Not too long ago, I wrote a post discussing the various categories of regulatory oversight for veterinary medicines. These range from pretty good evidence of safety and efficacy for approved drugs to no meaningful requirement for scientific evidence (and usually pretty little of it) for supplements and herbal remedies.
While I have focused a lot in the past on the weakest evidentiary category, unapproved supplements and remedies, I also regularly point out the problems with the others. In particular, I have repeatedly tried to get vets and pet owners to understand that even medications with a plausible, science-based rationale can turn out to be less effective, and less safe, than we hope if used without high-quality research evaluating them for the same problem and the same species we are trying to treat. Most of the examples in my latest lecture on practices we should consider abandoning involve such treatments.
I recently ran across a particularly egregious example of this in my own current field of canine aging and longevity science. Several vets (e.g. Petspan, Dr. Toman) are actively advertising their wiliness to prescribe the drug rapamycin to dogs and cats for the purposes of extending lifespan. This would count as an off-label use of a drug approved for humans but not for dogs and cats. This means that there is absolutely no clinical trial evidence showing this drug extends lifespan in these species. Even more problematic, that is not what the drug is approved for in humans, and there are no clinical studies showing it makes us live longer either! So this is definitely a practice based entirely on extrapolation from basic science and research in species and circumstances radically different from those of our pets.
Rapamycin is probably the most publicly well-known of the potential longevity medicines currently being studies. There is a solid physiologic rationale for why it might extend healthspan and lifespan, involving effects on cellular and molecular pathways known to significantly impact longevity. There is positive evidence of lifespan extension in animal models (e.g. fruit flies and mice), and some evidence from human studies of positive effects that might reduce age-related disease and extend lifespan (though no actual evidence yet exists showing increased longevity in humans attributable to this drug).
There is even some research on rapamycin in dogs and cats. One study in dogs found no significant objective effects, positive or negative, of low-dose rapamycin, though subjectively owners saw changes they perceived as positive more often in dogs on the drug than in those on a placebo. Another group ran a similar trial study which found no negative effects and no positive likely to be clinically meaningful, and a longer clinical trial is under way. Similar small studies have been done in cats, and one showed promising results for delaying the progression of a specific type of heart muscle disease.
Such research is a key step in the process of moving from basic biology to a clinically safe and effective therapy. However, while there is lots of excitement about the potential of rapamycin to extend healthspan and lifespan, and this is based on plausible and encouraging science, it is far too early to be prescribing this drug with lifespan claims. The vast majority of drugs which look promising in early research turn out to have less efficacy or more risks than first hoped once they are tested in larger, more diverse populations. While I think there is some reason for optimism about the potential benefits of rapamycin, I think it is not responsible to prescribe it and not ethical to make longevity claims about it in dogs based on the existing data. If we were talking about a medication that might treat an aggressively painful or fatal condition, acting on the basis of limited and early evidence might be justified. When we are talking about slowing aging and extending lifespan, which is effectively preventive medicine for health dogs, the bar for safety and efficacy should be much higher, and rapamycin has not yet cleared it.
I also suspect that such prescriptions are not legal, based on the rules for extra-label use of prescription medication in veterinary patients. These required-
- A valid ongoing veterinarian-client-patient relationship (VCPR). While some states are getting more flexible in their tolerance of virtual VCPRs, I think an online relationship with a vet for the sole purpose of prescribing an off-label drug to extend lifespan is pushing the limits and violating the spirit, if not the letter, of the law.
- “FDA’s requirements for extra-label drug use in animals limits this use to situations where an animal’s health is threatened or where the animal may suffer or die without treatment.” While it can be argued that aging is the #1 cause of suffering and death in the long run, this is clearly not how the rules were written or intended. When the risks and benefits of a drug are as uncertain as they currently are for long-term use of rapamycin in healthy dogs, these can only be offset by an urgent need for treatment based on current suffering and imminent death or disability, which is not the case with normal aging.
It is unlikely that the FDA will take action against this practice given their limited resources and the political climate, which seems to discourage enforcement of such rules intended to protect veterinary patients. Therefore, it is up to consumers and veterinarians to be both informed and mindful of the scientific uncertainty and the ethical concerns such practices entail.
