Talk:Metamizole/Archive 1

Archive 1

comment

I have removed part of a sentence suggesting that Hoechst and Merck produce Metamizole drugs they are unable to sell in their own country for 3rd world countries. This is factually incorrect as both companies are German and are obviously producing this drug for the German market too.

I also removed a reference to Ibuprofen being a lot safer - I would request data and references on this. NSAID gastrointestinal bleeds can be a bugger too. Refdoc 04:58, 16 May 2006 (UTC)

According to eMedicine, there were 4 recorded deaths caused by Ibuprofen in United States in 1998. The article seems to imply that adverse effects are usually due to overdose.

There's a number of links to studies on safety of ibuprofen in [1]. --Itinerant1 06:43, 18 May 2006 (UTC)

Dangers very unlikely to be true

Here in Hungary "Algopyrin" (metamizol-natrium) 500mg tablet is the most popular painkiller available without prescription. Hungary is a member of the European Union, not 3rd world and the procedure to authorize new medicines is very strict here and we have good chemists domestically, including three big pharmaceutical companies, Richter, Egis and ICN. So it would not be available if it was unsafe.

This whole scare is probably a 90% untrue hoax similar to the "brain tumor scandal" about phenil-alanin sweetened chewing gums. 195.70.32.136 16:51, 2 September 2006 (UTC)

Also, to say that aspirin is safer is a lie. Ad 1 nobody knows exactly how aspirin works, even though it is 120 years old. If we have no clue about its mechanism we cannot say it is safe. Ad 2 aspirin is known to destroy the tissue of stomach and cause intestinal bleedings after years. 195.70.32.136 16:55, 2 September 2006 (UTC)

I'm Portuguese and I'm taking it right now. it was prescribed by a dentist as a painkiller after a small cirugy. it's a powerful painkiller, paracetamol and ibuprofen wouldn't work, I would still have pain. I have huge doubts about being dangerous. it's a powerful drug nothing more then that. also in the article it doesn't explain WHY it was banned. I still don't known. —Preceding unsigned comment added by 92.250.116.240 (talk) 04:58, 7 January 2010 (UTC)

Paracetamol is nothing, zero, totally useless drug. Aspirin works only against fever, not pain. I am from Russia and I and my family and all my friends and collegues have been eating analgin for tens of years. It is the best drug when you have headache - extremely effective and extremely cheap (~$0.16 for 10 tablets) 128.73.201.224 (talk) 03:35, 16 September 2012 (UTC)

Common drug prescribed in Mexico and Latin-America.

I would like to note, that this is a _very_ common drug in Mexico, and that Doctors still prescribe it. I have never known anyonw to have a reaction to Metamizol aka. Neomelubrina. It would be good to know which drug bans have more of a economic/commercial purpose. This one sure sound like one. The article mentions a single boy having a problem in the US and they make a Federal Case out of it.

Well, I am allergic to it. --Pinnecco 16:10, 7 March 2007 (UTC)

Sweden lifted the ban on metamizole in 1995 and by 1999 they saw enough adverse reactions to the drug that they ended up banning it again. It's not just isolated cases. --Itinerant1 22:13, 6 October 2006 (UTC)

   It is known that the patients that reported problems were also taking other durgs.
   Hedenmalm K, Spigset O. Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole) Eur J Clin Pharmacol. 2002;58(4):265-274

Studies clearing the drug in the US

The following studies demonstrated no increase realtion between Metamizol and Agranulocytosis. FDA invitied Hoechst Marion Roussel to re-certify the product again but declined because of strategig/marketing issues

• No authors listed. Risks of agranulocytosis and aplastic anemia. A first report of their relation to drug use with special reference to analgesics. The International Agranulocytosis and Aplastic Anemia Study.JAMA. 1986 Oct 3;256(13):1749-57.
• Andrade SE, Martinez C, Walker AM. Comparative safety evaluation of non-narcotic analgesics. J Clin Epidemiol 1998; 51: 1357-1365
• CIOMS WORKING GROUP IV – Geneva, 1998 – Benefit-Risk Balance of Marketed Drugs: Evaluating Drug Signals —The preceding unsigned comment was added by 206.47.220.198

Spanish FAQ: http://www.zonapediatrica.com/Zonas/Fiebre/Dipirona/FAQ1.doc

(talk) 20:13, 15 March 2007 (UTC).

