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close this bookGuidelines for the Treatment of Malaria (WHO; 2006; 266 pages) View the PDF document
View the documentGlossary
View the documentAbbreviations
open this folder and view contents1. Introduction
View the document2. The clinical disease
open this folder and view contents3. Treatment objectives
open this folder and view contents4. Diagnosis of malaria
open this folder and view contents5. Resistance to antimalarial medicines9
open this folder and view contents6. Antimalarial treatment policy
close this folder7. Treatment of uncomplicated P. Falciparum malaria10
View the document7.1 Assessment
View the document7.2 Antimalarial combination therapy
View the document7.3 The choice of artemisinin-based combination therapy options
View the document7.4 Practical aspects of treatment with recommended ACTs
View the document7.5 Incorrect approaches to treatment
View the document7.6 Additional aspects of clinical management
View the document7.7 Operational issues in treatment management
View the document7.8 Management of treatment failures
View the document7.9 Treatment in specific populations and situations
View the document7.10 Coexisting morbidities
open this folder and view contents8. Treatment of severe falciparum malaria14
open this folder and view contents9. Treatment of malaria caused by P. vivax, P. ovale or P. malariae19
View the document10. Mixed malaria infections
open this folder and view contents11. Complex emergencies and epidemics
open this folder and view contentsAnnexes
 

7.4 Practical aspects of treatment with recommended ACTs

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.

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