Chloroquine has shown apparent efficacy in treatment of Covid-19 | Hacker News Reader

Chloroquine has shown apparent efficacy in treatment of Covid-19

jstage.jst.go.jp

462 pointsrobomartin254 comments

Previous discussion:

https://news.ycombinator.com/item?id=22565107

> It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system ... The wholesale cost in the developing world is about US$0.04. In the United States, it costs about US$5.30 per dose. [1]

That's a little over 132x more expensive. Compared to other common medicines like ibuprofen ($0.04 in the developing world, $0.05 in the USA [2]), what makes chloroquine so uniquely pricey in the USA? (or, I suppose, ibuprofen so uniquely cheap?)

[1] https://en.wikipedia.org/wiki/Chloroquine

[2] https://en.wikipedia.org/wiki/Ibuprofen

Ibuprofen can be sold on somewhat recurring cycle.

Not uniquely.

USA is famous for very high prices of essential medicines, and being an expensive country in general.

This was already implied in the question. They're asking why something like ibuprofen is different.

Maybe because it's one of few medicines being sold by foreign companies in USA?

America doesn't have a lot of opportunities for foreign players, let alone in such militantly overregulated sector like medicines.

I'm assuming because ibuprofen is OTC and chloroquin is prescription.

If a medicine isn’t used very often usually only one manufacturer will continue making it. They then can set monopoly pricing. I also have a belief that there is some actual or implicit collusion where they are dividing the market for generic drugs into monopolies by strategically dropping out.

FDA rules make it expensive to start new production or enter from abroad, so a new manufacturer is in for as price war they will probably lose.

There are lots of super cheap prescription meds. Many for a penny a dose wholesale. They have robust competition but still make money at that price point, although some makers may be selling fraudulent drugs.

In theory, when the patent on a popular medication is over, new players should pull the price down to marginal cost. These days that is not happening for many products and I’d like to know why. Any economists know?

I have in-laws in Nigeria. We just tipped them off a couple of days ago that now might be a good time to buy some Chloroquine and keep at the house, in case the situation gets worse. This is a commonly known medicine down there, that you can get from pharmacies without prescription.

But based on what we're seeing so far, it seems plausible that this virus prefers cooler northern climates. So hopefully it will turn out to be an unnecessary precaution.

In the east coast of Spain we have had great weathee (25+ degrees celsius) and it didn't seem to greatly influence transmission speed :(

The numbers so far suggest you need tropical heat and humidity to slow down transmission speed. That would need to be 35C+ weather, and no air conditioning.

Before I've read you message I was sure that dry air slows down transmission speed. But indeed, it's humidity https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3551767

The rapid transmission in industrialized countries is most likely helped by the daily indoor concentration of people in the big cities, during commute, in large schools and workplaces. Large cities in Africa will surely get it to some extent, but the spread might be slower since Africans don't spend as much time indoors, and the rural communities are already practicing "social distancing" to some degree.

I think you have a very Hollywood view of African societies...

Having lived in African countries for more than 5 years I don't rely on Hollywood for my sources.

I'd offer the Ebola outbreak as a counter-example.

Ebola is different: It does not spread over air like the Corona virus.

The Ebola virus " spreads to people initially through direct contact with the blood, body fluids and tissues of animals. Ebola virus then spreads to other people through direct contact with body fluids of a person who is sick with or has died from EVD". [0]

[0] https://www.cdc.gov/vhf/ebola/about.html

Only 2 Ebola outbreaks have had more than 1000 infected people.

This thing is in the early stages still and there are already 7x more recorded cases than the largest Ebola outbreak.

Nirobi, Metro Area Population 10 million

https://www.civitatis.com/en/nairobi/

Compare:

Largest cities in Africa

https://en.wikipedia.org/wiki/List_of_cities_in_Africa_by_po...

Largest cities in USA

https://en.wikipedia.org/wiki/List_of_United_States_cities_b...

It's not a matter of big cities only. People in the big cities in industrialized countries spend their time indoors with large crowds to a much higher degree. It indicates that the spread will be slower in Africa (while not absent)

What exactly do you expect those 10M people to do during the day?

Citation needed on it preferring colder climates. My own quick glimpse of the global numbers showed plenty of equatorial cases per capita. Many aren’t rigorously tested populations, too.

It's something I first read from the Goldman Sachs client call notes that has been circulating:

https://www.forbes.com/sites/abrambrown/2020/03/16/the-priva...

Certainly not the best citation, and I have no idea where GS gets their analyses, but seems plausible enough that I'm at least hoping there could be some truth to it. See e.g. India, the virus doesn't seem to have taken off there despite a few early cases.

If it's wrong, I fear things could get really bad, especially in heavily populated cities like Lagos.

I think this presentation is a great source of facts.

https://drive.google.com/file/d/1DqfSnlaW6N3GBc5YKyBOCGPfdqO...

Weather: Maybe 10 oF increases the doubling time 2x (steady-state reduction in exterior virus levels by 50% per Pubmed 22312351, plus reducing time × concentration of people indoors).

I don't think a paper about SARS-CoV-2 and temperature has been written yet (that I've seen), but people are hoping it reacts like SARS-CoV. See here: https://www.ncbi.nlm.nih.gov/pubmed/22312351

Keep in mind, that doesn't mean zero cases in hot weather, just that it is less contagious.

“ It may also explain why some Asian countries in tropical area (such as Malaysia, Indonesia or Thailand) with high temperature and high relative humidity environment did not have major community outbreaks of SARS.”

Iirc, Maylasia has a pretty strong breakout on its hands. They recorded their first death today and are at something like 670 cases. I think their double rate was 2-3 days. Edit-it’s 1 day today. See link. Not good news I think for the hypothesis.

https://ourworldindata.org/coronavirus

Sorry, I'm now picturing email offers from Nigerians that I would openly welcome.

> But based on what we're seeing so far, it seems plausible that this virus prefers cooler northern climates. So hopefully it will turn out to be an unnecessary precaution.

