Methotrexate Timing

Hi all, I’m new to this group, and wanted to say Hi. :slight_smile: I was diagnosed with PsA and erosive OA in July of last year after x-rays showed severe joint erosion in several finger joints, as well as moderate to severe joint space narrowing throughout both hands. I was given methotrexate, starting at 10 mg per week, and am now at 20 mg per week. I also take folic acid daily (except methotrexate day). When I was on 6 tablets a week, I took it on Tuesday night/Wednesday morning, had a bad Wednesday, then felt pretty good until Sunday when the pain would kick in again. My rheumatologist increased my dose to the 20 mg, and suggested I split it a few days apart, so I am taking 4 on Tuesday, and 4 on Friday nights.

I’ve been doing that since May, but now I feel like I’m have more bad days due to the medicine than I was having before taking it once a week and am considering going back to a Tuesday night/Wed morning routine. I’m very tired and foggy most days, and still have a fair amount of hand/foot/ankle/hip pain, etc. I’ve also had 2 bouts of episcleritis in my left eye, which they said was because of the PsA. I was wondering if others had tried splitting their dose like this and what your experience was with it.


Sorry you had to find us, but glad you did.

It sounds like it is time to add something to the MTX - not only does it seem to be not very effective, it sounds like the side effects have started to exceed the benefits.

I’m personally also not a fan of the split dose, because theoretically it raises the potential for toxicity, but I see with a quick search online it is a known thing, and I’m not a doctor.

Have you tried any other DMARDs or biologics or had any other conversations about this with your Rheumy? There are a number of other DMARDs you could try that can be safely added to MTX, and you’d normally continue taking MTX with a biologic as long as you are getting some benefit and the side effects aren’t too severe (ie go back to single day dosing).

Are you able to get an appointment where you are now?

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Thanks for the response. I have an appointment next month with her, and she would really like to get me on a biologic - she’s mentioned remicade, humira, otezla and a couple of others. Unfortunately, my insurance only covers a couple of them, and it looks like my out of pocket on it will be much more than we can handle - it will be around $1800/month until I hit my out of pocket max and it doesn’t look like I’ll be to get the normal assistance the companies give. She said there may be some other assistance options they will look into for me, so we’ll see.

I think I’m going to switch back to the once a week dose as I seemed to do better for a few days at least. She said that was up to my preference, so maybe it’s worth a try. had not seen the info on the toxicity of a split dose, so I’m off to look that up too.

Thanks again!

I don’t know if there is solid data on split doses - I only saw a couple of small retrospective observational studies, and they seemed to conclude that it was safe in the very limited number they observed (eg 29 people, and they didn’t seem to have any actual measurement parameters of what “safe” was).

The theoretical basis for toxicity is to do with bone marrow suppression, as I understand it. I don’t think there is much actual incidence of this, it is just something my Rheumy warmed me about (probably because he knew I was desperate and might be silly enough to self-administer on multiple days). Certainly there are case reports of toxicity in people who get confused and take it daily; that often results in very adverse outcomes.

I’m in Australia so don’t know about your insurance systems, but why don’t you start a new thread with a question about insurance and biologics so the folks in the US can help? Pretty much every time someone has thought they weren’t eligible for coverage, or it’s really expensive, someone on the forum seems to be able to direct them to the place where they can get access to better options. The biologics certainly have the best record of disease control, and in the long run, it’s going to be cheaper to prevent damage than deal with it (not to mention the vastly improved quality of life!).

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Welcome! I’ve been involved with the great folks on this forum since early 2019. Been on 25 mg Methotrexate per week and 5 mg folic acid everyday. My rheumy has no problem taking folic on the same day. I take the mtx on Sunday nights and feel pretty flu like on Mondays. I think my hair has thinned a bit but haven’t lost much. I’m on the final stages of having failed at three Dmards so that I can graduate to biologics. Our health care covers about 80% of the cost based on income. Hang in! I’m told that things can get better but it’s a slow train coming! Don’t get me talking about prednisone…I just got that monkey off my back! Peace and rest to you.


Thanks Jen, that was very helpful. Once a week it is, based on your insight and some quick searches I did for the dose. Seems like I’m constantly learning something new about this nasty beast on a regular basis.

Hi Amos, and thanks for the welcome! Good luck to you with the medications. Seems crazy that the pharmaceuticals tied the biologics up with patents to delay generic versions in the US. Not sure if it’s the same in other countries.

