What is the recommended dose of artesunate (intravenous antimalarial medication) for adults with severe malaria?

Recommended Dosage of Intravenous Artesunate for Adults with Severe Malaria

The recommended dose of intravenous artesunate for adults with severe malaria is 2.4 mg/kg administered at 0,12, and 24 hours, followed by 2.4 mg/kg once daily until the patient can take oral medication. 1

Dosing Protocol

1. Initial dosing schedule:

   • First dose: 2.4 mg/kg IV at 0 hours
   • Second dose: 2.4 mg/kg IV at 12 hours
   • Third dose: 2.4 mg/kg IV at 24 hours

2. Subsequent dosing:

   • Continue with 2.4 mg/kg IV once daily until:
     • Patient is able to take oral medication AND
     • Parasitemia has decreased to <1%

3. Transition to oral therapy:

   • Once the patient improves clinically and parasitemia is <1%, switch to a full course of oral artemisinin-based combination therapy (ACT) 1

Pharmacokinetic Considerations

The 2.4 mg/kg dose is critical as pharmacokinetic studies have demonstrated:

• Large inter-individual variability (up to 10-fold) in dihydroartemisinin (DHA, the active metabolite) peak concentrations and exposure 2
• Median elimination half-life of artesunate is approximately 0.25 hours 3
• Median elimination half-life of DHA is approximately 1.31 hours 3

Monitoring Requirements

• Parasitemia monitoring: Every 12 hours until parasitemia declines to <1%, then every 24 hours until negative 1
• Post-treatment monitoring: For patients treated with IV artesunate, monitor for post-artesunate delayed hemolysis (PADH) by checking hemoglobin, haptoglobin, and lactate dehydrogenase levels at days 7,14,21, and 28 1

Alternative Options

If intravenous artesunate is unavailable, alternative options include:

• Intramuscular artemether (3.2 mg/kg loading dose, followed by 1.6 mg/kg daily) 1
• Artesunate suppositories (8-16 mg/kg at 0 and 12 hours, then daily) 1
• Intravenous quinine (20 mg/kg loading dose over 4 hours, followed by 10 mg/kg over 4 hours every 8 hours) 1

Clinical Efficacy

Artesunate is superior to quinine for treatment of severe malaria:

• Mortality reduction of 34.7% compared to quinine 4
• More rapid parasite clearance 5
• Better safety profile with fewer adverse effects, particularly hypoglycemia 4

Important Considerations and Pitfalls

• Minimum effective dose: 2.4 mg/kg should be considered the minimum dose due to the high variability in drug absorption and metabolism among patients with severe malaria 2
• Fluid management: Unlike bacterial sepsis, fluid management should be more restrictive in severe malaria to avoid pulmonary or cerebral edema 1
• Concomitant antibiotics: Consider empiric antibiotics if bacterial co-infection is suspected 1
• Monitoring for complications: Continuous monitoring of cardiocirculatory, pulmonary, renal, and metabolic parameters is essential 1

Artesunate is now the first-line treatment for severe malaria worldwide, having received FDA approval in 2020 and European Medicines Agency approval in 2021 1.