What are the key uses of mefloquine for malaria prevention. How effective is mefloquine as an antimalarial prophylactic. What are the main side effects and safety concerns associated with mefloquine use. What are the recommended alternatives to mefloquine for malaria chemoprophylaxis. How do international health organizations currently view the use of mefloquine.

The Global Burden of Malaria and Need for Prophylaxis

Malaria continues to pose a significant global health challenge, particularly in Africa and parts of Southeast Asia. According to the World Health Organization (WHO), there were an estimated 229 million cases of malaria worldwide in 2019, with Africa accounting for 94% of cases. While progress has been made in reducing the malaria burden in some regions, effective prevention and treatment remain crucial.

Early diagnosis and prompt treatment form the cornerstone of malaria management. However, for travelers to endemic areas, chemoprophylaxis plays a vital role in preventing infection. As international travel has increased exponentially in recent years, the need for safe and effective antimalarial prophylaxis has become even more important.

Mefloquine: Development and Early Use

Mefloquine emerged as an antimalarial drug in the 1970s, developed by the United States military to address the growing threat of chloroquine-resistant Plasmodium strains. Its once-weekly dosing regimen made it an attractive option for prophylaxis, particularly for military personnel deployed to malaria-endemic regions.

How did mefloquine initially gain popularity as an antimalarial? The drug’s effectiveness against chloroquine-resistant parasites and its convenient dosing schedule contributed to its widespread adoption. For about a decade after its introduction, mefloquine was considered a first-line option for malaria prevention in many settings.

Emerging Concerns: Neuropsychiatric Side Effects

Despite its initial promise, reports of significant side effects associated with mefloquine use began to surface within a decade of its introduction. Of particular concern were the drug’s neuropsychiatric effects, which ranged from mild to severe.

What are the main neuropsychiatric side effects linked to mefloquine use?

• Anxiety
• Sleep disturbances
• Depression
• Dizziness
• Psychosis (in rare cases)

These side effects appear to be more pronounced in individuals with pre-existing psychiatric conditions. The severity and persistence of these adverse reactions have led many countries, including the United States and United Kingdom, to update their prescribing information for mefloquine, adding prominent warnings about potential neuropsychiatric effects.

Current Recommendations for Malaria Prophylaxis

Given the concerns surrounding mefloquine, international health organizations have revised their guidelines for malaria chemoprophylaxis. The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) now recommend several options for travelers to malaria-endemic areas:

1. Atovaquone-proguanil
2. Doxycycline
3. Chloroquine (in areas without chloroquine resistance)
4. Mefloquine (with caution)
5. Tafenoquine (a newer option)

How do these alternatives compare to mefloquine in terms of efficacy and safety? While all listed options can provide effective protection against malaria, their side effect profiles and contraindications vary. Atovaquone-proguanil and doxycycline are generally well-tolerated and have become preferred options for many travelers. Chloroquine remains useful in areas without resistant parasites, while tafenoquine offers a new alternative with its own set of considerations.

Special Considerations for Long-Term Use

For individuals requiring long-term malaria prophylaxis, such as expatriates or military personnel on extended deployments, the choice of antimalarial becomes even more critical. The WHO notes that while the list of recommended drugs remains the same for long-term use, special attention must be paid to potential side effects when a drug is taken for more than six months.

What factors should be considered for long-term malaria prophylaxis?

• Efficacy against local Plasmodium strains
• Tolerability and side effect profile
• Adherence to dosing schedule
• Individual health factors and contraindications
• Cost and availability

Mefloquine Use in Military Populations

The use of mefloquine in military settings has been a subject of particular scrutiny. Given the drug’s history of development for military use and its once-weekly dosing, it was initially favored for deployed troops. However, the emergence of neuropsychiatric side effects has led to a reevaluation of its role in this context.

According to current CDC guidelines for the U.S. military, atovaquone-proguanil is now the preferred choice for both short- and long-term deployments in high-transmission areas. This shift reflects the growing concern over mefloquine’s side effect profile and the availability of safer alternatives.

Alternatives for Military Personnel

For service members unable to take atovaquone-proguanil, doxycycline is often recommended as an alternative. The choice of prophylactic regimen may also depend on the specific deployment location, duration, and individual health factors. Military medical authorities typically provide guidance tailored to each mission’s requirements.

Reassessing Mefloquine’s Role in Malaria Prevention

The accumulating evidence regarding mefloquine’s side effects has prompted a global reassessment of its place in malaria prevention strategies. While the drug remains effective against many Plasmodium strains, its risk-benefit profile has shifted in light of newer, safer alternatives.

Why is there a need to revisit mefloquine use in national drug policies? The potential for severe and long-lasting neuropsychiatric effects, particularly in vulnerable populations, raises ethical and practical concerns. Countries must weigh the drug’s benefits against its risks, considering local malaria epidemiology, healthcare infrastructure, and available alternatives.

Updating Guidelines and Prescribing Practices

Many countries have already taken steps to update their guidelines on mefloquine use. These updates typically include:

• Stronger warnings about potential neuropsychiatric side effects
• Recommendations for careful screening of patients before prescribing mefloquine
• Guidance on monitoring patients for adverse reactions during use
• Emphasis on considering alternative prophylactic options when appropriate

Healthcare providers are encouraged to have thorough discussions with patients about the risks and benefits of mefloquine, as well as available alternatives, before prescribing the drug for malaria prophylaxis.

