What is the recommended dosage and administration of Malarone (atovaquone/proguanil) for malaria prophylaxis?

Malarone (Atovaquone-Proguanil) for Malaria Prophylaxis

For malaria prophylaxis, adults should take one Malarone tablet (250 mg atovaquone/100 mg proguanil) daily starting 1-2 days before travel, continuing daily throughout the stay, and for only 7 days after leaving the malarious area—a major advantage over other antimalarials that require 4 weeks post-travel. 1

Dosing by Weight and Age

Adults and Children >40 kg

• One adult-strength tablet daily (250 mg atovaquone/100 mg proguanil) 1
• Start 1-2 days before entering endemic area 2, 1
• Continue throughout stay 1
• Stop after only 7 days post-departure (not 4 weeks like other drugs) 2, 1

Pediatric Weight-Based Dosing

The CDC provides specific weight-based dosing using pediatric tablets (62.5 mg atovaquone/25 mg proguanil): 3

• 11-20 kg: 1 pediatric tablet daily
• 21-30 kg: 2 pediatric tablets daily
• 31-40 kg: 3 pediatric tablets daily
• >40 kg: 1 adult tablet daily (same as adult dose)

Children <11 kg should not receive Malarone; use chloroquine instead in chloroquine-sensitive areas. 3

Administration Details

• Take at the same time each day with food or a milky drink to enhance absorption and reduce gastrointestinal side effects 1
• If vomiting occurs within 1 hour of dosing, repeat the dose immediately 1
• The short post-travel duration (7 days vs 4 weeks) significantly improves compliance compared to mefloquine or doxycycline 2, 4

When to Choose Malarone Over Alternatives

Malarone is a first-line option for chloroquine-resistant malaria areas, alongside mefloquine and doxycycline. 2 However, Malarone has distinct advantages:

Superiority in Tolerability

• Significantly fewer neuropsychiatric adverse events than mefloquine (which causes severe effects in 0.01%-higher of users, with 70% occurring in first 3 doses) 2, 4
• Significantly fewer gastrointestinal adverse events than chloroquine plus proguanil 4
• Fewer treatment discontinuations due to adverse events compared to both mefloquine and chloroquine-proguanil combinations 4

Unique Mechanism and Resistance Profile

• No cross-resistance with other antimalarials because it acts via mitochondrial cytochrome bc complex inhibition, a different mechanism than chloroquine, mefloquine, or doxycycline 5
• 100% efficacy against P. falciparum in clinical trials of nonimmune travelers, matching mefloquine but superior to chloroquine-proguanil (70% efficacy) 4
• 95-100% efficacy in semi-immune populations from endemic regions 4

Causal Prophylaxis Advantage

Both atovaquone and proguanil are active against hepatic (pre-erythrocytic) stages of P. falciparum, providing true causal prophylaxis and eliminating the need for prolonged post-travel treatment. 4 This is why only 7 days post-travel is required versus 4 weeks for drugs that only suppress blood-stage parasites. 2, 1

Contraindications and Special Populations

Severe Renal Impairment

• Do not use for prophylaxis if creatinine clearance <30 mL/min 1
• May use with caution for treatment (not prophylaxis) 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 for mild-to-moderate hepatic impairment 1
• No data available for severe hepatic impairment 1

Pregnancy

• Pregnant women should use chloroquine as the safest option in chloroquine-sensitive areas 2
• Malarone is not recommended as first-line in pregnancy due to limited safety data 2

Critical Pitfalls to Avoid

Never Stop Early

• The most common cause of malaria deaths in travelers is non-compliance with prophylaxis regimens 2, 6
• Even though Malarone only requires 7 days post-travel (versus 4 weeks for others), complete the full 7-day post-exposure course 2, 1
• Starting 1-2 days before travel (not just on arrival) ensures adequate blood levels upon exposure 1

Does Not Prevent Relapsing Malaria

• Malarone does not eliminate dormant liver stages (hypnozoites) of P. vivax or P. ovale 6
• For areas with these species, consider primaquine 30 mg base daily during the last 2 weeks of prophylaxis after mandatory G6PD testing 2
• Primaquine is contraindicated in pregnancy and G6PD deficiency 2

Combine with Personal Protection

• No chemoprophylaxis provides 100% protection 6
• Use DEET-containing repellents on exposed skin, wear long sleeves/pants after sunset, sleep under permethrin-treated bed nets, and stay in well-screened areas between dusk and dawn 2
• Seek immediate medical evaluation if fever develops during or after travel, even while taking prophylaxis 6

Emerging Evidence on Alternative Dosing

One observational study in West African expatriates found zero malaria cases with twice-weekly Malarone (0/391 person-months) compared to 11.7/1000 person-months in the no-prophylaxis group and 2.06/1000 in the mefloquine group. 7 However, this is not FDA-approved or guideline-recommended; daily dosing remains the standard. 1 This may be considered only for long-term travelers with documented poor adherence to daily regimens, but requires shared decision-making about off-label use.