Hydroxychloroquine / Plaquenil and the Covid-19 / Coronavirus

[Sushi]

From: https://www.crediblemeds.org/

In such a crisis, drastic measures and innovative approaches are needed and can be justified, but one area under investigation requires a special caution. Several of the medicines now being tested for efficacy in the treatment of COVID-19 are on the list of drugs known to have a risk of Torsades de Pointes (TdP) arrhythmia. These include the antimalarials, chloroquine or hydroxychloroquine, that are being combined with azithromycin or with the antivirals, lopinavir/ritonavir. Each of these drugs alone can cause QT prolongation and chloroquine, hydroxychloroquine and azithromycin are on the CredibleMeds’ list of drugs known to cause TdP. Additional information on this topic is on our CredibleMeds home page.

 

[pattismith]

@Sushi

it's important to read the french study just published (link in my earlier post).

 

[pattismith]

@Sushi

"Our team has a very comprehensive experience in
successfully treating patients with chronic diseases due to intracellular bacteria (Q fever due
to Coxiella burnetii and Whipple’s disease due to Tropheryma whipplei) with long-term
hydroxychloroquine treatment (600 mg/day for 12 to 18 months) since more than 20 years."

"Among hydroxychloroquine-treated
patients six patients received azithromycin (500mg on day1 followed by 250mg per day, the
next four days) to prevent bacterial super-infection under daily electrocardiogram control."

"Clinical follow-up and occurrence of side-effects will be described in a further paper at the end
of the trial."

We have to wait for the complete trial to be published, I hope soon.

 

[Sushi]

@Sushi

it's important to read the french study just published (link in my earlier post).

Yes, I have read the study before—just pointing to a potential side-effect that should be watched for—particularly in cardiac patients with existing rhythm problems. I have Afib and this warning has been appearing on several Afib forums that I follow.

 

[pattismith]

Yes, I have read the study before—just pointing to a potential side-effect that should be watched for—particularly in cardiac patients with existing rhythm problems. I have Afib and this warning has been appearing on several Afib forums that I follow.

do people with Afib are at risk for Torsade de Pointe or QT prolongation?
The paper just said they excluded people with QT prolongation:

"Patients were excluded if they had a known allergy to hydroxychloroquine or chloroquine or
had another known contraindication to treatment with the study drug, including retinopathy,
G6PD deficiency and QT prolongation."

 

[Sushi]

do people with Afib are at risk for Torsade de Pointe or QT prolongation?
The paper just said they excluded people with QT prolongation:

Some of the risk factors for Afib are also risk factors for QT prolongation—such as slow heart rate and hypokalemia. Also Afib patients are much more likely to be taking medications with the risk of QT prolongation, so taking another medication with this risk is thought to be cumulative. Many Afib patients take Tikosin, which requires a 3 day hospital stay upon starting due to the risk of QT prolongation. Since the risk for Afib increases with age and the risk of serious complications with Covid-19 also increases with age, potentially the patient cohort that might be given hydroxychloroquine could include more Afib patients.

 

[stefanosstef]

It has been confirmed in multiple tests so far.Hydroxychloroquine + Azithromycin has 100% success rate in beating covid-19.

 

[junkcrap50]

Good critique of the hydroxychloroquine + azithromycin study:

https://twitter.com/i/web/status/1241216793844183041

. There's no data about viral load included.

It may be effective if viral load is below a certain threshold. But is too little, to late if your viral load/exposure is great. So, there will be arguments about this when people miss this nuance & don't account for it in studies.

 

[pattismith]

Good critique of the hydroxychloroquine + azithromycin study:

https://twitter.com/i/web/status/1241216793844183041

. There's no data about viral load included.

It may be effective if viral load is below a certain threshold. But is too little, to late if your viral load/exposure is great. So, there will be arguments about this when people miss this nuance & don't account for it in studies.

I don't have access to the twitter link, but in any case, I agree that antiviral drugs have better chances of success when given when the viral charge isn't too high. The earlier the better….
Unfortunately it's probably not the way it's currently done in most of the cases just now in France, because affected people are just told to stay at home, even if they have fever and coughing, and to call for emergency care only if they have breathing difficulties...

 

[junkcrap50]

Unfortunately it's probably not the way it's currently done in most of the cases just now in France, because affected people are just told to stay at home, even if they have fever and coughing, and to call for emergency care only if they have breathing difficulties...

Yeah. They'll ration the drugs. Save them for only the very sick. See its effectiveness is ambiquious. And then claim loudly that it doesn't work and strongly recommend their disuse.

 

[eon]

So it's either chloronique or hydrochloronique? One or the other or both? The latter being safer?

