[-] TrumpLyftAlles | 2 points | Jun 17 2020 03:04:54

This is a long article that talks about several drugs. I'll just present the ivermectin bits.

TL;DR: A lot about ivermectin is unknown so we shouldn't be using it.

I disagree, of course.

This article tries to paint ivermectin as dangerous, when (I would say) it's arguably the safest drug known.

Treating Covid-19: When enthusiasm trumps evidence

A few weeks ago, healthcare workers and volunteers wearing masks and medical gloves began distributing an estimated 350,000 doses of ivermectin to residents of Trinidad in the northern Bolivian province of Beni. The ivermectin, a drug used for decades to treat parasitic worms, was being offered as a prophylactic to protect Bolivians from the novel coronavirus in a region hard hit by Covid-19.

Marco Antonio Aponte, the doctor who designed the treatment protocol for ivermectin in Beni, went on Bolivia’s Radio Uno recently to explain the drug distribution campaign. “My approach is that we use it as preventive medicine and for mild cases for home treatment,” Aponte said. The drug was approved by Bolivia’s Ministry of Health on May 12 to combat Covid-19. Ivermectin, originally found in a bacterium in Japanese soil, developed into an antiparasitic by the pharmaceutical company Merck and subsequently donated to treat river blindness, is now produced generically and used to treat elephantiasis, scabies and roundworm infections.

But the evidence of ivermectin’s efficacy in treating Covid-19 in humans is slim. Aponte’s rationale for using the drug, he explained to CNN Español, was based on a study conducted by Australian researchers that showed the drug inhibited SARS-CoV-2, the virus which causes Covid-19, in vitro, meaning the drug was tested not in humans or animals but on mammalian cells in a dish – monkey kidney cells to be precise. Soon after its publication in the journal Antiviral Research, though, the study prompted a letter of caution from the U.S. Food and Drug Administration (FDA) as well as substantial blowback from the scientific community.

The FDA is (scientifically) conservative and is against everything that isn't thoroughly proven safe and effective. This doesn't indicate that ivermectin is dangerous, just that FDA-standard of proof doesn't exist (yet).

“In vitro promise leads to clinical failure in the vast majority of cases,” warned one letter to the editor published in the journal in response to the study. A guest editorial published in the American Journal of Tropical Medicine and Hygiene (AJTMH) echoed that fact and also pointed out that severely ill patients could experience neurotoxicity if the drug crosses the blood-brain barrier.

Neurotoxicity is extremely unlikely, as discussed here and almost never fatal. Out of billion(s) of people who have taken ivermectin over more than two decades, an adverse events database had 156 "serious" neurological disorders, which may have resulted in a grand total of 2 deaths. Both of those people had other stuff going on that might have killed them though.

Compare this to aspirin and penicillin, both of which kill 1000s annually.

“The discovery of ivermectin’s activity against SARS-CoV-2 gives reason for hope, but off-label and compassionate use requires careful risk–benefit considerations, especially in critically ill patients,” they wrote. The same point was raised by Doris Cully, an expert in ivermectin and former director of both Infectious Disease and Cardiovascular Research at Merck, in a recent episode of the podcast This Week in Virology. “When you get into this dose range, there is a lot unknown.”

Oh, there are unknowns. Doesn't make it dangerous. What is known about covid19 treatment, at this early stage? Remdesivir barely works, HCQ probably doesn't. Not much.

The study discussed here found that 10 times the usual 200mcg/dose was safe.

There are 3 (IIRC) trials underway testing 600mcg/kg.

Much of the ivermectin criticism from the scientific community boiled down to two simple facts: 1) in vitro and in vivo are vastly different universes when assessing a drug’s efficacy, and 2) administering any medication at high doses carries serious risks. In other words, showing antiviral activity in cells is one thing. Showing it works against SARS-CoV-2 in humans – and getting the dose right – is a much more complicated proposition and one that could lead to serious side effects. As Essalud, Peru’s social health insurance agency, recently concluded in a report discouraging the use of ivermectin for Covid-19: “the evidence available to date, on the viability of ivermectin as a Covid-19 treatment, is still in early stages of development; highlighting that pharmacokinetic predictions are theoretical and evidence from human studies is scarce.” Many of the doctors we spoke with expressed similar concerns.

Data is scarce. SHOCK! It's scarce for every treatment that anyone has proposed.

This is a red herring; no one is proposing dosing ivermectin at the "concentration too high" levels that are the routine, off-repeated attack on ivermectin.

“Several studies show that you can grow the virus in a test tube and then kill it off with high doses of various drugs we already have,” says Pranay Sinha, an infectious diseases physician and researcher at Boston Medical Center in Boston, Massachusetts. “But how does this translate to killing the virus in humans? If you’re going to give an innocuous FDA-approved drug like ivermectin at five or ten times the normal doses, of course you’re going to have toxicity.”

LOL. Nope, as shown by the study I linked above, 10 times the normal dose has expressly been found to be SAFE.

Drug development starts with in vitro tests followed by safety and efficacy tests in animals – such as rodents and primates – and finally clinical trials in humans. That process typically takes years and properly scaling up the dose without being toxic is highly complex. But in the face of a global pandemic, desperation has the public, politicians and even medical professionals seizing on early data and multiplying up the dose.

