Shelf Life of Malarone

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QUESTION

I’ve just finished reading several years’ worth of your responses to questions and I’m very impressed. Thank you for being surely one of the best sources on the web. My question pertains to the shelf life of Malarone tablets. My husband and I have been in Madagascar for three weeks now and will stay for another two and a half months. I am very preventive-oriented (long sleeves, pants and socks, mosquito tent at night) as mosquitos love me. I am not however taking a chemical prophylactic. I have brought with me 11 Malarone tablets (GlaxoKlineSmith) bought on prescription in France some years ago and whose expiration date is… 2010. If I do come down with the symptoms (likely falciparum) and test positive, would I not be better off taking these perimated pills than eventually buying counterfeit ones here, if you can get them, as I read on the internet that drug companies are very conservative re shelf life (the pills are in their original plastic/aluminum airtight wrappings)? I say I am preventive-oriented, though I admit that travelling with old Malarone (and not the 12 recommended but only 11) is not too wise.

ANSWER

Thanks so much for your question, and you certainly have done your research! I agree, often the expiry date of medications seems to be overly conservative, but unfortunately without testing the chemical properties of the tablets, you cannot know for sure whether the compounds in the drugs have begun to break down.

I understand your predicament that slightly weaker drugs might be better than counterfeit ones, but ultimately, both might not be completely effective and I would be very concerned about the possible contribution to drug resistance, if you try to treat malaria with a drug which is not fully operational. This is the same effect as taking only 11 out of the required 12 tablets for treatment; it’s like not completing a full course of antibiotics, and can assist the malaria parasite in developing drug resistance.

In your case, I have a couple of recommendations: First of all, you are unlikely to be able to find reliable Malarone, but doxycycline should be available and given how cheap it is as a generic, unlikely to be counterfeit. Given you will be in Madagascar for a reasonably long period of time, you probably should start chemical prophylaxis, and doxycycline could be a good option. The usual dose for prophylaxis is 100mg, taken orally, once a day. You will need to continue taking it every day for four weeks after you leave the malarial area. Most people tolerate doxycycline very well, but it can cause minor side effects such as stomach ache and sensitivity to the sun. You should also make sure to take it 2-3 hours before consuming any dairy products or other items containing calcium or magnesium (antacid tablets, etc), as doxycycline binds to calcium and magnesium, preventing it from being fully absorbed by the body.

Secondly, I would also investigate local pharmacies and clinics and find out which ones stock artemisinin-based combination therapies, such as Coartem, ASAQ, Pyramax or Duo-Cotecxin. Look for artemisinin-derivatives in the list of ingredients such as artesunate, dihydroartemisinin and artemether, together with a combination compound (having a second active ingredient is very important in terms of preventing development of drug resistance) such as lumefantrine, mefloquine, piperaquine and amodiaquine.

It is difficult to identify counterfeit drugs, but look for original packaging (including aluminum casings for the pills), manufacturer’s stamps and an expiry date (obviously you want to make sure the drugs have not expired!). Once you have sourced a suitable pharmacy, if you or your husband comes down with malaria (as you rightly say, once you have been positively tested for falciparum! I’m so happy you are aware of the importance of diagnosis), then you will have a sense of a pharmacy to turn to when you need treatment, though hopefully, if you start taking doxycycline, you will be completely protected!

Anti Malaria Tablets – When to Start

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QUESTION

I am due to travel to South Goa on 27th October 2012. It is 9th Oct now. It says I should start taking my tablets 1 week before traveling, however I was wondering if it was okay to start taking them now so my body can get used to the side affects before I travel. I do not want to be ill all the time whilst I am away.

ANSWER

Yes, you do need to take preventive medicine against malaria when visiting India and it is best to follow instructions given by your doctor or the drug insert. For India,  the US Center for Disease Control (CDC)  recommends Malarone (Atovaquone/proguanil), Doxycycline and Mefloquine as drugs to prevent malaria.

Malarone  needs to be started 1-2 days before travel to a malarial area, taken daily and continued for 7 days after leaving the area.

Doxycycline needs to be started 1-2 days before travel, is taken daily and needs to be continued for 4 weeks after leaving malarial areas.

Mefloquine needs to be started 2 weeks before travel, is taken weekly, and needs to be continued for 4 weeks after leaving.

