What is the recommended artesunate dosing regimen (route, dose per kilogram, frequency, and duration) for severe and uncomplicated Plasmodium falciparum malaria in adults and children?

Artesunate Dosing for Malaria

Severe Malaria (Intravenous Artesunate)

For severe Plasmodium falciparum malaria in adults and children, administer intravenous artesunate at 2.4 mg/kg body weight at 0,12, and 24 hours, then once daily until the patient can tolerate oral medication and parasitemia falls below 1%. 1, 2, 3

Detailed IV Artesunate Protocol

• Initial dosing schedule:

  • First dose: 2.4 mg/kg IV at 0 hours 3
  • Second dose: 2.4 mg/kg IV at 12 hours 3
  • Third dose: 2.4 mg/kg IV at 24 hours 3
  • Subsequent doses: 2.4 mg/kg IV once daily 1, 3

• Discontinuation criteria (all must be met):

  • Patient is hemodynamically stable and conscious 3
  • Able to tolerate oral intake 3
  • Peripheral parasitemia has declined to <1% of red blood cells 3
  • Minimum of three doses administered (do not stop earlier even if patient appears improved) 3

Transition to Oral Therapy

• After IV artesunate, immediately begin a complete 3-day course of oral artemisinin-based combination therapy (ACT) 3
• Preferred oral options:
  • Artemether-lumefantrine: 4 tablets at 0,8,24,36,48, and 60 hours (total 24 tablets over 72 hours for patients >35 kg) 1
  • Dihydroartemisinin-piperaquine: 3-4 tablets daily for 3 days (dose based on weight) 1, 3
• Plus doxycycline 100 mg orally every 12 hours for 7 days OR mefloquine 15 mg/kg once, then 10 mg/kg after 12 hours 1

Alternative Parenteral Treatment

• If IV artesunate is unavailable, use quinidine gluconate: 10 mg/kg IV loading dose over 1-2 hours, then 0.02 mg/kg/minute continuous infusion for ≥24 hours 1, 3
• Treatment duration: 7 days for patients from Southeast Asia or Oceania; otherwise 3 days 1
• Critical safety note: Quinidine requires cardiac monitoring due to risk of QTc prolongation, ventricular arrhythmia, severe hypoglycemia, and hypotension 1

Uncomplicated Malaria (Oral Therapy)

For uncomplicated P. falciparum malaria, first-line treatment is oral artemisinin-based combination therapy, NOT artesunate monotherapy. 1, 2

Recommended Oral ACT Regimens

• Artemether-lumefantrine (preferred):

  • Adults >35 kg: 4 tablets twice daily for 3 days (at 0,8,24,36,48,60 hours) 1
  • Must be taken with fatty meal or drink 1

• Dihydroartemisinin-piperaquine (preferred):

  • 36-75 kg: 3 tablets daily for 3 days 1

  • 75 kg: 4 tablets daily for 3 days 1

  • Must be taken in fasting condition 1

• Atovaquone-proguanil (alternative):

  • <40 kg: 3 tablets daily for 3 days 1

  • 40 kg: 4 tablets daily for 3 days 1

Critical Pitfall: Artesunate Monotherapy

Do NOT use artesunate monotherapy (3-day course) for uncomplicated malaria. Research from Gabon demonstrated that a 3-day course of artesunate alone (4 mg/kg daily) achieved only 72% cure rate by day 28, which is unacceptably low 4. The short half-life of artesunate necessitates combination with a longer-acting partner drug to prevent recrudescence 1, 4.

Monitoring Requirements

During Treatment

• Parasitemia monitoring:

  • Every 12 hours until <1% 3
  • Then every 24 hours until negative 3
  • Initial increase within first 24 hours does NOT indicate treatment failure 3

• Clinical monitoring:

  • Continuous cardiocirculatory, pulmonary, kidney, and metabolic parameters 3
  • Glycemia, plasma bicarbonate, and lactate levels 3

Post-Treatment Surveillance

Monitor for post-artesunate delayed hemolysis (PADH) at days 7,14,21, and 28 after IV artesunate completion 2, 3

• Check hemoglobin, haptoglobin, and lactate dehydrogenase 3
• PADH occurs in approximately 10-15% of patients treated with IV artesunate 3

Special Populations

Children

• Same weight-based dosing applies: 2.4 mg/kg IV for severe malaria 1, 2
• Artesunate suppositories (when parenteral route unavailable): 8-16 mg/kg at 0 and 12 hours, then daily 5
• Research in Papua New Guinea children demonstrated artesunate suppositories achieved faster parasite clearance than intramuscular artemether (mean time to 50% clearance: 9.1 vs 13.8 hours, p=0.008) 5

Pregnancy

• Artesunate is safe in all trimesters for severe malaria 2
• For uncomplicated malaria, artemether-lumefantrine can be used in all trimesters per WHO and CDC guidelines 1

Common Clinical Pitfalls

• Do not stop IV artesunate after only three doses if patient cannot tolerate oral intake—continue once-daily IV dosing until oral tolerance achieved 3
• Do not switch to oral ACT while parasitemia remains ≥1%—adequate parasite clearance has not been achieved 3
• Do not shorten the oral ACT regimen—a complete 3-day course is mandatory after IV artesunate cessation 3
• Do not delay PADH monitoring—complication can arise up to 4 weeks post-treatment and requires systematic surveillance 3
• Avoid artesunate-pyronaridine in patients with liver disease—biochemical liver enzyme elevation occurs 4 times more frequently than with other ACTs 6