Artemisinin Derivatives
Mechanism :
There are three common forms of artemisinin. The water-soluble form is called artesunate. It is the most active and the least toxic within the body. Artemether is the lipid soluble form. It has the longest life but also the most toxic in high dosage which is seldom needed. The biggest advantage of artemether is that it can cross the blood brain barrier. Artemisinin is the active parent compound of the plant. Its half-life is intermediate. It is also very safe and can cross the blood-brain barrier. Artemisinin has been shown to work through oxygen and carbon based free radical mechanisms.
Indication :
Contraindications :
First trimester of pregnancy.
Dosing :
Artemether:
3.2 mg/kg/IM loading dose followed by 1.6 mg/kg/IM after 24 hours & then 1.6 mg/kg/M 12 hourly till the child can eat orally. Then shift to oral therapy.
Artesunate:
In children <20 kg: 3 mg/kg/day IM or IV. In children >20 kg: 2.4 mg/kg/dose IM or IV till the child can eat orally. Then shift to oral therapy. As part of artemisinin combination therapy (ACT): 4 mg/kg/day for 3 days.
Artesunate + Amodiaquine: (Available as FDC containing 25 mg + 67.5 mg, 50 mg + 135 mg or 100 mg + 270 mg of
artesunate +
amodiaquine respectively) Oral therapy for 3 days.
Dihydroartemisinin + Piperaquine: Oral therapy for 3 days.
Children <25 kg-2.5 mg/kg/day OD of dihydroartemisinin and 20 mg/kg/day OD of piperaquine.
Children >25 kg: 4 mg/kg/day OD of dihydroartemisinin and 18 mg/kg/day OD of piperaquine.
Artesunate + Mefloquine: (Available as FDC containing 25 mg+55 mg or 100 mg + 220 mg of
artesunate +
mefloquine respectively)
As per weight bands:
Adverse Effect :
Gastrointestinal disturbances, dizziness, tinnitus and prolongation of QT interval.
Interaction :
Quinidine and halofantrine: Caution in concurrent usage with drugs that prolong QT interval.
Hepatic Dose :
No dosage adjustment necessary. Use with caution in severe hepatic impairment.