The Future of Malaria Chemoprophylaxis

As the global health community continues to combat malaria, research into new and improved prophylactic options remains crucial. The ideal antimalarial drug would combine high efficacy, excellent safety profile, and convenient dosing to ensure optimal protection and adherence.

What advancements are being made in malaria prevention? Ongoing research efforts focus on several areas:

• Development of new antimalarial compounds with novel mechanisms of action
• Improvement of existing drugs to enhance their safety and efficacy
• Exploration of combination therapies for prophylaxis
• Investigation of long-acting formulations to improve adherence
• Advancement of malaria vaccine technologies

While mefloquine may continue to play a role in certain situations, its use is likely to become increasingly limited as safer and equally effective alternatives become available. The ultimate goal remains the development of a highly effective, well-tolerated, and easily administered prophylactic regimen that can protect travelers and vulnerable populations from this persistent global health threat.

Balancing Efficacy and Safety in Malaria Prevention

The ongoing debate surrounding mefloquine highlights the complex challenges in malaria prevention. While the drug’s efficacy against various Plasmodium strains remains valuable, the potential for serious side effects necessitates a careful risk-benefit analysis for each individual case.

How can healthcare providers strike the right balance when recommending malaria prophylaxis? A personalized approach is key, taking into account factors such as:

• The specific destination and local malaria transmission patterns
• Duration of travel or exposure
• Individual health history, including any pre-existing conditions
• Potential drug interactions with other medications
• Patient preferences and likelihood of adherence to the chosen regimen

By carefully weighing these factors and engaging in thorough discussions with patients, healthcare providers can help ensure that the chosen prophylactic strategy offers the best possible protection with minimal risk.

The Role of Patient Education

Regardless of the chosen prophylactic regimen, patient education plays a crucial role in ensuring effective malaria prevention. Travelers should be well-informed about:

• The importance of adherence to the prescribed medication schedule
• Potential side effects and when to seek medical attention
• Additional preventive measures, such as insect repellents and bed nets
• The need for prompt medical evaluation if malaria symptoms develop, even after returning from travel

By empowering patients with knowledge and clear instructions, healthcare providers can enhance the effectiveness of malaria prophylaxis and minimize the risk of adverse outcomes.

Global Efforts in Malaria Control and Elimination

While chemoprophylaxis remains an important tool for protecting travelers and non-immune populations, it is just one component of the broader global effort to control and ultimately eliminate malaria. The WHO’s Global Technical Strategy for Malaria 2016-2030 outlines ambitious targets for reducing the global malaria burden.

What are the key strategies being employed in the fight against malaria?

• Vector control measures, including insecticide-treated bed nets and indoor residual spraying
• Rapid diagnostic testing to ensure prompt and accurate diagnosis
• Access to effective antimalarial treatments
• Chemoprevention for vulnerable populations, such as pregnant women and young children in high-transmission areas
• Surveillance and response systems to track and contain outbreaks
• Research and development of new tools, including vaccines and novel antimalarial compounds

These multifaceted approaches aim to reduce malaria transmission, prevent infections, and save lives on a global scale. As these efforts progress, the landscape of malaria prevention, including the role of drugs like mefloquine, will continue to evolve.

The Importance of Continued Vigilance

Despite significant progress in many regions, the fight against malaria requires ongoing commitment and adaptation. Challenges such as drug resistance, changing transmission patterns, and the impact of climate change on vector distributions necessitate constant reassessment of prevention and treatment strategies.

For travelers and healthcare providers, this means staying informed about the latest recommendations and being prepared to adjust prophylactic approaches as new evidence and options emerge. The case of mefloquine serves as a reminder of the importance of post-market surveillance and the need for continuous evaluation of even well-established interventions.

Conclusion: A Nuanced Approach to Malaria Prophylaxis

The reassessment of mefloquine’s role in malaria prevention underscores the complexities involved in protecting individuals from this potentially deadly disease. While the drug’s efficacy against chloroquine-resistant strains remains valuable, the risk of severe neuropsychiatric side effects has rightfully prompted a more cautious approach to its use.

As the global health community continues to refine strategies for malaria prevention and control, the emphasis on personalized risk assessment and informed decision-making becomes increasingly important. Healthcare providers must stay abreast of the latest guidelines, consider the full range of available prophylactic options, and engage in thorough discussions with patients to determine the most appropriate course of action.

Ultimately, the goal remains to provide effective protection against malaria while minimizing the risk of adverse effects. This requires a nuanced approach that considers not only the efficacy of antimalarial drugs but also their safety profiles, ease of use, and suitability for individual patients. As research continues and new options emerge, the landscape of malaria prophylaxis will undoubtedly continue to evolve, offering hope for even safer and more effective prevention strategies in the future.

Mefloquine as a prophylaxis for malaria needs to be revisited

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Int J Parasitol Drugs Drug Resist. 2021 Dec; 17: 23–26.