freely available over the counter in Spain

This article says that this drug is freely available over the counter in Spain... I am in Spain, looking at a packet right now (Nov 2006), just procured from the chemist with a prescription following a tooth extraction. It states clearly on the packet that a prescription is required. I will check with my local chemist before submitting an edit.

same in Portugal. my tooth was extracted, the dentist prescribed me nolotil, which is metamizole. —Preceding unsigned comment added by 92.250.116.240 (talk) 05:00, 7 January 2010 (UTC)

Peta-x 16:49, 29 November 2006 (UTC)

Yes, the previous poster is correct, I am also in Spain, (2009), I also have a packet in front of me and Metamizole is available as a prescription drug only. I also checked on-line and found the entry for the most popular Metamizole preparation in this pharmaceutical reference page:

http://www.vademecum.es/medicamento/farmacologia/n/2812/1/8/1/presentacion-y-pvp/nolotil.html

As you can see it states that Metamizole is available : "Con receta médica" meaning prescription only.

80.36.158.120 (talk) 03:44, 11 July 2009 (UTC)

IUPAC name and Molecular formula corrections

Dear wiki-editors,

I have changed the IUPAC-name for this metamizole, currently presented as sodium dipirone, by rewriting it as Sodium [(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)methylamino] methanesulfonate. This is the correct name of "such metamizole = sodium dipirone".

For the same purpose, the corresponding molecular formula has been changed to the correct form, showing sodium as: (C₁₃H₁₆N₃NaO₄S)

In fact it was graphed (C₁₃H₁₇N₃O₄S), that were not the correct form, for it not presented sodium.

EgídioCampos^Say! 15:25, 6 March 2007 (UTC)

study claiming that metamizole is safe

http://www.aerzteblatt.de/v4/archiv/artikel.asp?src=heft&id=16151 92.226.133.7 (talk) 18:36, 7 December 2007 (UTC)

Yes, meta-analyzed by an employee of the manufacturer (that day Hoechst-Marion Roussel), assuming that short-term (one week or less) treatment with metamizol is not so strongly associated with GI bleedings, however, with agranulocytosis. No mention of anaphylactic/allergic reactions whatsoever (deliberate? who knows...). And mentioning the re-introduction of metamizol in Sweden in 1995 as an pseudo-argument for safety of metamizol, which was once again nullified some 6 years later, after finding out, that agranulocytosis rates were inacceptably high (in order between 1 of 10,000 - 1 of 1,000 patients medicated). Really a strong argument for metamizol.--Spiperon (talk) 13:33, 5 August 2008 (UTC)

As also written in the German Wikipedia, mostly the death rates were compared. ASS for excample has death rates more than 10 times higher but is still commonly available. Strange. --88.68.233.119 (talk) 13:36, 15 July 2009 (UTC)

No NSAID!

Metamizole does not belong to this group. --88.70.243.244 (talk) 18:08, 12 April 2008 (UTC)

 Are you saying it does not reduce inflammation?192.88.165.35 (talk) 18:44, 29 May 2008 (UTC)

I don't know, what IP:88.70.243.244 would've say to you, but yes, you got it -- it isn't antiinflammatory (or, it is in a minimal excent, comparable to e.g. paracetamol). It is a potent analgesic, antipyretic and less so antispasmodic/spasmolytic, but it has very little antiinflammatory effects whatsoever. It isn't really a NSAID, rather an antipyretic analgesic.--Spiperon (talk) 13:19, 5 August 2008 (UTC)

I second Spiperon's comment. I think the reference to metamizole being an NSAID is erroneous and should be removed. Just one quick internet source with evidence to justify removal of the NSAID label [[2]] Nytewing07 (talk) 21:21, 7 June 2012 (UTC)

not only in the past!

Please consider that it's not all the US or UK (?). In Germany for example it's widely used - nowadays.. --88.70.253.228 (talk) 10:41, 13 April 2008 (UTC)

