What are the side effects of artesunate?

Side Effects of Artesunate

Intravenous artesunate can cause post-artesunate delayed hemolysis (PADH) and hemoglobinuria as its most serious adverse effects. 1

Common Side Effects

Artesunate is generally well-tolerated compared to other antimalarial medications, but several side effects have been documented:

Mild to Moderate Side Effects

• Nausea and vomiting 2
• Diarrhea 3
• Anorexia 2
• Dizziness 2

Serious Side Effects

• Post-artesunate delayed hemolysis (PADH) - A significant concern requiring monitoring on days 7,14,21, and 28 after treatment 1
• Hemoglobinuria - Presence of blood in urine 1
• Neutropenia - Abnormally low neutrophil count 4
• Anemia - Can occur during or after treatment 4
• Elevated liver enzymes - Indicating potential liver stress 4
• Severe allergic reactions - Including rare cases of anaphylaxis 4

Side Effects Based on Administration Route

Intravenous Artesunate

• Used for severe malaria (first-line treatment)
• Dosage: 2.4 mg/kg IV at 0,12,24 hours, then daily until oral medication can be taken 1
• Requires monitoring for PADH with hemoglobin, haptoglobin, and lactate dehydrogenase levels at days 7,14,21, and 28 1

Oral Artesunate

• Better tolerated than IV formulation
• Common side effects include mild nausea, vomiting, anorexia, and dizziness 2
• When combined with mefloquine, side effects increase significantly 2

Special Populations

Pregnancy

• Artesunate has shown embryotoxicity in animal studies with embryo loss and cardiovascular malformations at high doses 5
• No-effect levels were in the range of 5-7 mg/kg/day in animal studies 5
• Limited human data has not shown adverse developmental effects in pregnant women 5

Children

• Generally well-tolerated in children
• Dosing for severe malaria in children is the same as adults: 2.4 mg/kg IV at 0,12,24 hours, then daily 1

Monitoring Recommendations

For patients receiving IV artesunate for severe malaria:

1. Monitor parasitemia every 12 hours until decline to <1%, then every 24 hours until negative 1
2. Check complete blood count, liver function, kidney function, and metabolic parameters daily 1
3. Specifically monitor for PADH on days 7,14,21, and 28 after treatment 1
4. Parameters to check: hemoglobin, haptoglobin, and lactate dehydrogenase levels 1

Comparison with Other Antimalarials

Artesunate has fewer side effects compared to quinine, which can cause:

• Cinchonism (tinnitus, vertigo, headache, acute hearing loss)
• Hypoglycemia
• QT prolongation 1

Clinical Pearls

• Artesunate alone is well-tolerated, but side effects increase significantly when combined with other antimalarials like mefloquine 2
• High-dose artesunate (10 mg/kg/day, at the upper limit of WHO recommendations) has been associated with increased gastrointestinal side effects 3
• Anaphylactic reactions to artesunate are rare but have been reported 4
• For uncomplicated malaria, oral artesunate is typically given as part of combination therapy to prevent resistance development 6