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Febuxostat dose change. Or different time of day?

Stopping Gout Together Forums Help My Gout! The Gout Forum Febuxostat dose change. Or different time of day?

This topic contains 13 replies, has 3 voices, and was last updated by  nobody 6 days, 15 hours ago.

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  • #8086

    d q
    Participant
    Ŧallars: Ŧ 355.01


    Hi @nobody and @keith

    Firstly, where you been nobody? You seem to have gone awol..? 🙂

    Ok I finally have all the results in and wanted your opinions;

    18th April – 388 ummol (60mgs)
    23rd May – 413 ummol (80mgs) <— Strange result
    18th June – 377 ummol (80mgs)
    11th July – 360 ummol (80mgs)
    15th August – 346 ummol (80mgs)
    24th September – 350 ummol (80mgs)
    3rd October – 362 ummol (80mgs)

    So doing the most basic of maths (377+360+346+350+362 / 5) = 359 ummol.
    Best result being 346 and the worst at 377.
    It looks like the Febuxostat is maxing out at no lower then 346 ummol.
    I doubt more blood tests will change figures significantly so I guess I’m at the cross roads. Do I move up to 120mgs? Or try 100mgs? or Stick with 80mgs?
    (Liver markers all seems OK so far).

    Can sticking with 80mgs cut it as more crystals dissolve in the hope that the overall UA levels drop further cementing 80mgs or is it too risky?

    Thanks guys!

    p.s. @nobody – come on show yourself! The forum can get lonely without you! 🙂


    Gout Pills Before, During, or After Food?

    Gout Pills Before, During, or After Food?

  • #8087

    nobody
    Participant
    Ŧallars: Ŧ 478.51

    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.

    • #8109

      Keith Taylor
      Keymaster
      Ŧallars: Ŧ 1194.58

      Thanks, Nobody.

      I like to think that our experiences differ. So some of our conclusions and opinions might be different. But we both seem to share a passion for helping people with gout problems. So I hope that continues for a very long time.

      Ultimately, if we get gout patients to talk to their doctors with greater clarity on both sides, I think we’ve achieved something good.

      I’ll get back on topic in a separate reply.

    • #8169

      nobody
      Participant
      Ŧallars: Ŧ 478.51


      Certainly we seem to have had different experiences with doctors, Keith.
      Their expertise is obviously vital in some situations and I would sooner trust a NHS doctor than most others but I would still not trust everything the best doctors say because the demands of their jobs take a heavy toll on their ability to reason systematically… assmuming they are even willing which is in my experience generally not the case.

      The way I see it, your website’s most valuable contribution comes from the effort you invested in selecting and presenting some of the evidence about gout in an accessible manner. Even when I think you’re wrong, your work is typically helpful anyway because you’ve put int the time necessary to reference facts in a fairly unbiased manner.
      I’m afraid I don’t have that much patience. And even if I did, the effort would typically be wasted in a web forum post.

  • #8101

    d q
    Participant
    Ŧallars: Ŧ 355.01

    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.
    Totally true. Besides you know how much I value both your opinions. In most cases I seek no further opinion. You and Keith have been absolutely fantastic during my troubling times even though Keith goes missing sometimes and leaves us to deal with the boards 🙂 and you both continue to be, so thanks mate.

    Yes, the blood medication seems to have been and continues to be a total waste of time. I think I’ve been dealt the placebo with no way of telling until around May next year which is approximately when the unblinding occurs and if I am on the placebo I’ll finally be given the genuine drug around then too (hopefully). So I guess it’s going to have to be a XOI’s for the foreseeable future.

    Yep, I think your advice is spot on, I’ll try 100mgs from next week so to time with my next blood test in about 2 weeks. I really really hope I can return to 80mgs at some point. Just a few questions;

    1. How long would a fair trial of 100mgs be before attempting a return to 80mgs?
    2. Would another option be alternating between 80mgs on one day and 120mgs the other (or similar)? Otherwise its going to have to be pill cutting again.
    3. Would you recommend a tablet of colchicine nightly during the first 2 weeks or so? or have the numbers been low enough for long enough to not really worry too much?