yes, its really strange... banned in some countries, but popular where it isnt banned. i just got it prescribed after aspirine, ibuprofen, and diclofenac didnt manage to significantly reduce the pain (i tried each one at the highest dose that the packaging allows, one after the other). i guess thats why metamizole is so popular where it isnt banned: it seems to kill pain more effectively. in the german article it says that Metamizol is the strongest painkiller that is not an acid and not an opiate. i guess when your stomach starts complaining about diclofenac and the other acidic ones, and you still want to stay away from opiates, you will want to live in a country where you can get metamizol. you just need to watch out for the symptoms of agranulocytosis, but they should be easy to spot when you are aware of the risk, and in this case the information in the german packaging advises you to immediately stop taking it and get your blood checked and see a doctor. this article should make it very clear what symptoms you need to watch out for, and what you need to do if you get those symptoms. it may be banned in the US, but many users of this wikipedia from different nations are taking it, and if everyone that would be using it would be aware of the symptoms that you need to respond to when using metamizole, there really wouldnt be a reason to ban it. but of course im biased, if i wouldnt have metamizol right now the pain and resulting sleep deprivation would probarbly have prevented me from writing this, aspirine, ibuprofen and diclofenac really failed, constant pain and only 3-4 hours of sleep per night with those, hooray for metamizol. the only drawback i noticed so far is that the reflexes dont seem to fire as fast as usual when im juggling, i drop more often than i normally would, but its still better compared to not being able to juggle at all because the pain is too strong. 79.230.3.225 (talk) 13:57, 22 June 2009 (UTC)

I fell just like you. one of my molar tooth was extracted. after I was the taking paracetamol, ibuprofen, aspirin. the pain just didn't go away it was too strong. after the extraction pain would expect to be a lot more stronger. but the doctor prescribed me metamizole. It's really strong. I don't have any pain whatsoever. I clearly see that this is a very powerful medicine. the doctor advised me to be very careful and only take it when in pain and not exceed 2 pills per day (575mg). The medicine is not widely used as ibuprofen and paracetamol but it's still used a lot. —Preceding unsigned comment added by 92.250.116.240 (talk) 05:10, 7 January 2010 (UTC)

CheMoBot Verification

I don't know what is wrong with the CheMoBot, but it is asking for verification of the ChEMBL database number, and the number is absolutely correct. Click on that link, and you see it directs you to the page on "Analgin," which is one of the brand names for metamizole. Can someone fix that X in the window? — Preceding unsigned comment added by Deejaye6 (talk • contribs) 21:22, 12 April 2011 (UTC)

Article Barely Discusses Dipyrone Itself

There is ample discussion of the controversy and safety, which is v. appropriate in a "Dipyrone Safety" article. There is no mechanism of action, no pharmacokinetics, no drug interactions, dosage, proper classification, side effects etc. — Preceding unsigned comment added by 82.81.208.107 (talk) 15:00, 29 May 2011 (UTC)

Risk of agranulocytosis; A study in Sweden published in 2002

It appears that the mean prescribed daily dose in the Swedish study was 2.7 g, and that translates into 4+ pills (is it not way too much therefore potentially hazardous dosage‽). See http://www.ncbi.nlm.nih.gov/pubmed/12051124

Thankfully it is over the counter here in Bulgaria. — Preceding unsigned comment added by Special:Contributions/ ([[User talk:|talk]]) 12:06, 11 June 2011 (UTC)

No method of action, no drug interaction, no pharmacology etc.

This page lacks history of discovery, pharmacology, pharmacokinetics, drug interactions, side affects, mode of action. All of this is available through prescription only medical journals and resources.

Currently this page is just a "controversy of metamizole" brief stub and not a proper medication page. John Holly (talk) 23:47, 6 September 2011 (UTC)

Use in Brazil

I have removed the paragraph who claimed that doctors was prescribing less dipyrone for pediatric patients in Brazil. That paragraph said pediatrics preffer Aspirin (which is totally contraindicated due to Reye Syndrome risk) or Ibuprofen. In fact, due the modern studies showing agranulocytosis is a rare complication of dipyrone use, it's largely used in clinics an hospitals, especially because it is a cheap and safe drug, which encourages its use in the Brazilian public health system, supported through funding from the state. — Preceding unsigned comment added by 189.27.149.24 (talk) 03:39 17 November 2011 (UTC)

Primary source

Hi, now people I'm writing this to mention the fact I'm adding a primary source so we can start a dialogue so that those that don't see my point of view can argue their point, while those in support of my decision can also have their say. I am a firm believer in consensus although I used not to be but all the esteemed editors of this great work that have sent me messages have convinced me of its value.

