This wasn’t on my bingo card for 2023, but it looks like I need to comment on the use of Paxlovid in dogs with respiratory disease. I guess I shouldn’t be surprised, but there’s been a lot of buzz about a single report of a veterinarian using Paxlovid to treat one dog with respiratory disease – in the absence of any definitive diagnosis as to what was making the dog sick.

Some media reports are claiming Paxlovid cured the dog. Did it?

Probably not. I suspect the dog got better on its own despite Paxlovid (not because of it), but can’t say for sure. However, I can say that I don’t see any evidence that we should be using this drug in dogs, and I have a variety of concerns about its use in this manner.

Concerns about Paxlovid use in dogs (quick version)

Paxlovid is an antiviral that we know basically nothing about in dogs. We don’t have dosing or safety info in dogs, and we don’t have evidence that the respiratory disease we’re currently seeing in dogs in North America is caused by a virus that’s susceptible to Paxlovid. So, I don’t think its use is appropriate in such cases, and I suspect widespread use of Paxlovid in dogs would result in harming more dogs than it would help.

Concerns about Paxlovid use in dogs (longer version)

Using a human drug in a pet isn’t rare in veterinary medicine, and often it can be appropriate. Veterinarians often need to use drugs in an extra-label manner, since many important drugs are not licensed for use in animals. When we know how to use the drug, its safety and that it’s likely to work in an animal, this kind of extra-label use can be appropriate.

• The less we know about things like dosing and safety in animals (which can be very different across species), the greater the risk.
• The less we know about efficacy, the lower the value.

Treatment is typically a cost-benefit decision, based on assessing potential risks, potential unknowns and potential beneficial effects.

Paxlovid is a combination of two antiviral drugs, nirmatrelvir and ritonavir, which are both protease inhibitors, neither of which are used in dogs. The combination has been shown to be beneficial for treating COVID-19 in some types of people, in some circumstances, with the right timing. That’s based mainly on study of Paxlovid use in unvaccinated people. In Canada, it’s licensed for use in people with mild to moderate COVID-19 who are at increased risk of severe disease. It’s not meant for everyone, and it’s meant for early treatment. There are different opinions about whether it’s really of much use at this point in the pandemic, but I won’t get into that.

What do we know about Paxlovid in dogs?

Pretty much nothing. I’m not aware of any dosing or safety information.  The only thing I can find is a study that looked at Paxlovid in serum of different animal species, including dogs (i.e. they added the drug to serum in a tube, but they did not give the drug to the live animals) and did a pharmacokinetic study on just two healthy research dogs (Greenfield et al 2023). That’s a start, but the small number of dogs (2) means it still doesn’t tell us too much. The researchers reported some pretty major differences between species, including between dogs and people. They concluded that “Some species (rabbit,dog) demonstrated high plasma protein binding (PPB) that was concentration-dependent, whereas others (human, monkey, rat) did not. This can have a major impact on understanding concentration-effect relationships for both efficacy and safety endpoints. As such, it is important to consider PPB when selecting animal species for studies aimed towards understanding efficacy and safety in humans.”

My take home message from that study is it can’t tell us anything about how/if we can and should use Paxlovid in dogs, and we can’t assume safety and efficacy data in people apply to dogs.

Sometimes we use the same doses in people and dogs for a specific drug, but sometimes, the doses are quite different.

Some drugs that are useful in people also work in dogs, but some drugs do not.

Some drugs that are relatively safe in humans are relatively safe in dogs, but some human drugs are highly toxic to dogs.

If we don’t know dosing and safety in a particular species, it’s really hard to consider use of a particular drug if there isn’t a huge potential upside, e.g. because we need to treat a severe disease and we have no other options, and where the drug has a strong chance of working. That’s not the case here with canine respiratory disease and Paxlovid.

Could Paxlovid work in dogs?

Paxlovid could have an impact on some viral causes of canine infectious respiratory disease complex (CIRDC), such as canine respiratory coronavirus (which is a completely different virus than SARS-CoV-2, despite the similarity in name). However, even IF Paxlovid has effects on canine respiratory coronavirus, or other relevant viruses, that may not really mean a lot clinically. It might shorten disease and/or might reduce the risk that secondary complications developing, but that would probably still be dependent on very early treatment, something that is not likely to happen in a lot of dogs when illness is still mild, particularly given the cost of Paxlovid.

Could use of Paxlovid in dogs hurt?

Absolutely. We have no idea if the drug is safe in dogs. There are various known side effects in people, and the drug interacts with a lot of other medications. If we’re going to apply a cliché, it should be “above all, do not harm” vs “it can’t hurt.” The latter is not likely true.

What about developing resistance to Paxlovid?

There’s probably very little risk of viral resistance to Paxlovid increasing due to use in dogs. The concern would mainly be about development of resistance in viruses that can affect people, since that’s where the drug is most often used and where resistance is most likely to have a significant impact. Dogs can be infected with SARS-CoV-2, but for resistance to be a risk, a dog would have to be infected with SARS-CoV-2 at the time it had respiratory disease (likely unrelated, since SARS-CoV-2 is unlikely to cause clinical respiratory disease in dogs based on what we know) AND resistance would have to develop while the dog was infected AND that resistant virus would have to be transmitted back to a person. Dogs seem to pose very limited risk for transmission of SARS-CoV-2 to humans, so it’s fair to assume that the health risks posed to humans from use of Paxlovid in dogs are very low to negligible.

However, we understand little about antivirals and antiviral resistance in animals, and the precautionary principle would have us remain pretty conservative with their use, and to only do so after a thorough risk assessment.

At this point, my assumption is that widespread use of Paxlovid in dogs would harm more dogs that it would help.

In contrast, there’s a different story about another COVID-19 drug in cats. We have some good data about the antiviral drug Remdesivir in terms of dosing, safety and efficacy for feline infectious peritonitis, which is otherwise a pretty much invariably fatal disease. This is a drug we should be using in cats, but we still can’t get (legal) access to it in North America. We’re working on that, so it will probably be the topic of a post in the near future. Good or bad news? I don’t know yet.