A few things about HCQ -

• The Brazilian study was highly flawed and they used CQ or chloroquine, not HCQ.

• CQ and HCQ are quinolines, a class of drugs (btw, not related to quinolines).

• The only data on quinoline cardiotoxicity comes from CQ, not HCQ. There are no data to suggest HCQ is cardiotoxic.

• Even with "higher" doses of HCQ, I am not using "high" doses of HCQ. The rheumatoid arthritis and SLE literature use much higher doses, because HCQ keeps building up in a person's system.

• HCQ's 1/2 life is ~40 days, so steady-state isn't reached until 4.5 - 5.5 half lives or 6-7 months.

• This means that people taking a steady daily or weekly dose of HCQ don't reach steady state for a half a year or more and that the HCQ keeps building up.

• There are many articles on the lack of cardiotoxicity of HCQ.

• The FDA has approved or, at least, not intervened in hundreds of HCQ studies.

• Currently, there are 87 Non-Covid RCTs, being done in the USA and another 43 Covid studies.

• HCQ is being studied in hidradenitis suppurativa, myeloma, GBM, prediabetes/obesity, pancreatic cancer, breast cancer, CLL, lymphangioleiomyomatosis, and many other diseases. (I don't even know what lymphangioleiomyomatosis is.)

• Each of these non-Covid HCQ clinical trials uses a higher cumulative dose of HCQ over the first 3 weeks than any Covid pt ever gets.

• None of the HCQ-USA studies requires ECG monitoring at all.

• These are ongoing studies, which the FDA oversees.

• In April, the FDA warned doctors about HCQ's cardiotoxicity in Covid pts and ONLY Covid pts.

• The FDA has not required one alteration of any of these HCQ studies, including the Covid studies. None monitor ECGs or QTc intervals.

HCQ US studies -

https://clinicaltrials.gov/ct2/results?cond=&term=hydroxychloroquine&type=&rslt=&recrs=a&recrs=d&recrs=e&age_v=&gndr=&intr=&titles=&outc=&spons=&lead=&id=&cntry=US&state=&city=&dist=&locn=&rsub=&strd_s=&strd_e=&prcd_s=&prcd_e=&sfpd_s=&sfpd_e=&rfpd_s=&rfpd_e=&lupd_s=&lupd_e=&sort=

Summary of relevant articles:

Rheumatoid arthritis pts respond to HCQ, but the response takes months to occur, because it takes months for these pts to reach the HCQ level needed to achieve a response.

To shorten the time from starting to therapeutic response, Furst et al. used higher doses for the first 6 weeks of HCQ therapy.

The 1999 Furst et al. study was a "...6-week, double-blind trial comparing treatment with HCQ at 400 mg/day (n 5 71), 800

mg/day (n 5 71), and 1,200 mg/day (n 5 66), followed by 18 weeks of open-label HCQ treatment at 400 mg/day."

This study was NIH-sponsored and done a multiple sites in the US only.

They didn't monitor ECGs at all.

There was no report or hint of cardiotoxicity.

The highest dose used in this study was 1.2 GRAMS per day, every day for 6 weeks.

In 2002, Furst et al. published the PK data from these pts.

At the end of the 6-week period, this group's HCQ blood levels were over 5,000 ng/ml which is > 3-times the target level for SLE pts.

Similarly, in 2013 Costedoat-Chalumeau et al. studied HCQ dose escalation in Lupus pts. The usual HCQ dose for Lupus women was 200 or 400 mg per day. Costedoat-Chalumeau et al. randomized Lupus pts to received 600 mg or 800 mg per day. The researchers hoped that by increasing the HCQ dose, more pts would achieve the HCQ target lood level =1,500 ng/ml.

Obviously, Lupus women in general weigh less than the general population of men and women in the same age category.

And this study was done in France.

Again, they didn't monitor cardiotoxicity and again, there are no report or hint of cardiotoxicity.

To conclude, no Covid pt’s HCQ blood levels reach the HCQ blood levels of RA or Lupus pts. Further, a Covid pt’s exposure to HCQ is short in the range of 10 days or a few more.

RA pts take HCQ for years.

Lupus pts take HCQ for LIFE.

In April, the FDA issued a warning about HCQ in Covid pts causing cardiotoxicity.

This is the only warning about HCQ and cardiotoxicity.

The FDA has not warned RA or lupus pts about cardiotoxicity.

The FDA has not warned or required changes to all those HCQ clinical trials being conducted in the US. The FDA not only has the authority to do so; they have an obligation to protect the US population against a drug’s side effects.

The avg dose of HCQ used in those Covid pts, whom the FDA felt suffered HCQ cardiotoxicity, was less than 3 gms.

In the Furst study, pts passed the 3 gm total dose by Day 3.

Lupus women take 400 – 800 mg per day, for life. So, at those doses they pass the 3 gm cumulative dose by 8 days (400 mg/day) and 4 days (800 mg/day).

Since each of these HCQ studies uses a much, much higher cumulative dose, which achieves much, much higher HCQ blood and tissue levels, why hasn’t the FDA issued warnings to pts in these other trials?

Why hasn’t the FDA shut down all the HCQ studies in the US or required that the protocols be changed?

I reviewed the protocols of several dozen HCQ trials on www.ClinicalTrials.gov.

None monitors ECGs.

Why not?

Stephen

1999 Furst et al. - https://pubmed.ncbi.nlm.nih.gov/10025931/

2002 Munster & Furst et al. - https://onlinelibrary.wiley.com/doi/full/10.1002/art.10307

2013 Costedoat-Chalumeau et al. - https://ard.bmj.com/content/72/11/1786.long