Wuhan has temps around 50F-75F (~15C-22C). Certainty not hot, but not a cooler climate given how it's still winter in this hemisphere.

Italy and Spain aren't known for being especially cold either, mountainous areas notwithstanding.

All of these locations are still cooler northern climates. I agree that they're not exactly cold.

The Lancet has published a study this week that anti-inflamatory drugs may help Ncovid penetrate cell walls and actually speed up the process.

France has stopped over-the-counter sales of Ibuprofen as of mid January.

https://www.afrinik.com/anti-inflammatory-drugs-can-make-cor...

Not only anti inflammatory drugs but also ACE inhibitors used to treat hypertension.

This has been disputed:

"This speculation about the safety of ACE-i or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it. Indeed, there is evidence from studies in animals suggesting that these medications might be rather protective against serious lung complications in patients with COVID-19 infection, but to date there is no data in humans.

The Council on Hypertension of the European Society of Cardiology wish to highlight the lack of any evidence supporting harmful effect of ACE-I and ARB in the context of the pandemic COVID-19 outbreak.

The Council on Hypertension strongly recommend that physicians and patients should continue treatment with their usual anti-hypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACEi or ARBs should be discontinued because of the Covid-19 infection. " [1]

There are also the brilliant MedCram updates, where the issue of ace inhibitors et. al just happened to be discussed yesterday. In it he describes the mechanics of ACE-i and ARB treatment: https://www.youtube.com/watch?v=1vZDVbqRhyM

[1] https://www.escardio.org/Councils/Council-on-Hypertension-(C...

That is not actually a refutation.

Not a native speaker, but refutation to me translates to disputed… anyways edited for clarity.

To dispute something usually just means to disagree with it. Refutation generally implies positive evidence that a position is wrong.

Yeah, disputed is much better.

The GP was talking about NSAIDS and you're posting about blood pressure medicine. There are similarities, but still.

Not familiar with afrinik, but this has been reported in The Guardian

https://www.theguardian.com/world/2020/mar/16/health-experts...

The Lancet article was not a study, it was a "correspondence," an educated guess from a researcher.

https://www.thelancet.com/journals/lanres/article/PIIS2213-2...

I don't know if it's more responsible for the researchernto ouvlish their educated guess immediately - it's perhaps more likely than not to be right based on their expertise and they truley believe it's a really issue and might feel obligated to talk about it. Or, if it's more responsible to do the work first and get some preliminary evidence. Those few days during the pandemic could be crucial for rapid response, and if there's a strong rationale for it maybe it's worth communicating, but this isn't like "it can spread in xyz manner" that really changes behavior - you still be have to do social distancing whether or not Advil makes you more susceptible -is the panic that your painkiller will give you the coronavirus worth it?

btw, not sure if you cited the ibuprofen example merely as a comparison. I hope you are aware that early data is indicating that NSAIDs including ibuprofen have shown high degree of correlation with mortality in younger patients.

To an extent that the French govt has officially released it as a statement. https://edition.cnn.com/2020/03/16/health/coronavirus-ibupro...

Ibuprofen can be manufactured by almost any company and sold in almost any store. So open competition in the sector drives down prices.

Chloroquine exists in a walled garden where pharmaceutical companies and the government have rigged it so that rent-seeking behavior is the optimal financial strategy.

Why can't Chloroquine ? Maybe there's not as much money in it, unless it requires special permissions.

Does anyone know if there's a lot of supply in hand and if it can be made in large quantities fast?

The price reflects opportunity cost, there is low demand for Malaria treatment in the US. Ibuprofin is a staple drug.

Except drugs can be shipped around the world very cheaply, even in small doses, so demand alone can't explain price difference.

exactly. My point was this is prob a demand issue, not a government intervention. I wonder how fast they can make it...shipping can be done via charter planes this time.

False. Government prohibits importation of most medicines from abroad. It's corruption hidden in the form of "please just think of the children."

"FDA cannot assure the safety and efficacy of unapproved drugs" is the main excuse used in drug importation court cases.

Reference: https://www.pharmacycheckerblog.com/online-pharmacies-person...

But it wouldn't take an act of Congress to change that. Your link says it's up to the FDA, which could easily choose to allow importation to combat the pandemic.

Its a prescription drug in the US, and pharmacists get paid a bunch. Most developing countries you can buy OTC.

https://rxsaver.retailmenot.com/drugs/chloroquine-phosphate/... has it at 60c/dose in my area.

For what it is worth - on my surgery bill one tablet of ibuprofen was billed at $40+. Insurance accepted $20+. So I would guess it will heavily depends on provider as well.

For French speakers, a talk yesterday from Didier Raoult who is also testing Chloroquine in France [1] (and I believe who originally discovered the anti-viral benefits of that molecule on certain viruses). He finds that it reduces significantly the viral charge.

He made an interesting point. It appears infected people remain contagious for 3 weeks. Taking this drug allows to significantly reduce this period. The current advice for people who are sick is stay at home and only show up at an hospital if you start having respiratory problems. He thinks a better approach is to get them to get tested quickly, and take a combination of anti-viral drugs. This will likely result in less contagions.

[1] https://www.youtube.com/watch?v=n4J8kydOvbc

[edit] Adding slides link posted by chmike on this page: https://www.mediterranee-infection.com/wp-content/uploads/20...

[edit] corrected contagiousness from 4 weeks to 3 weeks.

that would make sense:

test everybody, if positive take the drug for 5 days, rest for 2 more and back to work you go. a win for everybody!

Because testing everybody is no big deal.

According to Raoult, it doesn’t seem to be a technical limitation, the test is a standard procedure that labs around the country already do routinely for other viruses.

It's the capacity that is the issue. Testing labs all over the world, are running far above capacity already. It's not something that can be scaled up overnight either.

South Korea managed to spin a system where they can test 20k people a day in just over two weeks[1]. What's stopping other countries from doing that?

