Classifications of Antimalarial Medications
Primary Classification by Disease Severity
Antimalarial drugs are classified into two main categories based on disease severity: treatments for uncomplicated malaria and treatments for severe malaria, with artemisinin-based combination therapies (ACTs) serving as first-line therapy for uncomplicated P. falciparum malaria and intravenous artesunate for severe disease. 1, 2
First-Line Agents for Uncomplicated P. falciparum Malaria
Artemisinin-Based Combination Therapies (ACTs)
Artemether-lumefantrine (AL) is the most widely adopted ACT regimen, administered as 4 tablets at 0 hours, 4 tablets at 8 hours on day 1, then 4 tablets twice daily on days 2-3, with cure rates of 96-100%. 1, 2 This medication must be taken with a fatty meal or drink to ensure adequate absorption—failure to do so is the most common cause of treatment failure. 1, 3
Dihydroartemisinin-piperaquine (DP) is an alternative first-line ACT with superior efficacy in preventing P. vivax recurrence (RR 0.32,95% CI 0.24-0.43 compared to AL). 1, 2 Dosing is 3 tablets daily for 3 days (36-75 kg) or 4 tablets daily for 3 days (>75 kg), taken in a fasting condition. 1
Critical caveat: Both AL and DP can cause QTc prolongation and should be avoided in patients at risk or taking QT-prolonging medications. 1, 3
Second-Line Agents for Uncomplicated Malaria
Atovaquone-proguanil is recommended for patients with contraindications to ACTs or those from Southeast Asia (especially Greater Mekong sub-region) with high ACT resistance levels. 4, 2 Dosing is 4 tablets daily for 3 days (>40 kg), taken with a fatty meal. 2, 3
Quinine sulfate plus doxycycline serves as an alternative regimen, with quinine dosed at 648 mg (two capsules) every 8 hours for 7 days. 2, 5 The FDA specifically indicates quinine sulfate for treatment of uncomplicated P. falciparum malaria in chloroquine-resistant regions. 5
Treatments for Non-Falciparum Species
Blood Schizontocides
Chloroquine remains the drug of choice for P. vivax, P. ovale, and P. malariae in chloroquine-sensitive regions, with a total dose of 25 mg base/kg over 3 days (1000 mg salt initially, then 500 mg at 6,24, and 48 hours). 1, 2, 3
In chloroquine-resistant regions (Papua New Guinea, Indonesia, Sabah where failure exceeds 10%), ACTs are recommended instead. 4, 1
Anti-Relapse Agents (Hypnozoitocides)
Primaquine is mandatory following blood schizontocidal treatment for P. vivax and P. ovale to eliminate liver hypnozoites, dosed at 30 mg base daily for 14 days. 1, 2, 3 Critical safety requirement: G6PD testing must be performed before administration to prevent severe hemolysis. 1, 3
Tafenoquine is an alternative requiring quantitative G6PD >70%, but is not widely available outside the US/Australia. 1
Both primaquine and tafenoquine are absolutely contraindicated in pregnancy. 1, 3
Treatments for Severe Malaria
Intravenous artesunate is the first-line treatment for all forms of severe malaria, dosed at 2.4 mg/kg IV at 0,12, and 24 hours, then daily until parasite density is <1% and the patient can take oral medication. 1, 2 Once clinically improved, treatment should be completed with a full course of oral ACT. 1
Intravenous quinine serves as a second-line option with a loading dose of 20 mg salt/kg over 4 hours, then maintenance dose of 10 mg/kg over 4 hours every 8 hours. 2
Special Population Considerations
Pregnancy
AL is recommended as a treatment option in all trimesters of pregnancy by WHO and CDC, with cure rates of 94.9-100% and no increased risk of adverse pregnancy outcomes. 1, 2, 3 Multiple trials found no association between ACT treatment and congenital malformations or miscarriage in second/third trimester. 1
Renal Impairment
For severe chronic renal impairment, quinine dosing should be reduced to one loading dose of 648 mg followed 12 hours later by 324 mg every 12 hours for 7 days. 5
High Body Weight Patients
Swiss guidelines recommend extending AL treatment to 5 days (four additional doses) in patients with high body weight or suspected malabsorption due to concerns about subtherapeutic lumefantrine concentrations. 4, 1
Critical Monitoring Requirements
Post-artemisinin delayed hemolysis (PADH) occurs in 37.4% of patients using strict definitions and requires monitoring on days 7,14,21, and 28 after treatment. 1, 3 This is the most serious adverse event associated with ACTs. 4
Common pitfall: Not testing for G6PD deficiency before primaquine administration can cause life-threatening hemolysis, particularly in Asian populations with severe G6PD deficiency. 3