Talk:Mefloquine

Dreams

This drug is crazy, it gives me insane dreams. —Preceding unsigned comment added by 122.167.178.159 (talk) 15:00, 28 April 2008 (UTC)

This is an entirely useless article. An article on a drug should contain : introduction. chemistry. pharmacological actions. adverse effects. Uses. medical and economic importance. As written the article can only be described as idiotic. Look, cars cause many many many injuries and deaths, but an article on "automobiles" that is more than 505 devoted to injuries wouldn/t pass as a decent article. If I get time I'll rewrite. —Preceding unsigned comment added by 64.251.32.254 (talk) 05:57, 3 March 2009 (UTC)

The majority of the information provided is from peer reviewed papers mostly from researchers at Walter Reed where mefloquine was invented who are currently researching replacements for this drug.

Any revisions or postings should include any conflict of interest statement with the drug manufacturer or the pharma industry. Economic importance is irrelevant.

There are several safe alternatives to Mefloquine....any analogy to automobile safety is irrational.

Dr. Prune's comments above are inaccurate and misleading. Per Walter Reed, 1 in 10,000 will be hospitalized, 25% will have neuropsychiatric side effects. —Preceding unsigned comment added by Moewackit1 (talk • contribs) 04:35, 6 March 2009 (UTC)

Problem with redirects

Can an editor help with this problem? Larium somehow (I can't track it) redirects to this page. The problem is that Larium, although a common misspelling of Lariam, is also a genus of brachiopod. A disambiguation page is needed, rather than a redirect. Thanks, Nadiatalent (talk) 15:50, 12 April 2009 (UTC).

Never mind, fixed it. Nadiatalent (talk) 17:55, 14 June 2009 (UTC)

Any G6PD issues?

Other antimalarials have issues with people of mediterranean descent/people who have G6PD, in some cases.

Does this drug? —Preceding unsigned comment added by 174.101.136.61 (talk) 04:31, 7 August 2009 (UTC)

Nasty drug

Warning! A friend of ours who suffered from malaria while in Africa was prescribed Lariam, and acquired Lariam toxcity. Symptoms: She thought she was going insane. Just broke down functionally. A cross check with a friend of hers who also was prescribed this in Africa revealed that she had the same symptoms diagnosed back in the States, Lariam toxicity. This stuff is bad news... —Preceding unsigned comment added by 151.207.242.4 (talk) 17:16, 28 July 2010 (UTC)

Guantanamo

It seemed Mefloquine was given to Guantanamo prisoners as - so it is claimed - a preventative measure against Malaria. In many cases it appears they were treated against their will. Should this be worked into the article?

http://www.andyworthington.co.uk/2010/12/02/all-guantanamo-prisoners-were-subjected-to-pharmacological-waterboarding/ —Preceding unsigned comment added by 213.122.248.226 (talk) 18:04, 7 December 2010 (UTC)

No, I don't think it would be relevant at all, even if it were based on a reliable source. -- Ed (Edgar181) 18:08, 7 December 2010 (UTC)

Ed, The credible sources for this info are the Army public affiars officer and former GITMO hospital commanding officer CDR Shimkas who readily admitted to Jeff Kaye of Truth-out.org that treatment dosages of Mefloquine at 1250 mg were administered to all GITMO prisoners on their arrival whether they had malaria or not. No prescreening for malaria was performed on any of the prisoners. Hoever I do agree that this issue should not be addressed in the Mefloquine article on wikipedia until all the facts are known.Moewackit (talk) 17:46, 17 March 2011 (UTC)

Mefloquine does not provide protection in the initial dosages

Ref 15 and 17 From Walter Reed, Bethesda Naval Hospital, and others reveals that it takes 7 to 9 weeks before you have enough Mefloquine in your blood to prevent Malaria. Doxycycline provides immediate protection. See the newly added comments and reference 15 and 17.Moewackit (talk) 17:18, 17 March 2011 (UTC)

External Links articles removed

Two external links were removed due to their violation of the Wikipedia "neutral point of view" policy due to their paid status with the company that manufactures Mefloquine.

The primary author of the article "The position of mefloquine as a 21st century malaria chemoprophylaxis" is a paid consultant to the drug company and the other authors are drug company employees.

The conflict of interest statement states: "This paper is based on data collated for an F. Hoffmann-La Roche regulatory update. PS was the external consultant who received consultancy fees for preparing the regulatory update. PS has also received research funding and/or speakers' honoraria from GlaxoSmithKlein, F. Hoffmann-La Roche and Pfizer.....MA, LR, MTS, HGR are employees of F. Hoffmann-La Roche, Basel, Switzerland"

The external link to the JAMA paper "Controversies and Misconceptions in Malaria Chemoprophylaxis for Travelers" was also removed since the co author is also the primary author of the the "21st century" paper above.