My reasoning behind adding this primary source is that I'm only using it to back up info already supported by a secondary source (namely the UN ref) and the info in it I'm using to support this secondary source is in the introduction of the primary source, which, by definition, is a minireview. The part of the primary source that I'm mentioning in the mechanism of action I'm mentioning as pure conjecture! The reason I'm trying to make an exception here is the article is pretty small after I trimmed all the primary sources out and I am using what seems like a worthy primary source. The primary source is:

Rogosch, T (January 2012). "Novel bioactive metabolites of dipyrone (metamizol)" (PDF). Bioorganic & Medicinal Chemistry. 20 (1): 101–7. doi:10.1016/j.bmc.2011.11.028. PMC 3248997. PMID 22172309. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

Now I normally wouldn't do this, but I think in this case it's reasonable to make an exception. I realise that WP:MEDRS says that primary sources should be avoided where possible, but I think this is one of those exceptions to this general rule. Fuse809 (talk) 03:30, 19 April 2014 (UTC)

Metamizole Contraindications

The section on contraindications refers to the German prescribing information.

In Israel Metamizole is approved for use in children and infancts. There is only a warning stating "use is not recommended in infants under 3 months of age or under 5 kg of weight unless deemed necessary".

Glucose-6-phosphate dehydrogenase deficiency is endemic in Israel, where Metamizole is also extensively used. The Israeli Medical association published a statement written by the Israeli Pediatrics Society and The Israeli Pharmacology Society detailing the use of medications in G6PD deficienty - according to this statement the available literature and experience in Israel does not support an association between Metamizole use and hemolysis in G6PD patients, and it can therefor be used as usual by G6PD deficient individuals. The statement (in Hebrew) can be accessed here:

http://www.assafh.org/clinic/consultation/Documents/%D7%A0%D7%99%D7%99%D7%A8%20%D7%A2%D7%9E%D7%93%D7%94%20G6PD%20-%202011.pdf

The statement is based on an extensive evidence based review the writing comitte published in a peer reviewed journal:

http://www.ncbi.nlm.nih.gov/pubmed/22149420

In Israel Metamizole is alse regarded as generally safe for use in pregnancy and lactation and is used extensively in the obstetrics department. For example here is a link to Israel's largest HMO drug information guide (in Hebrew):

http://www.clalit.co.il/ClalitAppGeneral.he-il/MedicineBook/MedDetails.aspx?id=5108

Data supporting the safety of Metamizole in pregnancy has been published based on experience in Israel & Italy: http://www.ncbi.nlm.nih.gov/pubmed/15808375

Similar data has been published based on the experience in Brazil - where metamizole is also extensively used in the general population, as well as during pregnancy and lactation:

http://www.ncbi.nlm.nih.gov/pubmed/18568358 — Preceding unsigned comment added by Amichp (talk • contribs) 23:07, 21 April 2014 (UTC)

Metamizole legal status by country2.png

An anonymous editor left this comment about File:Metamizole legal status by country2.png which is used in the article: "Description is not 100% correct, because in Russia it is sold over-the-counter without any restrictions". If someone could look into this, it would be helpful. -- Ed (Edgar181) 11:59, 22 May 2014 (UTC)

Revert due to massive misrepresentation of sources

Today's edits by Kmwittko will be reverted because of massive misrepresentation of sources. Only one - serious - example:

The source "T Kötter, BR da Costa, M Fässler, E Blozik, K Linde, P Jüni, S Reichenbach, M SchererMetamizole-associated adverse events: a systematic review and meta-analysis.. In: PloS one. 10, Nr. 4, 2015, S. e0122918. doi:10.1371/journal.pone.0122918. PMID 25875821."

was used to support this statement:

"In 2015, ...... a meta-analysis of 79 trials with a total of 4000 patients,[23] consistently confirmed a risk of 1/1,000,000 patient days."

In reality, the meta-analysis included only studies on short-term (2 weeks) effects, and none of them reported a case of agranulocytosis, which could not be expected anyway with such a design. So the meta-analysis contained no information on the subject. The authors themselves made this pretty clear by writing:

"The number and size of the trials included in our review would be too small to yield more than only a few agranulocytosis cases."

--Saidmann (talk) 18:32, 5 June 2016 (UTC)

Re-revert with correction

The statement has been updated to reflect just the fact - that neither agranulocytosis nor death were observed.

From the quote, if the 1/1439 estimate were realistic, the review could have yielded "a few agranulocytosis cases", but it didn't.

Re "only studies on short-term (2 weeks) effects" - this is what it is currently approved for in Germany:

• acute severe posttraumatic and postsurgical pain
• colic pain
• high fever if other measures fail.

