Talk:Molnupiravir

Treatments for COVID-19: Current consensus

A note on WP:MEDRS: Per this Wikipedia policy, we must rely on the highest quality secondary sources and the recommendations of professional organizations and government bodies when determining the scientific consensus about medical treatments.

1. Ivermectin: The highest quality sources (1 2 3 4) suggest Ivermectin is not an effective treatment for COVID-19. In all likelihood, ivermectin does not reduce all-cause mortality (moderate certainty) or improve quality of life (high certainty) when used to treat COVID-19 in the outpatient setting (4). Recommendations from relevant organizations can be summarized as: Evidence of efficacy for ivermectin is inconclusive. It should not be used outside of clinical trials. (May 2021, June 2021, June 2021, July 2021, July 2021) (WHO, FDA, IDSA, ASHP, CDC, NIH)
2. Chloroquine & hydroxychloroquine: The highest quality sources (1 2 3 4) demonstrate that neither is effective for treating COVID-19. These analyses accounted for use both alone and in combination with azithromycin. Some data suggest their usage may worsen outcomes. Recommendations from relevant organizations can be summarized: Neither hydroxychloroquine nor chloroquine should be used, either alone or in combination with azithromycin, in inpatient or outpatient settings. (July 2020, Aug 2020, Sep 2020, May 2021) (WHO, FDA, IDSA, ASHP, NIH)
3. Ivmmeta.com, c19ivermectin.com, c19hcq.com, hcqmeta.com, trialsitenews.com, etc: These sites are not reliable. The authors are pseudonymous. The findings have not been subject to peer review. We must rely on expert opinion, which describes these sites as unreliable. From published criticisms (1 2 3 4 5), it is clear that these analyses violate basic methodological norms which are known to cause spurious or false conclusions. These analyses include studies which have very small sample sizes, widely different dosages of treatment, open-label designs, different incompatible outcome measures, poor-quality control groups, and ad-hoc un-published trials which themselves did not undergo peer-review. (Dec 2020, Jan 2021, Feb 2021)

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Last updated (diff) on 27 February 2023 by Sumanuil (t · c)

400mg vs 800mg vs >800mg dose. 5 days vs >5 days treatment.

https://link.springer.com/article/10.1007/s40265-022-01684-5

20 Feb 2022.

• >800mg hasn't been tested, why? No adverse effects with 800mg (for the treated patient who is not pregnant), compared to placebo.

• 3.6% of patients should use Molnupiravir >5 days?:

At the end of treatment (day 5), molnupiravir 800 mg was associated with numerically higher rates of SARS-CoV-2 viral clearance versus placebo (12.7 vs 3.6% of patients).

• 400mg may be enough, instead of 800mg?:

Molnupiravir dose-dependently decreased infectious SARS-CoV-2. On day 5, the proportion of patients positive for infectious SARS-CoV-2 in nasopharyngeal swabs was significantly lower in the 400 mg (0% of 42; p = 0.034) and 800 mg (0% of 53; p = 0.027) groups than in the placebo group (11.1% of 54).

--91.159.188.74 (talk) 00:04, 23 February 2022 (UTC)

Structure

I haven't so far found a crystal structure for molnupiravir, but in Org. Process Res. Dev. (2021) 25, 1822–1830 there's the structure of a precursor. Both tautomers are present, leading to some crystallographic disorder. Ben (talk) 09:40, 30 October 2022 (UTC)

How about saying in the first paragraph something about how weak the effect is?

How about adding to the end of the first paragraph that, at best, it merely cuts the risk of death in half? It seems that at best, it cuts a patient's risk of death in half and for most people, probably not worth it, given the high cost of the drug, and the known side and unknown side effects.

For example, if you used the money that the pills cost instead to take a taxi to go shopping, or to make a downpayment on a car, instead of riding a motorcycle, you'd probably reduce your risk of death by even more than taking the pills, unless you are in a very high risk group for covid death.

I feel like it should be thought of a *correlation* more than a cure, or a treatment. Polar Apposite (talk) 15:08, 9 January 2024 (UTC)

How you feel about the drug should not be included in the article. What WP:MEDRS compliant sources are you proposing to use that compare the drug course to car down payments, shopping, etc? The lead already talks about the mutagenic risks of the drug. The case fatality rate for the high-risk persons that might be taking this drug is like 14%, by the way. VQuakr (talk) 18:08, 9 January 2024 (UTC)

Dang! I had an edit conflict. Here's my input:

Remember to follow the rules of WP. You don't get to just make your own random observations. Find a source (here's one: Doctors find limited use for less effective COVID pill) and figure out where it should go in the body of the article. Perhaps it deserves its own section. Then you can consider placing a brief "neutral" mention of this in the lede. Fabrickator (talk) 18:11, 9 January 2024 (UTC)

Maybe I should have been more succinct. All I meant was, how about adding a simple statement to the end of the first paragraph saying that at best the risk of death is cut by only fifty percent. It would be just a copy edit, at the information is already in the article. I'd just like to see it in a more prominent position, since it is the most, or one of the most, important facts about the treatment. The other stuff was not being proposed for inclusion in the article, but rather was just by way of argument for moving upward to the first paragraph that simple statement. Polar Apposite (talk) 19:23, 9 January 2024 (UTC)

I disagree that this would be "merely a copyedit". Stating that "at best the risk of death is cut by only fifty percent" is not simply stating a fact, it's attempting to minimize the value of this benefit. That's a "point of view", and it's the worse for what is tantamount to giving medical advice. Fabrickator (talk) 20:01, 9 January 2024 (UTC)

Agreed, what you're describing is not a copy edit (which is correcting for grammar, spelling, readability, or layout). You are talking about content changes. A value assessment like "only 50%" needs to be sourced to a WP:MEDRS-compliant source and probably also attributed in text. VQuakr (talk) 22:08, 9 January 2024 (UTC)

You got me. It wouldn't be a copy edit with "only". How about if it were instead neutrally phrased? Polar Apposite (talk) 16:34, 10 January 2024 (UTC)

I think moving a sentence about mutational and/or efficacy concerns from the last paragraph to the first paragraph of the lead may be reasonable. What exactly did you have in mind? VQuakr (talk) 17:36, 10 January 2024 (UTC)

Looking at it again, I think the best thing might be to make a new third paragraph in the lead section comprising either just the last sentence of the section called "Medical uses", or both sentences, abolishing that section in the latter case.

