Sildenafil was a drug invented to a treatment for heart-related chest pain. While it was ineffective at that, it did have some side effects. In a way, it was a cure for heart related pain. A man who would disappoint women in bed would no longer have his heart crushed when she broke up with him (most readers would have guessed that the brand name drug of sildenafil was Pfizer’s famous blue pill known as viagra). (There are lots of examples of repurposing drugs, another famous example is aspirin).
The point of the story is a drug created for one purpose (whether it is exceptionally good at that purpose or downright useless) can be used for other purposes. Satoshi Omura and William Campbell (Tu Youyou was jointly awarded it for a different drug) were awarded the 2015 Nobel Prize in physiology for their creation of “Avermectin B1a.” After some optimizations such as hydrogenation and was thus going to be named “Hivermectin,” until it was pointed out to them that in some languages, hiver means testicle; ergo, they named it ivermectin, the macrocyclic lactone of the year.
Campbell and Omura wouldn’t know it then, but they had created the most talked about drug in 2021, because just like sildenafil had a better use case, turns out ivermectin could have a better use case than being an anti-parasitic drug (even though it was already revolutionary for parasitic treatment in humans), it could inhibit SARS-CoV-2.
Before anyone says the data on ivermectin is cherry picked, it is easily the most studied repurposed drug for COVID-19. This website is a must read that meta analyzes the ivermectin studies.
“But, but, I saw a Colombian study saying ivermectin is bad!” or “The BBC debunked it, #factchecked you science-denier” or pehaps the most thorough “debunking” by Gideon MK on medium, or “that one study was retracted,” or your favorite fake infectious disease expert (albeit still a doctor) on twitter told you ivermectin is unsafe and leads to poisoning and overdosing. First of all anti-ivermectin reader, I’m surprised you’ve read a study at all, but I suppose you just read what the media (which has never overestimated covid before) told you. But next, let’s examine each of those.
The indict of the study below is taken from IVMMeta.
The Together Trial study is one of two ivermectin trials to date involving very large financial conflicts of interest [López-Medina, Together Trial] — companies closely involved with the trial or organizers stand to lose billions of dollars if ivermectin efficacy becomes more widely known. The design of these trials favors producing a null outcome as detailed in [López-Medina, Together Trial]. Note that biasing an RCT to produce a false positive result is difficult (suppressing adverse events is relatively easy [Evans]), but biasing a trial to produce a false negative result is very easy — for example, in a trial of an antiviral that works within the first 24 hours of symptom onset, trial organizers only need to avoid treating people within the first 24 hours; or with a disease like COVID-19, organizers only need to select a low-risk population where most people recover quickly without treatment. We note that, even under the very suboptimal designs, these trials produced positive results, although without statistical significance. Hundreds of doctors have signed a letter saying how flawed this study is. It meta-analyses that include it, its results heavily shift the results towards no statistical significance.
Discussing Elgazzar’s retracted study, despite his protests, I believe his study should be removed. From a meta-analysis done, the flawed study contributed to 15.5% of the effect of ivermectin’s statistically significant benefit to treating COVID-19. This was a bad study, it should be retracted. Samaha’s study should also be retracted. Luckily for us, ivmmeta.com has us covered and doesn’t include either. Out of the 64 studies on ivmmeta.com, for there to be no statistical significance, 53/64 must be excluded.
Let’s go over the BBC article next. Jack Lawrence, the lead author of the paper in question is a student. Now while that might be suspect, he could also just be that incredible. “More than a third of the major trials have found serious errors” is another way of saying 2/3 are fine. But I’d like to see which studies are in the third of major tirals found to have serious errors. The few the mentioned implicitly (in that they just say the countries and not link the studies from Iran and what I presume is Samaha’s study in Lebanon). Compare the meta-analysis which in the study which doesn’t even reference the studies they analyze to the one’s on ivmmeta.com
There’s a debate about things for sure. Dr. Morteza Niaee, who led the Iran study, defended the results and the methodology and disagreed with problems pointed out to him, adding that it was "very normal to see such randomisation" when lots of different factors were considered. This is not a “fact checkers destroy fake news Iran Doctor with facts and logic #deboonked.” However, even if we discount Niaee, ivmmeta.com re-runs the numbers: discounting [Niaee], late stage results go from 50% [28‑65%] to 46% [23‑62%]. Plenty more suspicious studies have been excluding on ivmmeta.com even some that the BBC didn’t consider. Concerns about [Cadegiani, Carvallo, Carvallo (B), Carvallo (C)] are valid and are thus not on ivmmeta.com. Perhapsthere are even more suspect studies, even if half are suspect, the results are still significant.
The last response is to GMK on twitter (who also claims ivmmeta.com is pseudoscience)
A more thorough debunking here.
GMK is an anti-treatment “influencer” on twitter so is clearly biased. Nonetheless, let’s discuss the flaws quickly. First is they conflate postive no statistical significance with no effect whatsoever. If dozens of study have nearly significant results, it’s very telling. GMK fixates on studies that are discounted by any serious analysis such as Elgazzar claiming that discounting 1/64 studies would greatly change results, thinks viral load is more important than symptoms, using alternate causality by equating a high degree of COVID-19 in a country partially adopting a treatment with a lack of efficacy, disregarding obvious confounding such as heavily affected areas being more likely to adopt treatment, and more (none of which has been corrected).
I remind you, this guy doesn’t believe COVID-19 is airborne (to be fair he said maybe ~1% is) and doesn’t think twice if something clearly ridiculous confirms his confirmation bias.