That is all "short-term (2 weeks)". The only exceptions are

• severe pain if other measures are not indicated, and
• cancer pain

You may find the discussion on p. 825 of http://www.ncbi.nlm.nih.gov/pubmed/15580488 interesting - the authors argue that the 2nd Swedish study used a-typical and unapproved long treatment (>1 month).

Re the other references in the previous version. I'm surprised that a book (Silverman (1992) "Bad Medicine: The Prescription Drug Industry in the Third World") is allowed to dominate the tenor of the page, even though it is

• old (1992),
• not peer reviewed,
• not accessible (at least I could't find a pdf with it), and
• not relevant (this is not about use of a drug in the third worlds.

From a review by Stephen Hilgartner in the Am J Sociol, http://www.jstor.org/stable/pdf/2781989.pdf?_=1465173656321

Over the years, Milton Silverman, Mia Lydecker, and Philip R.
Lee have critiqued pharmaceutical pricing practices, exposed instances of
drug companies exaggerating the efficacy or hiding the hazards of their
wares, and tenaciously pressed for reforms. This book continues in this
activist tradition. However, readers seeking a careful analysis of the  
drug industry in Third World contexts will be disappointed.

Bad Medicine badly needs an editor; the book is extremely fragmented.
Chapters-and on occasion photographs-arrive in a nearly random or-
der. New topics and anecdotes appear without warning. The book seems
to have been assembled, rather than written, by piecing together bits of
lectures and articles originally prepared for diverse audiences. At times
it reads like a muckraking expose aimed at a broad public audience. At
other times, it seems to be intended for drug-policy insiders. Sometimes
the authors offer opinionated commentary without much in the way of
support, and sometimes they present a set of facts without much interpre-
tation; they never develop a sustained argument in a systematic and
disciplined way.

Should Wikipedia pages be based on "activist" views, "muckracking", "opinionated commentary without much in the way of support"?

Kmwittko (talk) 00:54, 6 June 2016 (UTC)

Metamizole us in different countries

The article seems to indicate Metamizole is prescription only in Israel. I live in Israel and Metamizole is available without prescription (over the counter) as a single ingredient in the form of caplets, tablets, drops and syrup.

If you read Hebrew, you can consult the Israeli drug registry to verify my claims: http://www.old.health.gov.il/units/pharmacy/trufot/index.asp?safa=h

I just checked the reference for the "Legal Status" section and there too it is clearly stated:

Fixed dose combinations of metamizole sodium are not approved for registration. Parenteral preparations of metamizole sodium (single-dose product) may be administered only in hospitals and clinics where there are suitable facilities for resuscitation (in cases of anaphylactic shock). Enteral preparations of metamizole sodium (single-dose product) may be dispensed without prescription.

I have changed the section accordingly.

I believe Metamizole is used without prescription in many more countries, An article published in 2013 sites the following countries: Bulgaria,Brazil, Egypyt, Mexico, Poland, Russia, Turkey, Romania, The Republic of Macedonia, India and Israel. The section should probably be corrected accordingly.

http://www.diagnosisp.com/dp/journals/view_article.php?journal_id=1&archive=0&issue_id=44&article_id=1434

Amichp (talk) 22:23, 21 April 2014 (UTC)

I can see that the long list of countries has been taken away, and it's maybe impossible to list how a medicine is used in every single country on earth. It is changes all the time, and someone has to update such lists very often. And yes, Metamizole is used without prescription in many countries. One is Indonesia, where Metamizole is one of many ingredients in at least two medicines Proneuron and Neuralgin Rx. The one with the brand name Neuralgin Rx is one containing Metamizole, and sold over the counter in Indonesia. Neuralgin Rx (sold in some countries) has been mixed with Neuralgin (sold in many countries) on Wikipedia in English language. Neuralgin is NOT containing Metamizole like Neuralgin Rx. The wikipedia word Neuralgin is redirected to wikipedia word Metamizole. That should be changed to Neuralgin Rx → Metamizole. --Caspiax 12:34, 21 June 2015 (UTC) — Preceding unsigned comment added by Caspiax (talk • contribs)

Hi! I just wanted to point that there is data for Bulgaria (the small rectangular country directly north-east from Turkey) – it's sold "over-the-counter", so it should be coloured blue instead of gray.Didakis1 (talk) 02:42, 22 December 2015 (UTC)