[1] https://www.bbc.co.uk/news/world-asia-51836898

Wasn’t there a $1 test being proposed? You can start by testing people with high temperature at the entrance of buildings and metro. Still cheaper that closing schools and all the rest of the economy.

Proposed, yes, but you can't buy it yet. Also, the cheaper tests so far are all antibody tests, not the more accurate RNA tests that everyone is clamoring for. Antibody tests don't work until you have had the infection for a while.

And they are even worse at telling you when you're "all clear" (if they can do it at all, many antibody tests are a "once positive, always positive" deal).

Dr Raoult reports that after 6 days of treatment with Plaquenil (hydroxychloroquine) only 25% were still carrying the virus. Without treatment, 80% were still carrying the virus after 6 days. This result should be published soon.

But does that mean anything? Without hydroxychloroquine, how many people stop shedding active virus because the immune system starts to respond by day 6 of symptoms? It seems to be about the same.

The comment you reply to says that.

People carry it for up to five weeks.

I must admit as an immune supressed individual - if (uk) they might suggest prophylactic meds for us.

For non French speakers, Youtube will translate the subtitles to the language of your choice if you click settings a bit

So I’m not seeing mention of this anywhere else chloroquine is being talked about.

Chloroquine used to be taken daily in many of the tropical Britain colonies suffering from malaria.

chloroquine in the form of quinine is where the gin and tonic drink came from. Quinine mixed with carbonated water was drunk as a prophylactic.

The quinine tasted so terrible it had to be cut with something to make it tolerable - gin! That’s where gin and tonic came from - anti malaria treatment in the British colonies.

If you look at tonic water even today you’ll find quinine listed as an ingredient.

As a cheap, safe bet it’s not unreasonable to start having a g&t each day along with a zinc pill.

The more you know.

I recently spent three years driving around Africa. Chloroquine is still a very common anti-malarial in many parts of the continent.

Name specific countries, to the best of my knowledge, it's no longer in use because malaria has become resistant to Chloroquine.

And I was glad to see it go out of use cos it caused crazy itching in many people.

Touching water was like pouring fuel on fire.

Anyway, even though I hated it, Chloroquine really worked while it worked.

From wikipedia

> In the United States, the US Food and Drug Administration (FDA) limits the quinine content in tonic water to 83 ppm[3] (83 mg per liter if calculated by mass), while the daily therapeutic dose of quinine is in the range of 500–1000 mg,[4] and 10 mg/kg every eight hours for effective malaria prevention (2100 mg daily for a 70 kg adult).[5] It is often recommended as a relief for leg cramps, but medical research suggests some care is needed in monitoring doses.[6] Because of quinine's risks, the FDA cautions consumers against using "off-label" quinine drugs to treat leg cramps.[7]

For malaria prevention that's 25 liters of tonic or about about 200 gin and tonics per day.

Clarissa Dickson Wright suffered from organ damage caused by too much quinine, from the copious G&T she drank.

https://www.telegraph.co.uk/foodanddrink/foodanddrinknews/10...

about about 200 gin and tonics per day

Great news. I'll only have to cut down a little.

Thanks for the smile this gave me. Cheers, mate.

Yeah it's pointless now days, modern tonic water is very different to the what they mixed with gin basic when quanine was the purposes rather than a mild flavouring.

Challenge accepted!

I wish Douglas Adams were still around to comment on all this.

> As a cheap, safe bet it’s not unreasonable to start having a g&t each day along with a zinc pill.

The amount of quinine in tonic water off the mixers shelf is definitely not enough to have a medical impact. The flip side of how bitter it is, is that you need very little quinine to get the flavoring. "Real" tonic water like brits drank in india or whatever is muuuuch more bitter than the stuff you get today.

Maybe if you drank tonic syrup straight.

> each day along with a zinc pill.

The scientific studies being cited for these COVID-19 vaccines using Chloroquine specifically state zinc supplements by themselves are not ionized and are therefore useless for fighting the virus. Even though zinc entering cells is a key part of how it works, zinc can't enter the cells in question unless it's properly ionized, which is why they use Chloroquine... an ionized zinc delivery system... jumping to "lets all take some Zinc pills with gin & tonic" is irresponsible advice IMO.

These sorts of Naturopathy proposals is exactly how we got COVID-19 in the first place (ie, people eating Pangolins in east asia for Chinese medicine purposes - the most trafficked animal in the world - which just happens to be infected with a coronavirus that matches 99%+ to the one currently making the rounds).

This sort of weak adherence to a scientific approach to medicine + some vague historical reasoning is the problem, not the solution.

Pangolins aren’t the source and I’m not even gonna bother to explain.

It might not be that specific animal but the Chinese wet food markets have a history of pretty serious viruses, this is just the worst and most recent.

Remember, it’s this kind of thing that brought us HIV so it could get even worse.

I’m always open to being educated. I was referencing articles on Nature from February pointing to Pangolins more than any other mammal (without full certainty of course, that takes time).

Zinc supplementation is an effective treatment against many commonly found viruses. Are you saying the new virus is an exception to this? Seriously curious, as I haven't looked into it specifically.

Also: Gargling a zinc/water solution has an astringent effect and removes the bacterial film in your throat, which seems to help in the initial phase of an infection.

The scientific study wasn't even for COVID-19 but another very similar Coronavirus and yes they said it would have no effect on the cells without ionization (specifically zinc entering the cell to blocking an RNA that's needed by the virus to replicate).

There was a video of a doctor breaking down the biochemistry of it that got posted here the last time Chloroquine came up, which I can't find just now.

If it were only just as easy as taking zinc pills... I take vitamins daily already just to be safe (there's far more than coronaviruses floating around). I just don't expect them to be enough to prevent something as serious as COVID-19. There's a reason Chloroquine is being studied and not zinc by itself and is 100x more expensive to buy on the internet than zinc supplements, even before it became a meme. It's just not that simple.

That hasn't stopped naturopathy from spreading before though.

