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posted by Fnord666 on Monday April 13 2020, @01:12AM   Printer-friendly

The Latest Hydroxychloroquine Data, As of April 11:

We have new data on hydroxychloroquine therapy to discuss. The numbers will not clear anything up.

The good news is that the HCQ/sulfasalazine comparison does not show any real differences in adverse events over one-month courses of treatment. I should note that sulfasalazine is not the most side-effect-free medication in the whole pharmacopeia, but it has not been associated with (for example) QT prolongation, which is one of the things you worry about with hydroxychloroquine. The paper concludes that short-term HCQ monotherapy does appear to be safe, but notes that long-term HCQ dosing is indeed tied to increased cardiovascular mortality.

The trouble comes in with the azithromycin combination. Like many antibiotics (although not amoxicillin), AZM is in fact tied to QT prolongation in some patients, so what happens when it's given along with HCQ, which has the same problem?

Worryingly, significant risks are identified for combination users of HCQ+AZM even in the short-term as proposed for COVID19 management, with a 15-20% increased risk of angina/chest pain and heart failure, and a two-fold risk of cardiovascular mortality in the first month of treatment.

That isn't good. I am very glad to hear that the Raoult group has observed no cardiac events in their studies so far, but I wonder how they have managed to be so fortunate, given these numbers.

Update: here is another new preprint from a multinational team lead out of Brazil. It enrolled 81 patients in a trial of high-dose hydroxychloroquine  (600 mg b.i.d. over ten days, total dose 12g) or low-dose (450mg b.i.d. on the first day, qd thereafter for the next four, total dose 2.7g). All patients also received azithromycin and ceftriaxone (a cephalosporin antibiotic). The high-dose patients showed more severe QT prolongation and there a trend toward higher lethality compared to the low dose. The overall fatality rate across both arms of the study was 13.5% (so far), which they say overlaps with the historical fatality rate of patients not receiving hydroxychloroquine. The authors actually had to stop recruiting patients for the high-dose arm of the study due to the cardiovascular events, but they're continuing to enroll people in the low-dose group to look at overall mortality. The paper mentions that HCQ has been mandated as the standard therapy in Brazil, so there is no way to run a non-HCQ control group, though.


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  • (Score: 4, Interesting) by JoeMerchant on Monday April 13 2020, @02:57AM

    by JoeMerchant (3937) on Monday April 13 2020, @02:57AM (#981810)

    So... we have a late teens son with rather severe autism, very limited communication with the expected resulting anxiety and some pretty serious impulse control issues - above and beyond your normal teenager. He doesn't swear, but the behavior outbursts resemble Tourette's - sudden acting out of things he knows are wrong. A long explanation of why our doctor recommended a drug that's approved for Pseudobulbar affect - another uncontrolled behavior outburst condition, and our son has been on this drug for ~6 months now, with a very marked improvement in his (and our, and his school's) situation. Rambling around to the quinine connection... the drug is a combination of dextromethorphan (yes, the old cough suppressant) and quinidine, yet another member of that tonic water family associated with QT prolongation syndrome. Apparently, the dextromethorphan not only suppresses cough reflexes, but also these behavioral impulses as well - but not effectively until it's mixed with quinidine which prolongs its circulation in the blood and enables it to better cross the brain-blood barrier. Whatever, it works for him, and so far the side effects are minimal.

    Which is a long winded explanation of: even if you call something a monotherapy, you are putting it in a person - which is a complex system of interacting everything, expect different results in different people both due to their inherent genetics, their current microbiome profile, diet, levels of activity, other health conditions, etc.

    Quinidine and friends suppress certain aspects of liver function (like grapefruit also does), in many cases radically altering the serum levels and therefore effects of other drugs and miscellaneous substances in the body.

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