There is an updated map of countries in Stammschulte (2015) http://www.ncbi.nlm.nih.gov/pubmed/26169297 - I'm just not familiar with copyright issues regarding Figures. In short, it's not available in the former British Empire (Britain, US, Canada, Australia, India), France, and Scandinavia. Otherwise, it's approved in most European, South American, Asian, and some African countries that have regulatory agencies. Kmwittko (talk) 01:05, 6 June 2016 (UTC)

Content about side effects in the History section

So about this content

As early as in the 1930s had aminopyrine been linked to agranulocytosis, yet epidemiological data about metamizol-associated agranulocytosis (MAA) lacked until a Swedish study (1966-70, 27/1.2M population) estimated a risk of 1/3000 "drug consumers", An international prospective, population-based, case-control study (1980-86, 65/20.6M million) estimated an excess risk of 1.1/1,000,000 per week in Germany and Spain, but none in Israel and Hungary. Another Swedish study (1995-99, 8/10,892 prescriptions) estimated the risk as 1/1439 cases. The latter two studies have been questioned on methodological grounds, the former "for selection of cases and controls, ascertainment of exposure, and data analysis" and the latter because of the small number of cases (8) the duration of exposure (6 were treated for >4 weeks) and the use of concomitant risk drugs (omeprazole, flucloxacillin/tramadol, prednisolone, diclofenac, and olsalazine).

Two Polish studies (1997-2001, 6/34M population and 2006-7, 2/12.6M person days) estimated a risk of 0.20 and 0.16 per 1,000,000 person days, respectively. In Germany, a case control study (2000-2010, 26/27.5M person years) estimated a risk of .5/1,000,000 daily doses, consistent with spontaneous reports (1990-2012, 449/80M), while usage of metamizole increased from 11 to 142 million daily doses. From Swiss surveillance (2006-2012, 77/8,000,000), incidence was estimated as 0.46-1.63 per 1,000,000 person days. A meta-analysis of 79 trials of metamizole with a total of 4000 patients identified neither agranulocytosis nor death.

References

This is not OK in Wikipedia - this whole section is WP:OR - the editor is stringing together a series of primary sources to actually create, here in Wikipedia, a secondary source that tells a history of research into Metamizole and agranulocytosis/aplastic anaemia. That is not OK. The last sentence there is perfectly appropirate for the side effects section however. Jytdog (talk) 17:39, 6 June 2016 (UTC)

Even the last sentence is not appropriate. In the above section "Revert due to massive misrepresentation of sources" I pointed out that this source has no relevance whatsoever on the issue of frequency of agranulocytosis, and the authors stated that themselves! ..Saidmann (talk) 18:48, 6 June 2016 (UTC)

Actually sometimes it is very important to say "We don't know" and that is what the PlOS source supports. Jytdog (talk) 19:06, 6 June 2016 (UTC)

Agreed. Therefore I reinstalled the previous summary on this issue. --Saidmann (talk) 21:23, 6 June 2016 (UTC)

I rephrased, removing all the references mentioned in Nikolova (2014), from which everything above the reference is extracted, and Stammschulte (2015). Is less information more to your liking? — Preceding unsigned comment added by Kmwittko (talk • contribs) 21:47, 6 June 2016 (UTC)

History section redux

so now we have had the following added, which is again trying to use the history section as a [{WP:COATRACK]] for defining the agranulocytosis rate.

In 1974, metamizole was withdrawn in Sweden due to a Swedish study estimating the risk of agranulocytosis as 1/3000 patients. In 1977 it was also withdrawn in the USA. In September 1995, it was re-approved in Sweden based on the results of the International Agranulocytosis and Aplastic Anaemia Study (IAAAS), 1980-1986, which estimated the risk to be less or equal to 1.1/1,000,000 per week (depending on country). In April 1999 it was again withdrawn after another small Swedish study (1995-1999) estimated the risk as 1/1439 prescriptions. Larger studies conducted between 1987 and 2012 in Poland, Bulgaria, Thailand, and Spain confirmed the risk of agranulocytosis below 1/1,000,000. The 2014 review also discussed both possible methodological and genetical confounders for the higher risk estimates in Swedish studies. Three studies in Germany and Switzerland in 2015 also estimated the risk at 1-2/1,000,000.

A meta-analysis of 79 trials of metamizole with a total of 4000 patients identified neither agranulocytosis nor death.

References

-- Jytdog (talk) 22:38, 6 June 2016 (UTC)

Compare with previous history

Jytdog/Saidman,

If there had been a reply option in the email, I would not have posted here, but I'm willing to go with Wikipedia's policy of not using e-mail for a more private conversation.