Published online 2021 Jun 24. doi: 10.1016/j.ijpddr.2021.06.003

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According to WHO, 2019 witnessed 229 million cases of malaria globally, of which Africa accounted for 94% of cases. Early diagnosis and treatment are the basis of malaria management, and the need for good chemoprophylaxis especially for people travelling to endemic areas is vital. There are a number of drug options available for the prophylaxis of malaria, mefloquine being one of the drugs used. Mefloquine has been around from the 1970s, and was developed in the United States keeping in mind the soldiers that were being deployed to areas where chloroquine resistant strains of Plasmodium were discovered. Mefloquine was preferred for its once a week dosage. Within a decade of its introduction, reports of the side effects associated with its long-term use surfaced. Mefloquine is now reported to cause a myriad of neuropsychiatric side effects including anxiety, sleep disturbance, depression, dizziness and frank psychosis, especially in patients with pre-existing psychiatric disorders. Many countries like the United States and the United Kingdom have updated their drug boxes to include the warning of these potential neuropsychiatric effects. This paper reviews the side effects of mefloquine and why there is a need to revisit its use in Indian drug policy.

Keywords: Malaria, Mefloquine, Neuropsychiatric side effects

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Malaria continues to be a public health problem in India. Estimates by World Health Organization in 2019 (WHO) reported 229 million cases in comparison to 251 million in 2010 and 231 million in 2017 (World Malaria Report 2020). The African Region shouldered the largest burden with estimated 213 million cases (94%) whereas the South-East Asia Region reported 3% and the rest of the world accounted for 3% (World Malaria Report 2020). Almost 95% of all malaria cases globally in 2019 were in 29 countries, of which India reported the largest absolute reductions in cases over a decade i.e., 20 million cases in 2000 to 5.6 million in 2019 (World Malaria Report 2020).

Early diagnosis and timely treatment are the mainstay of malaria management and the chemoprevention of malaria is an important aspect. The need of chemoprophylaxis arises when people travel to malarious areas and desire protection against this potentially life-threatening infection, more so in susceptible populations. People travel for various reasons and travel has exponentially increased in recent times. Hence antimalarial prophylaxis is needed. International bodies like the World Health Organization (WHO: International Travel and Health, Chapter 7) and the Centre of Disease Control and Prevention (CDC Yellow Book 2020) recommend atovaquone–proguanil, doxycycline, chloroquine, mefloquine or tafenoquine (details listed in ) as prophylactics for both short and long-term travelers. The drug list remains the same but special attention has to be paid to side effects if drug is taken for more than 6 months (WHO: International Travel and Health, Chapter 7).

Table 1

Available drugs for malaria chemoprophylaxis for a non-immune traveler.

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Malaria prevention in armed forces, especially those deployed to endemic areas and forest areas (Ranjha and Sharma, 2021) is especially crucial. According to CDC guidelines (CDC Yellow Book 2020) in military population of USA, atovaquone-proguanil is the choice of prophylaxis for a short- and long-term deployments in high-transmission geographical areas. Those who are unable to take atovaquone-proguanil due to intolerance or contraindication, the second line prophylactic is doxycycline, followed by mefloquine. Prior to prescribing mefloquine for prophylaxis, absolute and relative contraindications are taken into consideration (HA Policy 2015). On the other hand, as per National Drug Policy on Malaria (2013) of India chemoprophylaxis is recommended in specific groups in P. falciparum malaria endemic areas. For short term travelers with stay of less than 6 weeks, daily dose of 100 mg of doxycycline is the drug of choice in adults, starting 2 days before travel to 4 weeks after departure. For a duration of more than 6 weeks, mefloquine chemoprophylaxis should be administered weekly, starting 2 weeks before travel to 4 weeks after departure (National Drug Policy on Malaria (2013) of India).

Like other drugs, antimalarial drugs also are contraindicated in certain health conditions. Most of the side effects experienced with chemoprophylactic anti-malarial drugs are minor. However, there can be serious adverse events, which can be life threatening, requiring hospitalization or prolonging it, and/or resulting in significant incapacity. These adverse effects are usually identified in post-marketing surveillance. In people experiencing serious adverse effects, immediate withdrawal of the drug and medical attention is recommended. There are a number of drugs available for chemoprophylaxis of malaria one of which is mefloquine. In this paper, we focus on prophylaxis by mefloquine, its related side effects and an appropriate alternative.

In the 1970s, the development of mefloquine was initiated by Walter Reed Army Institute of Research (WRAIR), USA, owing to emergence of chloroquine resistance in P.falciparum malaria in Southeast Asia (WHO and F. Hoffmann-La Roche, 1991). The drug was tested in clinical trials on prisoners and soldiers, and people in developing countries. In an extensive review by WHO, in late 1980s and early 1990s, after the licensing and introduction of mefloquine, it became extensively used for chemoprophylaxis. Over 20 million people consumed mefloquine as it was preferred for its weekly-single dose (WHO and F. Hoffmann-La Roche, 1991). Despite the lack of clinical safety and tolerability phase III data in civilian volunteers, initial license was granted (Croft, 2007) and numerous trials have been conducted since then.

