Methotrexate and ibuprofen?: Hi everyone,happy Tuesday... - NRAS


29,418 members35,091 posts

Methotrexate and ibuprofen?


Hi everyone,happy Tuesday to you writing to ask if it's ok to be taking methotrexate and ibuprofen 400 mg together? The reason I'm asking is I only asked if I could take painkillers while methotrexate kicks in,but I didn't ask iabout the ibuprofen.i only started on meth yesterday morning and just took painkillers this morning as too scared to take ibuprofen as I read you should be cautious when combining the two. Also after a dreadful weekend anticipating the thought of starting the methotrexate Monday morning,I took the plunge and went about my day waiting for all the side effects to kick in !!!! Wot a miserable anxious day I had but I was fine throughout,had a great sleep and up today to go shopping I thought I may have to cancel !! I took a folic acid with brekky today come I am told only to take one a week the day after meth and many of you take it every day?right well I'm off with hubby's credit card to treat myself to some nice clothes,as I deserve it don't I !!!!! Lol.bye for now and hope all of you are well today.michelle xx

14 Replies

Michelle i love the idea that your off with hubbys credit card to treat yourself to some new clothes. I have never had a problem with mtx. I used to take folic acid once a week,but then i had to take it three times a week as i wasn't up to par. I can't tell you about ibrobrufen,you must speak to you chemist or your rheumy if you are able to contact them.


I really don't know what the matter is with this site today - it is so slow to connect!

Anyway to answer your question. I have been on MTX for 4 years now and am on the highest dosage as my RA is very unstable. My Rheumy consultant told me also to take 400 mg of Nurofen and 1000mg of Paracetemol when the pain and inflammation is bad. It doesn't affect the MTX but be careful of the Nurofen/Ibuprofen etc and always take on a full stomach as it can cause irritation to the stomach lining.I use the Gel capsules which I find are more gentle than the tablets.

I also take folic acid 6 times a week (not on MTX days).

I have recently had an operation on my shoulder and was written up for these drugs whilst in hospital by the anaesthetist who had full knowledge of the MTX and Enbrel that I take.

Hope this helps. Paracetemol is one of the safest drugs you can take (in moderation) and is usually recommended when you can't take anything else. e.g. I can't take anything which is derived from morphine.

Lavendarlady xx

this was a question i did ask my rheumy ,, when i started on mtx ...

"is it ok to keep taking ibuprofen " ...??? his reply was ,, yeah sure ..

i found mtx no problem at all .. no side effects or anything .... unfortunately it did nothing for me .. on a good side .. it made my rheumy look abit deeper into my diagnosis

so i think your perfectly safe with the ibuprofen ...

not sure i can say the same about your hubbys credit :)



Hello there,

so glad to hear that you have not had any problems with the MTX. So many of us here have had the same experience - quaking in our boots followed by ..... nothing! I've been on it for 13 weeks now without any real problems. I do tend to wake up with a headache two days after taking MTX (??) but it goes once I get up.

I have been prescribed shed-loads of Ibuprofen but do not take it & my Rheumy listed it as one of the drugs I'm on along with Methotrexate on follow up letter so I'd assume that they go together okay, but do check it out with the professionals (phone Rheumy nurse?). I did try telling my Rheumy that I never take the stuff to which he murmured 'Good!' I've heard that it is not brilliant for bones, really, so that's why I avoid it tho' if the pain demanded it I'd just chuck it down my throat!

Rheumys do vary re. how often you should take Folic Acid. Apparently it can render the MTX a little less effective which is the thinking behind only taking it one day a week, I believe. However, Folic Acid helps prevent side effects so if you do get any then I wouldn't be surprised if you are asked to take it more often.

I think the retail therapy sounds just the job. Enjoy!

Christina xx

Hi Michelle

I took my 9th dose of mtx yesterday and so far have not had any side effects or in fact any relief. My rheumy told me to take 1 folic acid on the day before the mtx which is what I do. I asked my doctor if I could take co-codamol with the mtx and she said that was fine. I didn't ask about ibuprofen as that has never done much for me. Happy shopping! xx

It's always best to take as little painkillers as you can, but sometimes we just have to! After quite a while I managed to get myself off the stronger NSAIDs and now mainly use ibuprofen as my anti-inflammatory. But then I also take stomach protectors every day, so that helps cope with them.

