Malarone vs Mefloquine (Lariam): Side Effects, Cost & Effectiveness Compared

Malarone is the better-tolerated choice for most travelers, while mefloquine (brand name Lariam) works best for long trips or tight budgets. As a physician, I recommend Malarone as the first-line option for most of my patients because it causes significantly fewer neuropsychiatric side effects: a head-to-head clinical trial published in Clinical Infectious Diseases found that 29% of mefloquine users experienced neuropsychiatric adverse events compared to just 14% of Malarone users (P=.001). Both medications are over 90% effective at preventing malaria, and both are recommended by the CDC. The biggest differences come down to dosing schedule (Malarone is daily, mefloquine is weekly), side effect profile, and cost. Mefloquine costs roughly $33 for a 10-week supply versus $43 or more for a 30-day supply of generic Malarone, making mefloquine the more affordable option for extended travel.

What Are Malarone and Mefloquine?

Malarone and mefloquine are two antimalarials (malaria prevention medications) that your doctor might prescribe before a trip to a malaria-endemic region. Malarone is the brand name for atovaquone-proguanil, a combination drug that attacks the malaria parasite at two stages of its life cycle. It was approved by the FDA in 2000 and has become one of the most commonly prescribed antimalarials for travel. Mefloquine was originally developed by the U.S. Army in the 1970s and sold under the brand name Lariam. It's a quinoline-based antimalarial that kills the parasite inside red blood cells. In 2013, the FDA added a boxed warning to mefloquine for potential neuropsychiatric side effects, which reshaped how physicians prescribe it. Both medications require a prescription, and both are available in generic form.

How They Compare: The Key Differences

Malarone and mefloquine differ in meaningful ways for travelers. Here's the side-by-side comparison that matters when choosing between these two antimalarials.

Side Effects: Why This Matters More Than You Think

Mefloquine's side effect profile is the primary reason most physicians now prescribe Malarone. A landmark randomized controlled trial comparing the two medications, published in Clinical Infectious Diseases, found that neuropsychiatric adverse events occurred in 29% of mefloquine users versus 14% of Malarone users, a statistically significant difference (P=.001). The discontinuation rate due to adverse events was also dramatically different: 5.0% for mefloquine versus just 1.2% for Malarone (P=.001).

Malarone's common side effects are typically mild and gastrointestinal: nausea, abdominal pain, headache, and occasionally diarrhea. In my clinical experience, most patients tolerate Malarone well, and side effects tend to resolve within the first few days of use.

Mefloquine's side effects can be more disruptive. Beyond the GI symptoms it shares with most antimalarials, mefloquine is known for causing vivid or disturbing dreams, insomnia, dizziness, anxiety, and in rare cases, more severe neuropsychiatric reactions including depression, hallucinations, and psychosis. The FDA's 2013 boxed warning specifically addresses these risks, noting that neurologic side effects can persist long after the medication is stopped. Mefloquine should not be prescribed to travelers with a history of depression, anxiety disorders, psychosis, or seizures.

Cost Comparison: Daily vs Weekly Adds Up

Mefloquine has a meaningful cost advantage, especially for longer trips. Because mefloquine is dosed weekly rather than daily, you need far fewer tablets for the same trip duration.

For a 2-week trip:

• Malarone: approximately 21 tablets (14 travel days + 7 days after). Generic cost: roughly $30–$170.
• Mefloquine: approximately 6–7 tablets (2–3 pre-travel + 2 during + 4 after). Generic cost: roughly $20–$85.

For a 3-month trip:

• Malarone: approximately 97 tablets. Generic cost: can exceed $300–$700+.
• Mefloquine: approximately 16–17 tablets. Generic cost: roughly $55–$200.

The longer your trip, the wider the cost gap. For travelers spending months abroad, mefloquine's weekly dosing translates into substantial savings. That said, cost should never be the only factor. If mefloquine's side effects disrupt your trip, no amount of savings is worth it. Through Wandr Health, you can search your destination and get evidence-based recommendations, often saving hundreds compared to a traditional travel clinic visit.

Effectiveness: Both Prevent Malaria Well

Malarone and mefloquine are both highly effective antimalarials recommended by the CDC for travel to regions with chloroquine-resistant Plasmodium falciparum malaria, which includes most of sub-Saharan Africa, South Asia, and parts of South America and Oceania. Malarone's efficacy is generally cited above 95%, while mefloquine's efficacy ranges from 90% to 95% in most studies. One important caveat: mefloquine resistance has been documented in parts of Southeast Asia, particularly along the Thailand-Myanmar and Thailand-Cambodia borders. The CDC specifically advises against mefloquine for these regions. Malarone remains effective in areas with mefloquine resistance, making it the preferred option for travelers to Southeast Asia.

Who Should Choose Malarone?

Malarone is the better fit for most short-to-medium-length trips and for travelers who prioritize tolerability. Consider Malarone if you're traveling for 1 to 4 weeks, prefer a medication with fewer reported side effects, are heading to Southeast Asia (where mefloquine resistance exists), have a history of depression, anxiety, or other psychiatric conditions, or want the convenience of a shorter post-travel course (7 days versus 4 weeks). As a physician, I almost exclusively prescribe Malarone because most of my patients are taking trips of 2 to 3 weeks, and the tolerability difference is clinically significant.