And to quickly discuss the twitter statement: [not sic] “even Merck the creator of ivermectin (who aren’t even the most moral so they’d push for unsafe drugs) said ivermectin was so bad and ineffective they wouldn’t do studies on it.” Top tier researchers from Japan pleaded for Merck to conduct trials on ivermectin in Japan, but Merck responded they have no intention of conducting trials. A cynic may (wisely) claim it’s because ivermectin is no longer under patent (made in 1983, approved in 1996, 20 years of patent availability, awarded the Nobel Prize in Physiology in 2015, lost the patent in 2016 and since several generics have been made). An idiot may claim that it’s to avoid liability from lawsuits (even though it’s being used in 20+ countries for COVID-19 and over 3.7 billion doses have been given out with almost no problems, and on vigibase it has a very safe side effect profile).
Next on poisoning. Many critics deride it as horse paste (when pill form is unavailable) or dog heartworm medication even though it is approved for human consumption and billions of doses have been given out. The big story on ivermectin poisoning was from Rolling Stones (I thought they did music or something) about ER patients getting turned away because so many people were getting poisoned by overdosing on ivermectin. After their lie was exposed, they changed the headline (good job!)
Horse paste is probably not the way you should get your ivermectin, but if there is nothing else, what is there to do? Even if people can buy ivermectin, authorities are seizing them for being “misbranded” (read: something we don’t like so we use the word misbranded as pretext to seize them). Or even if your doctor prescribes it and the pharmacy refuses to fill out the prescription. It’s like banning opiates, people who really want one, will find a way through the backdoor (albeit it will reduce the amount of people and increase their risk).
Just because calls are made to poison control, it does not mean people are dying from overdosing. It would be easier to die from overdosing on tylenol (ibuprofen) at least according to vigibase’s side effect profile.
If you are still deadset on taking ivermectin, not all forms are created equal. I’ll try to explain how to take it. For all four types of ingestible ivermectin, for humans ingesting is the way to consume. Pills are the best, then comes paste, injectible solution that you ingest and don’t inject (1% ivermectin and 59% propylene glycol, 40% glycerol which are carriers for distributing the ivermectin), then comes the chewables. Make sure you get it pure ivermectin with nothing else (none of the plus, gold, stuff with extra stuff for other anti-liver flukes). For the pill, no brainer ask your doctor follow his/her instructions. For the paste, there is a clicker to measure quantity. One tube is for an 800-1500lb horse (same how aspirin tablet is the same dose for a teenage girl and 300lb body builder). For the chewable, I’d recommend against it but just chew as much as you should dose. For the injectible, it is 1ml per 50kg (110lbs) of body weight. Drop the liquid into something else to mask its horrendous taste. If you are taking multiple doses, space them 48 hours apart due to liver metabolism. Take doses on an empty or close to stomach to maximize bioavialbility and reduce likelihood of an upset stomach. It is very hard to overdose so aim high instead of low so your dosage is efficacious. Duramectin has the SDS available but erroneouly claim you will die if you take it.
As far as safety goes, typically mixing drugs aren’t great. People will say, even if ivermectin is safe by itself (and it probably is since the FDA approved it in 1996 it and hasn’t unapproved it), its pharmacokinetics and pharmacodynamics are too complex for a non-expert to understand. Except that Merck has said it is safe (though this is the same article that disavows it for treatment) and it has been seen to have no serious interactions. On that note, perhaps your doctor is also unaware, but even a specialist may not prescribe it due to political reasons. It also has approximately 4 billion doses given out and probably the side effect profile and interactions with other drugs are far more well known (other therapeutics such as the novel therapies or even the vaccine’s interactions are not well understood since they are so new). Vigibase (the gold standard from the WHO for searching about drugs) finds ivermectin (unfortunately it won’t let me link when I search ivermectin so you have to go type it in yourself) safer than Acetaminophen and Ibuprofen. You probably could get away with mild overdosing and taking it with other drugs (though you probably shouldn’t).
To be in the dissenting opinion is difficult: less funding, more likely to be censored, etc. In Copernicus’ time, the church did not have social media and search engines. Interestingly, twitter censors this but not flat earth, or Trump collusion, or Stacy Abrahms claiming she won the election, or other provably false conspiracies. It seems they only censor the inconvenient truth. If I didn’t believe in something and it suddenly got censored, I might dig in more and maybe even find merit. Perhaps today banned off twitter is a higher accolade than published in a journal (especially a social science journal).
In part II I will address its real world application and its comparison to Molnupiravir. Please let me know if I should cover anything else. Disclaimer: I am not a doctor don’t take any drugs without your doctor’s approval unless you’re *really* sure, (it’s a free country but then only you have liability). To be clear, I am not saying ivermectin is the cure to covid because there is not enough data. Likewise, due to paucity of data, I cannot conclude anything about the vaccine. It’s a shame better and more frequent studies especially in the first world are not conducted.
Once more I missed something. A friend pointed out to me there was a study about ivermectin and fertility issues (sounds like projection). Considering 3.7 billion doses have been given out mainly in Africa (which has the highest fertility of any continent), and few if any feritility issues have been pointed out other than this 2011 study, it seems unlikely to have fertility issues. If it did, there would be some measurable effect in the real world in Africa.
The bad cat, a better writer than I am, has already addressed this here: https://boriquagato.substack.com/p/data-crimes-ivermectin-and-sperm