 的誘導劑則會降低apixaban 血中濃度，降低治療療效，對肝毒性機轉可能是因為產生有毒或免疫原性的中間產物。Apixaban 上市後只有少數急性肝損傷的案例被報導過，屬於極為罕見。
本文敘述一位肺栓塞的病患，過去病史有高血壓, 慢性阻塞性肺病, 鬱血性心衰竭和肺纖維化，個案本身無肝炎疾病（HBsAg 與anti-HCV 皆為陰性）及自體免疫病史，口服apixaban 14 天後產生急性肝細胞毒性損傷，在停用藥物及採取相關治療後、狀況趨穩定後續由門診追蹤照護。藉由文獻回顧，探討使用apixaban 引發肝細胞毒性損傷之成因、可能性及因應處理方式，提供醫師、藥師及護理人員在給予藥物治療期間應隨時留意病患狀況並評估危險因子，確保病患之用藥安全。
Apixaban is a selective and reversible coagulation factor Xa inhibitor that indirectly inhibits the platelet coagulation reaction induced by thrombin. It is for reducing stroke and thrombosis risk in patients with atrial fibrillation. The Europe guideline for apixaban utilization in 2013 suggested monitoring liver function yearly due to all direct oral anticoagulants (DOACs) being metabolized by the liver except dabigatran. Apixaban is a substrate of CYP3A4 and P-glycoprotein. Potent CYP3A4 inhibitors increase the plasma concentration of apixaban, while CYP3A4 inducers decrease it. The mechanism of hepatotoxicity caused by apixaban could be the production of toxic or immunogenicity intermediates. Acute hepatic failure caused by apixaban is sporadic; only a few reports after marketing. The case report shared a pulmonary embolism patient with a history of hypertension, chronic obstructive pulmonary disease, congestive heart failure, pulmonary fibrosis, and autoimmune disease without hepatitis (HBsAg & anti- hepatitis C virus negative). The patient has been reported acute hepatotoxicity after taking apixaban for 14 days. Suspension of apixaban and proper treatments for the patient were initiated immediately, and the patient was followed up at the outpatient department when the patient’s physical condition got stable. We focus on investigating the mechanism, probability, and dealing approaches of apixaban-induced hepatotoxicity by reviewing articles. By providing our experience, we hope that healthcare professionals can know how to evaluate the risk of taking apixaban and ensure medication safety for patients.
Submitted for publication: 2022.6.21; Accepted for publication: 2022.9.20