Not in direct reply to your post, but slighty interesting anecdata: I likely caught COVID-19 1-2 days ago (light fever, headaches, loss of smell, but no runny nose): I gargled with Zinc as I noticed the first symptoms, had Cinchona bark tea yesterday. After a day, almost all symptoms disappeared except for the loss of smell, which is generally considered a late-stage symptom.

Given that the common cold without any treatment typically lasts around 5 days or so, it might point to some efficacy of the treatment.

Would you share your recipe for cinchona bark tea? How judge the strength and how much to drink per day?

I bought some cinchona bark (cut, but is powdery) and they have a recipe on the bag but no specification of strength or how much to drink.

Quinine is one of the most bitter substances in the world. In capsule form it's not used much any more for malaria because the taste of the dust on the outside of the capsule made people throw up. The amount in tonic water is tiny compared to what you need if you have malaria.

> Quinine is one of the most bitter substances in the world.

It is even used as the normalizing reference index for a common bitterness index, at least according to Wikipedia.[1]

> In capsule form it's not used much any more for malaria because the taste of the dust on the outside of the capsule made people throw up.

I would suspect that it is not used widely anymore for prophylaxis because there is chloroquine-resistant malaria parasites all over the (malarial) world.[2]

The sell coated capsules, which are't bitter; these have been around for a while [3]

[1] https://en.wikipedia.org/wiki/Bitterant [2] https://www.cdc.gov/malaria/malaria_worldwide/reduction/drug... [3] https://books.google.com/books?id=AjxrAAAAMAAJ&newbks=1&newb...

> chloroquine-resistant malaria parasites

Yes, that and other reasons. Quinine used to be over-the-counter in the US; people took it for leg cramps. But they made it Rx-only in the 80s (or 90s; not certain) because it can have dangerous side-effects (including cardiac issues) in some people. It's kind of a nasty drug, but it's better than malaria. There are now better drugs for the conditions Quinine was used for.

I didn't vomit, but easily one of the worst pills I've ever taken - and I like bitter.

It's totally unreasonable.

There isn't enough quinine in tonic water to benefit you and the alcohol is going to leach nutrients that your body needs, lower your white blood cell count, kill good flora in your mouth, lower your body's immune response, and leave you more susceptible to catching the virus.

You shouldn't present nonsense as fact, it doesn't help anyone, and in this case is actively dangerous.

Chloroquine and quinine are different compounds.

> As a cheap, safe bet it’s not unreasonable to start having a g&t each day along with a zinc pill.

Make that a zinc lozenge, though. Zinc works by coating the esophagus, and killing the virus on contact there. Zinc pills that you simply swallow don't work at all.

Not true. Zinc has a proliferation effect on lymphocytes and monocytes that leads to positive outcomes in immune function. There have been a number of clinical studies on the topic. Here is one: https://academic.oup.com/ajcn/article/79/3/444/4690140

There's a small, positive effect on immune function from swallowing zinc pills. But there's a large effect against the coronavirus family, specifically, from coating your throat with zinc.

https://www.ncbi.nlm.nih.gov/pubmed/28515951

Zinc supplements taste nasty and cause a burning sensation on damaged tissue. Zinc lozenges (e.g., Zicam cold-eze) have much lower dose of Zn++ and have sugar added. It is unclear exactly how much zinc in in Zicam. It is far lower than what is in most OTC zinc supplements.

I recommend the nasty zinc supplements: they're cheap, pack a lot of zinc and you'll know when you feel them work. One bottle of 100 tablets 50 mg Zinc gluconate costs for $7 should last you through years of pandemics. In contrast a package of 25 Zicam sugary zinc lozenges costs $15.

I usually split or even quarter a 50 mg zinc tablet - they're that bitter. Don't take too much b/c they may dull sense of smell. Some people claim to have lost their sense of smell due to zinc overdosing. I usually don't take zinc but for this pandemic I've committed to an occasional nasty disgusting fragment of a zinc tablet each day.

Best is to lie down on your back and allow the zinc lozenge or zinc pill to dissolve in your mouth slowly so you can coat the epithelial cells in the mouth, throat and nose. You could gargle with the zinc and then swallow it.

In any case, swallow the zinc b/c that will allow it to be absorbed by the stomach and intestines and then move to your bloodstream, where it can deactivate some virus (more below).

But new virus production occurs inside each cell in the cytoplasm, and little zinc normally passes through the cellular membrane.

Chloroquine and other quinine compounds apparently "punch holes" in the cellular membrane and allow Zn++ ions to flood through. Once inside the cytoplasm Zn++ halts viral replication.

Tonic water has very low levels of chloroquine/quinine but it is by no means established that the full 500 mg chloroquin/day dose used for malaria is necessary to stop covid-19. Probably less, perhaps even far less, will create enough ionic "gateways" to move Zn++ through the cells' membranes. But, in any case, this requires adequate zinc as Zn++ in your system.

And the Zn++ on your throat will inactivate most viruses that land in your throat, nose and mouth anyway.

The amount of quinine in a G&T is negligible, unfortunately.

You're going to need more than one ;)

To be more accurate - The cocktail was introduced by the army of the British East India Company in India.

Basically it was invented by the British to not die in India. We like to call it our national drink ;)

so it must be have been a British conspiracy. I knew it all along.

This is an increadibly potent drug with serious side effects according to anything I read, its not first-line treatment its last-line, when everything else fails. You can go blind, irreversibly.

Please people, speak to trained medical people before reaching to the drug cabinet.

I am not a doctor. This advice is not meant to contradict the rule of only taking medical advice from medical professionals.

The retinopathy happens only after years of use (like a decade). Also, as an immunosuppressant, it is pretty slow acting in that it takes two three months to even start working. The currently prescribed dosage for the viral infection is for 5-10 days (albeit at slightly higher dosage than used for malaria/lupus etc.).

From wikipedia.