Mefloquine, [2,8-bis(trifluoromethyl)quinolin-4-yl]-piperidin-2-ylmethanol is a 4-quinolinemethanol antimalarial and antiparasitic which acts as a blood schizonticide, structurally related to quinine. Since its development it is indicated for both prophylaxis and treatment of malaria, despite the inadequately understood mechanism of action (Taylor and White, 2004). A long half-life of 13–30 days provides an edge over other prophylactics as it can be used in a once-a-week format in lower doses (WHO and F. Hoffmann-La Roche, 1991).

Gastrointestinal adverse effects like vomiting, nausea, anorexia, abdominal pain and diarrhea were noted. Neurological disorders such as balance disorder, convulsions, encephalopathy, headache, hearing impairment, memory impairment, neuropathy (including paraesthesia, tremor, and ataxia), syncope, tremors and vestibular disorders were also experienced. Other side effects like fatigue, fever, muscle pain, palpitations, rashes and weakness were also noted (Toovey, 2009; Lee et al., 2017).

Nearly a decade after mefloquine’s use, neurotoxicity was reported in a French paper in 1987 (Bernard et al., 1987) and subsequently, after drawing attention of the media over this, it was further evaluated by the WHO in 1991. This report concluded that at doses of 500 mg and above, adverse effects have been seen with mefloquine intake but the data collected was not enough to change the treatment guideline pertaining to mefloquine (WHO and F. Hoffmann-La Roche, 1991).

In 2006, direct evidence was reported that mefloquine is neurotoxic at dosages used for malaria treatment, and animal models showed permanent brainstem lesions. Subsequent studies showed neurotoxicity in animal and human neurons (Mccarthy, 2015). Cognitive impairment similar to neurotoxic brainstem lesions were observed. Mefloquine neurotoxicity has been described as chronic sequelae of nervous system toxicity syndrome and possibly permanent neuronal degeneration of the brainstem (Mccarthy, 2015) and neurotoxic vestibulopathy (Nevin, 2014). The product information also mentions that if any sign such as acute anxiety, depression, confusion or restlessness occur, it is to be considered prodromal to a more serious event. In such a situation the drug should be discontinued (Nevin 2014).

The gastrointestinal side effects of mefloquine are known to be caused by pancreatic β-cell type-KATP channel Kir6.2/SUR1 inhibition. The mechanism behind these neurological and psychiatric effects is not completely known but the mechanisms implicated include: cholinesterases inhibition, non-receptor tyrosine kinase 2 (Pyk2 and/or interaction with adenosine A (2A) receptors (Lee et al. , 2017). Some studies have also shown mefloquine to cause GABAergic interneuron dysfunction, inhibition of cellular transport and depression of cortical activity (Martins et al., 2021).

Studies have focused on the role of mefloquine in causing hallucinations, nightmares and a flare up of symptoms of Post-Traumatic Stress Disorder (PTSD) (Janowsky et al., 2014). The detrimental effects mefloquine can produce, have the potential to continue even after drug is stopped leading to long-term neurotoxic effects (Quinn, 2015). Experiences in Armed Forces and civilian populations in different countries (summarized in ) have highlighted the significance of taking mefloquine’s adverse effects in cognizance.

Table 2

Results of studies pertaining to mefloquine prophylaxis safety.

Year	Study	Country	Participants	Result: % of participants suffering adverse effects	Result: % of participants suffering neuropsychiatric adverse effects
1993	Boudreau et al.	US	203	43%	Not determined
1996	Phillips and Kass	Australia	285	51.2%	6.3%
1996	Buma et al.	Netherlands	2289	22.8%	Not determined
1996	Schlagenhauf et al.	Switzerland	420	11. 2%	7.9%
1996	Croft and World	UK	317	29%	Not determined
1999	Peragallo et al.	Italy	1386	17%	Not determined
2001	Overbosch et al.	Netherland, Germany, UK, Canada and SA	483	42%	29%
2005	Kitchener et al.	Australia	1157	57%	29%
2005	Vaillancourt et al.	Canada	1413	74.7%	Not determined
2007	Fujii et al.	Japan	1876	24.4%	18.2%
2008	Andersson et al.	Sweden	488	57%	21. 7%
2010	Nasveld et al.	Australia	162	11.7%	5%
2014	Ringqvist et al.	Denmark	73	Not determined	55%
2014	Peragallo et al.	Italy	4123	21.2%	Not determined
2016	Ministry of defence	UK	116704	Not determined	10%
2017	Eick-Cost et al.	US	367840	Not determined	10.8%

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On the 29^th of July 2013, the FDA issued a Drug Safety Communication, reinforcing the updated warnings regarding these side effects of mefloquine and adding a black boxed warning to the drug label. The medication guide has also been revised by the FDA to include these side effects and that these may be persistent or become permanent. Since the FDA warning, drug regulatory agencies in various countries, including the UK, Ireland (Nevin and Byrd, 2016), and Canada (Nevin, 2017) have made it mandatory to add a warnings update in their mefloquine drug labels.

