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Famotidine, Histamine, and the Coronavirus

Here’s a new preprint on a drug-repurposing effort that many people have been wondering about: famotidine, the histamine antagonist that is sold under the brand name of Pepcid. There have been some retrospective data that have suggested that famotidine use can have a beneficial effect on the course of the disease, and a controlled trial is currently underway in New York. Update: here’s a small retrospective case study as well, also quite positive, for what it’s worth. The idea is an attractive one, since famotidine has been on the market for many years, is inexpensive, and has a good safety profile. But as with all such drug repurposing efforts, you naturally wonder (a) if the effect is real and can be reproduced, and (b) what’s going on mechanistically, if it is real.

The aforementioned trial should go a long way towards answering the first question, and I can add at this point that it’s very good to have such an effort at the very start, rather than some of the more chaotic things we’ve been seeing with other drugs. Some of that has of course been understandable, given the course of the epidemic, but we’ve also had people who have been adding to the confusion, or at the very least doing nothing to dispel it. So that’s good, but what about the mode of action? Is there any reason for famotidine to be doing something useful here?

The preprint, a large multicenter effort, has some interesting things to say about that. It has already been noted that use of cimetidine (another H2 receptor antagonist, sold under the brand name Tagamet) does not seem to be associated with any benefit in coronavirus patients, so naturally enough the speculation has been that there is some off-target effect associated with famotidine. As this new work details, an initial hypothesis was that the compound had some effect on one of the viral proteases, and you can still find that rationale if you start looking around for comments on the drug’s MOA. That hasn’t held up, though – the compound does not seem to be an inhibitor of these enzymes. Moreover, it is not effective in a cell-based infection model with the virus, either – basically, it’s not an antiviral in any sense of the term.

What does that leave you with? The downstream effects of being infected – all the cytokine storm stuff, the inappropriate immune response that gets so many patients into trouble. And that brings the histamine receptor mechanism back around again. The paper confirms that famotidine is a much more potent H2 ligand than is cimetidine (technically, it’s more of an inverse agonist than a classic antagonist), and moreover it seems to have different consequences on receptor binding. It seems to stimulate beta-arrestin binding to the receptor and subsequent internalization (a mechanism that complicates all sorts of G-protein coupled receptor signaling), and it appears that cimetidine doesn’t do this, either. There is also a possibility that the compound acts on the CCR2L and CXCR3 chemokine receptors, which would certainly be of interest, but this needs to be firmed up.

But one of the biggest differences between famotidine and cimetidine is in their pharmacokinetics. As the preprint illustrates, the higher potency and better blood levels of famotidine mean that it has much stronger coverage of the H2 mechanism in general, especially at the dosages that seem to have an effect in coronavirus infections. So here’s the paper’s mechanistic summary:

The most straightforward explanation of the apparent famotidine activity as a COVID-19 therapy is that the drug acts via its antagonism or inverse-agonism of histamine signaling and via its arrestin biased activation—all a result of its binding to H2. If true, then it is reasonable to infer that a SARS-CoV-2 infection that results in COVID-19 is at least partially mediated by pathologic histamine release.

That’s an interesting and plausible idea – mast cells are what are involved in sudden histamine release – they’re sitting there loaded up with granules of the stuff, which can be dumped out on short notice. That’s an important part of a sudden anaphylaxis reaction, and mast cells are also involved in other immune response pathways, tissue permeability, and other processes. It’s certainly possible that they could be part of the inappropriate response to coronavirus infection and that inhibiting histamine release could be beneficial. The paper goes into details about lung physiology that tie the receptor’s action to some of the pathology seen in patients – for example, one thing that’s been noted is a lack of neutrophils and eosinophils in lung tissue samples, and both of these cell types have their activities inhibited by histamine release. In addition, the edema seen in coronavirus-affected lung tissue is unusual by the standards of viral infection, but makes more sense in light of a histamine-driven response. Mast cell degranulation also matches up with some of the other well-known symptoms (effects on smell and taste sensation, etc.)

The authors advance the idea, then, that many of the unusual features of the current virus in the clinic can be tied to histaminergic effects, and finish up this way:

If COVID-19 is partially driven by dysfunctional mast cell degranulation, then a variety of medical interventions employing marketed drugs useful for treating mast cell-related disorders may help to reduce death and disease associated with SARS-CoV-2 infection. Examples include drugs with mast cell stabilizing activity, other histamine antagonists (for example H1 and H4 types), leukotriene antagonists and leukotriene receptor antagonists, anti-inflammatory agents such as those developed for inflammatory bowel diseases, and mast cell activation inhibitors. If such repurposed drugs are used in combination with pharmaceuticals that directly inhibit SARS-CoV-2 infection or replication, it may be possible to rapidly develop potent, safe and effective outpatient treatments for preventing or treating COVID-19 until such time as a safe and effective SARS-CoV-2 vaccine becomes available.

Famotidine itself could be part of this treatment regime, of course, and there are several other agents that would seem worth investigating, especially in combination with something like remdesivir. Something to keep an eye on!


91 comments on “Famotidine, Histamine, and the Coronavirus”

  1. Lane Simonian says:

    Despite the hullabaloo coming out of Madagascar and some other African countries (which I was unaware of until a poster alerted me to it), the artesunate/artemisinin/artemesia annua approach may be better yet.

