COARTEM
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for COARTEM (COARTEM).
| Breastfeeding | Artemether and lumefantrine are excreted into breast milk in low amounts. M/P ratio not determined. Based on limited data, the American Academy of Pediatrics considers it compatible with breastfeeding. Monitor infant for potential adverse effects (diarrhea, vomiting). |
| 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to artemether, lumefantrine, or any component of the formulation.","Concomitant therapy with drugs that are metabolized by CYP2D6 and have a narrow therapeutic index (e.g., flecainide, metoprolol, imipramine, amitriptyline, clomipramine) due to potential QT prolongation.","Severe malaria (parenteral therapy recommended)."]
| 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."] |
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| 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. |