My opinions and Keith’s differ in some respects so I thought it best to let you discuss your issues with him since he was (unusually?) available.

Seeing that your new blood medication doesn’t seem to do anything, yeah: the obvious thing to do would be to increase your febuxostat dose. In my opinion, your should try around 100mg (precision doesn’t matter) rather than 120mg to begin with. 80mg would probably be enough in the long run but a higher dose might help you bet better faster so as long as there are no obvious side effects, a moderate dose increase seems worth trying.
We had discussed all of this earlier but if it encourages you to see me restate it, it only takes a few minutes so here you are.

How long you would take 100mg should depend on your test results, gouty symptoms and the subjective side effects of the dose increase. We’re potentially talking years but maybe you could try to aim for a slightly lower dose such as 90mg after a while depending on what 100mg does.
I don’t know much about the effects of a large febuxostat dose over the day but based on the little I know, I’d cut rather than alternate. My rheuma agreed on that point but we were discussing much smaller doses. You could also try taking your dose at a different time to see if that makes a material difference by the way (tests have shown the effect is slightly different if you take the pill on an full as opposed to empty stomach).
At this stage, I wouldn’t recommend a daily colchicine dose. If you were to feel incoming gouty symptoms a few days after the dose increase though, you could go for a pill just in case (and quit colchicine once that went away).

You apparently get a taller peak but a lower average blood concentration if you take the drug on an empty stomach. So the drug might be more effective if you take it on a full stomach… assuming of course you haven’t eaten something which impairs absorption in the first place. But possibly it might be even more effective to take it at a time of the day when you wouldn’t normally eat (this is a wild guess but taking it in the morning doesn’t sound ideal).
I’m pretty sure none of this would make enough of a difference to warrant postponing your dose increase anyway. It’s just something pretty harmless you could try, like next year or something. If you’re going to have frequent blood tests anyway you could use the opportunity to run some experiments.

In response to Nobody’s:

At this stage, I wouldn’t recommend a daily colchicine dose. If you were to feel incoming gouty symptoms a few days after the dose increase though, you could go for a pill just in case (and quit colchicine once that went away).

The only gout doctor I ever trusted advised 2 weeks colchicine with each allopurinol dose increase. So because I trusted him that’s exactly what I did the first couple of times. Then I went back to “as-required”.

For me, that worked better. But I’d had many years of recognizing gouty symptoms. So I could know upon waking if a flare-up was imminent. In which case, ibuprofen almost always worked for me.

It’s not that I’ve anything against colchicine. But personally, I found ibuprofen a better choice for me. So I feel it’s very important to:
1. Understand how each different type of gout pain relief works.
2. Be aware of your gout symptoms each and every day.
3. Discuss your options with your doctor so everyone involved is “singing off the same sheet”.

In terms of uric acid treatment @d-q have you discussed uricosurics with your doctor in combination with febuxostat? I can’t see anything in your history here, but the search of topic histories is as fallible as my memory. 😉

I should have added that if uricosuric combinations are not an option, I agree with:
1. Cutting febuxostat pills to get 100 mg per day. Because alternating between 80 mg and 120 mg seems like too much of “rollercoaster”. If we were talking about allopurinol, I might have a different view. But febuxostat is metabolized differently.

2. Time of day, especially in relation to meals is likely to have an effect. Though studies disagree if the action of food is significant or not. But frustratingly I can’t find any real-world studies on gout patients. So it looks like ” If you’re going to have frequent blood tests anyway you could use the opportunity to run some experiments” is a good option. However, you need to be aware that experiments involving a single subject are extremely hard to get convincing results from 🙁

100mg Febuxostat
I think you might approach your pharmacist with the 100 mg febuxostat problem. Because some offer pill-splitting as a routine service. But it’s not something I have personal experience with. If your pharmacist does offer this, I suggest halving 80 mg and 120 mg tablets. Then half of each = 100 mg (my days of watching Rachel Riley have not been totally misspent 😀 )

Febuxostat time of day
If you were a mouse, I’d say 2 hours after your keeper turns on the light is the best time of day to take febuxostat. Because that worked well in:
Kanemitsu, Takumi, Yuya Tsurudome, Naoki Kusunose, Masayuki Oda, Naoya Matsunaga, Satoru Koyanagi, and Shigehiro Ohdo. “Periodic variation in bile acids controls circadian changes in uric acid via regulation of xanthine oxidase by the orphan nuclear receptor PPARα.” Journal of Biological Chemistry (2017): jbc-M117.

we also demonstrated that the antihyperuricemic effect of the XOD inhibitor febuxostat was enhanced by administering it at the time of day before hepatic XOD activity increased. These results suggest an underlying mechanism for the circadian alterations in uric acid production and also underscore the importance of selecting an appropriate time of day for administering XOD inhibitors. […] the excess production of uric acid induces hyperuricemia and gout in humans. XOD inhibitors are often administered to these patients after meals during the daytime. Febuxostat has an apparent elimination half-life of approximately 5 to 8 hours (46); therefore, this drug is generally taken once a day, mainly in the morning. In hyperuricemia model mice, the anti-hyperuricemic effect of febuxostat was enhanced by its administration in the early light phase (ZT2), during which nocturnally active mice begin to fall asleep.

