Coronavirus COVID-19 Update: Hydroxychloroquine and Other Treatments

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Politico, citing three officials, reported that the move would allow more manufacturers to produce the drugs.
“Let’s see how it works. It may. It may not,” Trump said at a press conference on Sunday, the report said.
 
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I didn't see that this study of hydrochloriquine was mentioned. If it has, my apologies

"This study aims to evaluate the efficacy of hydroxychloroquine (HCQ) in the treatment of patients with COVID-19. Main methods: From February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ. Key findings: For the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 32) compared with the control group (54.8%, 17 of 32). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group."
 
This may sound crazy but we have to keep an open mind. A friend from Pakistan sent it to me.




I checked the package insert

Pharmacokinetics: Following a single 200 mg oral dose of PLAQUENIL to healthy males, the mean peak blood concentration of hydroxychloroquine was 129.6 ng/mL, reached in 3.26 hours with a half-life of 537 hours (22.4 days). In the same study, the plasma peak concentration was 53 ng/mL reached in 3.74 hours with a half-life of 2963 hours (123.5 days). Urine hydroxychloroquine levels were still detectable after 3 months with approximately 10% of the dose excreted as the parent drug.


Update on April 20:

These two large studies are looking into one per week dosing:


 
Pharmacokinetics: Following a single 200 mg oral dose of PLAQUENIL to healthy males, the mean peak blood concentration of hydroxychloroquine was 129.6 ng/mL, reached in 3.26 hours with a half-life of 537 hours (22.4 days). In the same study, the plasma peak concentration was 53 ng/mL reached in 3.74 hours with a half-life of 2963 hours (123.5 days). Urine hydroxychloroquine levels were still detectable after 3 months with approximately 10% of the dose excreted as the parent drug.

That sounds like a strange typo. If the half life was that long, why would patients need to take it every day for arthritis, lupus etc.
 
That sounds like a strange typo. If the half life was that long, why would patients need to take it every day for arthritis, lupus etc.
I know. But that is what is in the package insert that the FDA approved.
 

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Initial Treatment Algorithm for Hospitalized, Non–Severe COVID-19 Patients
Posted by Physicians Weekly | Apr 2, 2020

Led by infectious disease physicians, the COVID-19 Treatment team created a treatment plan for non-severe and severe disease for use across Yale New Haven Health. Additionally, the updated algorithm includes a list of recommended medications, along with rationale for use, notable adverse reactions, and other considerations.

The COVID-19 Treatment team consist of experts from across many disciplines including in infectious diseases, pulmonary and critical care, allergy and immunology, rheumatology, hematology, hospital pharmacy, and others.

The Department of Internal Medicine is the largest department within the Yale School of Medicine and one of the nation’s premier departments, bringing together an elite cadre of clinicians, investigators, and educators in one of the world’s top medical schools.
 
From a Dr in Monroe NY
 

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There is no $$$$ in using existing drugs. Many ppl vested in PR claiming hydroxychloroquine is no good. Many things I have read Drs wait u are on death bed before they give. Of course it will not work in some if your almost dead.
 

An international poll of more than 6,000 doctors released Thursday found that the antimalarial drug hydroxychloroquine was the most highly rated treatment for the novel coronavirus.

The survey conducted by Sermo, a global health care polling company, of 6,227 physicians in 30 countries found that 37% of those treating COVID-19 patients rated hydroxychloroquine as the “most effective therapy” from a list of 15 options.
 
I checked the package insert

Pharmacokinetics: Following a single 200 mg oral dose of PLAQUENIL to healthy males, the mean peak blood concentration of hydroxychloroquine was 129.6 ng/mL, reached in 3.26 hours with a half-life of 537 hours (22.4 days). In the same study, the plasma peak concentration was 53 ng/mL reached in 3.74 hours with a half-life of 2963 hours (123.5 days). Urine hydroxychloroquine levels were still detectable after 3 months with approximately 10% of the dose excreted as the parent drug.

The in vitro effective concentration of Hydroxychloroquine sulphate (molar mass = 434 g/mol) against COVID-19 is cited as EC50 = 0.73 microM =
= 0.73 * 10^-6 mol/Liter =
= 0.73 * 10^-6 * 434 g /Liter =
= 3.17 * 10^-4 g/Liter =
= 3.17 * 10^-7 g/mL =
= 317 * 10^-9 g/mL =
= 317 ng/mL.

If the Plaquenil insert is correct, reaching the EC50 concentration will require 317/53 = 6 doses of 200mg Plaquenil pills. The French study uses 3 x 200mg pills each day so the EC50 will be reached at the end of the second day of dosing. That probably supports the idea that hydroxychloroquine has to be started EARLY not when the patient is already intubated and dying.
 
And even better, if Hydroxychloroquine is actually protective againgst COVID -19 infection if taken before the infection, just a regular dosing of several days will protect for months ....
 
Similar to post #50, but with a slightly different discussion and some good citations:


All patients in this study were already in a really bad shape when chloroquine started:
At the time of treatment initiation, 10/11 had fever and received nasal oxygen therapy. Within5 days, one patient died, two were transferred to the ICU.
There were 7 men and 4 women with a mean age of 58.7 years (range: 20-77), 8 had significant
comorbidities associated with poor outcomes (obesity: 2; solid cancer: 3; hematological
cancer: 2; HIV-infection: 1).

The study title is sensational instead of objectively saying "chloroquine could not save people with severe comorbidities in a late stage of covid-19 infection". I am surprised that people that supposedly work in an infectious decease department do not realize that many anti-virals do not work if taken too late - example anti-virals for influenza.
 
All patients in this study were already in a really bad shape when chloroquine started

Interesting. The article critiques the French study for choosing patients not in bad shape:

"Although some of their results appeared to be encouraging, it should also be noted that most of their patients only had mild symptoms. Furthermore, 85% of the patients didn’t even have a fever – one of the major telltale symptoms of the virus, thus suggesting that these patients likely would have naturally cleared the virus without any intervention."

I suppose better testing will eventually answer the question.
 
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The french study by Gautret did not "choose" the patients. They were all patients at the center that agreed to be included in the study about 4 days after onset of symptoms and some of them chose chloroquine (the treatment arm), other refused it (the control arm). The treatment started only 4 days on average after onset of symptoms that is why they were not in bad shape. They didn't wait for them to get bad.

The study by Molina does not specify but most probably waited until patients were already on oxygen and then started treatment and failed.

Comparing the two study clearly dictates that treatment has to start from the very beginning, regardless of symptoms. It is amazing how many "medical professionals" just don't get it despite numerous courses on statistics.
 
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