Who Should Choose Mefloquine?

Mefloquine remains a valid and important option for specific traveler profiles. Consider mefloquine if you're traveling for several months and daily dosing is impractical or expensive, you're pregnant in the second or third trimester and traveling to a chloroquine-resistant area (mefloquine is the only recommended option in this scenario, per CDC guidelines), you've taken mefloquine before without side effects, or budget is a primary concern. The weekly dosing schedule is genuinely convenient for long-term travelers. Taking one pill every week is simpler than remembering a daily tablet, and some travelers find that easier to maintain over months of travel.

Pregnancy and Special Populations

Mefloquine holds a unique position among antimalarials: it is currently the only option the CDC recommends for pregnant travelers in their second and third trimester visiting chloroquine-resistant malaria zones. Malarone lacks sufficient safety data in pregnancy, and doxycycline (the other common antimalarial) is contraindicated during pregnancy. For travelers who are breastfeeding, mefloquine is also considered acceptable if the infant weighs more than 5 kg. If you're pregnant or planning to become pregnant and traveling to a malaria-endemic area, consult with your physician early. Through Wandr, you can connect with a prescribing physician who can evaluate your specific situation and destination.

FAQ: Malarone vs Mefloquine

Is mefloquine still safe to take? Mefloquine is still FDA-approved and CDC-recommended for malaria prevention. The 2013 boxed warning highlights neuropsychiatric risks, but many travelers tolerate it without issues. Your physician should screen for psychiatric history before prescribing. It remains the only option for pregnant travelers in chloroquine-resistant regions.

Why did Lariam get a black box warning? The FDA added a boxed warning to mefloquine (Lariam) in 2013 after reports of serious neuropsychiatric side effects including anxiety, depression, hallucinations, and psychosis. Some effects persisted after stopping the medication. The warning ensures physicians discuss these risks before prescribing.

Can I switch from mefloquine to Malarone mid-trip? Yes, but consult your physician first. Because mefloquine has a long half-life (approximately 2 to 3 weeks), your doctor can help you time the transition correctly so you maintain continuous malaria protection without a gap in coverage.

Which malaria pill has fewer side effects? Malarone has a significantly better side effect profile. Clinical trial data shows neuropsychiatric adverse events in 14% of Malarone users versus 29% of mefloquine users. Only 1.2% of Malarone users discontinued due to side effects, compared to 5.0% of mefloquine users.

Is mefloquine cheaper than Malarone? Yes. Generic mefloquine costs roughly $33 for 10 tablets (a 10-week supply). Generic Malarone starts around $43 for 30 tablets (a 30-day supply). For a 3-month trip, mefloquine can cost $55 to $200 versus $300 to $700+ for Malarone.

Does mefloquine cause vivid dreams? Vivid or disturbing dreams are one of the most commonly reported mefloquine side effects. Clinical studies document sleep disturbances in a significant percentage of users. If vivid dreams become distressing, contact your physician about switching medications.

Can I take mefloquine if I have anxiety? The CDC and FDA advise against prescribing mefloquine to individuals with a history of anxiety disorders, depression, psychosis, or seizures. Malarone or doxycycline are safer alternatives for travelers with psychiatric history. Always disclose your full medical history to your prescribing physician.

How far in advance should I start mefloquine? Start mefloquine 2 to 3 weeks before entering a malaria zone. This lead time allows the medication to reach protective levels in your blood and gives you time to identify any side effects before departure. Malarone, by comparison, only requires 1 to 2 days of lead time.

Sources

1. CDC. Malaria Prevention — Choosing a Drug to Prevent Malaria. Centers for Disease Control and Prevention. Updated 2024. https://www.cdc.gov/malaria/prevention/drug-choice.html
2. Overbosch D, Schilthuis H, Bienzle U, et al. Atovaquone-Proguanil versus Mefloquine for Malaria Prophylaxis in Nonimmune Travelers: Results from a Randomized, Double-Blind Study. Clinical Infectious Diseases. 2001;33(7):1015-1021. https://doi.org/10.1086/322694
3. FDA. FDA Drug Safety Communication: FDA approves updated Lariam (mefloquine) labeling with boxed warning. U.S. Food and Drug Administration. 2013. https://www.fda.gov/drugs/drug-safety-and-availability/
4. WHO. International Travel and Health — Malaria. World Health Organization. https://www.who.int/health-topics/malaria
5. Schlagenhauf P, Adamcova M, Engbersen J, et al. Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa. Malaria Journal. 2003;2(1):16.

About the Author

Alec Freling, MD is an emergency medicine physician and the founder of Wandr Health. With years of experience treating returning travelers in the ER, including cases of severe malaria, Dr. Freling built Wandr to make travel health accessible, affordable, and hassle-free. Every article is written from real clinical experience, not copied from a textbook.

Medical Disclaimer

This article is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting any medication, including antimalarials. Individual health conditions, travel itineraries, and medication interactions may affect which antimalarial is right for you. Wandr Health connects you with licensed physicians who can evaluate your specific needs.