Small Chloroquine Study Halted Over Risk of Fatal Heart Complications

[Formerly Once-Ler]

https://www.nytimes.com/2020/04/12/health/chloroquine-coronavirus-trump.html

April 12, 2020

A small study in Brazil was halted early for safety reasons after coronavirus patients taking a higher dose of chloroquine developed irregular heart rates that increased their risk of a potentially fatal heart arrhythmia.

Chloroquine is closely related to the more widely used drug hydroxychloroquine. President Trump has enthusiastically promoted them as a potential treatment for the novel coronavirus despite little evidence that they work, and despite concerns from some of his top health officials. Last month, the Food and Drug Administration granted emergency approval to allow hospitals to use chloroquine and hydroxychloroquine from the national stockpile if clinical trials were not feasible. Companies that manufacture both drugs are ramping up production.

The Brazilian study involved 81 hospitalized patients in the city of Manaus and was sponsored by the Brazilian state of Amazonas. It was posted on Saturday at medRxiv, an online server for medical articles, before undergoing peer review by other researchers. Because Brazil’s national guidelines recommend the use of chloroquine in coronavirus patients, the researchers said including a placebo in their trial — considered the best way to evaluate a drug — was an “impossibility.”

More at link

[TomSea]

Dr. Zelenko said heart arrytmia was very rare and he had never seen it in the hundreds of patients he has treated, so someone may well be deceiving.

[txradioguy]

So here's what gets me about people losing their damn minds over using this malaria medicine in the treatment of the virus and the potential side effects...have none of the critics watched ANY of the commercials for the next wonder drug that air on television?

Holy crap the list of side effects (to include death) take up half the commercial.

No one is 1/10th as concerned about those as they are this medicine. 

But then there's not a political agenda behind not using those meds like there is this one.

[aligncare]

So here's what gets me about people losing their damn minds over using this malaria medicine in the treatment of the virus and the potential side effects...have none of the critics watched ANY of the commercials for the next wonder drug that air on television?

Holy crap the list of side effects (to include death) take up half the commercial.

No one is 1/10th as concerned about those as they are this medicine. 

But then there's not a political agenda behind not using those meds like there is this one.

The longer this goes on, the more convinced I am the Left has won and America is irreconcilably fractured. Adios America.

[TomSea]

"...  taking a higher dose of chloroquine"

What do you expect then? Don't abuse the drugs.

[Smokin Joe]

The longer this goes on, the more convinced I am the Left has won and America is irreconcilably fractured. Adios America.

Yes, America is divided into two main camps. One that only cares about being in power, (and to hell with America and Americans so long as they get that power), and another, which while it may be somewhat similarly afflicted, does not have the problem so badly that they are willing to completely sacrifice the Country they want to run.

Unfortunately, the former group is running the media--the tools of public opinion, and will use any means necessary to achieve the control they have shown themselves to be unfit to command.

[Smokin Joe]

"...  taking a higher dose of chloroquine"

What do you expect then? Don't abuse the drugs.

Good catch. Too much of a good thing can kill you, even water.

[dfwgator]

Good catch. Too much of a good thing can kill you, even water.

DHMO - Get the Facts!
http://dhmo.org/

[Smokin Joe]

DHMO - Get the Facts!
http://dhmo.org/

https://www.latimes.com/archives/la-xpm-2007-jan-14-me-water14-story.html

It isn't just the immersion threat.

[libertybele]

As a heart patient, I do know that my doctor will no longer prescribe the Zpack -- something about it not recommended for cardio patients. I'm wondering if its the combination Zpack and chloroquine that is causing the fatal heart complications?

[andy58-in-nh]

If Barack Obama were President and he had proposed the same course of treatment, the New York Times would have him up for a Nobel Prize in medicine and quite possibly, sainthood.

[Smokin Joe]

As a heart patient, I do know that my doctor will no longer prescribe the Zpack -- something about it not recommended for cardio patients. I'm wondering if its the combination Zpack and chloroquine that is causing the fatal heart complications?

