COARTEM
Clinical safety rating
cautionComprehensive clinical and safety monograph for COARTEM (COARTEM).
Artemether and lumefantrine are antimalarial agents that act as blood schizonticides. Artemether is rapidly metabolized to dihydroartemisinin, which generates free radicals that damage parasite proteins and membranes. Lumefantrine inhibits the formation of beta-hematin (hemozoin) by forming a complex with hemin, thereby preventing parasite detoxification of heme.
| Metabolism | Artemether is metabolized primarily by CYP3A4 and CYP3A5 to dihydroartemisinin. Lumefantrine is metabolized by CYP3A4. |
| Excretion | Artemether is primarily metabolized in the liver via CYP3A4; its metabolites are excreted in feces (approximately 80%) and urine (minor). Lumefantrine is also hepatically metabolized (CYP3A4) and excreted predominantly in feces (90%) with minimal renal excretion (<1%). Overall, both drugs are eliminated mainly via biliary/fecal routes. Renal excretion is negligible. |
| Half-life | Artemether: terminal elimination half-life ~1–3 hours (rapid, consistent with its role in rapid parasite clearance). Lumefantrine: terminal elimination half-life ~4–6 days (mean 4.5 days in healthy volunteers; longer in malaria patients due to increased Vd and protein binding). The prolonged half-life of lumefantrine ensures effective post-treatment prophylaxis. |
| Protein binding | Artemether: >95% bound to plasma proteins (primarily albumin and α1-acid glycoprotein). Lumefantrine: >99% bound to plasma proteins (mainly albumin and α1-acid glycoprotein). |
| Volume of Distribution | Artemether: Vd ~2–4 L/kg (large, indicating extensive tissue distribution). Lumefantrine: Vd ~10–20 L/kg (very large, suggesting deep tissue compartment, likely due to high lipophilicity and protein binding). |
| Bioavailability | Oral bioavailability of Coartem fixed-dose combination: artemether ~40% (with food) but highly variable; absorption is enhanced by fat. Lumefantrine oral bioavailability is highly variable (approximately 20–50%) and significantly increased when taken with food (especially fatty meals). Coartem should be taken with food to maximize absorption. |
| Onset of Action | Oral administration: Clinical effects (parasite clearance) begin within 2–4 hours for artemether component; lumefantrine takes longer to achieve therapeutic concentrations. Combination therapy shows initial antiparasitic effect by 2–4 hours. |
| Duration of Action | Artemether has a short duration of action (approximately 4–6 hours), requiring a partner drug. Lumefantrine provides sustained antimalarial effect for 4–6 weeks due to its long half-life, covering multiple asexual cycles. Full treatment course with Coartem (6 doses over 3 days) ensures complete cure. |
| Molecular Weight | Artemether: 298.4 Da; Lumefantrine: 528.9 Da |
4 tablets (each containing artemether 20 mg and lumefantrine 120 mg) orally twice daily for 3 days (total of 6 doses). Doses should be taken with fatty food to enhance absorption. Repeat dosing if vomiting occurs within 1 hour after administration.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Safety and efficacy not established in severe renal impairment (eGFR <30 mL/min/1.73 m²); use with caution. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh class A or B). Contraindicated in severe hepatic impairment (Child-Pugh class C). |
| Pediatric use | 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 orally twice daily for 3 days (total of 6 doses) with fatty food. |
| Geriatric use | No specific dose adjustment required; follow adult dosing. Caution in elderly due to potential for QT prolongation and concurrent medications. Monitor for cardiac effects. |
| 1st trimester | Avoid during first trimester due to potential teratogenic effects; based on animal studies indicating fetal abnormalities at high doses. |
| 2nd trimester | Use only if benefit outweighs risk; no adequate human studies, but animal data suggest risk. |
| 3rd trimester | Use only if benefit outweighs risk; no adequate human studies, but animal data suggest risk. |
Clinical note
Comprehensive clinical and safety monograph for COARTEM (COARTEM).
| Placental transfer | Artemether and lumefantrine cross the placenta. Lumefantrine is highly protein bound and has limited placental transfer, while artemether crosses more readily. |
| Breastfeeding | Artemether and lumefantrine are excreted into breast milk in small amounts. In a study, the estimated infant dose was <1% of the maternal weight-adjusted dose. Use with caution, especially in preterm or ill infants. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category C. First trimester: Avoid; teratogenic effects observed in animal studies (skeletal malformations) at clinically relevant doses. Second and third trimesters: Data limited; use only if benefit outweighs risk. Malaria infection poses higher fetal risk than treatment. |
| Fetal Monitoring | Monitor complete blood counts (especially CBC with differential) and liver function tests periodically due to risk of hemolytic anemia and hepatic injury. For prolonged use, consider ECG monitoring for QTc prolongation. In pregnancy, monitor for signs of hemolysis in G6PD-deficient patients. |
| Fertility Effects | Animal studies indicate no significant impact on fertility. In humans, no specific data on fertility impairment. Malaria infection itself may impair fertility; treatment likely beneficial. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to artemether, lumefantrine, or any componentSevere malaria (use IV artesunate instead)First trimester of pregnancy (unless no alternative)
| Precautions | QT interval prolongation: caution in patients with risk factors for QT prolongation, electrolyte abnormalities, or concomitant use of drugs that prolong QT interval., Parasite resistance: monitor for clinical failure., Re-evaluate if severe malaria develops., Use with caution in patients with hepatic or renal impairment., Potential for drug interactions with CYP3A4 inducers/inhibitors. |
| Food/Dietary | Take with fatty food (e.g., whole milk, cheese, or a meal containing fat) to increase absorption, especially of lumefantrine. Avoid grapefruit juice. Alcohol may increase risk of hepatotoxicity and should be avoided. |
| Clinical Pearls | Coartem (artemether/lumefantrine) is a first-line treatment for uncomplicated Plasmodium falciparum malaria. Administer with fatty food to enhance absorption (especially lumefantrine). Monitor for QT prolongation, especially in patients with electrolyte abnormalities, bradycardia, or concurrent use of QT-prolonging drugs. Do not use for severe malaria or as prophylaxis. Not recommended in children <5 kg. Repeat dose if vomiting occurs within 1 hour of administration. |
| Patient Advice | Take Coartem with a full meal or fatty food (e.g., milk, cheese) to help the medicine work better. · Complete the full course of 6 doses over 3 days even if you feel better. · If you vomit within 1 hour after taking a dose, take another dose with food. · Avoid grapefruit juice during treatment as it may affect the medication. · Report any signs of irregular heartbeat, dizziness, or fainting immediately. · Use effective birth control during treatment and for 1 month after the last dose, as Coartem may reduce hormonal contraceptive effectiveness. · Not to be used for prevention of malaria. · Keep out of reach of children. |
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