What is the dosing for uncomplicated malaria caused by Plasmodium (P.) falciparum?

Malaria Dosing for Uncomplicated Plasmodium falciparum

For uncomplicated P. falciparum malaria in adults, use artemether-lumefantrine (AL) as first-line therapy: 4 tablets at hour 0,4 tablets at hour 8 on day 1, then 4 tablets twice daily on days 2 and 3 (total 24 tablets over 72 hours), taken with a fatty meal or drink. 1

First-Line Treatment Options

Artemether-Lumefantrine (AL):

• Dosing for adults >35 kg: 4 tablets (80 mg artemether/480 mg lumefantrine) at 0 hours, 4 tablets at 8 hours on day 1, then 4 tablets at hours 36,48,60, and 72 (total 24 tablets) 1
• Critical requirement: Must be taken with a fatty meal or drink to ensure adequate absorption—failure to do this is a common cause of treatment failure 1, 2, 3
• Efficacy: Cure rates of 96-100% in most settings 2, 4
• Adverse effects: Headache, vertigo, digestive disorders, QTc prolongation 1

Dihydroartemisinin-Piperaquine (DP):

• Dosing: 36-75 kg: 3 tablets (120 mg DHA/960 mg piperaquine) daily for 3 days; >75 kg: 4 tablets daily for 3 days 1
• Critical requirement: Must be taken in fasting condition (opposite of AL) 1
• Efficacy: Cure rates 96-98.4%, superior to AL for preventing P. vivax recurrence 2, 3
• Adverse effects: Headache, vertigo, digestive disorders, QTc prolongation 1

Second-Line Treatment

Atovaquone-Proguanil:

• Dosing: <40 kg: 3 tablets daily for 3 days; >40 kg: 4 tablets (1000 mg atovaquone/400 mg proguanil) daily for 3 days 1
• Indication: Use when ACTs are contraindicated (QTc prolongation risk) or for infections from Southeast Asia with ACT resistance 1, 2
• Critical requirement: Must be taken with a fatty meal or drink 1
• Adverse effects: Digestive disorders (nausea, vomiting, diarrhea) 1

Third-Line Treatment

Quinine plus Doxycycline:

• Dosing: Quinine sulfate 648 mg (3 tablets of 250 mg salt) every 8 hours for 7 days PLUS doxycycline 100 mg twice daily for 7 days 1, 5
• Adverse effects: Cinchonism (tinnitus, vertigo, headache, hearing loss), hypoglycemia, esophagitis from doxycycline 1
• Contraindications: Not for use against P. falciparum from Southeast Asia due to resistance; avoid in neuropsychiatric history 1

Quinine plus Clindamycin (alternative to doxycycline):

• Dosing: Quinine sulfate 648 mg every 8 hours for 7 days PLUS clindamycin 20 mg/kg every 8 hours for 7 days 1
• Advantage: Can be used in pregnancy (all trimesters) 1

Dosing for Other Malaria Species

P. vivax, P. ovale, P. malariae (chloroquine-sensitive regions):

• Chloroquine: 4 tablets (1000 mg salt) initially, then 2 tablets (500 mg salt) at 6,24, and 48 hours 1
• For P. vivax/P. ovale: Add primaquine 30 mg base daily for 14 days for radical cure (check G6PD first) 1, 3

P. vivax chloroquine-resistant (Papua New Guinea, Indonesia, Sabah):

• Use same regimens as P. falciparum (AL or DP) PLUS primaquine for radical cure 1, 3

Severe Malaria Dosing

Intravenous Artesunate (first-line):

• Dosing: 2.4 mg/kg IV at 0,12, and 24 hours, then 2.4 mg/kg daily until parasite density <1% and patient can take oral medication 1, 2
• Follow-up: Complete treatment with full course of oral ACT once able to take oral medications 1, 2

Intravenous Quinine (second-line if artesunate unavailable):

• Dosing: 20 mg salt/kg over 4 hours (loading dose), then 10 mg/kg over 4 hours starting 8 hours after initiation, then every 8 hours 1
• Switch to oral: As soon as feasible (not before 48 hours IV treatment) 1

Special Populations

Pregnancy:

• AL can be used in all trimesters per WHO and CDC recommendations 1, 2
• Cure rates ≥94.9% with no increased risk of congenital malformations 1, 3
• Quinine plus clindamycin is alternative for all trimesters 1

Severe Renal Impairment:

• Quinine dosing adjustment: One loading dose of 648 mg, then 324 mg every 12 hours starting 12 hours after loading dose 5

Very Young Children (<3 years) and Underweight:

• These patients achieve 23-53% lower day 7 lumefantrine concentrations and are at higher risk of treatment failure 6
• Consider extending AL treatment to 5 days (Swiss guidelines recommendation) 1, 3

Critical Pitfalls to Avoid

Fat intake with AL: Failure to take AL with fatty food results in subtherapeutic drug levels—this is the most common preventable cause of treatment failure 2, 3, 4, 6

QTc prolongation: Both AL and DP prolong QTc interval—avoid in patients with baseline QTc prolongation or taking QTc-prolonging medications 1, 2

Post-artemisinin delayed hemolysis (PADH): Monitor hemoglobin, haptoglobin, and LDH on days 7,14,21, and 28 after treatment—occurs in 37.4% using strict definitions 1, 2, 3

G6PD testing: Always test before giving primaquine or tafenoquine to prevent severe hemolytic anemia 1, 3

Body weight considerations: Patients >75 kg require 4 tablets daily of DP (not 3), and very young/underweight children may need extended AL regimens 1, 6

Supervised vs. unsupervised treatment: Unsupervised treatment results in 44% lower day 7 lumefantrine concentrations—ensure adherence counseling 6