One of the most serious side effects is a toxicity in the eye (generally with chronic use).[11] People taking 400 mg of hydroxychloroquine or less per day generally have a negligible risk of macular toxicity, whereas the risk begins to go up when a person takes the medication over 5 years or has a cumulative dose of more than 1000 grams. The daily safe maximum dose for eye toxicity can be computed from one's height and weight using this calculator. Cumulative doses can also be calculated from this calculator. Macular toxicity is related to the total cumulative dose rather than the daily dose. Regular eye screening, even in the absence of visual symptoms, is recommended to begin when either of these risk factors occurs.[12]

> ... has a cumulative dose of more than 1000 grams. ...

woowza a Kg worth of drug !!! this doesn't look correct to me !

People taking 400 mg of hydroxychloroquine or less per day generally have a negligible risk of macular toxicity

400mg/day for 5 years is 730 grams.

only if everything gets stored, and there is no chance for that

The risk is for cumulative (not accumulated) dose:

has a cumulative dose of more than 1000 grams

And the calculator they link out to gives the same number I calculated.

A kg isn't necessarily that much over a lifetime. I'm over that with at least one drug.

This drug accumulates in various tissues, so for retinopathy what matters is the cumulative amount of the drug consumed over time.

oh man ! just like excess of vitamin-d can lead to vitamin-d toxicity, so can this. in my naïveté, i was assuming that excess of it would be just flushed out.

Its concentration in lung can be 100 times or more of that in serum. This may be helpful for its efficacy against the virus.

taken over the years

To the plus side, its cheap. So, absent drug companies motivations to make cheap drugs (low) it is affordable at scale, and if it turned out to be useful e.g. early in the stage of the disease, this might be very good for wild infections. Or, maybe it points to drugs which are safer, equally cheap, and able to be made with less side effects.

(see rule one: this is not medical advice)

Cheapish - as I recall about $300 for 90-day supply of generic hydroxychloroquine if paying cash in US. I mean, not cancer drug spends but if you are on it for life it’s an annoying annual expense.

US drug prices are pretty crazy. A random search in an internet pharmacy shows 100 tablets of 200mg hydroxychloroquine is like 30€ in Germany.

Quinine course used to cost around 1.5 RMBs in 1998.

Managed to catch malaria in Hebei out of all places, during my first trips to China with my father.

Indeed. Another example: https://twitter.com/jawj/status/1199026735980990465

I believe its around $30 in the US at Ralphs or Costco

It is, but in recent years it was much higher because of "shortages" (actually just lack of competition after one of the main suppliers got busted by USDA for poor quality control).

For Kenya, it works out as 0.3 USD/tablet for HCQS

Right, the only medication I sometimes bring from the US now is acetaminophen/paracetamol because it's the only one I've found that's much cheaper there. The rest are probably cheaper in Germany so I would just go there if I needed them.

For regulatory reasons, US drug list prices are completely detached from the actual price you end up paying (assuming you do a bit of research). See e.g. https://www.goodrx.com/hydroxychloroquine ($20 for 60x200mg)

I checked into this recently because a family member takes it for lupus. It's 10x to 30x more expensive in the US than everywhere else in the world.

Well, that reflects inflated American prices. In India, it is about 270 INR for 90x 200mg, or about $3.65. Non-generic hydroxychloroquine (Plaquenil) is about 3 times the price.

There are certain websites which will ship a 90-day supply for $10 plus change from India, paid with bitcoin. Just sayin'.

It has come down a lot in the past year actually. You can get a 30 day supply for an adult for like $30 for the generic brand without insurance if you shop around. I take it everyday, I don't have any side effects from it but do have to get my eyes checked annually with an expensive test.

You can just buy it over-the-counter in some countries, right? How dangerous can it really be? Follow the instructions on the box like citizens of those countries do.

IMO we in the US need to take the coronavirus as a wake up call to stop ignoring the medical systems of other countries and admit that they might have something to teach us. We shouldn’t just assume the American medical system is always the best one.

How dangerous is random medical advice from an internet forum? Over the counter drugs can potentially kill people, too, if used improperly.

When I was on hypertension meds, I was on S1 scheduled meds which required a script (in Australia). I visited an Asian city and bought them over the counter without a script.

These medicines are not something you should take if you do not need them. "how dangerous can it really be" is pretty much why rule one exists. Not the least of which is, antibiotics are available over-the-counter in some countries, and this contributes to why antibiotics are not as potent as they used to be.

The US medical system is only great to those that don't have to go through great struggles to afford it. It is the worlds worst and most dystopian to everyone else (the majority).

Financial status deciding who gets health care is the ultimate death panel.

The US health care system is awful in all ways.

> You can just buy it over-the-counter in some countries, right? How dangerous can it really be?

That's absolutely meaningless, some countries are nuts. Just about anything gets sold over the counter somewhere. There's even countries where guns are sold over the counter.

What kind insane countries could that be? Sounds like a black mirror episode ;-)

Given that governments of these countries are actually doing something in response, covid-19 must be way more dangerous than guns. Oh.

The UK has it otc

You can buy all kinds of super dangerous stuff in the cleaning aisle of your average supermarket. General availability is no indicator of toxicity. Ok, those are not made for ingestion. But even ignoring that factor you could list alcohol, tobacco and 30 different items from the grab-for-yourself stand at the local supermarket. You could likely kill yourself with just a handful of tablets from there if you knew what you were doing.

This seems a legit argument in 1000 years by a historian who wanted to logic why drugs clearly couldn't have needed prescriptions.

I was pretty excited when I realized you can buy fairly pure, concentrated sulfuric acid in the cleaning isle at Walmart. Nothing cleans dirty glassware quite like it! Accidentally got a stopper stuck in a flask? No problem, add some H2SO4 and just pour the stopper out a few days later.

Restricting what people can buy because they might hurt themselves with it doesn’t work (because everything can be misused) and only creates problems because sometimes restricted things turn out to be really important.

The therapeutic window for chloroquine is small, and there are very adverse side-effects if overdosed (heart arrythmias being the most dramatic I guess but macular toxicity is not something you'd want to risk either). I actually heard a story on that's how they dosed it "back in the days" - the sailors took it until they fainted our of various heart arrythmias and then they knew they had to back down a bit next time..

