NSAIDS with methotrexate?

Are any NSAIDS ok to take with low dose methotrexate?

I hurt my back and have been taking ibuprofen but just started a low dose of methotrexate and when I check for drug interactions it states that methotrexate interacts with ibuprofen. I think I read on this site that someone was taking methotrexate and aleve (ibuprofen) Any suggestions? Thanks!

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I take methotrexate and generic Aleve (Naproxen Sodium). Aleve and Ibuprofen are both NSAIDS but not the same thing. I used to take Ibuprofen but it was hard on my stomach. My doctor switched me to Aleve and have had very good luck with it. It took about a week to build up in my system so that I could really tell it was working. I also take Plaquenil which is an anti-inflammatory. I have sarcoidosis and arthritis.
Ask your doctor, but I would vote for Aleve - maybe 2 tabs am and pm for about a week and then taper off to 1 tab am and pm. Then you may be able to get off when your back feels better. Good Luck. Hannah

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I'm on mtx 15 mg weekly. I have a horrible time when it rains or snows. My inflammation goes nuts. As I have acid reflux, my doctor prescribed me meloxicam 15 mg. It's a NSAID. I have been told to take one a day, but I only take it on my bad days as it does a number on my stomach for multiple days. I was cautioned only to take tynenol for pain on days that I take meloxicam. I hope this helps.

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My pharmacist, who I've trusted for years, said to stay away from Advil and Aleve. Tylenol..acetaminophen, is the only recommended pain reliever to take with MTX.

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I also understood that you couldn't take ibuprofen with MTX. I was on MTX for a short while. I found a few comments regarding it .... In a nutshell, MTX is toxic and to mix it with drugs such as NSAIDs or antibiotics potentiates the toxcity. The Kidneys cannot clear the it as rapidly as the single drug and thus it increases the risk of the patient developing gastrointestinal, lung, kidney and bone marrow suppression problems.
The main worry with MTX is aplastic anemia. I had a mild kidney problem (no doubt as a result of sarc) when I went on it myself, and I had renal symptoms while on it. Glad I stopped taking it.

''Aspirin, NSAIDs, and/or low dose steroids may be continued, although the possibility of increased toxicity with concomitant use of NSAIDs including salicylates has not been fully explored (see PRECAUTIONS: DRUG INTERACTIONS.). ''

''Although a clinically significant interaction does not occur in all patients, numerous case reports are available that demonstrate possible problems following the coadministration of MTX and NSAIDs. To date, the specific circumstances during which the reaction may occur have not been well defined.

Especially at high MTX dosages, severe adverse effects with this combination may occur, usually resulting from an impaired renal elimination. It has been shown that the mechanism of this interaction cannot be fully attributed to inhibition of basolateral MTX uptake in renal proximal tubules. Here, we studied the effect of various NSAIDs on MTX transport in membrane vesicles isolated from cells overexpressing the proximal tubular apical efflux transporters human multidrug resistance protein (MRP) 2/ABCC2 and MRP4/ABCC4. MTX was transported by MRP2 and MRP4 with Km values of 480 ± 90 and 220 ± 70 μM, respectively. The inhibitory potency of the NSAIDs was generally higher against MRP4- than MRP2-mediated MTX transport, with therapeutically relevant IC50 values, ranging from approximately 2 μM to 1.8 mM. Salicylate, piroxicam, ibuprofen, naproxen, sulindac, tolmetin, and etodolac inhibited MRP2- and MRP4-mediated MTX transport according to a one-site competition model. In some cases, more complex interaction patterns were observed. Inhibition of MRP4 by diclofenac and MRP2 by indomethacin and ketoprofen followed a two-site competition model. Phenylbutazone stimulated MRP2 and celecoxib MRP4 transport at low concentrations and inhibited both transporters at high concentration. Our data suggest that the inhibition by NSAIDs of renal MTX efflux via MRP2 and MRP4 is a potential new site and mechanism contributing to the overall interaction between these drugs.''

Results: Among 4,583 (57.6%) exposed and 3,372 (42.4%) nonexposed patients, nonsteroidal anti-inflammatory drugs and antibiotics were the most common drugs with potential interactions. The exposed patients had significantly greater risks of developing renal [adjusted odds ratio (OR): 2.58; p = 0.0145], gastrointestinal (OR: 1.36; p = 0.0197) and pulmonary events (OR: 1.20; p = 0.0470), and significantly greater health care resource utilization (e.g. OR for inpatient and emergency department visits: 1.47; p < 0.0001) and costs (adjusted incremental cost: USD 1,722; p < 0.0001). Conclusions: MTX/CYC polypharmacy is prevalent in patients with psoriasis and associated with significant risks.