Hi and welcome @Suncntry. Mxt hated me but sulfasalazine loved me and indeed worked for a bit, just to throw another positive option out there. I’m in the UK so of no help on insurance and biologics save that we all use biosimilars to biologics where available here rather than the original.

Just a couple of other things that might help. PsA loves to moves around a lot. It’s not surprising really given its trigger is your now insane immune system. So what’s horridly sore this week might not be next month. Understanding that at the beginning of my disease helped me a lot and stopped me sort of panicking so much.

You many also find eventually that you might not have the extent of erosive osteoarthritis you presently believe, much of that might be PsA, sadly.

So once you can get insurance issues sorted out which the USA people on here can surely help you with, please know that there are several options to treat this disease and help you. It is possible to feel a whole lot better than you do now.


It’s possible to feel better - that’s such a relief to hear. Thank you!

Is there possibility for the erosions and other damage to repair themselves? I’m having a lot of difficulty with dexterity and dropping things. I have lots of tools to compensate for things like getting caps and seals off, opening boxes, and other things, but it’s such a painful process sometimes.

The biosimilar meds have been FDA approved, but won’t be available until 2023 unfortunately.

No sadly not really. Once the damage is done, it’s done. That’s one of the reasons why the protocol is to treat PsA as aggressively as possible from the off in order to prevent any damage occurring or at least slow it down considerably.

PsA tends to be a rollercoaster often, you find a med that works (often after trying a couple too) and you feel much better and then that med often stops working or your disease progression overtakes it and you then feel worse and then you find another med and so on it goes. To date I’ve tried mxt - completely a no go for me - it hated me. Sulfasalazine - it loved me and worked really well for several months at 3000mgs per day. Benepali a biosimilar to Enbrel it only worked for 3 months out of the 11 months I took it. Imraldi a biosimilar to Humira - it also hated me so I only lasted 8 weeks on it. And now I’m on Cosentyx which worked really well for the first 3 months and now I’m coasting a little on it. However anecdotally it can work a lot better after a year on it and I hit that come November, so we’ll see. I’m not prepared to stop it until after then at any rate.

It does though sort of ease up a little on the severity level because truly whether a med is working well enough for you or not, all the meds are trying to normalise your now insane immune system and that helps regardless.

Thanks Poo_therapy. I hope this one works out for you, sorry you’re having such a hard time finding a med that helps.

I was on methotrexate for many years. The trick I used was to eat a meat and potatoes meal for dinner on Friday and then take my dosage right before bed. I would sleep through a lot of the side effects and then have Saturday and Sunday to take it easy because I was always tired for a couple days after my weekly dosage.

So I’d suggest trying to time your dosages before bed after a heavy meal and do it on days when you came have a little down time until your body gets use to it.


Thank you, sadly I’m not the only one who has to search hard to find a med that helps and more importantly stays helping.

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Hello, sorry to read about your predicament. I tend to share the opinion that methotrexate should have something added to it, as will probably happen when you talk about the problem to your rheumatologist. Three years on from diagnosis and a wheelchair status am ok for the moment and walking round normally with methotrexate and Cosentix and a gluten sugar and carb free diet. In the beginning when rheumy increased dose to 20 from 10 I lost some hair, complained, so he put it back down to 10 and gave me cortisone too for a long time. In the end was given biologic after about a year or more. Hoping your added medication will help you soon, all the best

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Thanks Milo, I will give that a try. Now that I think about it, the side effects are better when I eat a heavier meal before taking it.

Letizia, that’s scary being in a wheelchair. I’m glad you’re up and walking around now! The rheumy would like to get me on something else, so hopefully we’ll be able to find something that’s affordable soon.

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I must add though that rheumy attributed a good part of my success to methotrexate, so consider it takes time for these medications to work, due to a cumulative effect. Let us know how you get on with your weekly doses, and drink lots of water.

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All of these DMARDs are such slow burners, some biologics too. For me it’s always a minimum of at least 6 months (unless encountering intolerable side effects) before you really know how they’re going to work.


Thanks all, I took all 8 pills last night after eating a good dinner. I’m real tired today, which is typical, but not having any other side effects. Not much pain this morning either. Fingers crossed for better days ahead. :slight_smile:


Hi all, thought I’d give an update on this. I really appreciate your input on the meds. The 8 methotrexate pills once a week were like a magic bullet for me, I have felt better the last 3 weeks than I have in a long time. The bad news is my liver enzymes are mildly elevated, so the doctor bumped me down to 6 pills a week to see if they will go back down. She wants to get me on Otezla, but it will be a challenge with insurance approval and the costs. We’ll just have to see what happens.