I guess I don't know the doses involved, but it's not that bad on it's face. I took it as an antimalarial for a few months.

Worst part is that it gives you weird dreams that puts you into a weird, almost bad trip head space.

I see this chloroquine thing all over twitter and elsewhere and I keep warning people to not take any without getting a doctor to ok it because of the side effect risk. Incredible what people will tell each other, your average griefer couldn't do much better.

Growing up in Kenya in the 80s, it was common to take chloroquine as an anti-malarial medicine. I took it several times and the same applied to almost every other person I knew. Other than being a very bitter medicine, I do not remember any other side effects. This was commonly prescribed and available over the counter. However, in the 90s, doctors started encouraging people to take newer anti-malarial medicines because the of drug resistance of the malaria parasites. However,I know of only one person who ever got blind from taking anti-malarial medicine and that was not exactly chloroquine but quinine. There are differences between the two. As per the Wikipedia page, chloroquine is considered a safe and essential medicine by the WHO.

I realise even quinine is in the list of essential medicines and also considered safe by the WHO.

There is a lot of stuff on this list that is definitely not "safe": for example, morphine, atropine.

It's not, I've taken Hydroxy-chloriquine for years and I feel fine and my doctor has said as much. You should get an eye check yearly to make sure it's not hurting your eyes.

I just recently watched an interesting video about COVID-19, Zinc and Clororquine. It explains some of the fundamentals: https://www.youtube.com/watch?v=U7F1cnWup9M

Medcram (which is the video linked) has had some great coverage of COV19. Numbers, trends, and conclusions all backed by the original published papers. Awesome.

Great video, thanks for sharing!

This is a good video describing the hypothesized method of action of Chloroquine. Chloroquine opens up receptors on the cell membrane to allow Zinc to enter cells - Zinc interfers with the replication of sars-cov-2. So, take Zinc supplements to increase general Zinc levels in plasma/tissue and let in Zinc with Chloroquine.

An alternative proposed method of action for Chloroquine is that it binds to proteins created by sars-cov-2 (ORF3a, ORF10, ORF8). Those ORF proteins bind to heme (red in red blood cells), preventing oxygen from being transported - https://twitter.com/davidasinclair/status/123897208275664896... David Sinclair based his tweets on this paper:

https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surf...

But most organizations are going with the Zinc theory of Chloroquine. So take Chloroquine with Zinc supplements (France, South Korea, China are doing clinical trials). Here is a translation of a Chinese study intermediate results - no data was released, which makes some people sceptical:

https://twitter.com/jim_dowling/status/1239255793171660800

Here is a great summary of available treatments used in different countries

https://epidemio.wiv-isp.be/ID/Documents/Covid19/COVID-19_In...

Although untested in-vivo, many clinicians prefer hydroxycholorquine due to its superior safety profile - and 4X better efficacy in-vivo (not in humans, in cells). I tried ordering that last week when the paper came out, not sure if i will get it, though.

Chloroquine is kind of old news. There has been a lot of talk around Chloroquine, starting around 6 weeks or so ago - the UK banned export of it nearly 4 weeks ago https://www.pharmaceutical-technology.com/comment/parallel-e.... I managed to order some before that.

References:

"Chloroquine Is a Zinc Ionophore" https://journals.plos.org/plosone/article?id=10.1371/journal...

The next episode 35 has some more infos on it, as well.

Given the dynamic nature of this situation, maybe this needs a [Feb 18th] tag.

400M+ people have G6PD deficiency which is a condition that has severely adverse reactions to chloroquine

Whoa didn't realize it was that prevalent. I looked into it for vitamin c infusions (long story), seemed to be an easy test to find. Something they could look at while looking for covid if there is an intent to treat it?

Yes, but hydroxycholoroquine is a safer alternative.

https://www.ncbi.nlm.nih.gov/pubmed/28556555

https://onlinelibrary.wiley.com/doi/full/10.1002/acr.23296

Previous discussion.

I'll repost the paper posted as a top response then: https://www.sciencedirect.com/science/article/pii/S016635422...

I'll also note that chloroquine is very dosage sensitive and lethal when overdosed.

I posted this a week ago. I guess a week is a long time in politics...

https://news.ycombinator.com/item?id=22523530

Here’s an article (without much information...) about an upcoming trial for Chloroquine in Australia.

https://www.news.com.au/lifestyle/health/health-problems/cor...

i currently take Plaquenil (Hydroxychloroquine) for rheumatoid arthritis, and my doctor did indicate it may be helpful against Covid but not enough tests to confirm. Is it close enough to chloroquine to be the same ?

The paper says clinical tests used both chloroquine and hydroxychloroquine. In discussing the results, they don't seem to differentiate between the two, unless I missed it.

Damn, another hydroxychloroquine user here.

Maybe that'd ameliorate the <70 factor.

When administering chloroquine, the hydroxy- form is a very long-lasting metabolite.

Yes. I think the half-life is ~ 1-2 months

"The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2 infected Vero cells."

https://academic.oup.com/cid/advance-article/doi/10.1093/cid...

Hydroxychloroquine is currently used by the Korean CDC for treating COVID-19

Source?

https://m-en.yna.co.kr/view/AEN20200213003553320

Keen to know this too. Hydroxychloroquine is the only common -quine drug in East Africa; odd but true, I think malarial chloroquine resistance has something to do with lack of demand/supply.

Additional possible drugs are alluvia, actemra. I think there's a study out for alluvia.

Things to avoid are aspirin (suspected basses on [1]) and ibuprofen (French govt recommendation).

Someone should come up with a summary page of the potential therapeutic drugs and their current state (suspected/in study/recommended)

Sorry for the brevity. On a phone.

1. https://academic.oup.com/cid/article/49/9/1405/301441?fbclid...