I’m finding it hard to interpret that in human terms. But if it does translate then the right time for humans is before going to sleep. Also that ties in with other claims I’ve read that uric acid rises through the night in humans. Sorry it’s not exact, but that’s the best I can suggest for now.

Good idea about halving both types of tablets! These tablets halve easily under a little finger pressure. No need for a cutting tool.
After one’s last meal of the day might be a good time to take the drug. But if you’re going to experiment, you might as well try different things. We might be surprised by what works best.

I have no idea what might impair febuxostat absorption. Trial and error will tell if anyting makes a significant difference.
For my own use I don’t care about the effectiveness of the drug anymore so I’m taking it pretty randomly. The perceived side effects have become milder over time but they’re still my main guide as to when’s the best time to take it.

350 umol/l is generally considered low enough but guidelines recommend aiming a bit lower in some cases. Check out the guidelines and studies for yourself if you have any doubt. Thing is, everyone is different and mesurements are unreliable. Experience might tell you should aim lower than is generally recommended. But it’s way too soon to assume your case in unusual.
Keith has shown evidence that large tophi shrink quicker when you go well under 350 umol/l but you can’t generalize that to people who have already dissolved all their superficial crystals and that study also showed diminishing returns after a certain point. So I can’t say I’ve ever seen any evidence supporting his recommendations on aggressive XOI dosing.
It would be a different matter if 300mg allopurinol was enough to drop your SUA under 300 umol/l without apparent side effects for instance. In that case, ir woudn’t be unreasonable to take 300mg instead of 200 even though the latter dose would be sufficient to reach the generally recommended SUA target. But febuxostat is a newer drug and you’re already taking a dose which isn’t as thoroughly tested as the doses originally recommended by the drug’s developper so there is the balance of risks to consider…
You didn’t try the maximum doses for either Naproxen or colchicine by the way. That said, it may not be prudent to take more than you did in your situation. Anti-inflammatories routinely kill their users.

First, it would indeed be safer for you to cut a bit off the 120mg pill than to combine two pills. I think the risk is neglibible and I would combine pills if I needed to but I’ve never actually tried it, I of course have no proof it is safe and I understand if you don’t want to take chances…

I have however been splitting a single pill in order to take it over several days for quite some time. And the blood tests have been consistent with the dose being controlled as one would expect by splitting. The test results aren’t subtle or overwhelmed by noise.
However it is conceivable that there are differences from one day to the next between the actual doses I’ve been taking and that these differences cancel out over time. If what mattered most for uric acid as well as the side effects I’ve experienced is how much febuxostat one takes over a week rather than over a single day then of course it wouldn’t matter much if the stuff was poorly distributed through the tablets I’ve been splitting.
Subjectively, I did experience different side effects over the course of a single day from taking half a pill as opposed to a quarter of a pill but these side effects haven’t been as consistent as the test restults and might conceivably have been driven more by the dose I thought I was taking than the dose I was actually taking. That’s kind of a strech since I was initially suprised by the side effects but I can’t rule it out nor can I prove it wrong with objective measurements.
Other potentially deadly side effects might conceivably show up if you were to take more than 120mg over a single day. I have zero experience with this and can’t rule it out either so again, I understand if you don’t want to combine pills.

This stuff about non-absorption in the stomach however is laughable considering that they do sell scored tablets which have no film between the scored halves of the pill. There also are ingredient lists on the packages… what do the scored tablets contain that would prevent absorption in the stomach? And the studies backing their marketing authorization in several countries look at the effect of 40mg which you can only get by splitting these tablets. Are we to believe than they spend money on separate manufacturing processes for no other purpose than to harm people who split non-scored tablets?
Please consider you are basically talking to a non-sadistic but murderous psychopath when you’re talking to people representing certain pharmaceutical interests. What they are doing kills people and they are doing it for profit. There are cheaper, less dangerous and more conveninent pills and dosing recommendations in many countries and there is no medical reason we couldn’t use them. But we have to put up with this shit for no other purpose than to create a monopolitic rent.