Chloroquine is NOT recommended for India because of resistance, so it is not effective.

Malaria Infection Even With Prevention

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QUESTION

Can you still get infected with Malaria even when taking a preventative such as doxycycline or Malarone?

ANSWER

Yes, no prophylactic medication is 100% effective though both Malarone and doxycycline are usually over 90% effective, when taken properly. It is important to make sure each tablet is taken approximately at the same time each day, and in the case of Malarone, it is important to take it with some fatty food as this assists in absorption. Conversely, doxycycline should not be taken within 6 hours of consuming dairy products, as the calcium present in milk can prevent uptake of doxycycline. For these reasons, it is important to also use other methods of preventing malaria, such as sleeping under a long-lasting insecticide treated bednet.

Preventative Medication for Malaria in Dominican Republic

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QUESTION

I just read the CDC recommended medicines for preventing malaria and I am confused. It gives the pros and cons for taking one drug over another. My husband and I are in excellent health, we need our td boosters. Our 15 year old is current in his vaccinations. We will be in D.R. for 2.5 weeks near Jarabacoa then Rio San Juan. We will be on a missionary trip. What medicine should be take in your opinion before hand?

ANSWER

Apart from some basic differences, particularly regarding which forms of malaria they are effective and against, and in what areas of the world, the choice of which anti-malarial to take mostly comes down to personal preferences. So, for example, in most of Africa, malaria is resistant to chloroquine, so this drug is not recommended for travellers; conversely, in parts of Thailand, malaria is resistant to mefloquine, so likewise, if travelling to those areas, you would need to pick another drug.

Having said that, in the Dominican Republic the malaria is sensitive to all forms of anti-malarial drugs, so you don’t have to worry about that. Between the four main types of drug you can take (atovaquone-proguanil, doxycycline, mefloquine and chloroquine), there are significant differences in price, frequency and duration of taking the tablets and side effects, all of which may influence your decision to take one over another. They are all roughly equal in terms of their efficacy in preventing malaria, apart from when resistance is an issue, as I’ve mentioned.

Of the four, chloroquine and mefloquine are taken weekly, while atovaquone-proguanil (often sold as Malarone) and doxycycline are taken daily. Some people prefer the convenience of only having to take a pill every week, but the disadvantage is that these both have to be started 2 weeks before you travel, whereas the daily medications can be started the day before you leave. While Malarone only needs to be taken for one week after returning from your trip, the others should be taken for a full four weeks, to ensure that malaria does not surface once you’re back.

All have some reported side effects, but in my experience, Malarone has the fewest and the most mild, though some people report upset stomachs and disturbed sleep. Chloroquine also has some potential gastrointestinal side effects and can also produce itching, which is a particularly common side effect in people of African descent. The tablets have a metallic taste which some people find unpleasant.

Doxycycline is also an antibiotic, which means it can also help prevent other infections while travelling, though one of its common side effects is sun sensitivity, which may make it less suitable for travelling in tropical areas (personally I have not experienced this side effect, though I have known many people who have).

Mefloquine (sold as Lariam) is not recommended for people with a history of mental illness, and is known to have psychiatric side effects, including nightmares, hallucinations and even altered behavior (again, my whole family took Lariam during one trip, and no one experienced any such side effects, but you should be aware of the possibilities).

Another important factor to consider is price: doxycycline is usually the cheapest drug, and Malarone the most expensive (could be as much as $100 for each of you, for enough to cover the 2.5 week trip, plus a week of tablets once you get back), with the others somewhere in between.

Again, ultimately the choice usually comes down to what factors are important to you and your personal preference. I tend to pay the extra for Malarone since I prefer the convenience of starting the pills right before I leave, and only taking them for a week when I return. Furthermore, when I am away, I am usually working outside, and so would rather not risk the potential sun sensitivity side effect of doxycycline. You should also talk with your doctor about what is usually available in your area from local pharmacies, as they may not carry the full selection of choices.

Malaria in Namibia

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QUESTION

could you please let me know, whether or not a malaria prophylaxe injection is necessary for a 3-weeks trip by car in Namibia, starting mid August.

