When should intravenous artesunate be discontinued in a patient with severe falciparum malaria?

When to Stop Intravenous Artesunate in Severe Malaria

Intravenous artesunate should be discontinued after 3 doses (given at 0,12, and 24 hours), then switched to once-daily dosing until the patient is clinically improved, able to take oral medications, and parasitemia has declined to less than 1%. 1, 2, 3

Specific Stopping Criteria

The transition from IV artesunate to oral therapy requires meeting all of the following conditions:

• Clinical improvement - Patient must be hemodynamically stable, conscious, and able to tolerate oral intake 1, 2
• Parasitemia threshold - Peripheral blood parasitemia must decline to <1% of red blood cells 1, 2, 3
• Oral tolerance - Patient must be able to swallow and retain oral medications 2, 3

Dosing Schedule Before Discontinuation

• First 24 hours: Give 2.4 mg/kg IV at 0,12, and 24 hours 2, 3, 4
• After 24 hours: Continue 2.4 mg/kg IV once daily until switching criteria are met 2, 3
• Do not stop prematurely - Even if the patient appears improved, complete at least the initial 3 doses before considering transition 1, 2

Transition to Oral Therapy

Once stopping criteria are met, immediately begin a full 3-day course of oral artemisinin-based combination therapy (ACT):

• Preferred options: Artemether-lumefantrine or dihydroartemisinin-piperaquine 1, 2, 3
• Critical point: The oral ACT course is a complete treatment, not a continuation - give the full 3-day regimen regardless of how many days of IV artesunate were given 1, 3

Monitoring Requirements During Treatment

Parasitemia Monitoring

• Check parasitemia every 12 hours until it declines to <1% 1, 2, 3
• After reaching <1%, check every 24 hours until negative 1, 2
• An initial increase in parasite density within the first 24 hours does not indicate treatment failure 1

Post-Treatment Surveillance

• Monitor for post-artesunate delayed hemolysis (PADH) by checking hemoglobin, haptoglobin, and lactate dehydrogenase at days 7,14,21, and 28 after treatment 1, 2, 3
• PADH occurs in approximately 10-15% of patients treated with IV artesunate 4

Common Pitfalls to Avoid

• Do not stop after just 3 doses if oral intake is not possible - Continue once-daily IV dosing until the patient can take oral medications 2, 3
• Do not switch to oral therapy if parasitemia remains ≥1% - This threshold must be met to ensure adequate parasite clearance 1, 2
• Do not give a shortened oral ACT course - Always complete the full 3-day oral regimen after stopping IV artesunate 1, 3
• Do not delay monitoring for PADH - This complication can occur up to 4 weeks after treatment and requires systematic surveillance 1, 2

Special Considerations

If IV Artesunate is Unavailable

• Use IV quinine as second-line: 20 mg salt/kg loading dose over 4 hours, then 10 mg/kg every 8 hours 2
• Do not switch from IV quinine to oral therapy before completing 48 hours of IV treatment 2

Pregnancy

• The same stopping criteria apply in all trimesters 4
• Artemether-lumefantrine is the preferred oral ACT for second and third trimesters 4