    @nobody – Believe me your posts definitely encourage me. 🙂 For that matter I don’t really know where I would be without your sound advice about this subject at times. It’s been a steep steep learning curve with bad bad times.

    @keith – anything to add sir?

  • #8102

    nobody
    Participant
    Ŧallars: Ŧ 478.51

    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).

  • #8104

    d q
    Participant
    Ŧallars: Ŧ 355.01

    Thank you so much for that advice @nobody !

    I’ve never ever tried taking it at different times actually or with a full or empty stomach. I presently take it on an empty stomach as soon as I wake up (would that be the most concentrated way? or could I achieve better results taking it after lunch or breakfast for example going by those studies/tests?

    Assuming any changes to the above causes a drops in UA by another 10 or 20 to say 330-320 would there still be a case to try 90-100mgs..?

    Yea, I thought I would reserve the colchicine for the potentially bad days too.

    Thank you so much mate. Thanks

  • #8105

    nobody
    Participant
    Ŧallars: Ŧ 478.51

    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.

  • #8110

    Keith Taylor
    Keymaster
    Ŧallars: Ŧ 1194.58

    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. 😉

  • #8116

    Keith Taylor
    Keymaster
    Ŧallars: Ŧ 1194.58

    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 🙁

  • #8120

    d q
    Participant
    Ŧallars: Ŧ 355.01

    @nobody – Very interesting indeed – thank you so much. Maybe I’ll start taking it after lunch as my next blood test is indeed in two weeks and I can use this as my last attempt to see if 80mgs made a difference or not. I normally have late lunches (2pm-4pm) so would an attempt to take it after then or maybe even dinner at around 9pm be a quick two week trial to run? Or would you consider trying after breakfast (normally two slices of toast, banana and some kiwi with a home made latte)? My only concern being the milk possibly impairing the absorption or is milk fine?

  • #8127

    d q
    Participant
    Ŧallars: Ŧ 355.01

    @keith – Thanks for that information. The only time I ever tried colchicine was during an attack I had about a month or so ago. I took the maximum dose and was able to reduce the term to around 3-4 days. During my previous attack I took maximum dose of 500mgs Naproxen twice a day with no real benefit.. It brought relief don’t get me wrong but it didn’t seem to end the gout attack. I believe Naproxen is even stronger Ibuprofen even?

    Uricosurics did come up in a few of our consultations however the general advice that was always given was “If we are able to control it with one medication then that would be the safest way – Uricosurics are generally taken twice a day and sometimes come with unwanted side effects” I’m personally not too sure about the dosing or the side effects since the Febuxostat would be there too but I guess if we still have a little more room with Febuxostat shouldn’t we explore that first?

    Yep, going by both of your recommendations cutting seems to be the best way however reducing a 120mgs pill to 100mgs or adding a further 20mgs to an 80mgs pill is indeed going to be challenging. My pill cutter only cuts pills in half so its going to have to be either a knife to the 120mgs or 80mgs cut twice in addition to a full tablet! There’s going to be a few bits here and there.

    The time of day situation is very interesting and I’ve never attempted to test it so since I have a blood test in about two weeks I’ve decided to give it one last shot. The question is when would be the best time to take it and what hinders its absorption. I know this can get very technical but in general how could one modify their schedule to potentially see the best or any benefit. @keith I know you take Allopurinol so things might be a little different but time of day? @nobody I know our doses are oceans apart but with what and when do you normally take your dose?

    If there wasn’t enough questions above already what UA level should one be targetting now. I know Keith loves the lower the better approach but what is considered adequate since I’m coming to the maximum dose?

    Thank you both so much. Means a lot really.

  • #8141

    Keith Taylor
    Keymaster
    Ŧallars: Ŧ 1194.58

    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 😀 )
    Rachel Riley photo
    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.

  • #8168

    nobody
    Participant
    Ŧallars: Ŧ 478.51

    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.

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