Hope this helps. Problems don't occur with many patients when the dosages of both drugs are low.


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Definately check w/your doc to be sure. But I am also on Mtx (15mg/wk) & I DO know it's imperative that you are also on folic acid while taking it (except day you take pills). It is a folic acid sparing drug. I also know that it can affect your liver, that's why they will frequently check your liver enzymes too. Tylenol can also affect the liver, so you can't take large doses (which is probably the only amount that would help-doesn't do a thing for me ; (. I would ask your pharmacist too about which NSAID/pain reliever would be least toxic for you. I'm sorry you are suffering. I take prescription-Norco for pain, which contains low dose of tylenol/acetominophen (325mg) & hydrocodone (10mg). My liver counts are slightly elevated. Hope you get some relief soon.-Jayne

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Hi i am on 25mg methatrexate and on 30/500 co/codamol if i have a headache or anything i do take ibebrufen with no side affects i hope this helps.

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I take 20. of MTX weekly with folic acid. I also have a lot of joint pain some may be sarcoid related but some is just artheritis. I read the warnings about ibuprofen but asked my Dr and he said OK take it. I have the lab work done every three months and have not seen any difference from having taken it.
I think it would be best not to take it but if you are in pain and cant get around without it, you have to weigh the benefits against damage done. I am trying to taper off but sometimes I can barely move in the morning if I don't take the ibuprofen.

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Hi Sunny,

My rheumie recommended Aleve (NSAID) and I have to say, I have no toxic med interactions and do get much relief from it. I'm also on Pred and MTX. Everyone is different. If you are high dose anti inflammatories it is not unreasonable to try half the recommended dose of Aleve which may be all you need for significant relief. I think Pippin is right and that is true about all the drugs we take - to weigh the benefits against the risks. Your body will tell you when it can't tolerate the drug.


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Being on anti-epileptic meds for the last 10 years as well as all the sarcoid meds, I'm always very careful to check with doctors & pharmacists about drug interactions. I also work in the health industry & have access to prescriber's information handbooks, for which I am very thankful also.
I'm especially careful to check for interactions between prescribed meds & over-the-counter drugs, which many doctors forget about.

I'm now coming off MTX after almost 3 years and during that time I've had 2 doctors and a pharmacist warn me against using ANY NSAIDs, because together they can cause terrible stomach problems. I don't mean the short-term nausea & diarrhoea that MTX brings, I mean things like gastric reflux gradually increasing to ulcers and more.

These things take time to develop, so although you may not seem to get "toxic med interactions" when you take the pills, the damage is happening. Remember, not all interactions mean immediate problems - rashes, anaphylaxis, fits or whatever. They very, very often silently cause slow, insidious & sometimes irreversible damage.

Personally I prefer the thought of the mild damage that I know is being done by taking acetaminophen with my anti-epileptic meds than the possibilities of my (currently) mild gastric reflux becoming a bleeding ulcer by mixing NSAIDs with MTX.

TAKE NOTE: Pharmacists will very often know a lot more than doctors about drug interactions - they spend years studying exactly that at university, while it makes up a very small percentage of a medical degree.!

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I've been told not to take Aleve or Advil. I had a bad eye ache and took three doses of Tylenol extra strength in one day. It took away the pain but next day, when I had my blood taken, my liver levels went up. I'm on MTX 25MG.

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Hi Ruth,

You make a good point. Toward the end of her life my Mom developed a ruptured peptic ulcer from taking an ASA/day. She had never been advised to take the enteric coated type to help prevent that from happening. In her mind taking an aspirin was better than taking coumadin forever after heart surgery.

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Wow! Thanks for all the great information and sharing! I saw my rheumy yesterday and he said it's OK to take ibuprofen. He said the info says not to, but that it's OK. I will certainly the minimum amount so as to prevent any bleeding ulcers or other stomach problems.

Aleve makes me feel nauseous so I'd rather stay away from that and yes, because methotrexate is hard on the liver I think Tylenol should also be kept at a minimum. Thanks again for all the great info!

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