National Drug Policy on Malaria (2013) of India entails mefloquine use as chemoprophylaxis when stay in a malarious region is for more than 6 weeks. This policy has implications for the general public but especially so for armed forces personnel who are posted in malarious areas where they are exposed to risks of contracting malaria. Generally, chemoprophylaxis for malaria is prescribed only in certain groups and in areas with high prevalence of P. falciparum. In addition to vector control products, for longer stays chemoprophylaxis is required. Armed personnel who are posted in malaria endemic regions for long-term are at high risk of infection and as per guidelines mefloquine is recommended for periods above 6 weeks. However, to our knowledge there are no reports pertaining to neuropsychiatric side effects till date in context of Indian troops, this may be due to lack of systematic studies. Further, mefloquine is still used in India in civilian populations as well albeit with warnings.

After years of use in international military, many of the risks of using mefloquine have been recognized and now more informed policies are being formulated in many countries. The change in policies is based on evidence generated by scientific studies and clinical experience of adverse side effects especially those of neuropsychiatric nature. Mefloquine still remains indicated for malaria prophylaxis for long-term use. Chemoprophylaxis of malaria can be achieved, especially in chloroquine-resistant P. falciparum regions by other drugs available like doxycycline and atovaquone/proguanil as both are well tolerated for longer prophylactic use. India has been considering tafenoquine for P. vivax treatment (Ahmad SS et al., 2021) and similarly there is a need in India to invest in research and evaluation of safer alternative drugs for chemoprophylaxis for various groups that have a high malaria burden like pregnant women (Pandey et al., 2021). In light of the scientific literature now available on the adverse effects of mefloquine there is a need to revisit the Indian national guidelines and consider adoption of alternative drugs.

AS conceived the idea, VR and SSA did extensive literature reviews. SSA and MR drafted the manuscript. MR made important additions. All authors wrote the paper. All authors read and approved the final manuscript.

The views expressed in the submitted article are authors’ and not an official position of the institution.

No additional data.

Not required.

None of the authors have any conflicts of interest to declare.

We thank Department of Science and Technology (DST) for the JC Bose fellowship to AS.

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Articles from International Journal for Parasitology: Drugs and Drug Resistance are provided here courtesy of Elsevier

Mefloquine – Uses, Side Effects, Interactions

How does this medication work? What will it do for me?

Mefloquine belongs to the class of medications called antimalarials. Mefloquine is used to treat and prevent malaria infections caused by certain types of parasites.

Malaria is an infection caused by a group of parasites called Plasmodia that enter the blood through bites from infected mosquitoes. The parasites first enter and destroy red blood cells, then they reproduce within the liver and are released into the blood. Mefloquine does not prevent the mosquitoes from biting or prevent the parasite from reproducing in the liver. Mefloquine works by destroying the parasite after it is released from the liver into the blood.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

Each white, round, biconvex tablet, cross scored on one side, and plain on the other side, contains 250 mg of mefloquine (base) as mefloquine hydrochloride. Nonmedicinal ingredients: microcrystalline cellulose, magnesium stearate, croscarmellose sodium, and colloidal silicon dioxide.

How should I use this medication?

The recommended preventative dose of mefloquine is 250 mg once a week. This medication should be taken on the same day of the week for the following time period:

• one week before arrival in a malaria area (to allow blood levels of the medication to be effective)
• throughout your stay in this area
• 4 weeks after leaving the area (in case you have been infected and the parasite is reproducing in the liver)

For people who weigh less than 45 kg (99 lbs), your doctor will adjust the dose of mefloquine according to your body weight.

Your doctor may recommend starting this medication 2 weeks before you travel to a malaria area in order to determine how this medication affects you and if you will be able to tolerate it.

The dose of mefloquine for treatment of malaria is based on body weight (20 mg/kg to 25 mg/kg for those with no immunity, and 15 mg/kg for those with partial immunity). The total dose is taken all at once or in 2 to 3 doses spaced 6 or 8 hours apart to reduce the occurrence or severity of side effects. If a person vomits less than 30 minutes after receiving the medication, a full additional dose should be taken as instructed by your doctor. If vomiting occurs 30 to 60 minutes after the dose, an additional one-half dose should be taken as instructed by your doctor.

Many things can affect the dose of a medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

Mefloquine should be taken with food (e.g., any meal) and with plenty of water (at least 240 mL, equivalent of 1 cup [8 ounces]). Do not chew the tablets, but you may crush and mix them with a small amount of water, milk, or other beverage.

It is very important to take this medication exactly as prescribed by your doctor. Do not take a double dose. For missed doses intended for prevention of malaria, take the dose as soon as you remember and take each remaining dose according to the weekly dosing schedule, counting from the day you took the missed dose. Do not take more than one dose in a week.

Immediately contact a doctor if you suspect that you have contracted malaria. Your doctor may recommend a self-treatment plan if you cannot get to a doctor within 12 to 24 hours.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not take this medication if you:

• are allergic to mefloquine or any ingredients of the medication
• are allergic to related medications (e.g., quinine, quinidine, chloroquine)
• are taking any of the following medications:
• quinine
• quinidine
• chloroquine
• ketoconazole
• halofantrine
• have a history of psychiatric disturbances (including depression, generalized anxiety disorder, schizophrenia, or other major psychiatric disorders)
• have a history of suicide attempt or self-harming thoughts or behaviour
• have a history of seizures

What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• abdominal pain
• abnormal dreams
• diarrhea
• dizziness
• fatigue
• headache
• loss of appetite
• loss of balance
• nausea
• spinning sensation
• trouble sleeping
• vomiting

