Malarone (Atovaquone/Proguanil) Dosing and Usage
Malarone is highly effective for both malaria prevention and treatment, with prophylaxis requiring one adult tablet (250mg/100mg) daily starting 1-2 days before travel and continuing for only 7 days after leaving endemic areas, while treatment requires 4 adult tablets once daily for 3 consecutive days. 1
Prophylaxis Dosing
Adults
- One adult tablet (250mg atovaquone/100mg proguanil) once daily 1
- Start 1-2 days before entering malaria-endemic area 1
- Continue daily during stay 1
- Continue for only 7 days after return (major advantage over other antimalarials) 1, 2
- Take at same time each day with food or milky drink 1
Pediatric Prophylaxis (Weight-Based)
- 11-20 kg: 1 pediatric tablet (62.5mg/25mg) daily 3
- 21-30 kg: 2 pediatric tablets daily 3
- 31-40 kg: 3 pediatric tablets daily 3
- >40 kg: 1 adult tablet daily 3
Key Prophylaxis Advantage
The 7-day post-travel continuation is significantly shorter than the 4-week requirement for chloroquine or mefloquine because both atovaquone and proguanil are active against hepatic (pre-erythrocytic) stages of P. falciparum, providing causal prophylaxis. 2
Treatment Dosing for Acute Uncomplicated Malaria
Adults
- 4 adult tablets (total 1000mg atovaquone/400mg proguanil) once daily for 3 consecutive days 1
- Take as single daily dose with food 1
Pediatric Treatment (Weight-Based)
- 5-8 kg: 2 pediatric tablets × 3 days 3
- 9-10 kg: 3 pediatric tablets × 3 days 3
- 11-20 kg: 4 pediatric tablets or 1 adult tablet × 3 days 3
- 21-30 kg: 2 adult tablets × 3 days 3
- 31-40 kg: 3 adult tablets × 3 days 3
- >40 kg: 4 adult tablets × 3 days 3
Clinical Efficacy
Prophylaxis Effectiveness
- 100% protective efficacy against P. falciparum in nonimmune travelers in comparative trials 2
- 84% protective efficacy for P. vivax, 96% for P. falciparum, and 93% overall in migrants to Papua, Indonesia 4
- 98% prophylaxis success rate versus 63% for placebo in Zambian field trial 5
Treatment Effectiveness
- >98% cure rate for uncomplicated P. falciparum malaria in over 500 patients 6
- Significantly more effective than mefloquine, amodiaquine, chloroquine, or chloroquine plus pyrimethamine/sulfadoxine in head-to-head trials 6
Special Populations and Contraindications
Renal Impairment
- Do NOT use for prophylaxis if creatinine clearance <30 mL/min 1
- May use with caution for treatment in severe renal impairment only if benefits outweigh risks 1
- No dose adjustment needed for mild (CrCl 50-80) or moderate (CrCl 30-50) renal impairment 1
Hepatic Impairment
- No dose adjustment needed for mild to moderate hepatic impairment 1
- No data available for severe hepatic impairment 1
Pregnancy and Children
- Treatment data in HIV-infected children shows efficacy across age groups 3
- Pediatric formulation available for children ≥11 kg 3
Important Clinical Considerations
Administration Details
- If vomiting occurs within 1 hour of dosing, repeat the dose 1
- Must be taken with food or milky drink to optimize absorption 1
Geographic Applicability
Malarone is the preferred agent for chloroquine-resistant areas (essentially all malaria-endemic regions except north of Panama Canal), which includes most of sub-Saharan Africa and Southeast Asia. 3
Tolerability Advantage
- Significantly fewer gastrointestinal adverse events than chloroquine plus proguanil 2
- Significantly fewer neuropsychiatric adverse events than mefloquine 2
- Most common adverse events (headache, abdominal pain) occur at similar rates to placebo 2, 5
- Significantly fewer treatment discontinuations due to adverse events compared to chloroquine plus proguanil or mefloquine 2
Common Pitfalls to Avoid
Critical Compliance Issues
- Most malaria deaths occur in travelers who do not fully comply with prophylaxis regimens 7
- Even with the shorter 7-day post-travel period, patients must complete the full course 2
Resistance Considerations
- Highly effective against drug-resistant P. falciparum strains 2
- No cross-resistance observed between atovaquone and other antimalarial agents 2
- Parasites that recrudesce after combination therapy are not resistant to atovaquone in vitro (unlike monotherapy) 6
Limitations
- Does not prevent relapses from P. vivax or P. ovale liver hypnozoites 7
- For prolonged P. vivax/P. ovale exposure, consider adding primaquine 15mg base daily for 14 days as terminal prophylaxis after G6PD testing 8
- No prophylactic regimen guarantees complete protection; patients must use insect repellents, protective clothing, and seek immediate evaluation for fever during or after travel 7