7.4.1 Artemether-lumefantrine
This is currently available as co-formulated tablets containing 20 mg of artemether and 120 mg of lumefantrine. The total recommended treatment is a 6-dose regimen of artemether-lumefantrine twice a day for 3 days.
Table 1. Dosing schedule for artemether-lumefantrine
Body weight in kg |
No. of tablets at approximate timing of dosinga |
(age in years) |
0 h |
8 h |
24 h |
36 h |
48 h |
60 h |
5-14 |
(<3) |
1 |
1 |
1 |
1 |
1 |
1 |
15-24 |
(≥ 3-8) |
2 |
2 |
2 |
2 |
2 |
2 |
25-34 |
(≥ 9-14) |
3 |
3 |
3 |
3 |
3 |
3 |
>34 |
(>1 4) |
4 |
4 |
4 |
4 |
4 |
4 |
a The regimen can be expressed more simply for ease of use at the programme level as follows: the second dose on the first day should be given any time between 8 h and 12 h after the first dose. Dosage on the second and third days is twice a day (morning and evening).
An advantage of this combination is that lumefantrine is not available as a monotherapy and has never been used by itself for the treatment of malaria. Recent evidence indicates that the therapeutic response and safety profile in young children of less than 10 kg is similar to that in older children, and artemether-lumefantrine is now recommended for patients ≥ 5 kg. Lumefantrine absorption is enhanced by co-administration with fat. Low blood levels, with resultant treatment failure, could potentially result from inadequate fat intake, and so it is essential that patients or carers are informed of the need to take this ACT with milk or fat-containing food - particularly on the second and third days of treatment.
7.4.2 Artesunate + amodiaquine
This is currently available as separate scored tablets containing 50 mg of artesunate and 153 mg base of amodiaquine, respectively. Co-formulated tablets are under development. The total recommended treatment is 4 mg/kg bw of artesunate and 10 mg base/kg bw of amodiaquine given once a day for 3 days.
Table 2. Dosing schedule for artesunate + amodiaquine
Age |
Dose in mg (No. of tablets) |
| |
Artesunate (50 mg) |
Amodiaquine (153 mg) |
| |
Day 1 |
Day 2 |
Day 3 |
Day 1 |
Day 2 |
Day 3 |
5-11 months |
25 (1/2) |
25 |
25 |
76 (1/2) |
76 |
76 |
≥1-6 years |
50 (1) |
50 |
50 |
153 (1) |
153 |
153 |
≥7-13 years |
100 (2) |
100 |
100 |
306 (2) |
306 |
306 |
>13 years |
200 (4) |
200 |
200 |
612 (4) |
612 |
612 |
This combination is sufficiently efficacious only where 28-day cure rates with amodiaquine monotherapy exceed 80%. Resistance is likely to worsen with continued availability of chloroquine and amodiaquine monotherapies. More information on the safety of artesunate + amodiaquine is needed from prospective pharmacovigilance programmes.
7.4.3 Artesunate + sulfadoxine-pyrimethamine
This is currently available as separate scored tablets containing 50 mg of artesunate, and tablets containing 500 mg of sulfadoxine and 25 mg of pyri-methamine.11 The total recommended treatment is 4 mg/kg bw of artesunate given once a day for 3 days and a single administration of sulfadoxine-pyrimethamine (25/1.25 mg base/kg bw) on day 1.
11 A similar medicine with tablets containing 500 mg of sulfalene and 25 mg of pyrimethamine is considered to be equivalent to sulfadoxine-pyrimethamine.
Table 3. Dosing schedule for artesunate + sulfadoxine-pyrimethamine
Age |
Dose in mg (No. of tablets) |
| |
Artesunate (50 mg) |
Sulfadoxine-pyrimethamine (500/25) |
| |
Day 1 |
Day 2 |
Day 3 |
Day 1 |
Day 2 |
Day 3 |
5-11 months |
25 (1/2) |
25 |
25 |
250/12.5 (1/2) |
- |
- |
≥1-6 years |
50 (1) |
50 |
50 |
500/25 (1) |
- |
- |
≥7-13 years |
100 (2) |
100 |
100 |
1000/50 (2) |
- |
- |
>13 years |
200 (4) |
200 |
200 |
1500/75 (3) |
- |
- |
While a single dose of sulfadoxine-pyrimethamine is sufficient, it is necessary for artesunate to be given for 3 days for satisfactory efficacy. This combination is sufficiently efficacious only where 28-day cure rates with sulfadoxine-pyrimethamine alone exceed 80%. Resistance is likely to worsen with continued availability of sulfadoxine-pyrimethamine, sulfalene-pyrimethamine and cotrimoxazole (trimethoprim-sulfamethoxazole).
7.4.4 Artesunate + mefloquine
This is currently available as separate scored tablets containing 50 mg of artesunate and 250 mg base of mefloquine, respectively. Co-formulated tablets are under development but are not available at present. The total recommended treatment is 4 mg/kg bw of artesunate given once a day for 3 days and 25 mg base/kg bw of mefloquine usually split over 2 or 3 days.
Table 4. Dosing schedule for artesunate + mefloquine
Age |
Dose in mg (No. of tablets) |
| |
Artesunate (50 mg) |
Mefloquine (250 mg) |
| |
Day 1 |
Day 2 |
Day 3 |
Day 1 |
Day 2 |
Day 3 |
5-11 months |
25 (1/2) |
25 |
25 |
- |
125 (1/2) |
- |
≥1-6 years |
50 (1) |
50 |
50 |
- |
250 (1) |
- |
≥7-13 years |
100 (2) |
100 |
100 |
- |
500 (2) |
250 (1) |
>13 years |
200 (4) |
200 |
200 |
- |
1000 (4) |
500 (2) |
Two different doses of mefloquine have been evaluated, 15 mg base/kg bw and 25 mg base/kg bw. The lower dose is associated with inferior efficacy and is not recommended. To reduce acute vomiting and optimize absorption, the 25 mg/kg dose is usually split and given either as 15 mg/kg (usually on the second day) followed by 10 mg/kg one day later, or as 8.3 mg/kg per day for 3 days. Pending development of a co-formulated product, malaria control programmes will have to decide on the optimum operational strategy of mefloquine dosing for their populations. Mefloquine is associated with an increased incidence of nausea, vomiting, dizziness, dysphoria and sleep disturbance in clinical trials, but these are seldom debilitating and in general, where this ACT has been deployed, it has been well tolerated.
