항혈소판제제와 프로톤펌프억제제 간의 약물 상호 작용:Unsafe 측면과 대책
Concerns on Drug Interactions between Proton Pump Inhibitors and Clopidogrel: Unsafe Perspective
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클로피도그렐과 일부 프로톤펌프억제제들 간에는 유의한 약물 상호작용에 의해 클로피도그렐의 활성도가 저하되어 심혈관계 위험도를 높이는 것으로 보고되었다. 이 주제에 대한 유일한 전향적 무작위 연구에서는 프로톤펌프억제제인 오메프라졸을 클로피도그렐과 병용 시에 위장관 합병증은 유의하게 감소시키고 심혈관계 위험도는 증가시키지 않는다는 고무적인 결과를 보였으나 연구의 여러 제한점들에 의해 우리나라 환자들에서 그 결과를 그대로 적용하기는 어려울 것으로 사료된다. 최근에 나온 일부 프로톤펌프억제제는 클로피도그렐과의 약물 상호작용이 적은 것으로 발표되었으나 임상적인 유용성에 대해서는 완전히 규명되지 않았다. 결론적으로 클로피도그렐을 투여 받는 환자에서 프로톤펌프억제제의 처방을 시작하거나 지속해야 하는 경우에 프로톤펌프억제제의 처방 필요성에 대해 보다 신중하게 재평가를 시행하고 처방하는 것이 필요하다. 불가피하게 처방해야 한다면 그 투여 시간을 클로피도그렐과 달리하여 처방하는 것이 합리적이라고 생각된다. 또한, 임상적인 유용성이 완전히 증명되지는 못했으나 약물 상호작용이 상대적으로 적은 프로톤펌프억제제(판토프라졸)를 선택하는 것도 고려해 볼 수 있다. 더불어 새로운 항혈소판제인 프라수그렐 혹은 티카그레롤을 클로피도그렐의 대용으로 고려할 수 있다. 향후 클로피도그렐과 프로톤펌프억제제 간의 약물 상호 작용 및 임상적 결과에 대한 추가적인 연구 결과의 확인이 필요하며 약제 상호작용이 상대적으로 적은 프로톤펌프억제제, 새로운 항혈소판 제제들의 유용성에 대한 임상 연구 결과들이 필요하리라 사료된다.
Abstract
Clopidogrel is a prodrug that is converted in the liver to an active thiol metabolite, which irreversibly inhibits the platelet P2Y12 adenosine diphosphate receptor. This mechanism requires cytochrome P450 2C19 (CYP 2C19) enzyme. Proton pump inhibitors (PPIs) competes against CYP 2C19 and inhibits the conversion of clopidogrel into its active metabolite, therefore, clopidogrel-PPIs drugs interaction may exist. These interactions could result in competitive inhibition decreasing the conversion of the clopidogrel pro-drug to the active metabolite and could potentially translate into an increased risk for cardiovascular events by inadequate platelet P2Y12 receptor inhibition. Many studies including retrospective cohort studies and studies using platelet function tests demonstrated the possible interactions between clopidogrel and PPIs leading to a decrease in the antiplatelet efficacy of clopidogrel and worse cardiovascular clinical outcomes than clopidogrel alone. In contrast, few comparative trials using clinical outcomes found no serious drug interactions between them. In this review, we introduce possible harmful effects of combined use of clopidogrel and PPIs on platelet function. In addition, we suggest how to overcome clopidogrel-PPIs interactions. (Korean J Med 2011;81:34-39)
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