This paper is also misleading in equally comparing mefloquine, doxycycline,and atovaquone-proguanil since it makes no statement that Mefloquine can take 7 to 9 weeks to be effective.Moewackit (talk) 17:17, 17 March 2011 (UTC)

NPOV

This article reads like it was written by someone with a poorly-disguised agenda to discredit the drug. It is almost comical how unprofessional it sounds. The whole thing should just be blanked and rewritten from scratch. —Preceding unsigned comment added by 71.185.49.174 (talk) 21:16, 12 March 2011 (UTC)

re written by whom?....by a bought and paid for drug company hack in yet another "comical" "peer reviewed" expose using cherry picked twenty year old data to once again gloss over and mislead the public about the neurotoxicty safety issues and the 7 to 9 week efficacy defect?? By the way, when are you going to tell people about that?....that they can take the drug for two weeks before a trip, then travel to a malaria area for a two week vacation and not be protected the entire time they are in country???? We took down the newspaper articles and only post journal papers...what more do you want? Moewackit (talk) 16:43, 17 March 2011 (UTC)

I think this article is more in danger from your foaming-at-the-mouth ranting than it is from any imaginary "drug company hack". 71.185.49.174 (talk) 01:14, 17 March 2011 (UTC)

Yes, sorting the factual warnings from the paranoid delusions that do not hold up to any statistical analysis is an insurmountable task with Moewackit believing it to be his personal webpage. 64.180.192.64 (talk) 22:17, 18 March 2011 (UTC)

Just posting the info from competant authority and legitimate sources that you don't want the rest of the world to see....by the way, you never answered the question about the 7 to 9 weeks....Moewackit (talk) 16:43, 17 March 2011 (UTC)

NPOV2

The information posted in this article is a compilation of the latest information from "professional" peer reviewed sources with no posted conflicts of interest. It is not an advertisment for the drug.

It also presents the latest policy statements from the "professionals" at the US Department of Defense including Bethesda Naval Hospital and Walter Reed where the drug was invented. The intent is to properly update the public on this latest unbiased research and information that continue to negate the safety and effacacy of Mefloquine.Moewackit (talk) 16:41, 17 March 2011 (UTC)

The corporate smoke screen

The corporate marketing literature for Mefloquine always includes three key points to give the illusion the drug is safe and that if you don't take it, you will catch malaria and die........

1. The corporate marketeers use the statement "24 million people have safely taken the drug worldwide". There is no data to support this claim. Why?....for several reasons...... A. Most people who take Mefloquine rarely report adverse effects to their doctor who issue the drug to them because i. they have the side effects when they have travelled far away to another country ii. the initial side effects are mainly psychiatric. The patients end up back in their home country after their "vacation" and see a psychiatrist for anxiety and panic attacks. The psychiatrist have no experience with Mefloquine or toxic poisoning from medications.

So travel doctors issuing the drug rarely hear of the problems it causes, thus leading to the false illusion that it is safe......

B. To make matters worse, the FDA adverse reaction reporting system called "MEDWATCH" is broken. This is one of the means for the FDA to collect postmarketing data. Since the data is grossly undercollected, it gives the illusion that Mefloquine is safe.

So unless the drug company has personally received data from all 24 million people who took the drug, their claim is baseless.

2. The corporate marketeers will also iniate any literature with a good dose of fear that malaria will kill you. This is pretty much true if you go to an area with a high transmission rate. What they have failed to tell people over the past 20 years is that Mefloquine may not work in preventing malaria in the first 7 to 9 weeks (two months) a person takes it. Of the 255 US Marines travelling to the very high transmission area of Liberia in 2003, 44 of them contracted cerebral malaria even thoug they had been taking mefloquine. The medical command concluded after this incident that the marines would have been better protected taking Doxycyline or Malarone since they provide immediate protection.

3. The corporate marketeers and apologists for the drug will also downplay the side effects by saying they are "rare" and only occur in 1 in 10,000 people.....this is a gross mis-statement.

The reality is that 1 in 10,000 taking Mefloquine will be hospitalized with a much larger 25% experiencing neurospychiatric side effects.Moewackit (talk) 18:47, 17 March 2011 (UTC)

Moved

I'm unfamiliar with the syntax for using wikipedia, but I recently found a US patent for the selective use of the (+)enantiomer of mefloquine, which also references various other papers to the same conclusions. I've put this in the references, albeit probably in the wrong format.

