Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
Artemether-Lumefantrine vs ALDORIL D30
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
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.
Aldoril D30 is a combination of methyldopa, a centrally acting alpha-2 adrenergic agonist that reduces sympathetic outflow, and hydrochlorothiazide, a thiazide diuretic that inhibits the sodium-chloride symporter in the distal convoluted tubule, decreasing plasma volume and peripheral resistance.
Treatment of uncomplicated malaria due to Plasmodium falciparum,Treatment of chloroquine-resistant malaria
Hypertension
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.
Oral: 1 tablet (hydrochlorothiazide 30 mg / methyldopa 500 mg) twice daily; maximum dose: 2 tablets twice daily.
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 hydrochlorothiazide is 6-15 hours; methyldopa half-life is 1.8 hours (normal renal function). In renal impairment, half-life of both components is prolonged.
Artemether is metabolized by CYP3A4 to dihydroartemisinin. Lumefantrine is metabolized by CYP3A4.
Methyldopa is metabolized by conjugation (catechol-O-methyltransferase) and hepatic sulfation; hydrochlorothiazide is not extensively metabolized and is excreted unchanged by the kidney.
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.
Renal: approximately 50% as parent drug and metabolites; biliary/fecal: minimal, less than 5%.
Artemether: 95% bound to plasma proteins (primarily albumin and α1-acid glycoprotein). Dihydroartemisinin: 93% bound. Lumefantrine: >99% bound to high-density lipoproteins (HDL) and, to a lesser extent, to albumin and α1-acid glycoprotein.
Methyldopa: <10% bound to plasma proteins; hydrochlorothiazide: 40-68% bound to albumin.
Artemether: Vd approximately 2–5 L/kg, indicating extensive tissue distribution. Dihydroartemisinin: Vd 0.5–1.5 L/kg. Lumefantrine: Vd extremely large, ranging from 10–30 L/kg (reported up to 31 L/kg), reflecting extensive tissue binding and accumulation in erythrocytes and organs (liver, lung, kidney).
Methyldopa: Vd 0.2-0.3 L/kg (distributes into tissues, crosses placenta); hydrochlorothiazide: Vd 0.75-1.5 L/kg (extensively distributed, does not cross blood-brain barrier significantly).
Oral bioavailability: Artemether is 30–40% due to extensive first-pass metabolism by CYP3A4/5 to dihydroartemisinin, which has 80% oral bioavailability. Lumefantrine has highly variable and food-dependent bioavailability; absorption increases 2–16 fold when taken with a high-fat meal. Bioavailability is approximately 5–10% in the fasted state and up to 85% when administered with fat-containing food. The combination is formulated to enhance lumefantrine absorption with a fixed ratio of artemether:lumefantrine 1:6.
Oral bioavailability of methyldopa is approximately 25% (variable, influenced by gut metabolism); hydrochlorothiazide bioavailability is 65-75%.
No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (Cr Cl <30 m L/min); use with caution.
GFR 30-60 m L/min: reduce dose by 50%; GFR <30 m L/min: not recommended.
No dose adjustment for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); avoid use.
Child-Pugh Class B or C: contraindicated; use not recommended.
Weight-based dosing: 5-<15 kg: 1 tablet per dose; 15-<25 kg: 2 tablets per dose; 25-<35 kg: 3 tablets per dose; ≥35 kg: 4 tablets per dose. Administer at 0, 8, 24, 36, 48, and 60 hours. Crush tablets if needed for children <5 kg.
Not recommended for use in pediatric patients due to lack of safety and efficacy data.
No specific dose adjustment required. Monitor for QT prolongation and electrolyte disturbances due to potential age-related decline in cardiac conduction.
Start with lowest dose; monitor for hypotension, electrolyte imbalance, and CNS effects; consider reduced initial dose.
None
None
QT interval prolongation,Arrhythmias,Recrudescence of infection,Hypersensitivity reactions,Use in hepatic impairment
May cause hemolytic anemia, liver disorders, positive Coombs test, sedation, depression, and hypersensitivity reactions. Hydrochlorothiazide may cause electrolyte imbalance, hyperuricemia, photosensitivity, and exacerbation of systemic lupus erythematosus. Use with caution in renal impairment, hepatic disease, and in patients with a history of drug-induced hemolytic anemia.
Hypersensitivity to artemether or lumefantrine,Severe malaria,Pregnancy (first trimester) unless no other option
Active hepatic disease, history of previous methyldopa therapy-associated liver disorders; anuria; hypersensitivity to methyldopa, hydrochlorothiazide, or sulfonamide-derived drugs.
High-fat meal increases absorption; grapefruit juice may increase lumefantrine levels; avoid concurrent use.
Food may decrease absorption of methyldopa. Avoid excessive intake of high-potassium foods (e.g., bananas, oranges) unless directed. Hydrochlorothiazide may cause potassium depletion; maintain adequate dietary potassium. Avoid natural licorice as it can worsen hypokalemia.
FDA Pregnancy Category C. Artemether-lumefantrine is not recommended in the first trimester unless no alternative; animal studies show embryotoxicity at high doses. Second and third trimester: limited human data but appears safe; no increased risk of congenital malformations reported. Use only if benefit outweighs risk.