Perhaps, but the article said "higher dosages" were used. Now, that doesn't say what those dosages were higher than, but that would indicate to me they were higher than the 200mg twice daily of chloroquine recommended by doctors who developed the regimen. I would think that higher dosages than ordinarily used would invite more extreme side effects, or even cause the onset thereof.

A little quick digging on the Z-pack provided this: Azithromycin ‘Z-packs’ tied to potentially fatal arrhythmia

The FDA said in a statement it’s updating all azithromycin labels to reflect the results of the two studies, pinpointing an arrhythmia known as torsades de pointes as the main culprit. Torsades de pointes, a polymorphic ventricular tachycardia characterized by a long QT interval, is a rare arrhythmia but remains one that can be fatal.

and perhaps some other macrolide antibiotic could be substituted which would have the same idiopathic viral replication retardation effect without causing the side effects but:

Other drugs in the macrolide class, as well as non-macrolide medications like fluoroquinolones, also have the potential to prolong the QT interval, the agency said, and those risks should be taken into account when mapping out a patient’s drug regimen.

>snip< and
Patients at a particular risk for arrhythmias include those with known prolongation of the QT interval or those taking other drugs that could prolong the QT interval, as well as patients with ongoing proarrhythmic conditions like uncorrected hypokalemia, hypomagnesemia and clinically significant bradycardia.

[Bigun]

If Barack Obama were President and he had proposed the same course of treatment, the New York Times would have him up for a Nobel Prize in medicine and quite possibly, sainthood.

  Absolutely!

[jmyrlefuller]

Given the lack of a scientific control group, would this study have been a value to anyone anyway?

[PeteS in CA]

Dr. Zelenko said heart arrytmia was very rare and he had never seen it in the hundreds of patients he has treated, so someone may well be deceiving.

Chloroquine and hydroxychloroquine have been in use since WW2 and probably before (it was discovered/created in 1934). Proper dosing, side effects, and contraindications for certain types of health problems are very well known. For example, a person who already has heartbeat irregularities probably would not be given (hydroxy)chloroquine. So Dr. Zelenko has probably been administering the drug with greater knowledge/understanding of the drug and his patients (some heartbeat irregularities can be found in 2 minutes or fewer by simply counting a person's pulse).

[PeteS in CA]

Given the lack of a scientific control group, would this study have been a value to anyone anyway?

Few or none of current treatment of patient groups would be considered a controlled study by the FDA. The FDA's whole drug and equipment approval process and culture is ill-suited for responding swiftly to a pandemic.

[sneakypete]

Dr. Zelenko said heart arrytmia was very rare and he had never seen it in the hundreds of patients he has treated, so someone may well be deceiving.

@TomSea

I am GUESSING it is even possible the drug has a different mixture in Brazil than it does the US?

[jmyrlefuller]

Few or none of current treatment of patient groups would be considered a controlled study by the FDA. The FDA's whole drug and equipment approval process and culture is ill-suited for responding swiftly to a pandemic.

Agreed. Red tape kills in situations such as these.

[sneakypete]

So here's what gets me about people losing their damn minds over using this malaria medicine in the treatment of the virus and the potential side effects...have none of the critics watched ANY of the commercials for the next wonder drug that air on television?

Holy crap the list of side effects (to include death) take up half the commercial.

@txradioguy

And that is just for the children's aspirin.

Can you say "Thank you,ambulance chasing law firms!"?

[Smokin Joe]

Chloroquine and hydroxychloroquine have been in use since WW2 and probably before (it was discovered/created in 1934). Proper dosing, side effects, and contraindications for certain types of health problems are very well known. For example, a person who already has heartbeat irregularities probably would not be given (hydroxy)chloroquine. So Dr. Zelenko has probably been administering the drug with greater knowledge/understanding of the drug and his patients (some heartbeat irregularities can be found in 2 minutes or fewer by simply counting a person's pulse).

As noted in a post above, Macrolide Antibiotics in general, and Zithromax (Azithromycin) in particular have been implicated in causing or exacerbating Torsades de pointes, a polymorphic ventricular tachycardia characterized by a long QT interval, a rare arrhythmia but ...one that can be fatal.