This entry has a great deal of alarmist claims about mefloquine. They are claims based often on anecdotal accounts of side effects, side effects that sometimes accompany the high therapeutic dose levels, or on studies (with rats for example) in which test subjects are given levels much greater than a normal prophylactic or even therapeutic dose. Unfortunately the results of these particular studies are being represented as if they are the expected results of normal prophylactic use and are thus misleading and, as I have said, alarmist. The tone of this account should be a little more sober and balanced. The extreme views should be represented but they should be represented against rigorous mainstream studies for comparison. If not, this page will remain biased. see http://www.rxlist.com/cgi/generic2/mefloq_ad.htm 216.8.121.1 22:54, 29 January 2007 (UTC)

There's quite an emphasis on the side effects. I think the risk of side effects is about 4% with the risk of severe s/e being about 1 in 10000 (i.e. psychiatric disturbance). When I get time I will find some evidence and put them in. Dr prune 11:43, 26 January 2006 (UTC)

The risk is higher: http://www.jpharmtechnol.com/abstracts/volume22/January-February/32.html http://www.journals.uchicago.edu/CID/journal/issues/v33n7/010125/010125.html http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14604928

Dr. Prune,

The following is an excerpt from a peer reviewd papaer from the drug researchers at Walter Reed Army Institute of Research where the drug was invented. Walter Reed in Table 1 indicates that the neurotoxicity of Mefloquine is 25 µM(Chloroquine is 600 µM and Quinine is 900 µM):

The antimalarial potential of 4-Quinolinecarbinolamines may be limited due to neurotoxicity and cross-resistance in mefloquine-resistant plasmodium falciparum strains. Dow, GS et al., Walter Reed Army Institute of Research (WRAIR), Antimicrobial Agents Chemotherapy, 48(7):2624-2632 (2004). Antimicrobial Agents and Chemotherapy, July 2004, p. 2624-2632, Vol. 48, No. 7.

"Adverse central nervous system (CNS) events have been associated with mefloquine use. Severe CNS events requiring hospitalization (e.g., seizures and hallucinations) occur in 1:10,000 patients taking mefloquinefor chemoprophylaxis (22). However, milder CNS events (e.g., dizziness, headache, insomnia, and vivid dreams) are more frequently observed, occurring in up to 25% of patients (22).

"we recently showed that mefloquine severely disrupts calcium homeostasis in rat neurons in vitro at concentrations in excess of 20 µM, an effect closely related to the acute neurotoxicity of the drug in terms of dose effect and kinetics (10)."

However, the drug crosses the blood-brain barrier and accumulates as much as 30-fold in the central nervous system and mefloquine brain concentrations as high as 50 µM have been reported in human postmortem cases (14, 21). Mefloquine brain concentrations as high as 90 µM have been reported in rats given a therapy-equivalent dose rate, with concentrations in subcompartments in the brain exceeding 100 µM (2). Since it has long been known that a prolonged disruption of neuronal calcium homeostasis may lead to neuronal cell death and injury (6, 13), it is reasonable to suppose that such events may contribute to the clinical neuropathy of the drug."

Essentially, treatment level concentrations can develop in the CNS with prophylactic use.

Additionally, Walter Reed published the following paper in Mar 2006 regardign treatment level brain stem damage in rats:

Mefloquine Induces Dose-Related Neurological Effects in a Rat Model G. Dow,1* R. Bauman,2 D. Caridha,1 M. Cabezas,3 F. Du,4 R. Gomez-Lobo,3 M. Park,2 K. Smith,1 and K. Cannard1 Divisions of Experimental Therapeutics,1 Military Casualty Research,2 Psychiatry and Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, Maryland, 20910,3 FD Neurotechnologies, Inc., P.O. Box 785, Ellicott City, Maryland 210414. Antimicrobial Agents and Chemotherapy, March 2006, p. 1045-1053, Vol. 50, No. 3.

It states:

1. "At the time this study was conceived, no formal FDA guidelines for neurotoxicity testing existed. In contrast, first-tier neurological screens, such as those recommended by the U.S. Environmental Protection Agency (EPA), are often employed to detect a broad range of possible neurological effects that may be induced by uncharacterized test compounds (43)."

The FDA "approval" process in 1970 did not require testing for neurotoxicity since no protocol existed at the time. Apparently it still does not exist since the Walter Reed researchers had to use a test protocol from the EPA to write this paper.

2. "It is also important to point out that the mefloquine-induced brain stem injury revealed by silver staining is permanent in nature."

Lastly, Walter Reed recently released a funding document STTR A06-T034 Neurotoxicity Associated with Mefloquine, an Anti-Malarial Drug. (see http://www.acq.osd.mil/osbp/sbir/solicitations/sttr06/army06.htm ) This document calls for the development of a commercially available "safety test" for Mefloquine users.

Proponents of Mefloquine report the drug to be "safe and effective". Then why would it need a "safety test"?