    Artesunate is comparable to Famotidine in its anti-inflammatory effects and likely superior to Famotidine in its anti-oxidant effects.

    Concerns have been risen about the potential for malaria resistance and liver toxicity using artemesia annua or it derivatives if turned to for the potential treatment of the novel coronavirus.

  2. JasonP says:

    Oh part of a “treatment” regime, not a silver bullet, not a perfect cure?

    Sure looks like stages of this disease require different approaches. Cytokine storm. Thrombosis.

    What I don’t get is why one part of a “treatment regime” gets hailed when it isn’t “the cure?”

    Since we have no Gold Standard “cure” Docs have to treat the resultant effects and one can only imagine there are a handful of strategies being employed.

    Would like to see a serious analysis of the thrombosis effects of this virus resulting from the effects on ACE-2 receptor found in Endothelium which appears to allow a flooding of von Willebrand factor, hence thrombosis, stroke, Kawaski like disease, etc.

    1. Some idiot says:

      Not my area, but I read a comment from a senior clinical virologist when the somewhat positive results for remdesivir came out. His point was that there basically are no “silver bullet” antivirals around, but that instead virologists in practice use multiple treatments in order to obtain efficacy. Think AIDS, for example. In each case, the “breakthrough” was to find ***something*** that gave a proven clinical improvement. Further work then found that A combined with B gave an even bigger effect, and so on. So, again, given that antiviral silver bullets basically don’t exist, the next best is to find numerous small spinners that are effective in getting stuck in different parts of the machinery for any given virus…

      1. RTW says:

        You find the same sort of effect in Cancer treatment synergetic effects with combinations. 5-FU, Irinotecan, oxaliplatin, and Avastin, sometimes even adding in Erbitux for Colon Cancer. Initially the cocktail might start with 5-FU and Oxaliplatin sometimes adding Avastin. Next cocktail after that one fails is 5-FU Irinotecan, and Avastin. Some Sometimes they get really aggressive and use the 1st 4. In my wife’s case they took out the 5-fu and added Erbitux. In Lung cancer, breast cancer et al.. They use many combinations. Due to advances in the genetic basis of cancer sometimes more targeted approaches work. The really instating thing about some of this Covid-19 work is that each insight bring another tool to bare on the problem, that perhaps based on the stage and in combination can speed up recovery or reduce the severity.

        1. drsnowboard says:

          The usual reason for antiviral combinations is mutation. Like bacteria, suppression of one organism allows others to supplant it, be it pre-existing variants or drug-induced mutation so a combo hits more than one variant, preferably by more than one mechanism and allows the immune system to mop up. Hence combinations of RRT inhibitors in HIV, multi mechanism cocktails in HCV , NS5A inhibitors + protease inhibitors etc.
          But the precedent in antivirals is for the direct acting antivirals to be most effective, compounds with tangible effects on viral replication, in vitro, in animal models, in challenge studies , in the clinic. A lot of this re-purposing effort is taking compounds that are not very good in vitro phenotypic inhibitors and chucking them at the pandemic. If you want to use the pandemic as house fire analogy, most of these are like throwing sand at it, earth, maybe that can of dead paint you had in your garage for ever…..

      2. B says:

        With HepC drugs perhaps being the exception.

    2. Shazbot says:

      Because the disease affects different people in different ways. Anything that works on even part of it, can and will be used to save lives and shorten the duration of the disease, when dosed on the right patients at the right time in the right method.

      That is the goal here. Anything that helps that happen is worth celebrating.

  3. Simon Auclair the Great and Terrible says:

    Yes an antiviral plus something to block cytokines…

  4. Derek Freyberg says:

    The entry for the study you link in line 4, the MATCH study, only appears to test famotidine in conjunction with the (now largely discredited) hydroxychloroquine – that is, it’s a test of HCQ + famotidine against HCQ alone, with a historical control arm. One might wonder if this particular trial is worth performing – is “standard of care” still administration of HCQ?; and I don’t see any modification to accommodate a new standard of care.

    1. Adam says:

      Well if we can assume that hydroxychloroquine does, at best, nothing, then having the control group take hydroxychloroquine doesn’t screw up the trial. It’s just going to cause people to drop out when they have long QT issues.

    2. Neli Stoyanova, 0966666664 says:

      Who said that Roxy chloroquine has been discredited full stop is currently the most effective draught against coronavirus

  5. RA says:

    Thanks for this post…really interesting! A few thoughts:

    1. Researchers might want to measure and control for asthma in clinical studies of this hypothesis. Asthma and reflux often go together clinically and there have been some studies that those with asthma are underrepresented in COVID hospitalizations…so I would hope that clinical studies will tease out any potential confounding impact of asthma and the asthma meds the patients on famotidine might be taking (i.e. inhaled they have an independent effect?).

    2. If the histamine mechanism is determinative, then one might expect a greater protective effect for those who also on an H1 antagonist (i.e. for seasonal allergies) if those agents have cross-reactivity with the H2 receptor. With patients who have anaphylaxis, we sometimes combine an H1 and H2 antagonist clinically…wonder if there might be a similar benefit with COVID. In acute hospitalized treatment, would IV diphenhydramine or hydroxyzine potentiate IV famotidine?