@d-q I spent some time a few days ago looking at pill-splitting. Then, I refrained from posting. Because I found that the bewildering range of opinions and practices was likely to cause more confusion. So welcome to my club for the bewildered.

To clarify some points:
– 40 mg Uloric is manufactured and sold in the USA with FDA approval. It’s also available in its home country of Japan alongside a 20mg dose. But the UK NHS approach is that 80 and 120 are acceptable doses.

– Doctors have always had the power to prescribe “off-label”. But that raises the question of how to supply it. In earlier discussions (regarding Colcry$) it has been suggested that compounding pharmacists could fill any off-label prescription to get round manufacturers “monopolitic rent”. At the time, I thought such pharmacies were USA-only. But I just found http://www.bcm-specials.co.uk/ as a UK example. Though I haven’t found if there is a UK compounding pharmacist who will create lower-dose pills.

– I also found a European study comparing 40 mg and 80 mg febuxostat. But they had to split 80 mg pills to get the 40 mg dose. They include the disclaimer in the report. Which is similar to my disclaimer below. So after considering all the data related to splitting or not, you should discuss this with your doctor.*

– During my research I stumbled across professional pharmacy forums which confirmed that pill-splitting is very much a pharmacists personal choice.

– Nobody hit the nail on the head about the coatings. If there was an enteric element, it would have to be listed in the ingredients.

In essence, there is no right or wrong answer to this. So if you always cross at the crossing, do not split pills. But if you save yourself the longer walk because you understand how traffic works, get a decent quality splitter and ignore the traffic pill wardens.

* Flendrie, M., B. van den Bemt, V. Huiskes, M. Hoefnagels, and F. van den Hoogen. “AB1034 The urate-lowering effect of febuxostat 80 mg and 40 mg (80 MG FILM-COATED TABLETS SPLIT IN HALF) in gout patients in daily clinical practice.” (2018): 1633-1633.

Uloric 80 mg vs 40 mg Uric Acid chart

I don’t think it’s about the weekly dose actually. I merely brought it up as a possibility to question my own conclusions. I go through such mental exercises because like most people, I’m prone to confirmation bias.

Yes, the UA elevation could have something to do with the pain. The elevation could have contributed to the pain or be merely an effect.

I think that going back down to 90mg is a waste of time since you’re already doing 100mg, especially given that disappointing test result.

re: “The commercial side of things applies to everything.”
It’s common for folks in medical research to have altruistic or simply scientific motives. Morally defunct bright people tend to choose more profitable careers. I’d trust developers over those who are only bright enough to profit off the work of others (and in this case, who are so unsrupulous as to call it “our product”).
There are Adenuric tablets featuring a score line out there. But they kept the biggest lie for the punchline: “We hope this information proves useful to you.”

Your guesses are as good as mine.

I don’t know anything about what the pH of water would do. I don’t watch it and my assuption is that the food you eat is what matters most (extreme situations excepted). And I don’t think it’s the pH as such which matters. But possibly my assumptions are wrong. In priciple, I don’t see why you couldn’t put enough minerals in water to make a difference.

It’s tawrikt. Or Tauriqt. The spelling is irrelevant. You’re not supposed to write it on stuff anyway. On the contrary, free men write on it.

To get back to your uric acid test results fluctuations @d-q

I can understand your “need to know reasons”. In fact, it’s one of the cornerstones of an article I’m researching about doctor-patient relationships in gout management.

But I’m sorry that I can’t really add to the points already discussed. Except to think that the most likely explanation is that clusters of uric acid crystals dissolve haphazardly. So no uric acid blood test can accurately measure the debulking process. Ironically, they only become “accurate” in this context once the debulking phase has ended. So without DECT, there’s no way of knowing.

Sorry, I can’t give comfort. But the best analyst of individual results has to be the doctor who ordered the test. I trust you voiced your concerns about your results. So what response did you get?

I think doctor’s answers are very important in gout management. Because when I was at a similar stage to you, I was extremely frustrated that I knew more about uric acid test results than 3/4 doctors I consulted. Happily, the last one gave me all the help and support I needed. I still remember how I felt as if I was walking on air when I strolled home after that consultation.

Our medical situations are different @d-q. But the strength of good doctor support is something that helps all gout sufferers.

See how long you stuck to 80mg before increasing your dose? It’s obviously too soon to think about increasing it further.
340 is only one result. You don’t know how your average on 100mg will look like. Comparing it to your 346 result is wrong. That was the lowest out of 7 results! Your average on 80mg has been 374.
And you should be monitored for sides effects for a while. 100mg is an uncommonly strong dose so make sure everything is being checked (for instance: not just ALT and AST but ALP as well). Mind your blood pressure, your weight, how well you are sleeping and so forth. Obviously hemo is a special concern… get it tested two or three times minimum on 100mg before moving further.