Other drugs in the macrolide class, as well as non-macrolide medications like fluoroquinolones, also have the potential to prolong the QT interval, the agency said, and those risks should be taken into account when mapping out a patient’s drug regimen.

What is the QT interval? The time, measured on an electrocardiogram, from when the ventricles start to contract to when they are finished relaxing. Prolonging that interval can cause the heart to enter into ventricular fibrillation.

Other things, from endocrine disorders to low potassium levels can produce the same effect, but it is a noted possible side effect of that class of antibiotics.

Further digging indicates that for Torsades de pointes:

Medications as causes
Knowledge that TdP may occur in patients taking certain prescription drugs has been both a major liability and reason for removal of 14 medications from the marketplace.[5] Forty nine drugs known to cause TdP and another 170 that are known to prolong QTc remain on the market because the drugs provide medical benefit and the risk of TdP can be managed and mitigated by instructions in the drug label.[6][7] Examples of compounds linked to clinical observations of TdP include amiodarone, most fluoroquinolones, methadone, lithium, chloroquine, erythromycin, azithromycin, pimozide, and phenothiazines.[8] The anti-emetic agent ondansetron may also increase the risk of developing TdP.[9] It has also been shown as a side effect of certain anti-arrhythmic medications, such as sotalol, procainamide, quinidine, ibutilide, and dofetilide[10] In one example, the gastrokinetic drug cisapride (Propulsid) was withdrawn from the US market in 2000 after it was linked to deaths caused by long QT syndrome-induced torsades de pointes.

(emphasis mine).

Links (and further information):
 Electrocardiography
Torsades de pointes
QT interval

[txradioguy]

@txradioguy

And that is just for the children's aspirin.

Can you say "Thank you,ambulance chasing law firms!"?

That's the other commercials that run on the shows I watch.

[sneakypete]

BTW,any of you have the latest scoop on how long an active virus of this type will stay "alive" and able to affect someone just sitting on a table top,door handle,etc,etc,etc?

I was telling my ex today that I had read 48 to 72 hours max,and she was telling me "up to 5 days".

5 days seems excessive to me under normal circumstances.

[Absalom]

Dr. Zelenko said heart arrytmia was very rare and he had never seen it in the hundreds of patients he has treated, so someone may well be deceiving.

----------------------------------
Equally important is the reality that an irregular heartbeat(arrhythmia/atrial fibrillation)
is both treatable and rarely fatal; from 2 family doctors.

[TomSea]

Also, as the article states, this is chloroquine, not hydroxychloroquine. So some difference, that's up to the experts. Zinc a mitigating factor as well?

Anyway, a test in Brazil? I'm not going to get too rapped up about that, nothing against Brazil.

[Smokin Joe]

Also, as the article states, this is chloroquine, not hydroxychloroquine. So some difference, that's up to the experts. Zinc a mitigating factor as well?

Anyway, a test in Brazil? I'm not going to get too rapped up about that, nothing against Brazil.

The hydroxychloroquine (or chloroquine) selectively allows he zinc ions to pass into the cell through the cell membrane. The zinc interferes with the virus' ability to enter and replicate and thus take over (and destroy) the cell. Azithromycin also interferes with the viral replication process, as well as wards off some bacterial infections as well.

The reduced damage to the pneumocytes in the lung and the action of the Azithromycin help prevent a cytokine storm, in which the immune system reacts to the degree that it causes more damage to the lungs and kills the patient.
@Absalom
As for arrhythmia, among known possible side effects of macrolide antibiotics (of which Azithromycin is one) and hydroxychloroquine/chloroquine is the lengthening of the QT interval, the time it takes between the contraction of the muscles in the ventricles and the time when they are completely relaxed. Too great an increase in that interval and the heart goes into ventricular fibrillation, which without prompt clinical intervention, is fatal. 

These side effects do not occur in all patients normally, and the Brazilian study may indicate dosages which were too high, or a group of patients who were already having problems, through genetics, diet, similar endocrine conditions, or some other individual or assemblage of conditions which can make them more likely to have cardiac arrhythmia.

We don't have enough data to pin down what happened there.