Artem

Approved Indications:

• Treatment of acute uncomplicated Plasmodium falciparum malaria, including malaria acquired in areas with resistance to chloroquine, mefloquine, or sulfadoxine/pyrimethamine.
• Treatment of mixed infections involving P. falciparum and other Plasmodium species, including where P. falciparum is confirmed or suspected.

Clinically Accepted/Off-label Uses:

• Presumptive treatment of malaria in returning travelers from endemic regions when diagnostic testing is delayed or inconclusive.
• Re-treatment in cases of recrudescence or relapse of P. falciparum malaria following prior ACT failure.
• Use in IPT (intermittent preventive treatment) in research settings and special endemic populations (under study protocols).

Dosage Regimen (6-dose schedule over 3 days):

Dosing Schedule:

• Initial dose: at time 0
• Second dose: after 8 hours
• Then twice daily (morning and evening) for the next 2 days

Administration Notes:

• Must be taken with food (preferably high-fat or milk-based) to enhance lumefantrine absorption.
• Tablets should be swallowed whole; for small children, tablets may be crushed and mixed with a small amount of water or milk.

Special Populations:

• Hepatic impairment: Caution advised in severe liver dysfunction.
• Renal impairment: No dosage adjustment generally required; monitor in severe renal dysfunction.
• Elderly: No dosage adjustment needed, but limited clinical data available.
• Children under 5 kg or under 3 months: Not recommended due to lack of data.

Artemether is a fast-acting antimalarial that generates reactive free radicals through cleavage of its endoperoxide bridge in the presence of heme iron within the parasite’s food vacuole, leading to parasite protein and membrane damage.

Lumefantrine is a longer-acting antimalarial that inhibits the conversion of toxic heme to non-toxic hemozoin, causing parasite death due to accumulation of toxic heme.

The combination offers:

• Rapid parasite clearance (Artemether)
• Prevention of recrudescence (Lumefantrine)

Absorption:

• Artemether and lumefantrine have poor oral bioavailability on an empty stomach but significantly improve when taken with food.
• Tmax: Artemether ~2 hours; Lumefantrine ~6–8 hours

Distribution:

• Both drugs are highly protein-bound (>95%) and widely distributed.

Metabolism:

• Artemether: Metabolized by CYP3A4 to active dihydroartemisinin (DHA)
• Lumefantrine: Metabolized by CYP3A4 to desbutyl-lumefantrine (active)

Elimination:

• Half-life: Artemether ~1–3 hours; Lumefantrine ~3–6 days
• Excretion: Mainly via feces (biliary); minimal renal elimination

Pregnancy:

• Recommended during 2nd and 3rd trimesters of pregnancy for uncomplicated malaria.
• First trimester use only if no suitable alternative is available; limited human data exist.

Lactation:

• Small amounts excreted in breast milk; considered compatible with breastfeeding.
• Monitor infants for gastrointestinal or neurologic symptoms.

• Antimalarial Agent
• Artemisinin-based Combination Therapy (ACT)

• Known hypersensitivity to artemether, lumefantrine, or formulation excipients
• Patients with QT interval prolongation or cardiac arrhythmias
• Use with drugs that prolong QT interval (e.g., quinidine, halofantrine, macrolides)
• Severe malaria or cerebral malaria (requires parenteral therapy)
• Co-administration with potent CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine)

• Cardiac risks: May cause QT prolongation—ECG monitoring advised for high-risk patients.
• Food intake: Taking with food is essential for therapeutic efficacy.
• Neurologic effects: Rare reports of dizziness, sleep disturbances, and ataxia.
• Recrudescence risk: Confirm parasite clearance; repeat treatment if relapse occurs.
• Drug resistance: Use only as per national or WHO treatment guidelines to avoid resistance development.

Common:

• Headache, dizziness
• Loss of appetite
• Nausea, vomiting, abdominal pain
• Fatigue, sleep disturbances

Less Common:

• Palpitations, bradycardia
• Skin rash or pruritus

Serious (Rare):

• QT interval prolongation
• Seizures (rare, mostly in predisposed individuals)
• Hypersensitivity reactions (e.g., angioedema)

Major:

• CYP3A4 inducers (e.g., rifampin, phenytoin): ↓ lumefantrine levels → therapeutic failure
• CYP3A4 inhibitors (e.g., ketoconazole, grapefruit juice): ↑ lumefantrine → ↑ QT prolongation risk
• Other QT-prolonging drugs (e.g., quinidine, erythromycin, amiodarone): Additive cardiotoxicity

Food Interaction:

• High-fat meals increase absorption → essential to take with food

Alcohol:

• No known interaction, but may worsen dehydration or confuse malaria symptoms

• WHO (2022): Artemether + Lumefantrine remains a first-line ACT for uncomplicated P. falciparum malaria.
• Clinical use in pregnancy further supported by updated safety data for 2nd and 3rd trimesters.
• Resistance monitoring emphasized in endemic areas—alternate ACTs may be recommended if resistance develops.

• Store below 30°C
• Protect from light and moisture
• Keep in original packaging until use
• Do not use if tablets are discolored or packaging is damaged