Although most of these side effects listed below don’t happen very often, they could lead to serious problems if you do seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• chills
• fever
• irregular heartbeat or palpitations
• irritability
• mood or mental changes (e.g., anxiety, paranoia, hallucinations, confusion, panic attacks)
• muscle aches or pain
• prickling or tingling sensation
• numbness and loss of ability to feel pain or temperature change, especially in the feet
• burning or sharp pain in feet
• loss of coordination or balance
• pain caused by a light touch
• restlessness
• ringing in the ears
• severe or continuing headache
• signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
• signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
• signs of inflammation of the lungs (e. g., fever, chills, shortness of breath, cough)
• skin rash
• unusual tiredness or weakness

Stop taking the medication and seek immediate medical attention if any of the following occur:

• seizures
• severe muscle weakness or paralysis
• signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)
• signs of a severe skin reaction such as blistering, peeling, a rash covering a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort
• thoughts of self-harm or suicide

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Anemia: Mefloquine may cause low levels of red blood cells. If you experience symptoms of reduced red blood cell count (anemia) such as shortness of breath, feeling unusually tired or pale skin, contact your doctor as soon as possible.

Dizziness/reduced alertness: Dizziness, a disturbed sense of balance, and other problems with the nervous system have been reported during and after the use of mefloquine. In some cases, these side effects have become permanent. Use caution when performing tasks requiring mental alertness and coordination (such as driving or operating machinery).

Drug interactions: Taking mefloquine at the same time as other medications, including quinine, quinidine, and chloroquine, may cause heart rhythm problems, cardiac arrest, or increase the risk of seizures. Do not take these medications at the same time as mefloquine. Halofantrine and ketoconazole may affect the electrical activity of the heart and cause QT prolongation. Do not take halofantrine or ketoconazole while taking mefloquine for the prevention or treatment of malaria, or for 15 weeks after the last dose of mefloquine.

Heart conditions: Mefloquine can cause heart rhythm problems. If you develop an abnormal or irregular heartbeat or palpitations while taking mefloquine to prevent malaria, contact a doctor as soon as possible. If you have heart rhythm problems, you should discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Liver disease: People with liver disease may experience higher blood levels of this medication. If you have liver disease, talk to your doctor about the benefits and risks of using this medication.

Mental problems: Some people taking mefloquine may experience psychiatric symptoms (including depression, generalized anxiety disorder, paranoia, hallucinations, and psychotic behaviour). In rare cases, they may have thoughts of suicide. If you have a history of psychiatric disturbances (including depression, generalized anxiety disorder, schizophrenia, or other major psychiatric disorders), you should not take this medication.

If you are taking mefloquine to prevent malaria and you experience a sudden onset of anxiety, depression, thoughts of self-harm or suicide, restlessness or irritability, or confusion (which are possible signs of more serious mental problems), contact a doctor or health care provider as soon as possible. You may need to stop taking mefloquine and use another malaria prevention medication instead.

Nervous System Problems: Some people taking mefloquine may experience serious nervous system problems. If you experience dizziness, vertigo or a spinning sensation, loss of balance, ringing in your ears, difficulty sleeping, or seizures, contact your doctor immediately.  These side effects may occur at any time while you are taking mefloquine and in some cases have lasted for months or years after stopping mefloquine.   In some people side effects of dizziness, vertigo, loss of balance and ringing in the ears have become permanent.

Seizure disorder: Mefloquine may increase the risk of seizures in people who have epilepsy. People with a history of seizures should not take mefloquine to prevent malaria, and should only take mefloquine to treat malaria if the benefits outweigh the risks.

Stopping the medication: If you are told by a doctor or other health care provider that you need to stop taking mefloquine because of side effects or other reasons, you will need to take another malaria prevention medication. Leave the malaria area if you cannot get another medication. However, leaving the malaria area may not protect you from getting malaria; you still need to take a malaria prevention medication.

Pregnancy: If possible, it is best if pregnant women avoid travelling to areas where they risk malaria exposure. This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately. Women of childbearing age should use reliable birth control while taking mefloquine and for 3 months after the last dose has been taken.

Breast-feeding: This medication passes into breast milk. If you are breast-feeding and are taking mefloquine, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of using this medication have not been established for children less than 3 months old or weighing less than 5 kg.

What other drugs could interact with this medication?

There may be an interaction between mefloquine and any of the following:

• acetazolamide
• alcohol
• amiodarone
• antihistamines (e.g., cetirizine, chlorpheniramine, dimenhydrinate, diphenhydramine, loratadine)
• other anti-malarial medications (e. g., hydroxychloroquine, primaquine)
• anti-psychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
• “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
• beta-blockers (e.g., atenolol, metoprolol, sotalol)
• bosentan
• cobicistat
• conivaptan
• dapsone
• disopyramide
• dronedarone
• enzalutamide
• flecainide
• HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., efavirenz, etravirine, nevirapine)
• HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
• macrolide antibiotics (e.g., clarithromycin, erythromycin)
• methadone
• mifepristone
• mitotane
• modafinil
• pregabalin
• procainamide
• quinidine
• quinine
• quinolone antibiotics (e.g., ciprofloxacin, norfloxacin)
• rifabutin
• rifampin
• St. John’s wort
• seizure medications (e.g., carbamazepine, gabapentin, levetiracetam, phenobarbital, phenytoin, topiramate)
• selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, paroxetine, sertraline)
• serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
• siltuximab
• tricyclic antidepressants (e.g., amitriptyline, imipramine, nortriptyline)
• tyrosine kinase inhibitors (e.g., lapatinib, pazopanib, sunitinib)
• warfarin