    3. As we chase “cures” for COVID, I wonder if there is a lot of low hanging fruit that could be accomplished if those with certain chronic conditions worked with physicians to tweak their medication regimens to favor meds that are known to be safe and that emerging evidence suggests may have benefit for COVID. Err on the side of treating borderline hyperlipidemia with statins and emphasize the need for those prescribed statins to take them. Consider having more patients with hypertension on ACE inhibitors. And, with these data, considering whether some patients with reflux would be better served on famotidine rather than a proton pump inhibitor…..yes, PPI’s are needed for some with severe reflux, but many folks go straight to them when famotidine might be enough for many patients…especially with some attention to dietary triggers. We are mostly thinking about this with an acute, infectious disease paradigm…which is necessary but not sufficient…I wonder if we need to have more attention to what management of chronic conditions makes a host less susceptible to severe COVID disease, given that those with chronic conditions are most at risk for severe disease.

    1. Melanie says:

      RA – for what it is worth, one of my asthma meds is a leukotriene receptor antagonist (Singulair). I don’t know how common it is, but I’ve taken it for years for asthma and it is sometimes prescribed just for allergies, too. I had seen some mention of a possible protective effect from allergies – but I wonder if any such effect is actually just from the meds us allergy sufferers are on? It will be interesting to see how that plays out.

      1. RA says:

        Good point! I wonder about all allergy meds…especially since the virus sets up shop in the nasopharynx…what is the impact of meds that reduce allergic rhinitis in terms of infection susceptibility and severity? And/or is there something about the immune systems of those who have atopic conditions that influence their immune response to COVID?

        In general, I wish all these studies on COVID hospitalization/death risk factors included full chronic condition and chronic medication histories of patients and reported them out. I have seen some data like that for certain meds of interest like ACE inhibitors, but what about other meds… It would be good to see if patients on certain medication regimens for various chronic conditions are more or less at risk compared to those with similar conditions on different treatment regimens.

        1. Some idiot says:

          Again, as an asthmatic, now on a number of medications (including singulair) I find these speculations intriguing… I posted a similar comment in reply to RA in another thread, but I think it got a bit swamped…!

          I’ve been on Montelukast/Singulair for quite a few years now. It does help my asthma a bit, but it makes a _very_ considerable positive contribution to controlling my (largely pollen) allergies. This was extremely noticeable… I saw my specialist after the first spring I was taking the medication, and I told him that it had that effect. His response was “yes, I have heard that from quite a few others!” For what it’s worth, I take an antihistamine during the spring months (loratidine), and the combination of the two really makes a difference… It would be wonderful if it also reduced the severity of COVID19 infection, especially since my use of an inhaled corticosteroid makes me a lot more susceptible to infection from airborne infections, compared to others…

      2. soulcoffr says:

        I was just going to say this. I’ve been treating my asthma with Singulair (montelukast) for close to 20 years, and with leukotriene inhibitors in the list, I’m wondering if that might explain a lower number of asthma sufferers being represented in COVID-19 numbers? In it’s single pill dose, I believe it’s a very common asthma medication.

        I also seem to remember something about cimetidine being somewhat effective in treating warts? (Although, I seem to recall there was some evidence against this effect too.)

        1. loupgarous says:

          A family member heard about Tagamet for warts and asked me about it. After the ritual “IANAP” disclaimer, I did a literature search and found that some dermatologists swear by it (to the extent of signed letters to the editors of medical journals that’d be embarrassing if the treatment was hokum) and some swear at it.

          I came away with a belief in geographical clusters of cimetidine-susceptible warts. Now the stuff’s OTC, the main issue is to read the “interactions and contraindications” parts of the package insert carefully before taking the plunge.

          Speaking of OTC, I was highly surprised to learn that diclofenac gel’s now over-the-counter. A long while back, I was prescribed the oral form of Voltaren only to find it made an incipient stomach ulcer painfully active – so it wasn’t part of my treatment plan, long term.

          20 years of diffuse skeletal hyperostosis later that made my xiphoid process into a twisted piece of modern art that scared my surgical oncologist during exploratory surgery, I tried diclofenac gel, which did wonders for the arthritic pain part of DISH syndrome, only to eventually cause a recurrence of the stomach ulcer, some endoscopic surgery and long-term PPI therapy. Diclofenac gel’s now OTC and off my insurance plan’s formulary. After a little huddling with my gastroenterologist and pain guy, I’m cautiously taking prescribed oral diclofenac paired with the PPI, and moderately happy with the small remaining low-level discomfort everywhere.

          All of this left me wondering about the wisdom of letting folks buy diclofenac gel for their aches and pains without careful medical supervision, but not everyone has free-flowing vertebral epiphyses from neck to coccyx and joint weirdness in the extremities who may as well get the diclofenac in there systemically.

    2. J Ritz says:

      Great comment. Exactly my thoughts. I think when this is all over you will see that many of these investigational medications all have a hand in mitigating much of the disease.

