Prescrire Int. 2014 Jan;23(145):5-8.
For the treatment of uncomplicated Plasmodium falciparum malaria, drug combinations based on artemisinin derivatives (such as artemether + lumefantrine in France) are an alternative to atovaquone + proguanil, especially when there is a high risk of resistance to drugs commonly used for malaria prevention. A second fixed-dose combination containing an artemisinin derivative was recently marketed in the EU. It consists of artenimol (aka dihydroartemisinin) and piperaquine, a compound chemically related to chloroquine. Artenimol is the main active metabolite of artemether and artesunate. In clinical trials involving thousands of adults and children living in areas of chloroquine resistance, the artenimol + piperaquine combination showed similar clinical and parasitological efficacy to that of other combinations based on artemisinin derivatives, including artemether + lumefantrine and artesunate + mefloquine. We found no randomised controlled trials versus atovaquone + proguanil or versus quinine. The artenimol + piperaquine combination prolongs the QT interval more than artemether + lumefantrine and artesunate + mefloquine. In clinical trials, this resulted in a larger number of cardiac adverse events (11.3% versus 9.2%). The potential for drug interactions with the artenimol + piperaquine combination is higher and longer-lasting than with artemether + lumefantrine. Piperaquine can act variably as a cytochrome P450 inducer or inhibitor. The dosing schedule is simpler with the artenimol + piperaquine combination than with artemether + lumefantrine. However, the long half-life of piperaquine (about 3 weeks) complicates treatment management, as the risk of interactions persists long after the end of treatment. It is therefore recommended that the artenimol + piperaquine combination be administered no more than twice a year. In practice, this fixed-dose combination based on an artemisinin derivative does not represent an advance in the treatment of uncomplicated P. falciparum malaria. When treatment with an artemisinin derivative is warranted, it is best to choose artemether + lumefantrine, a combination (available in France) that appears to carry a lower risk of serious cardiac rhythm disorders and drug-drug interactions.
对于非复杂性恶性疟的治疗，基于青蒿素衍生物的药物组合（如法国的蒿甲醚+本芴醇）是阿托伐醌+氯胍的替代方案，尤其是在对常用于疟疾预防的药物存在高耐药风险的情况下。一种含青蒿素衍生物的第二代固定剂量组合药物最近在欧盟上市。它由蒿酚醚（又称双氢青蒿素）和哌喹组成，哌喹是一种化学结构与氯喹相关的化合物。蒿酚醚是蒿甲醚和青蒿琥酯的主要活性代谢产物。在涉及数千名生活在氯喹耐药地区的成人和儿童的临床试验中，蒿酚醚+哌喹组合显示出与其他基于青蒿素衍生物的组合（包括蒿甲醚+本芴醇和青蒿琥酯+甲氟喹）相似的临床和寄生虫学疗效。我们未找到与阿托伐醌+氯胍或奎宁对比的随机对照试验。蒿酚醚+哌喹组合比蒿甲醚+本芴醇和青蒿琥酯+甲氟喹更易延长QT间期。在临床试验中，这导致了更多的心脏不良事件（11.3%对9.2%）。蒿酚醚+哌喹组合发生药物相互作用的可能性比蒿甲醚+本芴醇更高且持续时间更长。哌喹可作为细胞色素P450诱导剂或抑制剂发挥不同作用。蒿酚醚+哌喹组合的给药方案比蒿甲醚+本芴醇更简单。然而，哌喹的半衰期较长（约3周），这使治疗管理变得复杂，因为在治疗结束后很长时间内仍存在相互作用的风险。因此，建议蒿酚醚+哌喹组合每年使用不超过两次。实际上，这种基于青蒿素衍生物的固定剂量组合在非复杂性恶性疟的治疗中并未取得进展。当有必要使用青蒿素衍生物进行治疗时，最好选择蒿甲醚+本芴醇，该组合（法国有）似乎发生严重心律失常和药物相互作用的风险较低。