ANSWER

It depends on where you are going in Namibia. According to the US Centers for Disease Control, malaria is transmitted in Namibia in the provinces of  Kunene, Ohangwena, Okavango, Omaheke, Omusati, Oshana, Oshikoto, and Otjozondjupa and in the Caprivi Strip. As such, if you are travelling to any of these areas, you should consider taking medication to prevent malaria. Three types of medication are considered equally effective in these regions: atovaquone-proguanil (Malarone), mefloquine (Lariam) and doxycycline. Which one you decide to take is mainly a matter of personal preference, based on details such as how often you will need to take a tablet (every day for Malarone and doxy, once a week for Lariam), how long you want to take the medication (Malarone is started the day before your trip, and should be taken for a week after, doxy is also started 1-2 days before travelling but must be taken for 4 weeks after returning and Lariam is started 2 weeks before travelling and for 4 weeks afterwards) and price (Malarone is the most expensive, and doxy usually the cheapest). In addition, each has different potential side effects (Malarone usually has the fewest; doxy can result in sun sensitivity, and Lariam may have psychiatric side effects, and is not recommended for anyone with a history of mental illness).

What to do while on malaria medication

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QUESTION

Good day, I’m a 27yr old male currently in Nigeria. I would like to know my do’s and don’ts while on malaria medication. I ask this so I know what to forego in my athletic lifestyle- I visit the gym 3-4 times a week and have recently started horse riding.

ANSWER

There isn’t any restriction on the kinds of activities you can enjoy while on malaria medication! You should be able to continue with your normal healthy lifestyle. However, be aware that the foods you eat may have some impact on your body’s ability to uptake the anti-malarials. For example, it is recommended to take Malarone (atovaquone-proguanil) together with some food containing fat, as this aids absorption and reduces side effects. Conversely, if you are taking doxycycline, you should NOT take it within a few hours (and certainly not at the same time) as dairy products, as the calcium in milk can inhibit uptake of the drug.

Malaria Prophylaxis for Indonesia

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QUESTION

I have been working a 4-week rotation between the USA and East Kalimantan (Borneo) for about 2 years. While on Borneo, I am in the jungle much of the time. I have never contracted malaria. I am embarrassed to say I thought I had been inoculated for malaria when I first started working here. I just spent 10 days in a hospital last month fighting a blood degenerating viral infection not unlike hemophiliac dengue. Is there a preferred Rx I should take for malaria? I have no allergies to medicines that I am aware of. I am 57 year-old male.

ANSWER

Given the amount of time you spend in rural areas of Borneo, you probably should consider anti-malarial medication to prevent infection. There are three types of drug which are recommended against malaria in Indonesia: atovaquone-proguanil (sold as Malarone), mefloquine (sold as Lariam) and doxycycline. Each has pros and cons: Malarone and doxy have to be taken every day, while Lariam is only taken weekly, which might make it more convenient. However, both doxy and Lariam should be taken for a full 4 weeks after leaving the malarial area, while Malarone is only taken for a week after leaving.

In my opinion, Malarone has the fewest and mildest side effects (though some people complain of upset stomachs and disturbed sleep patterns), while doxycycline is sometimes a problem in the tropics since it can cause sun sensitivity. Lariam is not recommended for people with a history of mental illness, and has been reported to have psychiatric side effects, including nightmares, hallucinations and even altered behavior. Of the three, Malarone is the most expensive, and doxycycline usually the cheapest.

In terms of taking them long term, I don’t know of any studies that look at long term usage of Malarone (it is expensive enough that I doubt anyone takes it for very long trips!), while people do safely take doxycycline for periods of several months, and Peace Corps volunteers and American expats routinely take Lariam for periods of several years.

Of course, many people living long term in malarial areas do not find it convenient to take pills to prevent malaria, and focus on other preventative measures, mainly revolving around killing mosquitoes and avoiding being bitten. Sleeping under a long-lasting insecticide treated bednet is one such method, which is cheap, easy and very effective.

Incidentally, the area you are in is interesting from a malaria point of view since it is one of the few places where transmission of Plasmodium knowlesi occurs. This is a type of malaria which was thought to be only present in macaque monkeys, until human cases started becoming more prevalent a few years ago. Now it is considered a “human” type of malaria, and an emerging threat in south-east Asia. It’s important to be aware of it as the mosquitoes which transmit it tend to be forest-dwelling (since that is where the macaques live), and although very easily treated with chloroquine or other anti-malarials, an infection can progress rapidly into quite severe disease.