(NOTE: I am not a medical practitioner, I'm just parroting what I was told in a video)

The Medcram video shared elsewhere in this thread (https://www.youtube.com/watch?v=U7F1cnWup9M) does mention that hydrochloroquine is a relative of chloroquine and is also being administered in some places when chloroquine is not available (at a different dosage). They take pains to point out that they should not be administered at the same time as that can lead to a fatal complication, and also that chloroquine as a treatment overall has not been subjected to a rigorous medical study.

"Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than chloroquine (EC50=5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance."

https://academic.oup.com/cid/advance-article/doi/10.1093/cid...

Hydroxychloroquine has been used in ShangHai for COVID-19 treatment since February 6, 2020:

https://clinicaltrials.gov/ct2/show/NCT04261517

Yes.

Apparently the possible utility of chloroquine was discoevered because SLE patients on it in China weren't getting Covid-19 during the outbreak.

Source?

https://www.jqknews.com/news/388543-The_novel_coronavirus_pn...

And as discussed previously before in many submissions, hydroxichloroquine is already actively being used against Covid19 by at least the following EU countries:

- Belgium - Netherlands - Switzerland - Italy

any source for this? especially how the success rate is in Italy? How many people received it etc.?

Sure look at my comments on other threads

The publication is from 02/18/20 (as stated in the footer). Why didn’t gain it more traction?

> Why didn’t gain it more traction?

It did. Since then they've done more studies, have started even more studies, and have deployed it en masse as a treatment. It's part of the official treatment recommendations in China, South Korea, Poland, and Italy. It's been described as a "cure" where it was used in Australia after Chinese patients demanded they be treated with it, and Australia is starting a nationwide trial. Pakistan had Bayer start up the closed production line and deliver 300,000 doses.

But Italy is a mess... So it is not an actual cure?

The guidance was adopted far too late but may slow the spread and reduce deaths. You have to catch things early. In Australia, Chinese immigrants came to their doctors and said "I have a symptom and I demand this prescription and here is the research and I won't take no for an answer."

Chloroquine seems to work best if you start it within the first few days of infection. So if you are say the US and have widespread BS regarding testing and prevent people from getting it, by the time they are tested and their results back it's too late. There's no chance the US will come to their senses and start using or even producing this drug in time to help stop mass deaths. Some people bought animal grade chloroquine and are self treating, but all that supply is gone now for purchase. Doctors won't prescribe it in the US either, for their own reasons.

In China and South Korea you can get tested if you have symptoms and you can start treatment if you have symptoms. So we are seeing things turn around in both places because of this and other actions.

No but preliminary evidence is that it might speed up recovery. I'm not sure if that applies in elderly if they're already getting sever lung issues though. At that point maybe the damage is already done?

Here is more information regarding the possible Australia trial:

https://www.news.com.au/lifestyle/health/health-problems/cor...

UK gov banned parallel export of Kaletra and chloroquine phosphate on 26th Feb. There's traction in the media, then there's traction with competent men in boring grey suits.

(Although given that we seem to have a fairly aggressive mortality curve, I'm not optimistic about this one).

There are at least several other sources talking about this, from more than 20 days ago. Try to google the spanish word: Cloroquina

https://www.ncbi.nlm.nih.gov/pubmed/32147496

https://gacetamedica.com/investigacion/covid-19-el-fosfato-d...

https://www.sadi.org.ar/novedades/item/931-covid-19-uso-de-c...

Poland has formally registered Chloroquine as a drug for COVID-19 and will treat all patients with it. Chloroquine phosphate is a generic antimalarial drug derived from quinolone, in 10 trials for Covid-19 in China, including one in combination with Kaletra, as chloroquine phosphate is believed to have broad-spectrum antiviral activities.

Basically the goal is to allow zinc to get into a cell, it needs a helper to get inside the cell (a Zinc Ionophore). Apparently Hydroxychloroquine / Plaquenil (which you can buy here: InHousePharmacy.vu/p-1106-plaquenil-tablets-200mg.aspx or here easyshopping4health.com/buy-plaquenil-usa.html) is even more effective than Chloroquine.

Also see Medscape.com/viewarticle/736439 and https://www.ncbi.nlm.nih.gov/pubmed/32074550/ title: "Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies"

Quinolones like Chloroquine were used in malaria prevention for many, many years. they aren't used specifically against malaria anymore, because malaria adapted. But I always prefer a compound that can be manufactured easily and has been used by many many people over years.

Regarding Zinc Ionophores, the flavonoid Quercetin (which you can buy in many places) has been shown to rapidly increase labile zinc in mouse cells as well as in liposomes. Source: https://pubs.acs.org/doi/abs/10.1021/jf5014633

Dr Raoult has announced yesterday that the test of hydroxychloroquine on 24 patients showed positive results, especially when combined with an antibiotic against pneumonia. Slides of the presentation are here: https://www.mediterranee-infection.com/wp-content/uploads/20..., results are on the last slide.

Quercetin is over-the-counter and has similar properties Studies according to the video below on Ebola and Zikka used 50-100mg/KG - a lot lot.

This Medcram video talks about Chloroquine and the others: https://www.youtube.com/watch?v=vE4_LsftNKM

> Quercetin is over-the-counter and has similar properties

Source for the similarities between chloroquine and quercetin?

As far as I read over the past week or so this is in vitro, and not yet shown in vivo or humans.

This is an old paper, FYI. Published on Feb 20, which is eons ago given the state of things.

They haven't mentioned effect sizes or confidence intervals. Hopefully it is statistically significant - in which case the effect size has to be large to achieve statistical significance. I hope that is the case!

I have a fairly tame quinine allergy (and subsequently was incredibly relieved when artemisinin-based treatments became a thing) - this is interesting but also mildly horrifying news.

There's also an anti-HIV medication that seems to be effective, though I don't know too much about it.

https://www.news.com.au/lifestyle/health/health-problems/cor...

It should go without saying that we can cheerlead for the emergence of effective treatments, but actual treatment decisions should be made by a doctor.

> actual treatment decisions should be made by a doctor.

Medical advice is given by doctors and other health professionals.