But both sentences are in need of clarification, I think, which should probably be done before one or both are moved to the lead section. Polar Apposite (talk) 17:41, 11 January 2024 (UTC)

Lead summarizes the body so additions to the lead shouldn't result in removing info from the body. Also since the lead summarizes the body it generally isn't appropriate to copy paragraphs up wholesale. The lead is already four short paragraphs; it does not need more paragraphs. VQuakr (talk) 18:28, 11 January 2024 (UTC)

How about adding the one or two sentences to the end of the first paragraph? And if that makes the lead section to long, moving some other stuff out of the lead section into the body? There's quite a bit of stuff in the lead section that could easily be moved to the body, for example some or all of the details about the history of the development of the drug/prodrug that are in the lead section. Polar Apposite (talk) 19:12, 11 January 2024 (UTC)

I think I'd need to see a more specific proposal in order to have an informed opinion. The two sentences of history currently in the lead seem like a reasonably-sized summary of that aspect of the subject. VQuakr (talk) 19:27, 11 January 2024 (UTC)

How about adding "The efficacy of molnupiravir is about 30% (95% CI, 1–51%) against hospitalization or death in unvaccinated adults with mild or moderate COVID-19 and at least one risk factor for disease progression." to the end of the first paragraph, and if that makes the lead section too long, removing from the lead section its last paragraph, and finally adding the phrase, in parentheses, "that were vindicated in 2022" to where is says, in the lead section, "The emergency use authorization was only narrowly approved (13-10) because of questions about efficacy and concerns" to make up for removal of that last paragraph (to the body if the information is not already there). Polar Apposite (talk) 19:06, 12 January 2024 (UTC)

What source uses the loaded term "vindicated"? Still seems like we'd be overburdening the lead with body-level content. I don't see a lot of focus on the efficacy in MEDRS literature so I'm not convinced it's leadworthy. VQuakr (talk) 00:18, 13 January 2024 (UTC)

What is "high risk"? "Second" in what way?

The section called "Medical Uses" contains two long sentences, each of which needs clarification, IMHO.

In the first sentence, it's unclear what exactly "high risk for progression to severe COVID-19" means. In the second sentence, it's unclear what type of ranking is referred to by "second". Polar Apposite (talk) 17:43, 11 January 2024 (UTC)

"High risk" is the term used by the relevant source in the article, [1]. It references medical factors that increase the likelihood that COVID will progress in severity. Things like age and existing medical conditions. See [2], though if we're talking about article edits we need to be careful of WP:SYNTH concerns.

Second: as in first/second/third, chronologically. Molnupiravir was approved shortly after Nirmatrelvir for emergency use in COVID cases by the United States FDA.

I don't think either of these need clarification per se as they seem quite clear already. The "second" part may not be relevant enough to include (and is US-centric) since the two drugs were released nearly simultaneously in the USA and Molnupiravir was approved first in the UK. VQuakr (talk) 18:22, 11 January 2024 (UTC)

How about instead of using the undefined and almost meaningless phrase "high risk", we instead quote one or both of those sources as saying that? Because neither source says how much risk is "high risk".

I'd be in favor of removing "second" as US-centric and misleading. Polar Apposite (talk) 19:30, 11 January 2024 (UTC)

The phrase is commonly used and recognized, and certainly not meaningless. I added a wikilink to High-risk people. I also rephrased the bit about the "second" treatment. [3]. VQuakr (talk) 20:20, 11 January 2024 (UTC)

Its not meaningless, but in this context it is almost meaningless. It is incredibly vague. The wikilink doesn't contain anything to clarify the exact meaning of "high-risk". It seems to imply that anyone who is obese is a "high-risk" person, in the context of covid. Indeed, it seems to imply that anyone with even the slightest elevation of risk due to any reason, even lack of health care facilities in their area of the world mean they are "high-risk". And thus the Molnupirivir article seems to imply (although it's not clear) that anyone who is obese or living a part of the world lacking health facilities who has mild to moderate covid should be prescribed and/or should take a full course of Molnupirivir. Polar Apposite (talk) 19:15, 12 January 2024 (UTC)

It's possible to quantify risk, using probabilities, or [[micromort]]s, or just loss of life expectancy. For example, if the typical smoker has an extra cigarette, he or she typically loses about thirty minutes of life expectancy (equivalent to about one micromort). This is easy to understand, and is usable information. Of course, great care is still needed. A nonsmoker who smokes one cigarette as a result of peer pressure is of course going to lose much more life expectancy, because of the significant chance that he or she will become addicted and become a life long smoker as a result, and smoke many more cigarettes and thus loses perhaps several months of life expectancy if he or she yields to the peer pressure and smokes one cigarette, rather than saying, "I'm good for now." :) Polar Apposite (talk) 19:28, 12 January 2024 (UTC)

Are you proposing changes to the article, or outlining a study that you think should be done? VQuakr (talk) 00:13, 13 January 2024 (UTC)