24NOV2006

If you read the actual request, it talks about a single nucleotide polymorphism (SNP) which may and may not control whether someone will react badly to the drug. Basically, the idea is that if that's true, the drug is fine for most people and you could figure out based on genetic testing who would be affected. I think in terms of blood transfusions, so the parallel example would be a unit of type A blood. If you give it to someone with type A or AB, it'll probably be OK. If you give it to someone with type B, it's bad news. You just have to know who's type A and who's type B (and/or lots of other complications specific to transfusion compatibility that screw up my analogy). SDY (talk) 19:53, 13 April 2011 (UTC)

Referencing

Wikipedia is to be based on review articles (secondary sources) ideally rather than primary sources. I shall work on this. Doc James (talk · contribs · email) 19:34, 13 April 2011 (UTC)

You just took this article back 15 years to the old data on this drug.........You removed Dow's papers...he happens to be THE primary researcher at Walter Reed on Mefloquine...who are you to do this, have you even bothered to contact him to get is current take on the science? You make these edits simply beacause you took the drug and had no reaction. You took down the Boudreau paper from 1993 with real double blind data on efficacy. You take down the paper from Whitman about the Mairnes in Liberia which was co authored by Col McGill, Dow's boss at Walter Reed and Milhouse who preceeded McGill and was also part of the original FDA approval panel. The people are THE experts on Mefloquine.....You take down the Ellen Embry letter.....as assistant secretary of defense, she is the Army Surgeon General's boss. Her letter went to all US services, not just the Army. Essentially you eliminate all the latest peer reviewed research on mefloquine, yet you leave up two references to Schlagenhauf who is a paid consultant to Hoffman LaRouche. Please identify your connection to Hoffman LaRouche or any association you have with the company and its representatives..... I put in a complaint to the Wikipedia editors yesterday. Moewackit (talk) 16:49, 14 April 2011 (UTC) Moewackit (talk) 16:45, 14 April 2011 (UTC)

Wikipedia is based on review articles. Please assume good faith. I have no connection to any pharma company. Please read WP:MEDRS. If the above researchers publish review articles on the topic we can use their papers, if not we will not. Cheers. Doc James (talk · contribs · email) 17:32, 14 April 2011 (UTC)

The Brown university paper on Mefloquine conexin blockage was reviewed in the 17AUG2004 edition of PNAS vol 101 no. 33. Whitmans' paper on the marines in Libera was published in the American Journal of Tropical Medicine and Hygene 83(2) 2010 pp258-265. Yu's paper about vestibular hair cell damage was published by Springer in Neurotox Res 22Sept 2010. Boudreau's paper from 1993 showing hard data on the 7 to 9 weeks was published in Tropical Medicine Parasitol 44(1993) pp. 257-265. Dow's paper discussing his research on the 4 analogs to Mefloquine was published in July 2004 in Antimicrobal Agents and Chemotherapy pp. 2624 and 2632. Dow's rat study was published in the same jouranl in MAR2006 pp 1045-1053. Dow's paper on the disruption of calcium homeostasis by Mefloquine was published in the Malaria Journal in 12 June 2003. THese are all second source published peer reviewed articles by the top experts in this feild, yet you took all these articles down.... Even Ellen Embry's policy letter was distributed DoD wide to all the troops and you removed it and left the Surgeon General's letter in place. Moewackit (talk) 21:32, 14 April 2011 (UTC)

Molecular mass

The medication guide indicates a calculated molecular weight of 414.78. This is different from the article. Is it possible that the higher weight is the hydrochloride salt and the weight (well, mass) in the article is the free base? If so, which should we ues? SDY (talk) 18:09, 14 April 2011 (UTC)

The MW in the article is for the free base, and the MW in the medication guide is for the hydrochloride salt. Wikipedia:WikiProject Pharmacology prefers that all info in the {{drugbox}} be for the active pharmaceutical ingredient (free base in this case), not for any salts because salt forms can vary depending on formulation, manufacturer, etc. -- Ed (Edgar181) 19:19, 14 April 2011 (UTC)

2008 review withdrawn?