If you suspect you might have malaria at any point, therefore, it is crucial to get out and get tested at a clinic or hospital, where they can promptly treat you if you test positive. Be aware also that if tested via microscopy, P. knowlesi can often be confused with P. malariae or P. vivax; while the initial treatment is likely to be the same for all three, if you had P. vivax you might be told about taking an additional medication, called primaquine, to prevent future relapses, whereas relapses do not occur with P. knowlesi.

Doxycycline After Malaria Diagnosis

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QUESTION

My daughter is 24 and in rural Uganda for 4 months. She has been diagnosed with malaria (plasmodium falciparum) and is taking treatment now. Treatment is 3 tablets of Neosidar tablets contain of sulfadoxine BP and of pyrimethamine followed tonight and for the next 3 days by 4 tablets of Lumarten in the morning and at bedtime with milk. Lumarten is a mix of artemether and lumefantrine. Her doctor in Entebbe recommended she should stop taking doxycycline: “the doxy is like a lock on the door, and now someone has broken the lock, so it’s better to treat the malaria as it comes (while still using nets, bug spray, long sleeves, etc. to avoid bites) rather than keep taking the doxy every day.”

Should she stop taking doxycycline and should she be taking the Lumarten with milk? Thank you very much.

ANSWER

I am not personally familiar with Lumarten, but these antimalarials are often taken with food. Of more concern is that she has been given a sulfadoxine-pyramethamine treatment—these are no longer recommended as first line treatment against malaria, and so she should just take the artemisinin-based combination therapy (artemether-lumefantrine is such a combination therapy).

In terms of the doxycycline, I do not understand the doctor’s advice. There is no harm in continuing to take doxycycline after having malaria, and in fact it might prevent re-infection! Of course this depends on how long she is still in Uganda for—the doxy must be taken for four weeks after leaving the malarial area, so if she is returning home soon, she should weigh up the continued preventive benefit against the inconvenience of a long continuation of taking the medication. In general, I don’t like the doctor’s attitude that your daughter should just accept continuing infections with malaria, and “treat them as they come.” It’s much better to use all available methods for prevention. One thing to consider is that dairy products inhibit the uptake of doxycycline, so if your daughter was also taking her doxy with milk (some doctors mistakenly advise this, to prevent stomach upsets when taking the medication), that might have been one reason why she still got infected.

Malaria Fever and Recovery

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QUESTION

My 21 year old daughter spent 4 months on a study abroad program in Dakar. A week before returning home she started having night fevers and would complain of retrosternal pain and rib and neck and shoulder pain. The next day she would be fine.

The episodes came every other day and eventually it occurred to her that it might be malaria. It was evening so she went to a pharmacy for a rapid diagnostic test which they didn’t have but they felt she had malaria based on her symptoms and gave her a 3 day course of artesunate-mefloquine.

She returned to the United States and a day after taking her last dose, she was seen by a physician and tests were done which showed that she had contracted Plasmodium falciparum malaria. Other than the smears, all her lab tests and CXR were normal and there were no abnormal findings on physical exam, in fact she was the picture of health.

We were told that she was cured and that no follow up was necessary and that she could continue with her planned trip to Thailand the next day. About 6 hours before boarding the plane to Bangkok she developed fever of 100.9 but had absolutely no other symptoms or pain. About an hour later she had a bout of diarrhea. She had one more low grade fever on the flight (99.8). I spoke to another physician who seems more familiar with malaria and was told that she is not actually cured and may continue to have episodic fevers and symptoms for a while or it’s possible she was just suffering from an ordinary garden variety gastrointestinal bug.

I have many questions. I understand that her malaria is the most virulent type. How is it that all her lab work and physical exam is normal 1 day after completing treatment? Can we expect it to remain normal? What causes the episodic fevers if she is supposedly cured? She is on doxycycline again prophylactically (which she was on in Senegal) while in Thailand. Should she be on something else since she did contract malaria on doxycycline? (She took it religiously). Thanks for any advice. She will be seeing a physician in Bangkok ASAP, but since I won’t be there to ask questions, I am hoping you can give me some answers. Your site is the best information I have found on malaria.