    3. Adrian says:

      All this “emerging evidence” is only hype when it comes to medication for preventing COVID-19 or preventing serious COVID-19, and should be taken with a barrel of salt – we have already learned this the hard way. (yes, I am referring to the “only with zinc!!!!!” hype for a substance even the President of the United States of America said to have used for that purpose)

      And your “low hanging fruit” of changing medication for hundreds of millions of people would in any case do more harm than good – the safety aspects of changing medication for no good reason is horrible. Everyone with hypertension in a first world country with a functioning healthcare system is already getting some medication, but moving everyone with a sartan prescription to an ACE inhibitor would be hilarious.

      You are also missing where the real problems are. In the US a large risk group are obese people without proper healthcare treatment for their preexisting conditions, tackling the obesity epidemic and ensuring affordable healthcare for everyone would help not only for COVID-19.

      1. confused says:

        I am kind of surprised we are not seeing more emphasis from the CDC etc. on “if you’re obese, take this time when you’re not eating as much restaurant food to lose weight; it’s likely to help with your chances if you get COVID, and it’ll certainly help your overall health”.

        I’ve lost 15-20 pounds in the 10 weeks or so I’ve been staying home, pretty much just because I’ve stopped eating at restaurants.

      2. RA says:

        Haha…I would disagree there is substantial “hype” with regard to statins, ACE inhibitors, and famotidine with for COVID. Seems like the hype is more focused on other, more shiny objects! Given that those with chronic conditions are at elevated risk for severe COVID, I think it is legitimate to ask whether better/different management of those chronic conditions makes a difference in progression to severe disease! Even in a world with no COVID, we should always be thinking about how to better manage chronic conditions…better approaches to obesity, like you mentioned, are a big part of that. However, I am skeptical that we will solve America’s obesity in time to impact this pandemic…I mean, people are stress eating, putting on the “quarantine fifteen,” and weight watchers just fired thousands of people over Zoom!

        The safety of medication changes can indeed cut in a number of ways depending on the medication, the indication, and the patient….which is why I said that I think people should discuss with their physician and decisions should be made on a case by case basis. In real life, there is often wiggle room/discretion with particular chronic medication regimens, many patients are not consistently taking meds for which they are prescribed, or don’t have their chronic conditions treated at all….so I do think it is worth researching and exploring whether we can do better.

        1. Adrian says:

          Hype has been for many substances already for COVID-19. I remember pharmacies running out of paracetamol when the WHO suggested that ibuprofen might be harmful.

          It is important to repeat again that there is no evidence that any medication change you suggest actually helps. It might be plausible and there might be anecdotal reports, but this might still turn out to not actually help. This is not a good basis for recommending any change, unless the change is a good idea in any case.

          Tackling obesity, treating hypertension or avoiding vitamin deficits are examples where the change is recommended in any case.

          Recommending changing working medication for hundreds of millions is simply a bad idea, unless you have clear evidence that the change has substantial benefits. To give an example, moving 50 million prescriptions in the US from Losartan to Lisinopril would be expected to give 1 million people in the US the adverse effect of hyperkalemia.

          1. RA says:

            Hmmmm..I never advocated for the medication switch you are so worried about, but since you brought it up, FYI….both ARB’s like losartan and ACE Inhibitors can cause hyperkalemia, but it is usually mild and mainly a concern in those who have renal dysfunction. I’m curious…where did you get those 50 million/1 million numbers?

            In any case, just to be clear…I never made any “recommendations” to make any particular medication changes…by qualifying words with “I wonder” and “consider” that is admitted speculation not “recommendation!” Of course, we need more data for lots of things!!!

            If anything, my comment was speculating about patients on other classes of anti-hypertensive meds besides ACEI’s/ARBs. There may not even be a “switch” involved…maybe we need to think about adding ACEI (or ARBs like your favorite, losartan!!) as adjunctive antihypertensive therapy in some patients, not simply thinking about zero-sum/either or monotherapy decisions.

            For example, I have a specific question for further research and expert consideration: (NOTE: NOT A “RECOMMENDATION!!!”): While the evidence is pretty clear that ACEI/ARB’s are not effective antihypertensive monotherapy in black patients, is there a potential role as adjunctive antihypertensive therapy in combination with other agents that might both help their hypertension (which is often poorly controlled in this population) and make black patients less susceptible to severe COVID Disease? The hypothesis, maybe right maybe wrong, is that some (obviously not ALL…many other factors here likely) of the excess risk of death we are seeing in infected black patients is attributable to less use of ACEIs/ARBs (including your beloved losartan!!!) as adjunctive antihypertensive therapy (again, not monotherapy) than might be optimal because these agents have too bad of a rap in black patients when compared to patients of other races who are more likely to be on this class of antihypertensives.

            Here’s a review suggesting that combination therapy including ACEI/ARB’s in black patients can be effective, even if monotherapy is not:


            I do agree we have to be very careful with changing such meds…but that doesn’t mean a knee jerk assumption that everyone is managed optimally now. Your statement that “Everyone with hypertension in a first world country with a functioning healthcare system is already getting some medication” is sadly not true, assuming you consider the US a 1st world country with a functioning health care system…which, as an aside, is debatable especially given our performance in the last few months in response to COVID!

            Moreover, I don’t think the sky is going to fall if we try to pay a little more attention to who is getting statins (God forbid we inadvertently prevent a few more heart attacks long down the road!), or whether there are some patients for whom famotidine might be just fine for their reflux !!! Or whether asthmatics borderline for use of an inhaled corticosteroid or who are non-adherent (many don’t stick to the program) with their inhaled corticosteroid should be nudged to more use of it during the pandemic.