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them.  Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

All material copyright MediResource Inc. 1996 – 2023. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Mefloquine

Doctors warn about the dangers of mefloquine in the prevention of COVID-19

The antimalarial drug mefloquine has proven effective in the treatment of COVID-19 – its small dose can destroy the coronavirus in just 48 hours, the FMBA said. It was also recommended to use it for the prevention of infection. However, this drug is known for its toxicity and side effects, including heart problems and even hallucinations. The pharmacologist told Gazeta.Ru whether mefloquine is really dangerous and whether it will help to avoid infection.

The antimalarial drug mefloquine can destroy the coronavirus infection in 48 hours, Veronika Skvortsova, head of the Federal Medical and Biological Agency (FMBA), said.

She said that 347 people with coronavirus participated in a clinical study of this drug, which was conducted by the FMBA. According to the results of the experiment, 78% of patients with moderate condition at the beginning of the course of mefloquine showed positive clinical dynamics.

As a result, 70% of volunteers got rid of the infection by the end of the first week of taking this drug. At the same time, according to the head of the agency, a very small dose of it was required to destroy the virus – only two micrograms per milliliter.

New clinical trials of mefloquine are currently underway at four leading FMBA centers, comparing it with other antiviral drugs.

“And we see certain advantages in patients of moderate severity. At least 70% have sustained consistent improvement on this drug.”

– said Veronika Skvortsova.

Clinical pharmacologist Gleb Putsman clarifies that mefloquine is a first-line drug and is used for all severity of the disease.

“Nevertheless, the mechanism of action of antiviral activity is not fully understood. There was evidence that it affects endosomes (membrane intracellular structure – Gazeta.Ru), changing the acidity inside them. Presumably, COVID-19 just uses endosomes to enter the cell. Accordingly, when the acidity of their environment changes, the viral particle breaks down, ”the doctor explained to Gazeta.Ru.

Veronika Skvortsova said that mefloquine can also be taken as a preventive measure against coronavirus infection. Due to the cytopathic effect (destruction of viruses in cells – Gazeta. Ru), the drug can reduce the likelihood of a disease by 50-75%, the expert is convinced.

At the same time, the executive director of the Atlas biomedical holding, Alexander Karasev, said that the effect of mefloquine during mass use is unpredictable. “Despite the fact that this drug has already passed the necessary preclinical and clinical trials – showed the suppression of the virus, it is impossible to predict that the effectiveness of the drug will outweigh the large list of known side effects,” he said in a conversation with Forbes magazine.

Skvortsova herself has previously stated about the side effects of the medicine. According to her, they were observed in 26% of patients taking the drug. Most often these were interruptions in the work of the heart, as well as sleep disturbances.

In addition, mefloquine can cause dizziness, balance problems and tinnitus, the US Food and Drug Administration warned in 2013. According to American experts, these symptoms can persist from several months to several years after stopping the drug. Feelings of anxiety, depression, and even hallucinations may also occur.

According to clinical pharmacologist Oleg Talibov, this is why it is quite dangerous to use mefloquine as a prophylaxis. He told TASS that this drug can adversely affect the functioning of the liver and central nervous system.

“The drug is very difficult, the Americans have abandoned its preventive use due to serious toxicity”,

– said the physician.

In addition, mefloquine is excreted from the body for a long time, which can also adversely affect health. “The feature of the drug compared to hydroxychloroquine (an antimalarial drug also used to treat COVID-19, – “Gazeta.Ru”) also in the fact that it has a long withdrawal period, it is several times longer. That is, if you get a toxic effect on mefloquine, it will last much longer than on hydroxychloroquine, ”the pharmacologist explained.

Gleb Putsman told Gazeta.Ru that the use of this drug should be justified – for example, doctors who are in the focus of COVID-19 can take it for prevention. “Ordinary people are not recommended. In addition, due to toxicity, every doctor working in the risk zone decides for himself whether it is worth taking it, ”the pharmacologist summed up.

Previously, Veronika Skvortsova also called for mefloquine to be used with caution and to take into account the state of her heart and intracardiac conduction when using it.

Despite the high toxicity of this agent, the scientific community still considers the positive results of clinical trials conducted by FMBA to be a success. “In a situation where therapy and treatment protocols for COVID-19 are just being formed, by trial and error, alas, each, even the relative success of a particular therapy, is extremely positive news,” Evgeny Kuznetsov, head of the venture capital fund Orbita Capital Partners, told Forbes magazine.

He added that there is still a relative benefit from mefloquine in moderate cases of coronavirus, which means that it can be used in the treatment of COVID-19 until more effective methods are developed.

“Still, we are too far away to say that mefloquine will help everyone. Probably, its long-term side effects, as is often the case in pharmacology, will not allow its use, ”Alexander Karasev concluded.