While Sinha understands these are desperate times, he thinks the medical community and the public need to better separate enthusiasm from evidence, faith from facts. “Hope is very important, but truth is necessary.”

Really going out on a limb there, Dr. Sinha. That's what every medical student is taught in their first year.

It's not that useful in the midst of a pandemic, though.

Yet unproven treatments have become a hallmark of the Covid-19 pandemic. With drugs like hydroxychloroquine, azithromycin, remdesivir, tocilizumab and ivermectin, the scientific evidence they work for Covid-19 is limited and oftentimes shaky, and there exist serious risks of adverse reactions and side effects.

But news reports have heralded these drugs as panaceas and “game-changers,” often without citing studies or pointing out the risks.

Not US news reports. With the solitary exception of NewsMax, which has covered exactly one story (Broward County), US media are peculiarly silent about ivermectin. Searching the NYTimes and Washington Post today, for example, turn up only two articles, neither of which are remotely endorsements.

[-] TrumpLyftAlles | 1 points | Jun 17 2020 03:05:07

And, to make matters worse, politicians with no medical expertise are prescribing these drugs. Hydroxychloroquine and azithromycin, an antimalarial and antibiotic both produced generically, have been promoted by Brazilian president Jair Bolsonaro and U.S. president Donald Trump as being effective treatments against Covid-19. Yesterday, the FDA revoked its "emergency use authorization" for hydroxychloroquine and chloroquine for the treatment of Covid-19 due to a lack of scientific evidence.

Has nothing to do with ivermectin, if HCQ is dangerous.

These drugs are proliferating – especially across Latin America. In early May, ivermectin was approved by Peru’s Ministry of Health, along with hydroxychloroquine and azithromycin, to treat Covid-19. Last month, Brazil’s Ministry of Health released guidelines for the use of hydroxychloroquine in treating Covid-19 patients. Last week, the United States announced that it would be sending two million doses of hydroxychloroquine to Brazil for prophylactic use by nurses, doctors and other health care workers. And a few days ago, the city of Natal, in northeast Brazil, approved ivermectin, hydroxychloroquine and azithromycin for the treatment of Covid-19.

Brazil has rapidly accelerating infections. Its health system is broken and broke. Ivermectin is cheap. Should Brazil lets 1000s died because proof of ivermectin's efficacy doesn't meet the FDA's standards?

Many of these drugs, of course, were never meant to treat Covid-19. Hydroxychloroquine is an antimalarial, azithromycin is an antibiotic, ivermectin is an antiparasitic, tocilizumab is a cancer and rheumatoid arthritis drug, and remdesivir is an antiviral. Because they have other indications, clinical trial data with Covid-19 patients are sparse or nonexistent. Yet today, all five are being used to treat Covid-19 patients.

Ivermectin is also an antiviral; here is a very long paper about it's antiviral properties.

To fill the evidence gap, researchers around the globe are scrambling to launch and complete clinical trials to test these drugs for Covid-19 and accumulate evidence as to whether they do or don’t work. The timeline to completion for these clinical trials vary from later this year to as far away as 2023. In the meantime, however, patients in the clinic and people taking these drugs prophylactically risk serious side effects and potentially lethal adverse reactions, especially if they are taken without a doctor’s supervision, says César Ugarte, an epidemiologist at the Instituto de Medicina Tropical Alexander von Humboldt at the Universidad Peruana Cayetano Heredia.

IIRC, about 9 ivermectin trials are supposed to be completed before 2020-09-01.

“Ivermectin is not a drug that should be given without medical supervision,” says Ugarte, pointing out that the use of these drugs at home or in an outpatient setting compounds the risks.

And yet they are doing that, in Trinidad, Bolivia and elsewhere, with no negative reports. Doctors want you to need them.

When US doctors prescribe ivermectin for the treatment of scabies, do they check their patients into the hospital so they can keep an eye on them? NO, they give the patient a prescription, and the patient fills it then takes the drug at home.

Indeed, ivermectin has been shown to have serious side effects in patients with multiple parasitic infections.

This is misleading to the verge of being a lie. If the patient has a lot of parasites, they feel really lousy for a few days, because the body is clearing a lot of dead worms. No one needs hospitalization, no one dies.

What's more dangerous, feeling crappy because of your heavy worm infestation, or dying of covid19?

Take ivermectin, and avoid both hazards!

That’s not a far-fetched scenario in Latin America, says Sinha, of Boston Medical Center. “In areas where there are multiple parasitic infections, receiving ivermectin could cause a Mazzotti reaction which can at times be lethal,” he explains.

Sounds scary, right? Relax: "Mazzotti reaction" just means "adverse events".

Never mind. Ivermectin is ridiculously safe.

“You can’t just hand ivermectin out like aspirin,” says Sinha. “There needs to be thoughtful use, especially in the tropics.”

LOL. Actually, aspirin shouldn't be handed out like aspirin.

Daily aspirin behind more than 3,000 deaths a year, study suggests

That's 3000 deaths/year -- in just the UK, a country of 67 million people. That number corresponds to about 15,000 killed every year in the US.