If you are against scientists contributing, I will gladly cease and desist, but let me explain my motivation to even try to contribute to this article.

(1) As others have noted, the map was never correct. A map that was (more) correct at least at some time is available in .

(2) Metamizole is a prodrug, but of MAA/AA, not of pyramidon. (If it were, we wouldn't have a AE problem different from pyramidon.)

I didn't touch those, because there should be others with more competency.

(3) What I found appalling though - even though you approved of it -, were the two paragraphs in "History", which were almost entirely based on a single book of questionable quality (see above). Hoechst had not "commissioned" the IAAAS and several subsequent studies have confirmed its results. Here are the two paragraphs I edited:

Metamizole had strong worldwide sales up until the 1970s, but there had been reports of agranulocytosis in the literature since the 1930s. In the 1970s AMA Drug Evaluations and other formularies called attention to these events and warned physicians against liberal use of metamizole, and the drug was banned in several countries. International controversy became heated in the 1970s and 1980s, especially with regard to marketing of the drug in the developing world, where agranulocytosis was difficult to manage and usually led to death, unlike in the developed world, where patients could generally be saved.

(not really, letality was 25%)

One difficulty in determining the risk of agranulocytosis was the lack of consistent epidemiological data; estimates ranged from 9 cases per 1000 uses to 2 cases per 10 million uses, and there was no known mechanism of toxicity. Hoechst commissioned a study of the drug to get better data, which published in JAMA in 1986. The International Agranulocytosis and Aplastic Anemia Study. Risks of agranulocytosis and aplastic anemia. A first report of their relation to drug use with special reference to analgesics. JAMA 256(13) 1749-1757 PMID 3747087 The study reported wildly inconsistent country-to-country variation in agranulocytosis and only intensified the controversy with supporters of the drug finding vindication and critics now additionally angry over the conduct of the study. As of 2014 the safety of the drug remained controversial.

The only thing I did was to replace these two paragraphs with information that were based on actual publications. If this was the right place to address these issues before, why are you criticizing me now for providing actual evidence in the same place where you had previously accepted activist statements based on a single book?

I'm not "at war". You asked for the evidence to actual literature being removed and replaced by references to a review articles that quote them and that's what I did - you had not mentioned that the whole discussion should be moved somewhere else, which I'd gladly have agreed with - just suggest a place where you'd like to see it.

Why are you now 'banning' me for responding to your requests?

Kmwittko (talk) 01:44, 7 June 2016 (UTC)

Please see your talk page. Thanks. Jytdog (talk) 18:06, 10 June 2016 (UTC)

Risk and history separated

Jytdog/Saidman,

is splitting the information ok with you?

Append to first paragraph:

Two small studies conducted in Sweden estimated the risk as 1/3000 (1966-1970) and 1/1439 (1995-1999), respectively; several large studies conducted in Poland, Bulgaria, Thailand, Spain, Germany, and Switzerland between 1987 and 2015 estimated the risk below 2/1,000,000. A meta-analysis of 79 trials of metamizole with a total of 4000 patients identified neither agranulocytosis nor death.

Append to History:

In 1974, metamizole was withdrawn in Sweden due to a Swedish study estimating the risk of agranulocytosis as 1/3000 patients. In 1977 it was also withdrawn in the USA. In September 1995, it was re-approved in Sweden based on the results of the International Agranulocytosis and Aplastic Anaemia Study (IAAAS), 1980-1986. In April 1999 it was again withdrawn in Sweden based on the results of another Swedish study (1995-1999).

References

We don't use primary sources, really we don't. The two swedish studies are primary. we use review articles. Jytdog (talk) 18:05, 10 June 2016 (UTC)

There are no references to the primary sources (Bottiger 1973, Hedenmalm 2002, ...) anymore (see the only three references), only to a review article (Nikolova 2014: ... a review profile ...)

I'm just trying to learn. You criticized me for

(a) using primary sources, so I'm using a review

(b) putting information in the wrong place (all in History), so I'm splitting the information (estimates in the Intro, where agranulozytosis is mentioned as a risk, and history of regulatory actions in the History) and

(c) not discussing on the talk page before inserting, so I'm using the talk page to discuss.

If I can find the user talk again, I will read more about the general principles, but what else do you to be done in this case? Kmwittko (talk) 19:24, 10 June 2016 (UTC)