            In the practice of medicine, you have to do the best you can with the often imperfect information you have at the moment and there is a middle ground between being a chicken little and a reckless prescriber/medication switcher. In normal times, yes, you don’t wily nily change prescriptions…but these are not normal times and I think particularly for those in the highest risk groups with chronic conditions, thoughtful physicians should be considering case by case changes to chronic disease management in light of COVID doing the best they can with the evidence available at the time. The status quo, where most people are not even in touch with their doctors about anything other than emergencies, is part of the problem I think. If I were to “recommend” anything it would be that more patients with chronic conditions have a visit, probably over telehealth, with a primary care physician to discuss lots of things…medication regimens, yes…but also general wellness in the crises, personalized guidance on avoiding exposure to COVID, etc.

    4. small voice says:

      RA (your original post)

      I am not sure if the asthma correlation with gastric reflux is represented by the correlation that brought famotidine to light.

      It was originally identified because poorer patients in Wuhan were doing better than richer patients. The hypothesis was that the poorer patients were taking famotidine rather than the more expensive omeprazole.

      If asthma was a protective factor, then the patients taking omeprazole would also be expected to have a better outcome.

      1. RA says:

        Thanks! I was only saying that since asthma and reflux tend to go together clinically, that any (future) clinical studies of famotidine in relation to COVID should measure and control for the asthma/asthma treatment to avoid confounding bad….not trying to posit that “asthma correlation with gastric reflux is represented by the correlation that brought famotidine to light.”

        Looking around, I found some interesting work looking at ACE2 and use of inhaled corticosteroids in asthma…wouldn’t say there is anything definitive at this point, but certainly there is reason to investigate further!

        1. Sandeep Sharma says:

          RA I have classical symptoms of covid last 8 daya. I had fever which I am able to control by taking antibiotics. But my shortness of breath and.middle chest pain is something I am experiencing from last 2 month. I learned that ICS work well by mitigating covid symptoms it has some anti viral property. Some detail study done on korea suggest that it work as miracle medicine. I am using it from last 4 days but don’t see any major effect..shall I continue or stop it.

    5. Lisa says:

      Yes, yes, and yes. I agree with all of what you are saying here.
      Has there been any follow up on the use of famotidine that you have read since?
      I feel awful for people that are affected by this, and I’m confused and quite frustrated that finding any actual evidence provided facts are so hard to dig up.
      Just wanna give kudos to all who seek the the truth, and know that “real science” are the facts.

    6. KM says:

      Creating a basic environment ( viral envelope synthesis mechanism) and the mechanism of the viroporins (viral ion channel exchange inducing life cycle of the virus ), virus has an ideal replication environment, in this case the normal homeostasis of our normal cells is such, but by altering the acidity and ion exchange could be the key to slowing replication. As well as normal, non-repurposing, functions do have their mechanisms of action of benefit.

  6. BHN says:

    Simon, a remdesivir + baricitinib trial was recently begun to test the hypothesis you suggest. I like this combo.

  7. Kevin R says:

    Thanks! I read that paper about 4 times and as a lay person grasped every other word. But your write up is an immense help in a now fuller understanding!

  8. David Young MD says:

    Let me point out that almost all ICU patients get Pepcid intravenously already. Anyone “under the stress” of being in the ICU and especially if they are on steroids, is at risk for gastric bleeding. To prevent this, they are put on an H2 blocker or a proton pump inhibitor. At the hospital that I work at, Pepcid is the formulary choice. Most patients get it intravenously.

    It may be difficult to do a randomized study, for it might be hard for the attending physician to not give Pepcid. I suppose you could randomize patients getting Pepcid versus Prilosec.

    1. Treatments that clinicians are diffident about studying are often studied in dose-control trials. For example, it was at one time customary for patients having some kinds of orthopedic surgery to receive broad-spectrum antibiotic coverage for a week after surgery. The orthopedists wouldn’t think of trying antibiotics-versus-placebo, but they were willing to recruit patients to be randomized between (as I recall) 3 days of coverage and 7 days. Three days seemed to be just as good as 7, so then I think they studied 1 day versus 3.

      In the current situation, patients might be randomized between two different doses of famotidine. If the outcomes were indistinguishable (yes, it takes a lot of patients before you can credibly say that), then an even lower dose could be studied, and at some point, it might be recognized — if it were true — that the drug is probably noncontributory.

    2. Academic Med Chemist says:

      If you look at the preprint from New York, only a small percentage of patients (5%) got Pepcid. They did a lot better than the ones that got one of the other blockers, though being only 5%, the numbers were small.

    3. blogreader01 says:

      If Pepcid is already being often given to those being admitted to ICUs, is it therefore not-improbable that a lot of ICU-admitted/covid-19 sufferers have already received the drug? Would there be records of these patients which would reflect this fact?

  9. David Young MD says:

    When patients received Taxol (Paclitaxel) intravenously for ovarian cancer (or lung, or breast, etc), they are pre-medicated with Benadryl and Pepcid routinely.