This is listed as withdrawn. Anyone know why? It seems like it would be a useful source for the article. This is another excellent source, though it outright admits that some of the evidence is weak. SDY (talk) 22:50, 14 April 2011 (UTC)

Not sure Cochrane just does that once in a while. This one looks good too Doc James (talk · contribs · email) 23:00, 14 April 2011 (UTC)

Ellen Embry letter

Doc James,

You need not have taken down the letter from Ellen Embry that says for all of the Department of defense to switch to Doxy while still leaving up the arm surgeon general's (ASG) letter. A problem that came from the ASG's letter in the middle east. Since the ASG is army only, then the Air Force, Navy and Marines do not come under his command. They have their own surgeon generals. Also, in Iraq and Afghanistan, the army can come under a joint command like CENTCOM which may be run by the Air Force or the Navy at any given time. So the joint medical types under CETNCOM are able to ignore the ASG letter since they are not under the army command. Embry is the Assistant SECDEF for health and outranks the Army Surgeon General. Her letter covers all services, no just the army. It makes no sense to take her letter down and leave the ASG's. I am a retired Navy commander who served in these wars. You should defer to my experience particularly since you are Canadian, to determine which of the letters should be posted. Please return the Embry letter to the article beacuse it does any US military member a disservice to no have it posted. Moewackit (talk) 20:23, 15 April 2011 (UTC)

I also request that the word "rare" in the article be more narrowly defined to only apply to hospitalization only and not to all neuropsychiatric side effects. 1 in 4 people who take this drug have neuropsychiatric side effets. This is hardley considered "rare". There is history to the use of this word too. Roche uses "rare" to give the illusion that the drug is "Safe" anhd "effective". Considering the Army and the drug company skipped the phase III safety trials in the 1970's, and considering the latest data from Walter Reed, the drug in not safe. However, using the marketing term "rare" in a very general way makes the layman assume that "it will never happen to me"......I was the "rare" 1 in 10,000 that was hospitalized. I know several others. As a GP/ER doc would have very limitied exposure to this drug compared to someone like me in the military who saw this stuff given out to hudreds at any one time. I personally witnessed a much larger cohort have many many different side effects from dreams to suicide. It is now being assumed that the vivid dreams are the lead in to some very serious nerve damage. This is to be published soon.Moewackit (talk) 20:38, 15 April 2011 (UTC)

We are not here to discuss our own personally opinions about medications. All that you mention is very US specific. But to clarify my real issue with much of what was there before regarding the US military was the excessive use of long quotes. We wish to summarized different groups opinions on a topic and reflect them here. If you wish to summarized Ellen's position as spokes person for the US DOD than please feel free to do so and add. A few of us I am sure will verify your summary. This is how Wiki works. Doc James (talk · contribs · email) 23:17, 15 April 2011 (UTC)

Then replace the statements about the Army switiching to Doxy with Embry's letter switching the entire department of defense, not just the Army, to Doxy. Again, she is not just a spokes person....the Army Surgeon General reports to her. She reports to Gates, the Secretary of Defense, who then reports to Obama, the president. If you only focus on just the Army's position, you will be incorrect. The Army Surgeon General does not dicated medical policy to the Navy, Marines or the Air Force. Embry does.......

Also, regarding long quotes....I did not feel it was appropraite for me to shorten any of the verbage. I just copied it as I as I read it with the assumption that if I did any edits, I would get slammed.

And yes, most of what I posed is US specific because the US created the mess, established a corporate relationship with the drug comapny (Mefloquine was the first Public Private Venture with any drug comapny), continued to back the drug in the early 2000's out of fear Roche would pull it off the market at the same time several thousand adverse reports had been made......and now they are trying to fix the mess. I think it is in the public interest that they are provided updates to the latest research from the Army. The only thing that came out of Canada was the disbanding of the airborne unit that Matchee was in after the mess in Somalia.....Moewackit (talk) 00:35, 16 April 2011 (UTC)

Feel free to make those changes. Doc James (talk · contribs · email) 03:27, 16 April 2011 (UTC)

References are still needed. Thus restored what was there before until they are provided. Doc James (talk · contribs · email) 23:30, 16 April 2011 (UTC)

a section called "recent developments"

Doc James,

Can there at least be a section at the bottom to provide updates including shorter quotes from the papers you removed?

The Boudreau paper and the Whiltman paper on the Marines in Liberia are very significant realting to the poor initial efficacy of the drug. People need to know that they can still not be protected from malaria even though they are on Mefloquine. The only reason why they don't catch malaria is they go into areas with a very low malaria innocualtion rate. Whitman's conclusion is very important. To have McDill and Milhous co author that paper is stunning since they were the original proponents of Mefloquine at Walter Reed.

You really need to understand that the Army was caught between a rock and a hard spot in early 2000 when Malarone was not cost effective. With only one drug (Doxy) left in the stable, the Army decided to keep positively promoting the drug and cut a deal with Roche to keep Mefloquine on the market. I am not making this up. This is first hand information from the source. This did the general public a big disservice since the Army came out promoting Mefloquine all the while they were looking for a safer version or eliminate it entirely. This is why Dow asked me to take his papers to congress since he could not. He worked for both Milhous and McDill. They have since done an about face with co authoring the Liberia paper which came out after Roche took MEfloquine off the market. Yet no one has told the public! And the drug keeps being prescribed.

