I’ve completed the course of Paxlovid (five days, b.i.d.) so I thought I’ve give my impressions, for what they’re worth. I had no gastrointestinal issues, no liver side effects, and no body pains, to pick three from the package insert, so that’s good. The listed effect that was very clear was the “altered sense of taste” one, and that appears to be via the drug showing up in the saliva. It’s extremely bitter (you notice that when you put the tablet on your tongue to swallow it), so I’m sure that it doesn’t take much to be noticed. The bitter taste seems to track the blood levels pretty well – by the end of a twelve-hour dosing period it’s much less noticeable. That’s not because you’re getting used to it, as the next dose makes clear! It’s unpleasant, but hardly a deal-breaker. I’m sure that anything that reminds me of it in years to come will immediately take me back to my Week of Paxlovid in May of ’22, though.
We don’t think too much about drug distribution into saliva, but it’s certainly a real phenomenon. It probably gets noticed the most in anti-infectives (antivirals and antibiotics) since those tend to be dosed at high levels. Here, for example, is an attempt to see if saliva levels of antibiotics could be used as a proxy for plasma levels (the existing data weren’t good enough, and seemed rather variable). There are some broad guidelines about what sorts of compounds distribute into saliva, but that last paper didn’t seem to find them very predictive. Whatever properties are needed, though, paxlovid possesses. It’s certainly the parent compound and not a metabolite – the drug is a substrate for CYP3A4, but that’s why you take it with ritonavir, to inhibit that enzyme’s effects. The package insert says that metabolism is “minimal” under those conditions, and that the bulk of the dose is excreted unchanged via the renal pathway. So as is usually the case with a course of oral medication, I have been producing some fancy urine for the last week.
Whenever I got annoyed at the taste, though, I reminded myself that it was a good sign. You want to have active compound saturating thoughout your various fluids and compartments when you’re fighting a systemic pathogen like this one. It’s clear that while the coronavirus affects the respiratory system first (its site of entry) that it hits a lot of other organs as well, some of them with potential long-term sequelae. That’s why I was taking the drug in the first place, in hopes of reducing the chances of that sort of thing by reducing the viral load as much as possible, so I tried to make the best of the you’re-soaking-in-it sensation that the bitter taste brought to mind.
How effective was it? Well, here’s where you see up close and personal why we run clinical trials under controlled conditions. Because as one person, it’s really impossible for me to say. After I started taking the drug, my symptoms went down quite a bit (which was welcome), but at the same time, I have no way of knowing what would have happened had I not taken the drug. I would like to think that this was the antiviral doing its thing, but the only way to prove that would be to take a large number of people, controlling for age, gender, time of symptom onset and other factors, and comparing them to a very similar group of people who did not take the drug. You’d then monitor them for symptoms, time to resolution, viral load and so on, and ideally compare them for months afterwards for signs of “long covid” problems. In short, a clinical trial!
I did take another rapid antigen test partway through the course of treatment, and I was still positive (as I had thought likely), but you’d want a lot more data than that, in a lot more people and with real numbers instead of a red antigen line. I’ll do another antigen test in a day or two to see how things are receding. It’s been 36 hours since my last dose, and so far I see no signs of the “rebound” that some have experienced (return of symptoms before eventual recovery). That’s another thing you’d want to quantify in a larger cohort.
Pfizer of course ran such a trial in high-risk unvaccinated patients to get the drug’s Emergency Use Authorization, where I believe that they showed about 2% of the participants having such a rebound. They have another trial going in lower-risk vaccinated patients. The RECOVERY trial has a Paxlovid arm collecting data as well. These are the sorts of places that you’ll want to go for hard data, not to me. I made the decision that the potential benefits of the drug outweighed the potential disadvantages. I hope to have been correct about that, and since I experienced no real side effects that I can see other than than spitting tonic water for a work week, I think that the odds of “no harm” are quite good.