  10. Christophe L Verlinde says:

    I don’t know if it’s relevant but CHEMBL reveals that famotidine inhibits an number of human carbonic anhydrases in the nM range: CA-VII Ki=3.0 nM, CA-XII Ki=45.3 nM, CA-II Ki=57.9 nM, CA-VI Ki=98.2 nM. Is there anyone who is an expert in carbonic anhydrases who wants to comment.
    and go to Bioactivities, click on Activity types, select Ki in the left column, and sort by
    standard value.

    1. Trew says:

      The sulfonamide moity binds to the Zn(II) ion in carbonic anhydrase.

      1. steve says:

        Once again if it doesn’t work we can blame it on zinc!!! 😉

  11. Giannis says:

    No animal model data. I don’t like that at all.

    1. Another One says:

      It’s a drug already approved for use in humans. No animal trial is needed.

    2. Robert W Malone, MD, MS says:

      Homo Sapiens.

  12. Trew says:

    They also need to check Pepcid’s metabolites and known impurities for inhibition activity against the virus.

    1. Troll says:

      Could be contaminated with Zinc! Just sayin’.

      1. loupgarous says:

        I wonder how clean the process water is in some of those API factories. In the Indian foothills, arsenic’s a feature not just of the landscape but the water table. All of arsenic’s co-minerals might be in there, too. The plan for filtering all of that out is probably Urdu for “Once upon a time… “

  13. Alan Goldhammer says:

    Time to repurpose sodium cromolyn! It was a great drug in its day for treating mild asthma with minimal side effects.
    There is one monteleukast trial registered by McGill up in Canada.

      1. George Stanchev says:

        Another quercetin (isoquercetin) from University of Michigan

        “This is a randomized clinical trial designed to evaluate the efficacy of ICQ-950AN to prevent COVID-19 clinical infection in high risk individuals (HRIs) such as health care workers, first responders, essential workers, and their families. We will also evaluate SARS-CoV-2 seroconversion in participants taking ICQ-950AN, as well as the safety and tolerability of ICQ-950AN.”

    1. Tom says:

      Interestingly, cromolyn has been shown to reduce mortality in H5N1 infected mice. It also inhibits NF-kB signalling, which drives the IL-6 production.

    2. Some idiot says:

      Disodium cromoglyxate! Used that for donkeys years! Not recently though… 😊

  14. loupgarous says:

    Speaking of repurposing:
    “Gallium disrupts bacterial iron metabolism and has therapeutic effects in mice and humans with lung infections” Christopher H. Goss, Yukihiro Kaneko, […], and Pradeep K. Singh. I’m surprised this hasn’t become the center of a new whirlwind of speculation of the utility of a new member of the Periodic Table in late-stage COVID-19.

    1. Trew says:

      Melt in your mouth goodness. Shout out to Sam Kean….

    2. eub says:

      kill that viral iron metabolism >_<

      Selling the elements, colloidal Ag is old hat. These days I bet there's a good business model selling hormetic As for your immune system.

      1. loupgarous says:

        Pick your marks late enough in life, and the cancers from the As show up about the time you’d expect them to, anyway.

    3. Druid says:

      If I can’t find gallium, would thallium do instead?

  15. aleister perdurabo says:

    A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
    David E. Gordon, Gwendolyn M. Jang, […]Nevan J. Krogan
    Nature (2020)Cite this article

    264k Accesses

    12 Citations

    3082 Altmetric


    The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.

  16. I was sick the last three weeks of March, presumably with COVID since we couldn’t get tested, and then ever since have struggled with what I believe to be a flare-up of Mast Cell Activation Syndrome (MCAS), with signs of anaphylaxis (throat tightening, flushing, tachycardia and palpitations, breathing issues that resolved with montelukast) . Still awaiting allergy tests, but I have Ehlers-Danlos Syndrome and MCAS tends to come with it, previously had mild issues with alcohol and heat. I’ve had to cut out all high-histamine foods in order to get through the day. I’m convinced that understanding mast cell disorders will be the key to understanding the cytokine-related deaths of COVID!
    Another MCAS patient and I started a Facebook group for understanding MCAS and COVID:

    1. eub says:

      That’s an intriguing observation and I hope it gets looked into! I know a couple of people with E-D (neither of whom have gotten sick, knock wood) and will point them at this.

    2. Star Dorminey says:

      Very interesting. I also have hEDS, though apparently without the mast cell involvement – knock on wood – and I’ve been wondering how we tend to fare with covid. I know a few other zebras who take cromolyn as a mast cell stabilizer, so it’d be interesting to see how EDS patients with and without MCAS fare, and if their meds help them.

      Hopefully I won’t experience it for myself!

    3. Kai says:

      I’m a bit late to this thread but I have MCAS (Also EDS), been on treatment for a couple years but have been dealing with the condition/misdiagnosed for well over a decade. When I read about healthy people rapidly dying of severe lung inflammation I thought hey, this looks like disordered mast cell degranulation! So I’m happy to see this getting attention. The case reports remind me of what happens when I get a normal cold. A few days after getting a cold my peak flow readings would drop by half and I knew I was in trouble. In hospital my ABG’s would be shit, O2 in the 80’s, super low BP, tachycardic, and that feeling like if you stop thinking about breathing, your body will just give up and quit doing it. It takes so much effort just to remember to breathe, and its so exhausting but you don’t want to fall asleep. Prednisone and nebs would take the edge off (they thought I had atypical asthma) but nothing really helped until I got on treatment for MCAS.

