Practical Info Formulations: Currently available as a fixed-dose combination in tablets containing 40 mg dihydroartemisinin and 320 mg piperaquine and paediatric tablets contain 20 mg dihydroartemisinin and 160 mg piperaquine. Target dose and range: A target dose (range) of 4 (2–10) mg/kg bw per day dihydroartemisinin and 18 (16–27) mg/kg bw per day piperaquine given once a day for 3 days for adults and children weighing ≥ 25 kg. The target doses and ranges for children weighing < 25 kg are 4 (2.5–10) mg/kg bw per day dihydroartemisinin and 24 (20–32) mg/kg bw per day piperaquine once a day for 3 days. Recommended dosage regimen: The dose regimen currently recommended by the manufacturer provides adequate exposure to piperaquine and excellent cure rates (> 95%), except in children < 5 years, who have a threefold increased risk for treatment failure. Children in this age group have significantly lower plasma piperaquine concentrations than older children and adults given the same mg/kg bw dose. Children weighing < 25 kg should receive at least 2.5 mg/kg bw dihydroartemisinin and 20 mg/kg bw piperaquine to achieve the same exposure as children weighing ≥ 25 kg and adults. Dihydroartemisinin + piperaquine should be given daily for 3 days. Body weight (kg): Dihydroartemisinin + piperaquine dose (mg) given daily for 3 days 5 to < 8: 20 + 160 8 to < 11: 30 + 240 11 to < 17: 40 + 320 17 to < 25: 60 + 480 25 to < 36: 80 + 640 36 to < 60: 120 + 960 60 < 80: 160 + 1280 >80: 200 + 1600 Factors associated with altered drug exposure and treatment response: High-fat meals should be avoided, as they significantly accelerate the absorption of piperaquine, thereby increasing the risk for potentially arrhythmogenic delayed ventricular repolarization (prolongation of the corrected electrocardiogram QT interval). Normal meals do not alter the absorption of piperaquine. As malnourished children are at increased risk for treatment failure, their response to treatment should be monitored closely.

• Dihydroartemisinin exposure is lower in pregnant women.
• Piperaquine is eliminated more rapidly by pregnant women, shortening the post-treatment prophylactic effect of dihydroartemisinin + piperaquine. As this does not affect primary efficacy, no dosage adjustment is recommended for pregnant women. Additional comments: Piperaquine prolongs the QT interval by approximately the same amount as chloroquine but by less than quinine. It is not necessary to perform an electrocardiogram before prescribing dihydroartemisinin + piperaquine, but this ACT should not be used in patients with congenital QT prolongation or who have a clinical condition or are on medications that prolong the QT interval. There has been no evidence of cardiotoxicity in large randomized trials or in extensive deployment.