7.5 P ractical aspects of treatment with recommended ACTs
An increasing variety of formulations and products are available for the recommended artemisinin-based drug combinations. The drug concentrations achieved in an individual patient depend on variables that include the pharmacokinetic properties of the drug, drug quality, and dose taken related to dosing schedules and adherence.
7.5.1 Artemether plus lumefantrine
This is currently available as a fixed-dose formulation with dispersible or standard tablets containing 20 mg of artemether and 120 mg of lumefantrine.
20 Therapeutic dose.
The recommended treatment is a 6-dose regimen over a 3-day period. The dosing is based on the number of tablets per dose according to pre-defined weight bands (5–14 kg: 1 tablet; 15–24 kg: 2 tablets; 25–34 kg: 3 tablets; and > 34 kg: 4 tablets), given twice a day for 3 days. This extrapolates to 1.7/12 mg/kg body weight of artemether and lumefantrine, respectively, per dose, given twice a day for 3 days, with a therapeutic dose range of 1.4–4 mg/kg of artemether and 10–16 mg/kg of lumefantrine.
An advantage of this combination is that lumefantrine is not available as a monotherapy, and it has never been used by itself for the treatment of malaria. Lumefantrine absorption is enhanced by co-administration with fat. It is essential that patients or caregivers are informed of the need to take this ACT immediately after a meal or drink containing at least 1.2 g fat – particularly on the second and third days of treatment. A flavoured dispersible tablet paediatric formulation of artemether plus lumefantrine is now available, enhancing its use in young children (see details in Annex 3, sections A3.6.2, A3.7).
7.5.2 Artesunate plus amodiaquine
This is currently available as a fixed-dose formulation with tablets containing 25/67.5 mg, 50/135 mg or 100/270 mg of artesunate and amodiaquine. Blister packs of separate scored tablets containing 50 mg of artesunate and 153 mg base of amodiaquine, respectively, are also available.
A target dose of 4 mg/kg/day artesunate and 10 mg/kg/day amodiaquine once a day for 3 days, with a therapeutic dose range between 2–10 mg/kg/day artesunate and 7.5–15 mg/kg/dose amodiaquine. This combination was sufficiently efficacious only where 28-day cure rates with amodiaquine monotherapy exceeded 80%. Resistance is likely to worsen with continued availability of chloroquine and amodiaquine monotherapies
7.5.3 Artesunate plus mefloquine
This is currently available as blister packs with separate scored tablets containing 50 mg of artesunate and 250 mg base of mefloquine, respectively. A fixed-dose formulation of artesunate and mefloquine is at an advanced stage of development.
A target dose of 4 mg/kg/day artesunate given once a day for 3 days and 25 mg/kg of mefloquine either split over 2 days as 15mg/kg and 10mg/kg or over 3 days as 8.3 mg/kg/day once a day for 3 days. The therapeutic dose range is between 2– 10 mg/kg/dose/day of artesunate and 7–11 mg/kg/dose/day of mefloquine. Mefloquine is associated with an increased incidence of nausea, vomiting, dizziness, dysphoria and sleep disturbance in clinical trials, but these are seldom debilitating – where this ACT has been deployed it has been well tolerated. To reduce acute vomiting and optimize absorption, the 25 mg/kg dose is usually split and given either as 15 mg/kg Guidelines for the treatment of malaria – 2nd edition 7. Treatment of uncomplicated P. falciparum malaria 21 (usually on the second day) followed by 10 mg/kg one day later, or as a daily dose of 8.3 mg/kg for 3 days.
7.5.4 Artesunate plus 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 pyrimethamine.9
Therapeutic dose. A target dose of 4 mg/kg/day artesunate given once a day for 3 days and a single administration of 25/1.25 mg/kg sulfadoxine-pyrimethamine on day 1, with a therapeutic dose range between 2–10 mg/kg/day artesunate and 25–70/1.25–3.5 mg/kg sulfadoxine-pyrimethamine.
This combination was sufficiently efficacious only where 28-day cure rates with sulfadoxinepyrimethamine alone exceeded 80%. Resistance is likely to worsen with continued widespread use of sulfadoxine-pyrimethamine, sulfalene plus pyrimethamine and cotrimoxazole (trimethoprim plus sulfamethoxazole)
7.5.5 Dihydroartemisinin plus piperaquine
This is currently available as a fixed-dose combination with tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine.
A target dose of 4 mg/kg/day dihydroartemisinin and 18 mg/kg/day piperaquine once a day for 3 days, with a therapeutic dose range between 2–10 mg/kg/day dihydroartemisinin and 16–26 mg/kg/dose piperaquine.
7.5.6 Artesunate plus tetracycline or doxycycline or clindamycin
There are no blister co-packaged forms of any of these combination options. These are reserved for very rare occasions of treatment failures to the recommended ACTs and in some special groups, e.g. pregnant women failing ACT treatment. They are dosed separately and should only be used in a hospital setting. Therapeutic dose. Artesunate (2 mg/kg once a day) plus tetracycline (4 mg/kg four times a day or doxycycline (3.5 mg/kg once a day) or clindamycin (10 mg/kg twice a day).
Any of these combinations should be given for 7 days.