— Preceding unsigned comment added by Moewackit (talk • contribs) 15:26, 16 April 2011 (UTC)

We really need to use review articles. This is essential. Doc James (talk · contribs · email) 23:28, 16 April 2011 (UTC)

Doc James,

The Whitman paper on the Marines in does not originate the science behind the 7 to 9 week efficacy issue. In fact it clearly references the Boudreau paper from 1993. In fact Whitmans study on the Marines in 2003 confirms the double blind study on the marines in 1993. Is then the WHitman paper a second source??????

Whitman T.J., Coyne P., Magill A., Blazes D., Green M., Milhous W., Burgess T., Freilich D., Tasker S., Azar R., Endy T., CLagett C., Deye G., Shanks G., Martin G. | title=An Outbreak of Plasmodium falciparum Malaria in U.S. Marines Deployed to Liberia | journal=The American Society of Tropical Medicine and Hygene | year=2010 | volume=83 | issue=2 | pages=258–265 | doi=10.4269/ajtmh. 2010.09-0774 | pmid=20682864 | pmc=PMC2911167}}</ref>

If so, I want to re-post the following conclusion from Whitman under the Efficacy section.....

".....for the next precipitous deployment into a high transmission area,....the use of a drug that is dosed weekly, can take up to 7 to 9 weeks to achieve protective concentrations, and requires four weeks of post-exposure is clearly suboptimal....the use of chemoprophylactic drugs such as atovaquone/proguanil(Malarone) or doxycycline, which provide protection after the first dose, would offer more rapidly attainable malaria chemoprophylaxis...."

The general public needs to know that it can take 7 to 9 weeks for this drug to be effective. Wikipedia is here to provide current scientific opinion not cutting edge results.Moewackit (talk) 23:37, 16 April 2011 (UTC)

No it is not a review article / secondary source. To find review articles go to pubmed and click on the review button.Doc James (talk · contribs · email) 00:02, 17 April 2011 (UTC)

Removed section

This

===Alcohol use===

The US Department of Defense has posted significant warnings to military memebers and unit leaders against alcohol use while taking Mefloquine. Various country versions of the Mefloquine product guide also warn against the use of alcohol while taking the drug. Alcohol use and/or the use of any other agent or medication that reduces liver function or colon function, such as opiate pain killers, can significantly increase the chances of a serious neuropsychiatirc episode and permanent central nervous system damage.

Mefloqine has a blood plasma half life of 15 to 33 days. Since it is lipid solubale and can cross the blood brain barrier, the half life of Mefloquine in the central nervous system is much longer. The drug is also primarily metabolized through the bile and the colon and not through the bladder. Since the drug is taken every 7 days, proper liver function is necessary to keep a user from breaching the toxic threshold and elevating Mefloquine to treatment levels in the brain and central nervous system.

needs references. Doc James (talk · contribs · email) 23:28, 16 April 2011 (UTC)

you took one of them down already...the Dow paper on the 4 quinolonecarbinolamines cleary states that Mefloquine can go into the CNS 30 fold over plasma. I also wrote verbatum what Dow told me in one of the many conversations I had with him.

Here's the others: http://www.lariaminfo.org/pdfs/MefloquineMilitaryFamilies.pdf http://www.lariaminfo.org/pages/pdfs/deployment-health-mefloquine-for-clinicians-2005-160.pdf

15 to 30 day half life: http://www.lariaminfo.org/pages/wp-content/uploads/va-white-paper-long-term-mef-eff-04.pdf

I have more......Moewackit (talk) 23:50, 16 April 2011 (UTC)

We need printed (i.e. published) sources. We can't verify what he might have said to you, however true it might be. The alcohol references in the .pdfs that are provided don't specify a mechanism, and the sources there are gray literature at best and don't really get to the standard of sourcing we'd like to see. SDY (talk) 04:21, 17 April 2011 (UTC)

SDY/Doc,

You must understand that it is dangerous to take mefloquine while drinking alcohol. Removing an alcohol warning is not good form....Roche deliberately did not include an alcohol warning in the product guide......they were selctive by country at where they would include it. The early Canadian drug label had the alcohol warning. So ask yourself why the .pdf's from the largest US user of mefloquine have multiple warnings about alcohol and you don't see it on the drug label.....