The “good” vs. “safe” thing is misleading in your situation. Your UA was recently much higher so you wouldn’t be safe regardless of your test results.
In light of your test results, 100mg febux is highly likely to be sufficient to cure your gout in the long run if you stick to a decent diet and stay clear of alcohol as well as other diuretics. There’s of course the chance you are a special case but the only studies I remember reading in which a few patients didn’t heal while testing at 350 umol/l or less were looking at bone disease (which is known to develop after successful ULT anyway). So the issue as I see it is: if your lingering symptoms aren’t giving you too much trouble and you aren’t endangering your health by taking anti-inflammatories all the time, endangering it with poorly-tested febuxostat doses seems unwise. On the other hand, if more febuxostat might help you get off other drugs, that would be a different matter…
And if there was something fairly safe your could do to lower your SUA further, it’d be worth trying. So if you haven’t already given a good look at your dairy and minerals consumption… well, here’s a new year resolution for you. Alternatively, see if you can find a doctor who has experience with combination therapies (XOI+excretion booster).

Hi again!
I’m glad you didn’t disappear because you got a CVE from febuxostat. This is the most controversial thing about this drug.
You almost certainly still have a significant amount of solid UA in your system. This could cause spikes and I don’t think they’re a concern. The therapeutic targets include a safety margin so it’s OK if you exceed them occasionally. Certainly I used to have a lot more variance in my results when the lowest result I could achieve was between 310 and 320 and I still had serious attacks. I guess issues with febuxostat absorption might also explain the spikes (maybe take a look at what you’re eating or drinking around the time you take your dose).
I doubt you really need 120mg but the side effects shouldn’t be much worse than 100mg and increasing your dose might well get you cured faster. You’ve also been on the stuff long enough that slow-onset side effects ought to have shown up by now. I assume there’s no sign of stress in your liver function tests for instance (as with UA, don’t bother with “normal” but compare actual numbers). Maybe get your cardiac-vascular system thoroughly checked out before moving on to a higher dose?
I wouldn’t change my dose from one day to the next if it can be avoided. If your doctor doesn’t want to move to 120mg straight away, could they write you a script for a custom dose such as 110mg? Pharmacists should be able to fill custom prescriptions (they are typically used for young children) but I don’t know if the NHS covers that.

I don’t have your email by the way. I’m not going to visit your island anytime soon (especially not given current events) but I could still write if I had it.

I don’t think dietary changes have much to do with how much liquid or solid UA there is in your tissues. While uric acid is definitely found in significant amounts in solution outside of the blood, I have found doctors to be unaware of the modern evidence regarding crystals. Not that it matters: whether small crystals would show up with expensive imagery or not is irrelevant to your treatment at this stage.
You never know when all the crystals are gone. You can only guess. And I would recommend not lowering your dose immediately after they’re all gone anyway (see the other long thread I posted in recently). In any case, it’s too early to concern yourself with this. You’re clearly not out of the woods yet.

I found the ALT/AST ratio more useful than AST alone though I suppose the absolute value might be important to deal with different issues. Either way, I don’t understand why they don’t test AST. I suppose ALT is the number most likely to become “abnormal” but AST is necessary for a more cogent interpretation of test results (my ALT has typically been “abnormal” even when I didn’t take any drug).
I got one or two high ALP results but that number has been pretty noisy in my case.

You could always take a small bit off a 120mg pill every day instead of alternating. It would be imprecise but you’d still get smaller daily variations. It’s not so much the UA variations which worry me but the side-effects. Maybe this is an unwarranted concern but if our bodies are better able to process a steady dose, that would be one fewer potential cause for these rare but nasty side-effects which might possibly be associated with febuxostat (the evidence is quite weak so far).
That said, my guess is that you’d handle 120mg per day just fine. You could always lower your dose later. But that’s only a guess and high febuxostat does aren’t that well-tested…

I believe I have previously suggested you simply post your email here if you want me to write. Posts can be edited so your email wouldn’t have to stay up forever. Yes, you could set up a temporary email address and add it to your email client (if you use one) or forward it to your main email account (if your webmail provider offers that feature) but I’m not sure it’s worth the bother. I certainly wouldn’t recommend one of these services which requires you to check your email on their website (that’s only good when you know you’re going to get an email right away).
There are of course other ways to exchange information or chat but I don’t suppose you use IRC or GPG for instance.

Let me know if my email didn’t get through (but check your spam folder first).