ARTESUNATE
Clinical safety rating
cautionComprehensive clinical and safety monograph for ARTESUNATE (ARTESUNATE).
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.
| Metabolism | Primarily hydrolyzed in the stomach and in plasma by esterases to dihydroartemisinin (DHA), the active metabolite. DHA undergoes glucuronidation via UGT1A9 and UGT2B7. |
| Excretion | 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. |
| Half-life | 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. |
| Protein binding | Artemisinin derivatives: ~93% bound to serum proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd approximately 0.6-0.8 L/kg, indicating distribution into total body water. Higher Vd in severe malaria due to increased capillary permeability. |
| Bioavailability | Oral: ~40% (range 20-50%) due to first-pass metabolism. Rectal: ~40-60%. IV: 100%. |
| Onset of Action | IV: Onset of clinical effect (parasite clearance) within 30 minutes. Oral: Onset within 1-2 hours. Rectal: Onset within 2-4 hours. |
| Duration of Action | Antimalarial effect lasts approximately 4-6 hours due to rapid metabolism. Requires q12h dosing for 24 hours or longer in severe malaria to ensure complete elimination of parasites. |
| Molecular Weight | 384.43 |
2.4 mg/kg IV at 0, 12, 24, and 48 hours, then daily until oral therapy can be initiated.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for any degree of renal impairment. |
| Liver impairment | No dose adjustment required for Child-Pugh A or B; caution in Child-Pugh C due to limited data. |
| Pediatric use | 2.4 mg/kg IV at 0, 12, 24, and 48 hours; weight-based (minimum 2.4 mg/kg per dose). |
| Geriatric use | No specific dose adjustment; use same dosing as adults with monitoring for adverse effects. |
| 1st trimester | Use only if benefit outweighs risk; limited human data, but animal studies show embryotoxicity at high doses. Malaria infection itself poses risks. |
| 2nd trimester | Generally considered safe; no increased risk of birth defects observed; used for malaria treatment in second trimester. |
| 3rd trimester | Generally considered safe; used for malaria treatment in third trimester; no adverse fetal effects reported. |
Clinical note
Comprehensive clinical and safety monograph for ARTESUNATE (ARTESUNATE).
| Placental transfer | Crosses placenta readily; measurable concentrations in fetal blood, but no evidence of significant adverse effects at therapeutic doses. |
| Breastfeeding | Artesunate is excreted into breast milk in low concentrations. The amount is unlikely to cause adverse effects in the nursing infant. However, caution is advised due to potential for infant gastrointestinal effects. Monitor infant for diarrhea or rash. |
| Lactation Rating | L2 - Possibly Compatible |
| Teratogenic Risk | Artesunate is contraindicated in the first trimester of pregnancy due to embryotoxicity and teratogenicity observed in animal studies. In the second and third trimesters, the benefit of treating life-threatening malaria generally outweighs risks, as untreated malaria poses significant fetal risks. However, the drug should be used with caution and only when clearly needed. |
| Fetal Monitoring | Monitor maternal complete blood count, liver and renal function tests, and electrocardiogram (QT prolongation risk). Fetal monitoring includes ultrasound for growth and well-being, especially if used in the second or third trimester. Monitor for signs of hemolysis in newborns if used near term. |
| Fertility Effects | Artesunate has no known significant effects on fertility in humans. Animal studies have not shown impairment of fertility at clinically relevant doses. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to artemisinin derivatives
| Precautions | Hemolysis: Cases of delayed hemolytic anemia have been reported, especially in patients with high parasitemia., Cardiotoxicity: Theoretical risk of QT prolongation with co-administration of other QT-prolonging drugs., Hypersensitivity: Severe allergic reactions (e.g., anaphylaxis) have occurred. |
| Food/Dietary | No known significant food interactions. However, avoid grapefruit and grapefruit juice as they may alter drug metabolism (CYP2A6 inhibition). Maintain adequate hydration and nutrition to support recovery. |
| Clinical Pearls | Artesunate is the first-line therapy for severe malaria (WHO recommendation). Administer IV or IM; IV dose is 2.4 mg/kg at 0, 12, and 24 hours then daily. Monitor for hypoglycemia and delayed hemolytic anemia (post-artesunate hemolysis). Not recommended for uncomplicated malaria due to risk of resistance. Artesunate is rapidly acting with a short half-life; always combine with a partner drug (e.g., artemether-lumefantrine) for complete cure. Do not use in first trimester of pregnancy unless life-threatening. |
| Patient Advice | Take this medication exactly as prescribed; do not stop early even if you feel better. · You may experience temporary side effects such as dizziness, nausea, or fatigue; report any severe reactions. · This drug is used for severe malaria; you will likely be hospitalized for close monitoring. · Watch for signs of low blood sugar (sweating, confusion, rapid heartbeat) and report immediately. · Inform your healthcare provider about all medications you are taking, especially blood thinners or anti-seizure drugs. · Complete the full course of treatment, including any follow-up medications to prevent recurrence. |
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