 

[nyanko_the_sane]

Hydroxychloroquine branded as Plaquenil is indicated to be safer. It is often prescribed by the Stanford ME/CFS Clinic to combat inflammation.

https://www.nature.com/articles/s41421-020-0156-0

 

[pattismith]

In France:
At less four elected people (deputies or other) that were tested positive for covid (but not necessarily showing symptoms) have been treated by Pr Raoult with his protocol.

One deputy treated wants GP to be authorized to prescribe it to their patients.

 

[pattismith]

medical community is currently split in two camps, docs that want to wait more trials before advising chloroquine/hydroxychloroquine + azithromycin, and those that would like to distribute chloroquine to anybody in order to stop the spread of the virus….
In France Dr Raoult left the government scientific committee because he doesn't agree with their position (not enough testing done, no chloroquine authorized yet apart for more clinical trial and only for severely affected people, which I think is useless).

Here articles by other docs :

Repositioning Chloroquine as Ideal Antiviral Prophylactic against COVID-19 - Time is Now


Version 1 : Received: 16 March 2020 / Approved: 17 March 2020 / Online: 17 March 2020 (15:57:38 CET)
Taiwan
How to cite: Chang, R.; Sun, W. Repositioning Chloroquine as Ideal Antiviral Prophylactic against COVID-19 - Time is Now. Preprints 2020, 2020030279 (doi: 10.20944/preprints202003.0279.v1). Chang, R.; Sun, W. Repositioning Chloroquine as Ideal Antiviral Prophylactic against COVID-19 - Time is Now. Preprints 2020, 2020030279 (doi: 10.20944/preprints202003.0279.v1).
Abstract

The novel coronavirus 2019 (COVID-19) pandemic is rapidly advancing despite public health measures. Pharmaceutical prophylaxis is an established approach to potentially control infectious diseases and is one solution to the urgent public health challenge posed by COVID-19. Screening and development of new vaccines and antivirals is expensive and time consuming while the repositioning of available drugs should receive priority attention as well as international government and agency support. Here we propose an old drug chloroquine (CQ) to be urgently repositioned as an ideal antiviral prophylactic against COVID-19. CQ has ability to block viral attachment and entry to host cells. Its proven clinical efficacy against a variety of viruses including COVID-19 and its current deployment in COVID-19 therapeutic trials strengthens its potential candidacy as a prophylactic. Furthermore, CQ has a long safety record, is inexpensive and widely available. Here we reviewed CQ's antiviral mechanisms, its laboratory efficacy activity against COVID-19, as well as CQ's pharmacokinetics in its established use against malaria and autoimmune diseases to recommend safe and potentially efficacious dose regimens for protection against COVID-19: a pre-exposure prophylaxis of 250-500mg daily and post-exposure prophylaxis at 8mg/kg/day for 3 days. We recommend further urgent research on CQ for COVID-19 prevention and urge that the above regimens be investigated in parallel with mass deployment by relevant agencies in attempts to contain the pandemic without unnecessary regulatory delays as benefits far outweigh risks or costs.
Subject Areas

chloroquine; COVID-19; SARS-CoV2; antiviral; viral prophylaxis

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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Comments (1)



Comment 1
Received: 21 March 2020
Commenter: DR NEIL RANGEL
The commenter has declared there is no conflict of interests.
Comment: EXCELLENT


Subject: VERY URGENT / SUGGESTION- CHLOROQUINE . HYDROXYCHLOROQUINE PROPHYLAXIS FOR NCOVID-19

KIND ATTENTION
Kindly find an urgent recommendation for - consideration/ concerning CHEMOPROPHYLAXIS against the NCOVID -19 pandemic
I am frustrated by the kind of silly responses and lackadaisical attitude of many- in relation to my suggestion to urgently formulate a policy on chloroquine/hydroxychloroquine prophlyaxis against NCOVID19. People are dying like flies by the 100s and they tell me we need to wait for clinical trials! I believe this intervention will slow transmission, reduce severity and save lives. We used to give chloroquine even empirically in the villages. All I am asking for is a supervised 1 tablet stat or weekly – a harmless dose. 1$ could easily get 100 tabs. This is an emergency and all protocol requirements for a drug trial have to be waived. I am appalled that face masks are not being made mandatory- it makes sense to believe any protection is better than no protection

