Neurologic Side Effects of Malarone (Atovaquone-Proguanil)
Malarone (atovaquone-proguanil) can cause neurologic side effects including headache (10%), dizziness (5%), and rarely more serious reactions such as hallucinations and seizures, though these serious effects are less common than with other antimalarials like mefloquine. 1
Common Neurologic Side Effects
The FDA-approved drug label for atovaquone-proguanil identifies several neurologic adverse effects that can occur during treatment or prophylaxis:
- Headache: Occurs in approximately 10% of adults treated for malaria and is one of the most commonly reported adverse experiences in prophylactic use 1
- Dizziness: Reported in about 5% of adults treated for malaria 1
- Asthenia (weakness): Observed in 8% of adults receiving treatment doses 1
Comparison with Other Antimalarials
Malarone has a more favorable neuropsychiatric side effect profile compared to other antimalarials:
- Significantly fewer neuropsychiatric adverse events were reported with atovaquone-proguanil than with mefloquine in clinical trials 1, 2
- Unlike mefloquine, which has been associated with serious neuropsychiatric effects including hallucinations and convulsions even at prophylactic doses, these reactions are much less common with Malarone 3
Risk Factors and Monitoring
Certain factors may increase the risk of neurologic side effects:
- Higher treatment doses of atovaquone-proguanil were less well tolerated than lower prophylactic doses 1
- Absorption of atovaquone may be reduced in patients with diarrhea or vomiting, potentially affecting efficacy rather than side effects 1
Management of Neurologic Side Effects
If neurologic side effects occur:
- Most mild neurologic side effects (headache, dizziness) are transient and self-limited 3
- For persistent or severe neurologic symptoms, discontinuation of the medication may be necessary
- Treatment was discontinued prematurely due to adverse experiences in only 4 of 436 adults treated with atovaquone-proguanil 1
Special Populations
Children: Neurologic side effects appear less common in pediatric populations. In studies of children receiving Malarone, headache was reported in 13% of cases, but other neurologic side effects were not prominently reported 1
Pregnant women: Limited data exists on neurologic side effects specifically in pregnant women
Rare but Serious Neurologic Effects
The FDA label notes that "rare serious adverse events such as hepatitis, severe skin reactions, neurological, and hematological events have been reported when atovaquone and proguanil hydrochloride was used for the prophylaxis or treatment of malaria" 1
Drug Interactions Affecting Neurologic Side Effects
- Concomitant administration of rifampin or rifabutin reduces atovaquone levels by approximately 50% and 34%, respectively, which could potentially affect both efficacy and side effect profiles 1
- Tetracycline has been associated with approximately a 40% reduction in plasma concentrations of atovaquone 1
Conclusion
While Malarone can cause neurologic side effects, it generally has a favorable neurologic safety profile compared to other antimalarials like mefloquine. Headache and dizziness are the most common neurologic adverse effects, with serious neurologic reactions being rare. This favorable neuropsychiatric profile makes it a preferred option for many travelers requiring malaria prophylaxis or treatment 2, 4.