We're all on slightly different folic acid routines, so stick to what your rheumy has said and chances are that that will be enough. I was on one a week for a long time, and only recently have had to increase because of mouth ulcers. And well done for coping with first MTX dose, suggests that you'll be absolutely fine with it. Now you just have to wait a bit for it to work! Polly

as helix has said, folic acid routines can vary, but the main thing is that you don't take it too close (usually not the same day) as MTX. If you keep on having problems like mouth ulcers, you may need to ask about taking folic acid more regularly, but a lot of folk get away with just a once a week dose.

I do find it surprising that a lot of folk are being told to only take ibuprofen as a pain killer. I am possibly a bit different having spondyloarthritis rather than RA, but I have always been told that ibuprofen and similar NSAID drugs work best as anti-inflammatory drugs if taken regularly and at full strength. There isn't any bad interaction between ibuprofen and MTX, though you need to be aware that both can affect your liver with long term use, so you need to be monitored every now and then for liver function.

When I had MTX added the chemist at first didn't want to give it me because I was taking Bruffen Retard for pain relief (slow releasing ibuprofen type drug),the computer had flagged up that it shouldn't been taken together. I won't bore you with the details of what happened, but when I contacted my specialist nurse she told me that the benefits of taking it, outweighed the risks. Been taking them together for a few years now.

Folic acid.......well from what I've learned from reading various forums there is a wide range of when to take it and how much. I was first told to take it three days after taking MTX, nurse told me that that was when the MTX is at it's optimum level (been told by another nurse that it's always at the same level in your system, so who's right there is anyone's guess). When I told my consultant that my hair was getting thinner, he told me to up it to one a day. I replied...Not on MTX day.....he replied......It didn't make any difference...... so now I take one seven days a week.

NRAS a while back did do a survey on how we had been told to take it, not sure how to find the results.


Morning shell, I take ibuprofen when I need inflammation to go down along with paracetamol and a stomach protector. I take folic acid 3 times a week which was increased when I said I felt a bit sick along time ago and have been told to carry on since then, I'm about 9 weeks into taking 20mg MTX for the second time, first time when 15mg had no effects on flares I stopped in protest but now I am behaving myself having found this site and friends to support me, only side effects I seem to encounter is a rush to the loo a day after then a headache towards the end of the week, but seriously my pains and swelling are really much better now that I have stopped worrying alll the time. All the best and increasing painfreeness Oh and yes its not a word in the dictionary! Carol



My consultant told me not to take ibuprofen with MTX due to the toxicity. Maybe this was because my blood results for my liver were not good. Told that paracetamol is fine though.

I know lots of people have to take the two together but thought I would just tell you what happened to me.


Hi, just to add my experiences as well.... I have been on MTX for about 18 months and take ibuprofen most days as it is the only thing that helps with my inflammation. I was a bit concerned about taking it so often but I saw my consultant last week so asked him about it. He said it was absolutely fine to take 400mg 3 times a day (which is more than I take anyway).

I take folic acid just once on a Friday and then MTX on a Monday. Glad you have not had any side effects from your dose - I hope it continues in this vain and that you've had fun shopping!

Mags x

Hi Shell1967

As many others have mentioned lots of people do take anti-inflammatories and painkillers alongside their DMARDs (like methotrexate) but it is always best to check with a health professional as everyone is different. The GP or a pharmacist should be able to answer this question for you.

As for folic acid, as you can see, this does seem to vary widely. I have included a link to the survey that Paula mentioned which we ran a couple of months ago:

Again its always best to follow the advice of your own rheumatology team.