Wha tis the difference between warnings on written guidlines from the DHCC at Walter Reed where the drug was invented and any information found on the drug label? I can see it being a gray area if it were some obscure publication from a travel clinic in South Carolina, but Walter Reed is Gray Literature?...come on, you guys are taking this a little too far.....the general public reads this and needs the information, not just pharmachemists.

the mechanism with alcohol should be obvious....the drug is lipid soluable. Moewackit (talk) 06:49, 17 April 2011 (UTC)

There is a lot of review that goes into the drug labeling, even if it isn't the peer review we'd prefer to see. That something isn't there isn't all that conclusive, but if the alcohol mechanism is "obvious" then it should be fairly easy to cite. If there are simply advisories not to use alcohol while on mefloquine, that would be supported by the sources you've given. The mechanism is specialist knowledge and requires sources that actually put the pieces together. "The threshold for inclusion in Wikipedia is verifiability, not truth: whether readers can check that material in Wikipedia has already been published by a reliable source, not whether editors think it is true." That's the first line of our verifiability policy, and it's the only reason Wikipedia isn't just a bunch of people on the internet makin' stuff up. SDY (talk) 16:40, 17 April 2011 (UTC)

FDA approval process skipped safety tests...

Doc James,

More info to bring you up to speed:

A paper from LCOL Croft. He is the head infection disease specialist for the British miltiary. The brit miltiary has significantly more time-in-country expereince with malaria.

http://www.lariaminfo.org/pages/pdfs/alessonlearntlariamhalfancroft.pdf

I also had a direct conversation with Col Milhous of Walter Reed. He participated in the "FDA" approval process with Roche in the late 1980's. We have the transcript from that. They definiteluy ONLY focused on compliance and compeltely ignored saftey and efficacy. Milhous told me that the original preferred dosage from Dr. Lobel was a 4 day loading dose of 250mg per day followed by every TWO(2) weeks. He said that when participant's serum level dropped below 400 nangrams, they contracted malaria. This is why they then switched to once a week. He also said that during the approval process, the need for a loading dose simply "went away"......the Boudreau 1993 paper confirms the need for the loadiong dose, however, the FDA will not approve it.Moewackit (talk) 00:02, 17 April 2011 (UTC)Moewackit (talk) 00:07, 17 April 2011 (UTC)

Mefloquine edits

"moved from my talk page" Doc,

When discussing Mefloquine, you must consider four areas seperately.....safety, tolerability, compliance and efficacy.

The 1 to 2 weeks only has to do with tolerability.....you make a big reach to assume it has to do with efficacy....particularly when Ref. 1 says nothing about it. Did you not get the point about loading dose that was not FDA approved?

Yes, steady state means efficacy...a person needs more than 500ng per ml serum level to be protected and it takes more than two weeks to get to that level. I have actaully seen papers that say 1000ng/ml.

I took the 7 to 9 weeks out a review paper(from Schlagenhauf too...) and have two non review papers fromt he US military to back it up, and you remove it. Then you replace it with 1 to 2 weeks from a website???........which makes no realtion between the 1 to 2 weeks and efficacy....It just says to take it for 1 to 2 weeks....The 1 to 2 weeks realtes to the possibility of an initial reaction...to see if a person is one of the rare exceptions that has a reaction in the first few pills. They don't want this happening when the person is already on their trip. It has nothing to to with building up to a protective level. Call Doc Whitman at Bethesada and he will explain it to you.

Per your requirements, the only legitimate sources are review papers. I assume the only other legitimate source is the product guide from Roche. I am confused then why Ref 1 is allowed when the drug guides I posted from the Walter Reed Deployment Health Clinical Center that were taken down.Moewackit (talk) 16:14, 19 April 2011 (UTC)

I do not see in the paper from 1999 where it says it requires 7-9 weeks to be effective? The American Society of Health-System Pharmacists is a review. What I added is based on this line "Initiate prophylaxis 1–2 weeks prior to entering a malarious area and continue for 4 weeks after leaving the area" Doc James (talk · contribs · email) 22:33, 19 April 2011 (UTC)

Then where does ref.1 say specifically that it takes 1 to 2 weeks to be effective against malaria? If you say I am incorrect, you are just as incorrect. This is a very complicated pharmokinetics here and dumbing down the article really just confuses the issue. Do you even know why they say to take it for 4 weeks after leaving a malaria area? Moewackit (talk) 23:25, 19 April 2011 (UTC)

Lets see what others opinions of the literature is. The recommend you take it for 1 to 2 weeks before as it is affective after this time. If you could cut and paste the line here that you feel says it takes 7 - 9 weeks to be clinically effective... Doc James (talk · contribs · email) 23:40, 19 April 2011 (UTC)

Unfortunately, I do not have free access to the full text of all the review papers. However, the ref #3 in the article is pretty clear....it is also a REVIEW article:

Schlagenhauf, P. (1999). "Mefloquine for malaria chemoprophylaxis 1992-1998.". Travel Med 6: 122-123. PMID 10381965