I THINK MEDICAL PROFESSIONALS THEMSELVES MUST NOW ACTIVELY LOBBY THE HEALTH AUTHORITIES TO RECOMMEND CHLOROQUINE/ HYDROXYCHLOROQUINE PROPHYLAXIS AGAINST NCOVID19- URGENTLY. EVIDENCE FOR USE IS REASONABLY GOOD AND THE DRUG IS SAFE IN SAID DOSES
I HAVE WRITTEN TO EVERY THINKABLE EXCEPT DONALD TRUMP I HAVE NO ACCESS TO - PMs, PRESIDENTS, HEALTH MINISTERS, SECRETARIES, WHO, CDC, MR FAUCCI, MR COLLINS, NIH, LANCET, BMJ, JAMA, NHS, - UK GOV, IRELAND, SINGAPORE, INDIA, HOLLAND, DENMARK, NORDIC, ITALY, FRANCE, PORTUGAL...LETS SEE. I THINK WE ARE RUNNING OUT OF TIME

Will appreciate of my comments can be forwarded widely and to those in authority/ decision – guideline making


DR NEIL DE JESUS RANGEL/ Endocrinologist, Mediclinic Welcare Hospital, Dubai, UAE

 

[Gingergrrl]

I apologize if this has already been asked and answered in this or another thread but is there any connection between chloroquine and fluoroquinolone antibiotics?

Initially I thought there was not and about 4-5 years ago someone on PR asked me this exact question and I said there was not.

But now I am not sure?!!!

@valentinelynx Do you know if there is ANY connection between Chloroquine and Fluoroquinolones?

 

[pattismith]

I apologize if this has already been asked and answered in this or another thread but is there any connection between chloroquine and fluoroquinolone antibiotics?

Initially I thought there was not and about 4-5 years ago someone on PR asked me this exact question and I said there was not.

?

I think chloroquine is a quinolone sensus stricto but not a fluoroquinolone...
(What are usually called quinolones are mostly fluoroquinolones)

 

[valentinelynx]

I apologize if this has already been asked and answered in this or another thread but is there any connection between chloroquine and fluoroquinolone antibiotics?

Initially I thought there was not and about 4-5 years ago someone on PR asked me this exact question and I said there was not.

But now I am not sure?!!!

@valentinelynx Do you know if there is ANY connection between Chloroquine and Fluoroquinolones?

The simple answer is no, the two types of drugs have very difference mechanisms of action and side effect profiles (with the exception that both can cause QT-prolongation in the EKG).

On a chemical basis, there is a resemblance: both have a similar bicyclic nitrogen containing ring structure. However, on the quinolones (the antibiotics) that structure has a ketone added to it, which I imagine (not being an organic chemistry expert) drastically changes its behavior. If you want to know the nitty gritty of the organic chemistry of this, I can ask my husband .

Chloroquine and hydroxychloroquine work by increasing the pH inside of lysozymes in antigen-presenting (immune) cells, blocking toll-like receptors, and damping down inflammation. In malaria treatment, the mechanism is still not fully elucidated, but it is known that these chemicals cause the accumulation of heme, which is toxic to the parasite, preventing heme conversion to a non-toxic form.

Quinolone antibiotics inhibit bacterial DNA synthesis by preventing the proper winding of bacterial (but not human) DNA. The mechanism of the toxicity of fluoroquinolones, such as tendinopathy and neuropathy is unknown, but some research indicates toxicity to the mitochondria.

The toxic effects of the chloroquines include: retinopathy and other eye effects, mainly with long term use (decades), and these:
Nausea, abdominal pain, and vomiting
Occasionally, skin conditions, such as rashes, pruritus, and sensitivity to ultraviolet light
Rarely, neurologic symptoms, such as vertigo, tinnitus, irritability, cranial nerve palsies, and myasthenialike muscle weakness (from Medscape)

The toxic effects of the fluoroquinolone antibiotics, on the other hand, are (from Wikipedia): tendonitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathies associated with paraesthesia, depression, fatigue, memory impairment, sleep disorders, and impaired hearing, vision, taste and smell.

There is no suggestion that a hypersensitivity to one of these drug classes would indicate a similar sensitivity to the other.

Nor is there any good evidence yet that hydroxychloroquine (or hydroxychloroquine plus azithromycin) is a real treatment for Covid-19. No controlled studies have been done and the French study was on only 26 patients and had several problems, as described in this New York Times article. Here's a quote (underline added by me),

"Some of the 26 were not counted in the final results because they didn't complete the study — what's known as 'lost to followup' — but that included three who worsened and were sent to intensive care, one who died a day after later testing negative for the virus, and one who stopped treatment because of nausea.​

​

After six days, no patients given hydroxychloroquine plus azithromycin had virus detected in swabs from the back of the nose, versus 57% of those given the malaria drug alone and 12.5% of some other patients who received neither drug."​

I hope this rambling discourse is of some help!