Kind regards

Sarah Kate



I can't offer a detailed answer as to compatibility of Ibuprofen and Methotrexate; however, Ibuprofen is an NSAID and there have been fatalities caused by NSAIDS and high dose Methotrexate as used for chemotherapy. High dose means hundreds of milligrams, not the usual 15-20mg of MTX used for RA. Nonetheless. both WebMD and the UK NHS web sites say Ibuprofen and Methotraxate can interfere with each other. Here is the NHS link:

The problem with MTX and Ibuprofen and/or Paracetamol (Acetaminophen and Tylenol are brand names in the USA) or Cocodamol (Tylenol 3 in the USA) is that all of these drugs can be toxic to the liver in high doses. When first diagnosed with RA, I was taking 8 Cocodamol, 4 Iboprofen and 3 Gabapentin per day. This is 4,000mg of Paracetamol with 240mg of Codeine and 1600mg of Ibuprofen. My liver enzymes were off the charts and the docs kept asking how much I drink. I had to stop using Ibuprofen completely before I could start Methotrexate. Two injection of Prednisolone got the RA in check enough that I didn't need so much painkiller for the few months it took for the MTX and Hydroxychloroquine to kick in and relieve the RA. Nowadays I use Ibuprofen about 3 days a week, but I avoid it on MTX days. I have taken up swimming 3 days a week and I find this is the best thing yet for pain reduction.

As to how often to take Folic Acid when using MTX for RA, the variation reported here may be down to numerous factors ranging from each Rheumy's preference to each patient's dietary habits. Green leafy vegetables are high in folate, so people that eat a lot of kale and spinach might need less folic acid. If put on one dose a week, they may get on just fine, while others may need it 3 or even 6 days a week. Taking Folic Acid on your Methotrexate days is a waste of Folic Acid, but it won't harm you. It just won't be used by your body. Read on to see why.

The chemical structure of Methotrexate (MTX) and Folic Acid are very similar. You can see them together here: but don't get bogged down in the text because the web page is about MTX for chemotherapy against leukaemia. The structural similarity is why MTX works as a competitive inhibitor to normal Folic Acid metabolism and this is all you need to take away from the images of the molecular structure of each drug.

The important thing to bear in mind regarding Folic Acid is that it is necessary for normal cell division because it is a building block of DNA. Your body needs Folic Acid to synthesize DNA, repair DNA and to methylate DNA. Because it is necessary for DNA synthesis, a folic acid deficiency can lead to improper replication of DNA which can cause mutation of healthy cells into cancerous cells. MTX interferes with metabolism of Folic Acid and this is why it works as a chemotherapy agent. It just kills more newly forming cancer cells than normal cells because cancer cells replicate more rapidly. MTX also interferes with a few other metabolic processes having to do with nucleotides needed to make proteins for immune cells. This is believed to be the reason it works for treating RA.

To understand how MTX interferes, you need to know a few basic steps in the normal Folic Acid metabolism process that MTX interferes with. Your liver turns Folic Acid into Dihydrofolic Acid (DFA). Dihydrofolate Reductase (DHFR) then turns the Dihydrofolic Acid into Tetrahydrofolic Acid or THF. Tetrahydrofolic Acid is involved in the synthesis of dTMP (2′-deoxythymidine-5′-phosphate). While it is tempting to think of the 'deoxy' on the front of this thymidine as the deoxy in Deoxiribonucleic Acid (DNA), I don't understand the chemistry of DNA replication well enough to know for sure that this is the case, but dTMP is a substrate for an important reaction that is necessary for the synthesis of DNA, and so required for all dividing cells.

The reason Methotrexate interferes with the above process is simple. Dihydrofolate Reductase has about 1,000 times the affinity for Methotrexate as it does for Dihydrofolic Acid, so MTX is a competitive inhibitor. DHFR can not turn Methotrexate into Tetrahydrofolate (THF) the way it can do this with Dihydrofolate, but it tries really hard to do it. Without THF, DNA replication can't proceed as normal and this means MTX can both slow the replication of cancer cells and suppress the over production of immune system cells present in RA.

I have been taken MTX now for 8 years and I take folic acid once a day. I replaced prednisone with turmeric capsules. I take 2 a day. if I feel a flare up coming on my doctor said take ibuprofen instead of the prednisone. I really believe turmeric helps. prayers for you.

You may also like...