      My current treatment regime is a bunch of stuff that is under investigation for COVID – Quercetin (instead of cromolyn thankfully) as a mast cell stabilizer, singulair, cetirizine (at 40mg/ day, a quadruple dose), famotidine, bunch of supplements. I’m crossing my fingers that my med supply doesn’t get disrupted, but also hopeful that this might generate a surge in research and practitioner education surrounding mast cell degranulation and its impacts.

  17. John Hasler says:

    > Examples include drugs with mast cell stabilizing activity, other histamine antagonists (for
    > example H1 and H4 types), leukotriene antagonists and leukotriene receptor antagonists, anti-
    > inflammatory agents such as those developed for inflammatory bowel diseases, and mast cell
    > activation inhibitors.


  18. Hydroxychloroquine as a novel therapeutic approach in mast cell activation diseases (MCAS).

  19. Weldlock says:

    Been taking famotidine for over three years, want to test me?

  20. Andrew Molitor says:

    A general question:

    Is the pathogenesis of COVID-19 particularly byzantine, or is this sort of “what the hell is it actually doing?” struggle pretty normal a few months into a novel disease?

    1. Adrian says:

      No this is not normal, usually this struggle takes years.

      The other novel disease with an ongoing pandemic is AIDS.

      The earliest confirmed case of AIDS in the US was in 1969 (sic). It took over 10 years just to recognize that there was a novel disease going around killing people.
      After that it still took years for identifying the virus and understanding what it does.

    2. J N says:

      I’m concerned about sequelae and in general the public and news media seem to be thinking of it as alive/dead.

      It is slowly trickling out though that a fair number of people (I am unable to find any statistics on this) are experiencing weeks/months of fatigue and associated symptoms after “recovery.”

      We haven’t had long enough to suss out whether this is something that goes away after the damage to the body is slowly repaired (a la pertussis, SARS) or is more permanent (unlucky with EBV). Would be nice to know, and would be nice for the public to be more aware.

      1. Andy says:

        Yeah, anecdotal, but mountains of it: go read some of the accounts and comment threads at

        They universally refer to where they are with COVID as “currently on day X” e.g. “currently on day 84” and it is stunning how many “long haulers” there are and how severe their symptoms are/how easily they flare up. This thing is scary.

  21. J N says:

    Well, maybe I should:

    (1) Lose some weight (the obvious thing)
    (2) Take OTC famotidine (I’ve done it before, unnecessary if I watch my diet)
    (3) Take aspirin (good for nagging bursitis anyway)

    And when someone finally contaminates me maybe I’ll just have “the flu.”

    1. Robert W Malone, MD, MS says:

      Suggest Motrin, not ASA.

      1. Andy says:

        Honest question, doc: wouldn’t aspirin be preferable vis a vis the blood-thickening tendencies of COVID-19? Curious why the ibu suggestion.

  22. Robert Yancey says:

    It would be nice to block the virus in some way but at least slow it down until the immune system in most people can take it out. Blood clots are a major factor. Preventing them with an anticoagulant might work but this is very hard do with an outpatient with covid-19. Nattokinase an OTC supplement is very good at dissolving blood clots and stimulating plasmin. Given early maybe it could at least “keep up” with the clotting. Clots left more than a week or so turn to scar tissue and are unlikely to go away. It may be that the damage is vascular damage especially in the lungs first with blood clots and then scar tissue. Sick patients almost by definition are low on glutathione – IV glutathione could help. B vitamins are necessary for making cellular energy, are water soluble, short half life, and these sickest patients probably can’t make enough energy to fight anymore. Once low just giving thiamine IV is not going to jump start much. Mega dose allithiamine with magnesium and other B vitamins in their best form might get the cells going again. Treat the problems and let the body clear the virus.

  23. Lambchops says:

    In other re-purposing news there are several drugs being tested in small scale trials in the UK:

    A bit of me hopes that this trial isn’t a success because they are unable to recruit enough patients, but the shambolic approach of the UK government to exiting lockdown isn’t exactly filling me with confidence.

  24. yenwoda says:

    What do people who know things think about nafamostat/camostat, which was recently approved for another trial, in India this time? As a total layman the theorized mechanism of action and in vitro results sounded interesting, but I don’t really know how to evaluate those.

    1. Derek Lowe says:

      The tox profile will need watching – these drugs have a reputation for unselective inhibition of serine proteases.