 

[Gingergrrl]

(What are usually called quinolones are mostly fluoroquinolones)

Quinolones and Fluoroquinolones definitely refer to the same thing (antibiotics) and the two terms are used inter-changeably. I was trying to figure out where Chloroquine fit into the equation.

The simple answer is no, the two types of drugs have very difference mechanisms of action and side effect profiles (with the exception that both can cause QT-prolongation in the EKG).

My research said "no" as well but then I started to get confused (and am still a bit confused ). I knew they had different mechanisms of action but was not sure if they would be grouped together into the same larger class of meds. Forgive the basic analogy but for example... the way that ibuprofen and naproxen are both in the NSAID class, would Fluoroquinolones and Chloroquine both be in the same larger class (of something) or are they in two totally different classes of meds? I hope that made sense

On a chemical basis, there is a resemblance: both have a similar bicyclic nitrogen containing ring structure. However, on the quinolones (the antibiotics) that structure has a ketone added to it, which I imagine (not being an organic chemistry expert) drastically changes its behavior. If you want to know the nitty gritty of the organic chemistry of this, I can ask my husband .

I won't understand the chemistry so please don't bother your husband about this

The mechanism of the toxicity of fluoroquinolones, such as tendinopathy and neuropathy is unknown, but some research indicates toxicity to the mitochondria.

My entire illness started with a neurotoxic reaction to Levaquin (Fluoroquinolone) in which I was hospitalized in 2010 in addition to acute (and now life-long) damage to my right triceps tendon.

I know that Chloroquine isn't associated with the tendon damage part, but do you think that someone who had a neurotoxic reaction to a Fluoroquinolone should avoid Chloroquine, too?

The toxic effects of the chloroquines include: retinopathy and other eye effects, mainly with long term use (decades), and these:

Levaquin (and some of the other Fluoroquinolones) is also associated retinal detachment and eye injuries (thank God this part did not happen to me).

and myasthenialike muscle weakness

This was one of my worst symptoms (myasthenia like muscle weakness) and it affected my breathing (lungs and diaphragm). This symptom is 100% in remission from Rituximab. If Cloroquine carries this risk, I would have to decline it (if it were proven to fight COVID-19 which I know it is not at this point). It was the worst thing I ever experienced (second only to anaphylaxis).

There is no suggestion that a hypersensitivity to one of these drug classes would indicate a similar sensitivity to the other.

That is good to know. I'm not certain if what happened to me with Levaquin would be considered a "hypersensitivity" and I will Google what that means. I was told at the time that it was an "adverse reaction" and later that I had "Fluoroquinolone Toxicity Syndrome". Not much was known about it back in 2010 (when it happened to me) and it was taken about as seriously as ME/CFS. I believe it is taken more seriously now.

hydroxychloroquine plus azithromycin

So both hydroxychloroquine and azithromycin cause prolongation of the QT interval ?

I hope this rambling discourse is of some help!

Absolutely and it was extremely helpful! Thank you so much VL!

 

[eon]

Careful with self medicating and make sure you have the right version of the drug.

Man Dead From Taking Chloroquine Product After Trump Touts Drug For Coronavirus

Man Dead From Taking Chloroquine Product After Trump Touts Drug For Coronavirus
https://www.forbes.com/sites/taraha...quine-after-trump-touts-drug-for-coronavirus/

 

[pattismith]

Nor is there any good evidence yet that hydroxychloroquine (or hydroxychloroquine plus azithromycin) is a real treatment for Covid-19. No controlled studies have been done and the French study was on only 26 patients and had several problems, as described in this New York Times article. Here's a quote (underline added by me),

"Some of the 26 were not counted in the final results because they didn't complete the study — what's known as 'lost to followup' — but that included three who worsened and were sent to intensive care, one who died a day after later testing negative for the virus, and one who stopped treatment because of nausea.​

​

After six days, no patients given hydroxychloroquine plus azithromycin had virus detected in swabs from the back of the nose, versus 57% of those given the malaria drug alone and 12.5% of some other patients who received neither drug."​

I hope this rambling discourse is of some help!

This three patients that got worse and one who died after a negative test need more explanations, I hope we will have it in the final paper about the side effect they got and if heart toxicity was involved.
The Covid-19 himself seems to affect the heart function as @Mary pointed, so the hydroxychloroquine may not be well tolerated by some patients, especially those
-overweighted
-with high blood pressure
-with hypokalemia
-with severe infection

The fact this protocol was agreed for more trial in France only for very severe patients is probably a very good way to bury it for ever: it is not likely to be helpful when the virus load is too heavy, and probably more armful than good for these patients because of the covid/heart damages...