What is the recommended dosage and regimen for Malarone (atovaquone/proguanil) for malaria prevention?

Malarone (Atovaquone-Proguanil) for Malaria Prevention

Recommended Dosage and Regimen

For malaria prophylaxis, adults should take one Malarone tablet (250 mg atovaquone/100 mg proguanil) daily, starting 1-2 days before entering a malarious area, continuing daily throughout the stay, and for only 7 days after leaving the endemic region. 1

Adult Dosing

• One tablet daily (250 mg atovaquone/100 mg proguanil hydrochloride) 1
• Take at the same time each day with food or a milky drink 1
• If vomiting occurs within 1 hour of dosing, repeat the dose 1

Pediatric Weight-Based Dosing

• 11-20 kg: 1 pediatric tablet daily (62.5 mg atovaquone/25 mg proguanil) 2
• 21-30 kg: 2 pediatric tablets daily 2
• 31-40 kg: 3 pediatric tablets daily 2
• >40 kg: 4 pediatric tablets daily (adult dose) 2

Timing Protocol

The key advantage of Malarone over other antimalarials is the shortened post-travel duration—only 7 days versus 4 weeks for alternatives. 1, 3

Start-Stop Algorithm

• Pre-travel: Begin 1-2 days before entering malarious area 1
• During travel: Continue daily throughout stay 1
• Post-travel: Continue for only 7 days after departure 1, 4

This shortened post-travel regimen is possible because both atovaquone and proguanil are active against hepatic (pre-erythrocytic) stages of P. falciparum, providing causal prophylaxis rather than just suppressive prophylaxis 3

Clinical Efficacy

Malarone demonstrates 98-100% prophylactic efficacy against P. falciparum malaria, including chloroquine-resistant and mefloquine-resistant strains. 3, 5

• In placebo-controlled trials in Zambia, prophylaxis success rate was 98% versus 63% for placebo 5
• No cases of breakthrough malaria occurred in nonimmune travelers taking Malarone in comparative trials 3
• Efficacy is maintained against drug-resistant strains with no cross-resistance to other antimalarials 3, 6

Special Populations and Contraindications

Renal Impairment

• Severe renal impairment (CrCl <30 mL/min): Do not use for prophylaxis 1
• Mild-moderate impairment (CrCl 30-80 mL/min): No dosage adjustment needed 1

Hepatic Impairment

• Mild-moderate: No dosage adjustment needed 1
• Severe: No data available; use with caution 1

Pregnancy and Children

• Safety in pregnancy not established; chloroquine remains the preferred option for pregnant women 4
• Not recommended for children <11 kg 2

Comparative Advantages Over Alternatives

Malarone offers superior tolerability compared to mefloquine and chloroquine-proguanil combinations, with significantly fewer treatment discontinuations due to adverse events. 3

Tolerability Profile

• Gastrointestinal events: Significantly fewer than chloroquine plus proguanil 3
• Neuropsychiatric events: Significantly fewer than mefloquine 3
• Most common adverse events (headache, abdominal pain) occur at rates similar to placebo 3, 5
• No withdrawals due to treatment-related adverse events in clinical trials 5

Versus Mefloquine

• Mefloquine requires weekly dosing starting 1-2 weeks before travel and continuing 4 weeks after 4
• Mefloquine has 0.01%-higher risk of neuropsychiatric effects (70% occurring in first three doses) 4, 7
• Mefloquine contraindicated in those with seizure history, psychiatric disorders, or requiring precision movements 4

Versus Doxycycline

• Doxycycline requires 4 weeks post-travel prophylaxis versus 7 days for Malarone 4
• Doxycycline causes photosensitivity that can be severe and prolonged 7, 4
• Doxycycline contraindicated in pregnancy and children <8 years 4

Critical Pitfalls to Avoid

• Never stop early: Complete the full 7-day post-travel course even if asymptomatic 4, 1
• Food requirement: Always take with food or milky drink to optimize absorption 1
• Repeat if vomiting: If vomiting within 1 hour, take another dose 1
• Not for relapsing malaria: Malarone does not prevent relapses from P. vivax or P. ovale liver stages; primaquine needed after G6PD testing 4
• Severe renal impairment: Absolute contraindication for prophylaxis 1

Alternative Dosing for Long-Term Travelers

Emerging evidence suggests twice-weekly Malarone may be effective for long-term travelers, though this is off-label and not FDA-approved. 8

• Observational study in West Africa showed 0/391 person-months malaria incidence with twice-weekly dosing versus 11.7/1000 person-months with no prophylaxis 8
• This approach may improve adherence in long-term expatriates unwilling to take daily medication 8
• However, daily dosing remains the only FDA-approved and guideline-recommended regimen 1, 4