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Guidelines for the treatment of malaria – 2 edition

8.7 practical aspects of treatment

8.7.1 Artemisinins

Although artesunate has preferable pharmacokinetic properties to artemether or artemotil,
as it is water-soluble and can be given either by intravenous or intramuscular injection.
Artemether and artemotil are formulated in oil and are given by intramuscular injection.
They are both absorbed erratically, particularly in very severely ill patients. There are
rectal formulations of artesunate, artemether, artemisinin and dihydroartemisinin.

The dosing of artemisinin derivatives has been largely empirical. The doses recommended
here are those that have been most widely studied. The only recent change is the higher
maintenance dose of parenteral artesunate recommended (2.4 mg/kg body weight),
which is based on pharmacokinetic and pharmacodynamic studies, and by extrapolation
from studies with oral artesunate. Expert opinion is that the previously recommended
maintenance dose of 1.2 mg/kg body weight may have been insufficient in some patients.

Artesunate is dispensed as a powder of artesunic acid. This is dissolved in sodium
bicarbonate (5%) to form sodium artesunate. The solution is then diluted in approximately
5 ml of 5% dextrose and given by intravenous injection or by intramuscular injection to
the anterior thigh. The solution should be prepared freshly for each administration and
should not be stored.

Artemether and artemotil are dispensed dissolved in oil (groundnut, sesame seed), and
then given by IM injection into the anterior thigh.

8.7.2 Quinine
Whereas many antimalarials are prescribed in terms of base, for historical reasons quinine
doses are often recommended in terms of salt (usually sulfate for oral use and dihydrochloride
for parenteral use). Recommendations for doses of this and other antimalarials should state
clearly whether the salt or base is being referred to (doses with different salts must have
the same base equivalents). Quinine must never be given by intravenous bolus injection, as
lethal hypotension may result. Quinine dihydrochloride should be given by rate-controlled
infusion in saline or dextrose solutions at a rate not exceeding 5 mg salt/kg body weight
per hour. If this is not possible, then it should be given by intramuscular injection to the
anterior thigh not the buttock (to avoid sciatic nerve injury). The first dose should be split,
10 mg/kg body weight to each thigh. Undiluted quinine dihydrochloride at a concentration
of 300 mg/ml is acidic (pH 2) and painful when given by intramuscular injection, so it is
best either formulated or diluted to concentrations of 60–100 mg/ml for intramuscular
injection. Gluconate salts are less acidic and better tolerated than the dihydrochloride salt
when given by the intramuscular and rectal routes.
As the first (loading) dose is the most important in the treatment of severe malaria,
this should be reduced only if there is clear evidence of adequate pre-treatment before
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