嵌合酶鏈轉移抑制劑之肌肉毒性探討

嵌合酶鏈轉移抑制劑(integrase strand transfer inhibitors, INSTIs)是近年來治療愛滋病的第一線治療處方之一。臨床上，INSTIs被認為是相當安全的治療藥物，但偶有病人服用後會出現血中肌酸激酶 (creatine kinase, CK)升高以及肌炎、肌痛等肌肉毒性副作用。在大型臨床試驗中，使用INSTIs後出現血中CK濃度上升10倍以上的發生率各為raltegravir：4.1～9.9%、elvitegravir：2.4～10.8%、dolutegravir：2.0～5.2%、bictegravir：3.4～3.5%與cabotegravir：7.5%。依據觀察性研究指出，當患者基礎CK較高、近期曾激烈運動、男性、身體質量指數較高，以及曾經使用zidovudine者，是發生INSTIs相關之肌肉毒性事件的風險因子。INSTIs相關之CK升高雖大多為無症狀、具自限性的輕度不良反應，但全球仍有8例INSTIs相關之橫紋肌溶解症案例被報導，顯示此副作用亦可能惡化為需住院治療，甚至是危及生命之嚴重不良反應。INSTIs造成肌肉毒性的原因迄今未知，仍有待更多研究以釐清其致病機轉。對於部分具有上述風險因子的患者，藥師於執行藥事照護時，應衛教患者若出現肌肉痠痛、無力等症狀，且於休息後仍未見改善甚至漸趨惡化，請儘速回診接受評估與治療。醫療團隊於首次處方INSTIs予個案時應檢測其基礎CK數值，並於治療期間定期追蹤肌肉症狀與CK濃度，以早期發現並及時介入處理，避免進程為嚴重之橫紋肌溶解症。

關鍵字

嵌合酶鏈轉移抑制劑；嵌合酶抑制劑；肌肉毒性；橫紋肌溶解症；肌酸激酶

並列摘要

Integrase strand transfer inhibitors (INSTIs) are considered first-line regimen for antiretroviral therapy-naïve human immunodeficiency virus (HIV)-positive adult patients in recent years due to their capability of rapidly viral-suppression and relative well tolerability. However, grade III-IV creatine kinase (CK) elevation has been reported in several phase 3 trials with the incidence rate around 2.0-10.8%. These adverse events (AEs) are usually asymptomatic, self-limiting and of mild severity. Nevertheless, there are 8 cases of INSTIs-related rhabdomyolysis reported, which indicates the possibility of aggravation of these events. The mechanism for muscle toxicity remains unclear. Higher baseline CK level, male gender, habit of strenuous exercise, higher body mass index and previous exposure to zidovudine were identified as independent risk factors of INSTIs-related CK elevation and/or muscle toxicity. In this article, we reviewed published literature to discuss INSTIs-related muscle toxicity. Health professionals should exercise caution when INSTIs are administered to individuals who are high risk of this complication and CK levels should be closely monitored.

並列關鍵字

Integrase Strand Transfer Inhibitors ； Integrase Inhibitors ； Muscle Toxicity ； Rhabdomyolysis ； Creatine Kinase

國際替代計量

嵌合酶鏈轉移抑制劑之肌肉毒性探討

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