First trimester: Limited data; no clear evidence of major malformations but methyldopa crosses placenta. Second and third trimesters: Associated with reduced placental perfusion; possible fetal bradycardia and neonatal hypotension. Hydrochlorothiazide may cause fetal/neonatal jaundice, thrombocytopenia, and electrolyte disturbances.
Both artemether and lumefantrine are excreted in breast milk in low amounts. M/P ratio: artemether ~0.3, lumefantrine ~0.5. Considered compatible with breastfeeding; no adverse effects observed in infants. Use caution if infant has G6PD deficiency due to theoretical risk of hemolysis.
Methyldopa is excreted in breast milk in low concentrations; M/P ratio approximately 0.2. Hydrochlorothiazide is excreted in minimal amounts; may suppress lactation. Consider risks versus benefits.
No dose adjustment required for uncomplicated malaria in second and third trimester. First trimester: avoid unless no alternative; use same weight-based dosing. Pharmacokinetic changes in pregnancy (increased volume of distribution, altered metabolism) do not mandate dose changes; standard 6-dose regimen over 3 days is recommended.
Methyldopa: Pregnancy-induced plasma volume expansion may require dose titration; monitor blood pressure and adjust accordingly. Hydrochlorothiazide: Often avoided in pregnancy due to volume depletion risks; if used, monitor electrolytes and renal function, no pharmacokinetic data necessitate routine dose adjustment.
Monitor ECG for QTc prolongation; administer with fatty food to enhance absorption; avoid in patients with severe hepatic impairment; pregnancy category C; caution with CYP3A4 inhibitors or inducers.
ALDORIL D30 combines methyldopa (central alpha-2 agonist) and hydrochlorothiazide (thiazide diuretic). Monitor for orthostatic hypotension, especially at initiation. Taper not needed for methyldopa but discontinue if fever or liver dysfunction occurs. Interferes with urinary catecholamine measurements (false elevation). Hydrochlorothiazide may cause hyponatremia, hypokalemia, and hyperglycemia; check electrolytes and glucose periodically.
Take with a high-fat meal or whole milk to improve absorption.,Complete the full 3-day course even if symptoms improve.,Seek medical attention for signs of severe malaria (e.g., altered consciousness, difficulty breathing).,Avoid grapefruit juice during treatment.,Use effective contraception if of childbearing potential.
Take exactly as prescribed, preferably with food to reduce stomach upset.,Rise slowly from sitting or lying down to prevent dizziness.,This drug may make you drowsy; avoid driving or operating machinery until you know how it affects you.,Report fever, unexplained fatigue, jaundice, or dark urine immediately.,Weigh yourself daily and report rapid weight gain or swelling.,Limit alcohol intake as it can increase side effects.,Do not use salt substitutes containing potassium without consulting your doctor.
"Anagrelide, a phosphodiesterase 3 (PDE3) inhibitor used for thrombocythemia, and artemether, an antimalarial artemisinin derivative, both prolong the QT interval by inhibiting cardiac potassium channels (specifically IKr). Concurrent use may result in additive QTc prolongation, increasing the risk of Torsade de Pointes and other ventricular arrhythmias. This risk is particularly relevant in patients with electrolyte imbalances, bradycardia, or pre-existing cardiac disease."
"Acepromazine, a phenothiazine antipsychotic/antiemetic, inhibits cytochrome P450 3A4 (CYP3A4), the primary enzyme responsible for metabolizing the antimalarial artemether. Concomitant administration can lead to significantly reduced clearance of artemether, elevating its plasma concentrations. This may increase the risk of dose-dependent toxicities, including neurotoxicity (e.g., ataxia, seizures) and cardiotoxicity (e.g., QT prolongation)."
"Concomitant administration of thioridazine, a potent CYP2D6 inhibitor, with artemether, a substrate of CYP2D6, can significantly increase the serum concentration of artemether. This elevation may potentiate the antimalarial effect but also heightens the risk of artemether-related adverse effects such as QT prolongation and neurotoxicity. Clinically, this interaction warrants caution due to potential cardiotoxicity and altered drug exposure."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about Artemether-Lumefantrine vs ALDORIL D30, answered by our medical review team.
Artemether-Lumefantrine is a Antimalarial that works by 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.. ALDORIL D30 is a Antihypertensive Combination that works by Aldoril D30 is a combination of methyldopa, a centrally acting alpha-2 adrenergic agonist that reduces sympathetic outflow, and hydrochlorothiazide, a thiazide diuretic that inhibits the sodium-chloride symporter in the distal convoluted tubule, decreasing plasma volume and peripheral resistance.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between Artemether-Lumefantrine and ALDORIL D30 depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of Artemether-Lumefantrine is: 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.. The standard adult dose of ALDORIL D30 is: Oral: 1 tablet (hydrochlorothiazide 30 mg / methyldopa 500 mg) twice daily; maximum dose: 2 tablets twice daily.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between Artemether-Lumefantrine and ALDORIL D30 in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. Artemether-Lumefantrine is classified as Category C. FDA Pregnancy Category C. Artemether-lumefantrine is not recommended in the first trimester unless no alternative; animal studies show embryotoxicity at high doses. Second and thir. ALDORIL D30 is classified as Category C. First trimester: Limited data; no clear evidence of major malformations but methyldopa crosses placenta. Second and third trimesters: Associated with reduced placental perfusion; p. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.