ANSWER

Many thanks for the comprehensive information you have provided regarding your daughter’s condition. Even though your daughter did have the most virulent form of malaria, she was very smart to seek treatment relatively promptly, and lucky to receive appropriate medication (artemisinin-based combination therapies, such as artesunate-mefloquine, are recommended by the World Health Organization as first-line treatment against malaria). It is likely due to this prompt and effective action that her lab tests and blood parameters were all normal so soon after treatment; had she waited longer for treatment, the consequences could have been much more severe. No resistance to this medication has been detected in Africa as of yet, so she should be fully cured and thus her health should remain stable; a blood smear, where her blood is examined under a microscope, can determine this; this is a very standard procedure so could easily be carried out in Thailand if she wants.

Fever is a side effect of the body’s immune system responding to a disease threat, so it is not uncommon for some symptoms to carry on after treatment. In addition, mild side effects of anti-malarial medication can often mimic the symptoms of malaria itself, including fever and nausea.

Given also the (entirely reasonable) possibility of an additional, unrelated stomach bug, I suspect that your daughter has successfully beaten off this malaria attack, and while she should remain vigilant if similar symptoms arise again, her health in the future should not be adversely affected at all by this episode.

Also, as mentioned briefly above, medical professionals in Thailand should be well equipped to diagnose and treat malaria if she suspects she has been reinfected. It is worth noting that malaria in south-east Asia has shown signs of resistance to mefloquine (as well as other drugs, such as chloroquine and sulfadoxine-pyrimethamine), so if she does require treatment while there, she should make sure the medication they provide does not contain any of the afore-mentioned compounds.

Regarding doxycycline, it’s great that your daughter took it religiously—that is certainly the first step towards protection. Randomized placebo controlled trials have shown it is between 92-96% effective in preventing P. falciparum malaria, which is very good, but obviously not 100% perfect – even when taken perfectly, some infections do occur. In addition, there is some data which suggests that dairy products, taken together with doxycycline, may limit  the uptake of the drug. This is rarely communicated to patients, who are instead contrarily told sometimes that taking the pills together with dairy products can reduce side effects! As such, please let your daughter know that she should avoid dairy products for 2-3 hours around the time she takes her doxycycline.

Malaria in Ivory Coast

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QUESTION

I am going to work in the Ivory Coast on an oil and gas platform out at sea I will be in the Ivory Coast for about 30 Days and home for 26 Days and back in the Ivory Coast for 30 Days this could go on for a couple of years. What would you suggest that I take for anti malaria? Would O need a prescription or can I get it from the chemist?

ANSWER
You usually need a prescription to get anti-malarials. None of the available anti-malarials are really recommended for long-term use, except possibly for doxycycline, and since that one requires you to take for four weeks after you have left the malarial area, you might find yourself taking a pill every day for several years! Some people on doxycycline experience sun sensitivity as a side effect, which means it might not be the best choice for people working outdoors in the tropics.

Likewise, Lariam must be taken for four weeks after leaving the malarial area, but is only taken weekly, so it might be more convenient. Lariam is unsuitable for people with certain psychiatric disorders, and many people report side effects such as anxiety and increased aggression. Moreover, I am not sure what the recommendations are regarding long term use.

Malarone (atovaquone-proguanil) is convenient in that it only has to be taken for one week after leaving a malarial area, but again it is a daily pill, and while it probably has the least number of side effects, it is also the most expensive, and could be prohibitively so for long term use.

So, as you can see, there are pros and cons with all the main forms of preventive anti-malarial medications! Since you will be working out at sea, I actually wonder how great the risk of malaria actually is—the mosquitoes which carry the malaria parasite require stagnant freshwater in order to breed, and so if the platform does not contain these areas of still freshwater and if you are sufficiently off-shore so that mosquitoes cannot fly readily from the mainland, you may actually find there is not very much malaria there, and you will only be at risk if and when you visit the mainland.

In those cases, you could look into taking Malarone or another type of medication to protect you when you are on the mainland. In addition, for peace of mind, while on the rig you could use other types of prevention against malaria, such as sleeping under a long-lasting insecticide treated bednet at night and taking care not to be bitten by any mosquitoes that might be around.

As such, I would advise you trying to find out how far the platform is from the mainland and whether there is known malarial risk there. If there is, then you should talk to your doctor about the above anti-malarial drugs and decide which one would be best for you, if any—like bednets, there are also measures you can take to protect yourself from mosquitoes which can also be very effective is used regularly and correctly.