It CLEARLY states at the bottom right of page 123 and the top left of 124: "USE of a Loading Dose - In order to reach steady state levels of mefloquine in a reduced time frame (4 days rather than the 7-9 weeks with regular 250mg per week regimen) some studies 10-13 have used a loading dose strategy of 250 mg mefloquine daily for 3 days followed thereafter by weekly dosage. This strategy has also been suggested for last minute travellers to high-risk areas with chloroquine-resistant CRPF. The advantege being rapid attainment of mefloquine protective levels (620ng/ml) within 4 days but this is offset to some extent by a higher proportion of individuals with AE using a loading dos strategy. 10,11

Also, under "Prophylactic Failures" on the middle right of page 124, it defines "Mefloquine blood concentrations of 620 ng/ml are considered necessary to achieve 95% prophylactic efficacy. A prophylactic FAILURE is defined as confirmed Plasmodium falciparum infection in persons with mefloquine blood levels in excess of the 95% protective level of 620ng/ml as defined by Lobel et al."

Again, Lobel from the CDC lead the FDA approval study in 1989......

So Doc, your assumption about mefloquine being effective after the first week ONLY applies if the user takes 250mg of the drug EVERY DAY......but this loading dose is not approved by the FDA.

Do you really want to imply that a person can achieve the 95% protective level of 620ng/ml in just the first weekly single pill dose?

NOTE: the use of the term "steady state" is synonymous with "mefloquine protective level".

In addition, if you are considering all the drug guide websites as review documents, the 1 week and 1 to 2 weeks they mention are just parroting the Roche product guide which refers to tolerability only. If they just happen to include the phrase, "to prevent malaria take 1 to 2 weeks before entering a malariaous area", that is simply prefaces the entire regimen that also is extended to include the weekly doses and the follow on 4 weekly dosages. The statement 1 to 2 weeks does not stand alone and does not relfect any of the actual data in the published stuides.

....Moewackit (talk) 03:46, 20 April 2011 (UTC)

Neutrality Tag

I'm not an expert on this at all, but this article seems like it needs a disputed neutrality tag. Some paragraphs appear on first read to be highly unbalanced and one sided, using unecessary adjetives to imply authority when none should be implied. There also appears to be an editing war between several people (some have self admitted bias and use unreliable/uncitable soucres), and many sections are poorly written and use unecessary adjetives to imply authority when none should be implied.

For evidence of poor quality/neutrality, reference the second paragraph of the history section, which includes such lines as "Mefloquine was essentially authorized for public use on the basis of incomplete knowledge and at too early a stage in the drug's development." (speculative, the word essentially is being used as a weasel word, others ("incomplete", "too early") send red flags. Other examples: "To make matters worse, this post marketing data was easily discounted as anecdotal and "media hype" by an overzealous US Department of Defense". "To make matters worse" and "overzelous" appear to have no place in a balanced article. I suggest a rewrite of this paragraph by an unbiased, experienced source or a disputed neutrality tag. 146.79.244.130 (talk) 06:07, 22 May 2011 (UTC)

Feel free to fix these. Doc James (talk · contribs · email) 06:08, 22 May 2011 (UTC)

The "unbiased, experienced" source who wrote the review article from which thes quotes originated just happens to be the lead infectious disease doctor for the Britich military.............for 20 years the drug company and the US military glossed voer the truth about this drug. They deliberately put lipstick on this pig and the result was a lot of people have been injured or worse. There is nothing neutral about that. The review article speaks the truth about how the drug was developed. Yes, mefloquine was authorized for public use on the basis of incomplete knowledge and at too early a stage in the drug's development because the pahse III safety trials were completely skipped......yes, this post marketing data was discounted. Gen Peake, the US army surgeon general even called it "internet mystique" in sworn testimony before Congress. These are the actaul events as they happened. There is nothing un-neutral about it. The only thing that is not neutral are supporters for the continued use of this drug as a prophylactic. It is dangerous and should be stated as such. Anyone who thinks differently because of a limited personal use is a fool. Moewackit (talk) 14:46, 29 May 2011 (UTC)

The problem is that when the article sounds like an internet rant, people will assume it's just a biased editorial and ignore it. The instant you start throwing around words like "overzealous" and "to make matters worse" it becomes opinion, not facts. The facts are fairly troubling (though not, in the grand scheme of pharmacology, "worst case"), and they should stand on their own. Wailing and gnashing of teeth don't go in encyclopedia articles. SDY (talk) 16:10, 29 May 2011 (UTC)

citations needed in history section

......I get slammed for copyright issues by posting exact quotes from articles so as to not come off as being biased.....so I then paraphrase directly from a "review" article written by one of the world's experts on tropical medicine for the history section and end up with multiple "citation needed"......read the article ...it's right there. Moewackit (talk) 15:23, 12 June 2011 (UTC)