What is the maximum recommended dose of artesunate (antimalarial medication) per kilogram?

From the Guidelines

The maximum recommended dose of artesunate is 2.4 mg/kg IV at 0,12, and 24 hours, then continue with 2.4 mg/kg daily for 7 days. This dose is typically administered intravenously for the treatment of severe malaria, as recommended by the World Health Organization 1. The treatment should be initiated promptly in cases of severe malaria, as delays can lead to increased mortality. After completing the course of parenteral artesunate, patients should receive a complete course of oral antimalarial therapy to ensure complete parasite clearance. It's worth noting that for children weighing less than 20 kg, the dose may need to be adjusted to ensure adequate drug exposure. Artesunate works by rapidly reducing parasite burden through its action against blood-stage parasites, particularly the ring stages, and it converts to dihydroartemisinin in the body, which generates free radicals that damage parasite proteins 1.

Some key points to consider when administering artesunate include:

• The dose should not exceed 2.4 mg/kg per dose
• The treatment should be administered intravenously or intramuscularly
• The total duration of artesunate treatment should not exceed 7 days
• Patients should receive a complete course of oral antimalarial therapy after completing the course of parenteral artesunate
• Clinical complications of severe malaria should be managed by intensivists according to guidelines and more recent achievements 1.

It's also important to note that artesunate has been shown to have a faster parasite clearance time and a shorter ICU stay compared to quinine in the treatment of severe falciparum malaria 1. However, the treatment of severe malaria should be individualized and based on the specific clinical presentation and laboratory findings of the patient.

From the Research

Maximum Dose of Artesunate per kg

The maximum recommended dose of artesunate per kilogram is a crucial aspect of treating severe malaria. According to the provided studies:

• A study published in 2012 2 compared a conventional empirically derived regimen with a simplified regimen for parenteral artesunate in severe malaria, with a total dose of artesunate in each group being 12 mg/kg.
• Another study from 2010 3 used intramuscular artesunate at a dose of 2.4 mg/kg immediately followed by 1.2 mg/kg at 12 hours, then 24 hours, then daily.
• A 2023 study 4 performed population pharmacokinetic modeling of plasma concentration data from children with severe falciparum malaria given 2.4 mg/kg of artesunate intravenously, suggesting that this dose may not be sufficient for younger children.
• A randomized clinical trial from 2011 5 investigated the impact of different artesunate doses on clinical and parasitological responses in malaria patients, using daily doses of 2,4, or 6 mg/kg/day, with a total dose of 14,28, and 42 mg/kg, respectively.
• A study from 2003 6 used oral artesunate with or without high-dose primaquine for the treatment of vivax malaria in Thailand, but did not specify a maximum dose per kilogram.

Key Findings

• The total dose of artesunate used in the 2012 study was 12 mg/kg 2.
• The dose of 2.4 mg/kg used in the 2010 study was effective, but the 2023 study suggests that this dose may not be sufficient for younger children 3, 4.
• The 2011 study found no benefit in increasing the daily dose of artesunate above 4 mg/kg/day, but used total doses of up to 42 mg/kg 5.
• The maximum dose per kilogram is not explicitly stated in the 2003 study 6.

Dosing Considerations

• The dosing regimens used in the studies varied, with some using a total dose of 12 mg/kg 2 and others using daily doses of 2-6 mg/kg/day 3, 5.
• The 2023 study suggests that the dose of 2.4 mg/kg may not be sufficient for younger children, implying that a higher dose may be necessary 4.
• The World Health Organization has recommended individual doses of 3 mg/kg for children weighing <20 kg since 2015, as mentioned in the 2023 study 4.