  25. Joe Psycho says:

    Speaking of asthma and COVID I am a severe chronic asthmatic who takes high dose inhaled corticosteroids (160 micrograms of beclomethasone dipropionate(Qvar) +160 micrograms of ciclesonide (Alvesco) TWICE DAILY) as well as 5 micrograms of tiotropium bromide daily and a total of 720 milligrams of fexofenadine (Allegra) daily PLUS the meager 5 milligrams of prednisone every day. And I STILL HAVE TO DO MY RESCUE INHALER AT LEAST TWICE DAILY. And this is with 2 military grade air purifiers in the house on top of that the ONLY THING THAT REALLY WORKS IS PREDNISONE AND DOCTORS ARE LIKE SCROOGE WITH IT. 20 MILLIGRAMS OF THE STUFF IS LIKE A MIRACLE. And if I go outdoors things get worse, so all of these people who are like “l’m so bored” during quarantine and go crazy after 5 days in their house have no idea what it is like actually staying indoors really piss me off, try having an asthma attack 8 out of 10 times you are outside for more than 5 minutes plus the normal 2 per day and having to use a rescue inhaler that makes you BATSHIT CRAZY and feeling like dog shit every single day. And yes I know prednisone can be harmful but it is the only thing that makes me feel human and not like shit and the fact that smokers can not only harm themselves but me with cigarettes that they got over the counter for NO GOD DAMN REASON and I cannot get enough prednisone to breathe because “it’s harmful” is the epitome of sheer idiocy and arrogance ask yourself this “does prednisone harm people other than the user like cigarettes”No it doesn’t therefore I should be able to go to a pharmacy And show ID and get a 30 day supply of 20 milligram prednisone pills for $75 this is blatant discrimination against asthmatics

    1. Joe Psycho says:

      Sorry albuterol (my rescue inhaler) induced psychotic rant/tangent. I have severe psychiatric side effects with albuterol (hence my username) sorry for any inconveniences.

      P.S albuterol is also called salbutamol just like acetaminophen and paracetamol (same drug different generic name)

  26. Val says:

    I’m over here with my stockpile of NasalCrom wondering when you all are going to start taking AI seriously.

  27. jangas says:

    Is Angioedema susceptibility part of why black population with hypertension aren’t on ACEi?
    Could this be worth focussing on with regards to the mast cell/Covid 19 possible etiology, also given interest in BCG and trials: ‘Therapeutic effect of Bacillus Calmette–Guerin polysaccharide nucleic acid on mast cell at the transcriptional level’

    Carbonic anhydrase: inhibitor used for altitude sickness (re the similarity to ‘happy hypoxics’) acetazolamide. Ketogenic diet also has carbonic anhydrase inhibitor effect.
    Both useful in bipolar disorder- anybody have any info on BPD and covid 19? More/less susceptible? Might be a good place to look for more genetics/pharmacotherapy/virus interactions.
    Nature drug repurposing study- loratidine in there too, if I remember right
    Inhibitor of SLC6A15/BoAT2 : ‘B(0)AT2, encoded by the SLC6A15 gene, is a transporter for neutral amino acids that has recently been implicated in mood and metabolic disorders.’
    Not sure if any relation for this amino acid transporter with ACE2 i.e similar to intestinal ACE2/ BoAT1 (expression increased by ACEi: )

  28. T says:

    Cyststatin C, a powerful inhibitor of cysteine proteases, is often elevated with asthma. Prevalent in extracellular fluids. Might play a role in reducing viral replication by suppressing activity of the viral papain-like protease. Perhaps a factor in reported lower risk for those with asthma.

  29. BW says:

    The clinical information about Indomethacin from NY is interesting (, as well as the studies (;

    Could famotidine be combined with indomethacin as a treatment? Apparently sometimes famotidine is used to mitigate the potential GI effects of endomethacin anyway, so it doesn’t seem the drugs have a negative interaction.

  30. Barry says:

    Dexamethasone does not cure the coronavirus infection, but it does blunt the cytokine storm. That’s enough to show up where it counts: “delta Death”

    “In the trial, led by a team from Oxford University, about 2,000 hospital patients were given dexamethasone and compared with more than 4,000 who were not.

    For patients on ventilators, it cut the risk of death from 40% to 28%.”

  31. G. Scott Weston says:

    One would think that, if the mast cell hypothesis is true, an inhaled mast cell stabilizer like nedocromil (Tilade(R)) would also show positive effects in managing COVID-19 infections.

  32. Dr rey says:

    Hi what s the evidence grade of this article

  33. Steff says:

    Using biochemical and biophysical methods we assessed the binding and inhibitory effect of famotidine on the sars-cov-2 3CLpro and Plpro + the antiviral activity was tested in Vero E6 and A549 lung cells.
    Results are negative across the board! No binding, no inhibition and no effect on reducing viral replication!

    You can read our findings here

    1. Derek Lowe says:

      And given the proposed mechanism of action, that’s exactly what one would expect. Right?

      1. Steff says:

        At first everybody was thinking that famotidine had some antiviral activity. Which was maybe unlikely, but off-target binding can happen. Since then our understanding of covid-19 has improved and it has become clear that covid-19 can be treated (more an improvement in mortality rate at the moment) via two ways: 1) targeting the virus itself with antivirals (remdesivir) or 2) tempering the inflammatory response of the body (dexamethasone, IL-6 antibodies,…). Famotidine will be under the second category, as it has zero antiviral activity and as mentioned has an effect on the inflammatory response, which might be beneficial for covid-19 outcome.

        I hope that the clinical tests prove that famotidine has a positive effect on covid-19 outcome. Otherwise a lot of money has been wasted on those trials, which could have been of good use at other places. Unusual times ask for unusual matters, but the famotidine case wasn’t the strongest from the start. As the initial clinical data from China wasn’t perfect and questionable.

  34. rob b says:

    i know 5 people who have walked out of the hospital after hydroxychloiquine in less than 7 days. a coincidence? i doubt it.

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