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ANNEX 3. Pharmacology of antimalarial medicines

Formulations
A wide variety of formulations for oral, parenteral and rectal use are available. These
include:
• Tablets and capsules containing 250 mg of artemisinin.
• Suppositories containing 100 mg, 200 mg, 300 mg, 400 mg or 500 mg of artemisinin.

Pharmacokinetics
Peak plasma concentrations occur around 3 h and 11 h following oral and rectal
administration respectively (30). Artemisinin is converted to inactive metabolites via the A3
cytochrome P450 enzyme CYP2B6 and other enzymes. Artemisinin is a potent inducer
of its own metabolism. The elimination half-life is approximately 1 h (31).

Toxicity

Artemisinin and its derivatives are safe and remarkably well tolerated (32, 33). There have
been reports of mild gastrointestinal disturbances, dizziness, tinnitus, reticulocytopenia,
neutropenia, elevated liver enzyme values, and electrocardiographic abnormalities,
including bradycardia and prolongation of the QT interval, although most studies
have not found any electrocardiographic abnormalities. The only potentially serious
adverse effect been reported with this class of drugs is type 1 hypersensitivity reactions
in approximately 1 in 3000 patients (34). Neurotoxicity has been reported in animal
studies, particularly with very high doses of intramuscular artemotil and artemether, but
has not been substantiated in humans (35–37). Similarly, evidence of death of embryos
and morphological abnormalities in early pregnancy have been demonstrated in animal
studies (37a). Artemisinin has not been evaluated in the first trimester of pregnancy so
should be avoided in first trimester patients with uncomplicated malaria until more
information is available.

Drug interactions
None known.

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