“70% are getting better”: can mefloquine be a cure for coronavirus?

In Russia, the antimalarial drug mefloquine showed positive results in the preclinical phase of the study: the drug suppressed the virus within 48 hours, although this was accompanied by side effects in about a quarter of patients. Forbes figured out whether the substance can become a cure for coronavirus.

What happened. Preclinical studies of the antimalarial drug mefloquine showed that it completely suppresses the effect of coronavirus after 48 hours at a very small dose – two micrograms per milliliter, Veronika Skvortsova, head of the Federal Medical and Biological Agency (FMBA), said during an online conference on May 15. She said that mefloquine may also be used for prevention. If the drug is used before infection, the effect of the virus is reduced by 50-75%, said Skvortsova.

“We are currently conducting a clinical study of mefloquine in comparison with other antiviral drugs at our four leading FMBA centers and see some benefits in patients of moderate severity, at least 70% have a steady consistent improvement in the condition on this drug,” said head of the FMBA (quote from RIA Novosti). The agency previously promised to provide conclusions on the efficacy and safety of the drug in people with coronavirus infection after the end of clinical trials by May 20, 2020.

Mefloquine is an antimalarial drug. It was developed in the 1970s for the needs of the American army, and after another 10 years it was brought to the mass market. Mefloquine in tablets is produced by the Pharmzashchita Research and Production Center, subordinate to the FMBA. FMBA is studying the efficacy and safety of treating patients with COVID-19 with this drug in Russia.

What really happened. Preclinical studies are the study of a drug on models that are built either in a computer or in real life, for example, on cells or chicken embryos, said Alexander Karasev, executive director of the Atlas biomedical holding. Researchers add a drug to these models and see that the number of infected cells has become smaller, he gives an example. “But no one knows how this drug will behave in the human body. When preclinical trials are underway, sometimes 10,000 candidate substances are selected that have the potential to work well. The next phase to get the drug into clinical trials is to determine the right dose to give to patients,” says Karasev.

Every drug has a main effect and a side effect, he notes. The patient is given a certain dose of the drug, after which they are observed for a long time to identify side effects. Only after that, clinical trials begin with an effective dose, adds the executive director of Atlas. And only after passing through these multi-stage clinical trials, it is possible to decide whether the drug is effective in comparison with other treatments or placebo, he emphasizes.

“Despite the fact that mefloquine has already passed the necessary pre-clinical trials – showed suppression of the virus, as well as clinical trials in the last century in the treatment of malaria, it is impossible to predict that the effectiveness of the drug will outweigh the large list of known side effects,” Karasev concluded.

Why it matters . “In a situation where therapy and treatment protocols for COVID-19 are just being formed, by trial and error, alas, each, even the relative success of a particular therapy, is extremely positive news,” said Evgeny Kuznetsov, head of the Orbita Capital Partners venture fund. According to him, mefloquine shows a relative usefulness in moderate-to-severe cases, which will allow it to gain a foothold in the practice of treating coronavirus until more effective and accurate methods are developed.

Other side. The mechanism of action of antimalarial drugs against viral infections is not fully understood, according to the sixth version of the interim guidelines of the Ministry of Health for the treatment of COVID-19. Among the frequent side effects, the document lists sleep disturbance, anorexia, and headache. When taking mefloquine, the Ministry of Health recommends avoiding activities that require a high concentration of attention.

Mefloquine may cause dizziness, balance problems and tinnitus, warned in 2013 by the US Food and Drug Administration (FDA). Symptoms can appear at any time while using mefloquine and may last from several months to several years after stopping the drug. Feelings of depression, anxiety, and hallucinations may occur.

Veronika Skvortsova also spoke about side effects of mefloquine. “The drug has certain side effects, which, according to our data, occur in 26% of patients, this is one in four. They are easily tolerated, but nevertheless, they exist, therefore, when choosing which drug to treat, it is necessary to take into account various factors, for example, the state of the heart and intracardiac conduction, ”she noted. Skvortsova said that in a number of patients, mefloquine can cause a feeling of interruptions in the work of the heart, some of them have disturbed sleep.

What the experts say. Mefloquine belongs to the group of antimalarial drugs, like its related chloroquine and hydroxychloroquine, says Yulia Tkachenko, head of the medical development department at BestDoctor, which develops a technological service for supplementary medical insurance. The use of antimalarial drugs for COVID-19 is due to their antiviral and immunosuppressive (immune-suppressing) effects, she explains. “However, at present, according to conducted clinical studies, the benefits of chloroquine and hydroxychloroquine in COVID-19not confirmed, international recommendations warn against the use of these drugs in high doses due to their potential toxicity and insufficiently high efficiency, and the combination of hydroxychloroquine and the antibacterial drug azithromycin is completely recognized as toxic and is not recommended for use,” Tkachenko said.

International guidelines also warn against the use of hydroxychloroquine and chloroquine for prophylactic purposes. It is, of course, too early to say that mefloquine, a drug related to chloroquine and hydroxychloroquine, may be highly effective against coronavirus infection until clinical trials are completed, Tkachenko is sure. And it is not yet possible to evaluate the results of the study, since they have not yet been published, she emphasizes.