Treatment decisions are made by patients, those entrusted by patients to make decisions, or parents, guardians, or custodians who make decisions on behalf of patients.

For everything but OTC meds, it takes both a doctor’s and a patient’s consent.

I take your point, but prescriptions need to be made by doctors, and that is the main point here.

I actually have more nuanced views on this. Doctors are not gods, and there are situations where patients have better medical knowledge than the doctor on an important issue. But based on what I've seen so far (including confidently spread misinformation on HN) I strongly suspect that numerically these cases are far outweighed by people with just enough knowledge to be dangerous. That's all am cautioning here.

so when it says: "In the early in vitro studies, chloroquine was found to block COVID-19 infection at low-micromolar concentration,"

does this mean it might be a good idea to be taking it regularly to keep from getting covid-19 from contact with surfaces with low concentration of the virus?

When I first went backpacking in the 90s I remember people were sharing stories about really disturbing nightmares from taking Chloroquine and generally complaining about mental and emotional side-effects. Google returns a bit of corroboration but that isn't mentioned on the Wikipedia page.

Are you sure you’re not talking about Malarone? That’s the other anti-malaria drug which has very intense and emotional dreams as a side effect.

Lariam (Mefloquine) was the one I took in the 90s that had the psychological warnings attached. IIRC, Malarone is newer, and may not align with the OP's timeline.

Whoops. You are correct. We were both wrong, Lariam is what I was thinking of.

Yep. It was Lariam I was thinking of.

Do other malaria drugs such as Atovaquone/Proquanil (250/100 mg aka Malarone), or Mefloquine have any promise in combating Coronavirus COVID-19.

I've seen chloroquine come up a ton and am hopeful for the efficacy of its use in treatment of COVID-19. It's surreal to be observing the global impact of a novel pandemic, and anything that can save lives or blunt the propagation of the virus feels like a gasp of hope.

Of course, chloroquine is not a vaccine, it's not a tool to contain the spread of SARS-CoV-2. We need massive and rapid propagation of testing, and meaningful progress toward a vaccine.

Except a vaccine won't be ready until long after everyone is either dead or recovered.

But if chloroquin , with or without zinc, halts viral replication as is proposed

" Chloroquine Is a Zinc Ionophore"

https://www.ncbi.nlm.nih.gov/pubmed/25271834

then it _is_ a tool to contain the spread of SARS-CoV-2 b/c it could also be used prophylactically. i.e., the virus can't replicate in the human cell if the cell already has adequate chloroquin + Zn++ present.

Do other malaria drugs also have potential for attacking COVID-19; ie Malarone (Atovaquone + Proquanil 250/100mm tab)? If also supplemented with Zinc?

I think this is a red herring, everyone knows the only treatment is Forsythia.

Previous previous discussion:

https://news.ycombinator.com/item?id=22500063

Can anyone point to data about chloroquine use by people with quinine allergies? I am allergic to tonic water, perhaps to the quinine in it. Thanks.

Watch out for Chloroquine retinopathy

Yeah, they check my retinas at six month interval.

Usually takes years to develop. This is really a non issue for the 5-10 days use in this case.

Is this the same drug that was given to Harbert in Jule Verne's The Mysterious Island ?

No. The Mysterious Island was written in 1874. Chloroquine was discovered in 1934:

https://www.mmv.org/malaria-medicines/history-antimalarials

Does this mean you can treat coronavirus with tonic water?

Yeah, 10 litres per day.

That's going to require a lot of gin.

I volunteer.

83 milligrams per liter for tonic water, so about 6 liters to get a 500mg therapeutic dose.

Sign me up. I’ll also need about 13 liters of gin and a bag of ice.

Don't forget the limes.

I'm an NFL person...

But who can drink that much gin a day?

But rather insoluble in water. Boil that stuff down, filter it, toss the sugary filtrate and eat the filter.

edit: might be able to do some acid-base work for better results.

In the US tonic what is only allowed to have very low levels of quinine. The old imperial British stuff might have been effective.

could there be interactions with anti IL-17a treatments such as cosentyx ?

ELI5: Neem leaf will cure corona.

Why haven't the markets reacted positively to this news?

You know, I read this, and then I read other things implying we will fix climate change from this crisis, and I wonder ...

The markets has not reacted positively to this news because something possibly helping makes no difference. Actually making a difference to the situation makes a difference. Until the point where there clearly is something that makes a difference the outlook is really bleak.

I suppose that may be the case. But let me play devil's advocate against it. Markets are supposed to price in values from expected future returns. Since this is "a cure", there should be positive sentiment for the future economic environment rather than the current negative sentiment.

The paper says that people are being successfully treated with this medication. It sounds like a slam dunk and a definite end to all the uncertainty we're experiencing. It's somewhat akin to magically having a vaccine available today, no? A situation in which we'd expect markets to react positively. Maybe, this information has not disseminated widely enough in the media, and the markets are acting as a trailing, not leading, indicator.

After reading a bit more, maybe it's not such a panacea. Seems like it's standard of care, but may not help patients who have advanced symptoms; and, obviously, does not prevent infection. Therefore it may not stop us from imposing the preventative measures (quarantine, travel restrictions, the like) which are causing all the economic catastrophe. Still, seems like it would push a bit of a positive spin on things rather than allowing the economic free-fall we've witnessed.

Guessing why the markets do something is like reading the future in the guts of a chicken!

But I think the market is reacting not to the virus, which by itself would have a limited economic impact (and if you think that it affects mostly the elderly, from a pure, cold economic point of view, would rather reduce the long term burden on healthcare, so would be a net economic benefit).

I think the market instead reacts to the actions taken to contain the virus, which will likely severely supress the economic activity. Until there is any sign of these actions being reversed (and everything is pointing to the opposite, with France and the EU hinting at more restrictions yesterday), it is rational for the market to be bearish.

Then as always there are other considerations, stocks were overly expensive, economic cycles, over leverage, etc.

Reply on news.ycombinator.com