Comparative Pharmacology
Head-to-head clinical analysis: ARTEMETHER LUMEFANTRINE versus ARTESUNATE.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ARTEMETHER LUMEFANTRINE versus ARTESUNATE.
Artemether-Lumefantrine vs ARTESUNATE
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Artemether is rapidly converted to dihydroartemisinin, which produces free radicals that damage parasite proteins and membranes. Lumefantrine inhibits heme detoxification in the parasite food vacuole.
Artesunate is a water-soluble artemisinin derivative that produces rapid parasite clearance. It is converted in vivo to dihydroartemisinin, which generates free radicals that alkylate and damage parasite proteins, particularly targeting the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) of Plasmodium species.
Oral, 4 tablets (each containing 20 mg artemether and 120 mg lumefantrine) at 0, 8, 24, 36, 48, and 60 hours (total 6 doses). For patients ≥35 kg, alternatively 4 tablets at 0, 8, 24, 36, 48, and 60 hours.
2.4 mg/kg IV at 0, 12, 24, and 48 hours, then daily until oral therapy can be initiated.
None Documented
None Documented
Clinical Note
moderateMethoxsalen + Artesunate
"The serum concentration of the active metabolites of Artesunate can be reduced when Artesunate is used in combination with Methoxsalen resulting in a loss in efficacy."
Clinical Note
moderateRifampicin + Artesunate
"The serum concentration of the active metabolites of Artesunate can be reduced when Artesunate is used in combination with Rifampicin resulting in a loss in efficacy."
Clinical Note
moderatePhenobarbital + Artesunate
"The serum concentration of the active metabolites of Artesunate can be reduced when Artesunate is used in combination with Phenobarbital resulting in a loss in efficacy."
Clinical Note
Artemether: terminal elimination half-life approximately 1–2 hours. Dihydroartemisinin: approximately 1–2 hours. Lumefantrine: terminal elimination half-life 4–5 days (range 2–6 days) in patients with uncomplicated malaria; prolonged half-life contributes to post-treatment prophylaxis but may lead to accumulation with repeated dosing.
Terminal elimination half-life of artesunate is approximately 1 hour. The active metabolite dihydroartemisinin has a half-life of 1-2 hours. This short half-life supports rapid parasite clearance in severe malaria.
Primarily fecal (biliary) elimination of unchanged drug and metabolites; renal excretion is negligible (<1% for artemether and <0.1% for lumefantrine). Artemether is extensively metabolized by CYP3A4/5 to dihydroartemisinin, which is further glucuronidated and excreted in bile. Lumefantrine is metabolized by CYP3A4 to desbutyl-lumefantrine; both parent and metabolite are eliminated via feces.
Primarily hepatic metabolism; renal excretion of metabolites accounts for <10% as unchanged drug. Biliary/fecal elimination is minimal. ~80% of the dose is recovered in urine as metabolites, mainly dihydroartemisinin.
Category C
Category C
Antimalarial
Antimalarial
Nevirapine + Artesunate
"The serum concentration of the active metabolites of Artesunate can be reduced when Artesunate is used in combination with Nevirapine resulting in a loss in efficacy."