Artemether-Lumefantrine Dosing for Uncomplicated Malaria
For adults weighing >35 kg with uncomplicated P. falciparum malaria, administer artemether-lumefantrine (20 mg/120 mg) as 4 tablets at hour 0,4 tablets at hour 8 on day 1, then 4 tablets twice daily (at hours 36,48,60, and 72) for a total of 24 tablets over 72 hours, taken with a fatty meal or drink. 1
Weight-Based Dosing Regimen
Adult and Adolescent Dosing (>35 kg):
- Day 1: 4 tablets at 0 hours, 4 tablets at 8 hours
- Day 2: 4 tablets at 24 hours (hour 36), 4 tablets at 36 hours (hour 48)
- Day 3: 4 tablets at 48 hours (hour 60), 4 tablets at 60 hours (hour 72)
- Total: 24 tablets over 72 hours 1, 2
Pediatric Dosing:
- 5 to <15 kg: 1 tablet per dose (6 doses total)
- 15 to <25 kg: 2 tablets per dose (12 doses total)
- 25 to <35 kg: 3 tablets per dose (18 doses total)
- ≥35 kg: 4 tablets per dose (24 doses total) 1
Critical Administration Requirements
Mandatory fat intake: Artemether-lumefantrine must be taken with a fatty meal or drink to ensure adequate absorption. 1, 3 Failure to ensure adequate fat intake results in subtherapeutic drug levels and treatment failure. 4 The absorption of lumefantrine is dose-limited, making proper administration with fat essential. 5
Target therapeutic level: Day 7 lumefantrine concentrations ≥200 ng/mL are associated with >98% cure rates in patients with parasitemia <135,000/μL. 6
Special Populations Requiring Attention
Young children (<3 years):
- Achieve 23% lower day 7 lumefantrine concentrations than adequately nourished children of the same age and 53% lower concentrations than adults when adjusted for mg/kg dose. 6
- Underweight-for-age children in this group are at particularly high risk of treatment failure. 6
- Consider extending treatment to 5 days (twice daily dosing) or intensifying frequency to 3 times daily for 3 days in this population. 5
Pregnant women (second and third trimesters):
- Artemether-lumefantrine can be used in all trimesters of pregnancy as indicated by WHO and CDC. 1, 2, 4
- Pregnant women achieve 20.2% lower day 7 lumefantrine concentrations compared to non-pregnant adults. 5
- Multiple trials demonstrated cure rates of 99.3-100% with standard dosing in pregnancy. 1
- No association found between ACT treatment and congenital malformations or miscarriage in second/third trimester. 4
Alternative First-Line Option
Dihydroartemisinin-piperaquine (320 mg/40 mg):
- 36-75 kg: 3 tablets per day for 3 days
75 kg: 4 tablets per day for 3 days
- Must be taken in fasting condition (opposite of artemether-lumefantrine)
- Rapid onset of action with simpler dosing regimen 1, 2
Important Safety Considerations
QTc prolongation risk: Both artemether-lumefantrine and dihydroartemisinin-piperaquine can cause QTc interval prolongation. Avoid in patients at risk of QTc prolongation or taking medications that prolong QTc. 1, 3, 4
Post-treatment monitoring: Monitor for post-artemisinin delayed hemolysis (PADH) on days 7,14,21, and 28 after treatment, which occurs in 37.4% of patients using strict definitions. 3, 4
High-risk scenarios for treatment failure:
- Very young children, particularly if underweight-for-age 6
- Patients with high baseline parasitemia (>135,000/μL) 6
- Areas of very low transmission intensity with emerging artemisinin resistance 6
- Unsupervised treatment (results in 44% lower day 7 concentrations) 6
Efficacy Data
The six-dose regimen of artemether-lumefantrine provides adjusted 28-day cure rates of 96.9-99.1% in multidrug-resistant P. falciparum malaria, compared to 83.3% for the previously used four-dose regimen. 7 In comparative trials, artemether-lumefantrine demonstrated cure rates of 97.7-100% and was better tolerated than artesunate-mefloquine. 8