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Research · Medication

Methotrexate

In rheumatoid arthritis, weekly methotrexate raised major improvement against placebo, about 1 more responder per 7 treated, and injection under the skin did slightly better than tablets. It cleared psoriasis more than placebo but did not ease joint swelling in a psoriatic arthritis trial. Liver enzyme rises were common. Taking it daily instead of weekly has caused deaths.

Add to Bio HackChecked 2026-11-14
Status
Prescription drug in the US, taken by mouth once a week or injected under the skin, into a muscle or into a vein. FDA-approved at low weekly doses for rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and severe psoriasis, and at other doses for some cancers. The label carries an FDA boxed warning for embryo-fetal toxicity, hypersensitivity reactions, severe adverse reactions and fatal medication errors. Use in Crohn's disease and psoriatic arthritis is off-label.
Also called
methotrexate sodium, MTX, low-dose methotrexate, weekly methotrexate, Trexall, Otrexup, Rasuvo, Xatmep, Jylamvo, amethopterin, methotrexate injection
Taken for
rheumatoid arthritis, juvenile arthritis, psoriasis, psoriatic arthritis, Crohn's disease, inflammatory bowel disease, joint pain and swelling, autoimmune disease, eczema

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help5

Reported risks10

What people take it for, and what was found

Shown to help5

ModerateVery common

Rheumatoid arthritis

Shown to raise the share with a 50% improvement in rheumatoid arthritis about 3-fold against placebo at 52 weeks, about 1 more responder per 7 treated.

Compared with placebo [1]

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Methotrexate alone raised ACR50 response against placebo at 52 weeks (RR 3.0, 95% CI 1.5 to 6.0, number needed to treat 7), 15 more responders per 100 (95% CI 8 to 23). Physical function improved 0.27 points more on a 0 to 3 scale (number needed to treat 4) [1].
Population
732 people with rheumatoid arthritis who had failed earlier drugs such as gold or azathioprine, in 7 trials of 12 to 52 weeks at 5 to 25 mg a week [1].
Sources
[1]
Caveats
The trials are old and small, and enrolled people with long-standing disease [1].
Strong

Rheumatoid arthritis, injected under the skin compared with tablets

Shown in two meta-analyses to give slightly more 20% improvements and fewer gut side effects under the skin than the same weekly dose by mouth.

Compared with the same weekly dose of methotrexate by mouth [3][4][5]

The numbers and sources
Effect
In a double-blind trial of 15 mg a week, ACR20 at 24 weeks was reached by 78% under the skin and 70% by mouth, and ACR70 by 41% and 33%, with similar adverse event rates [3]. Pooling 7 studies, injection under the skin raised drug exposure, raised ACR20 (OR 1.68, 95% CI 1.09 to 2.61) and ACR70 (OR 1.52), and lowered nausea (OR 0.53) and diarrhea (OR 0.43), without a difference in ACR50 or treatment failure [4]. Pooling 9 RCTs, injection under the skin raised ACR20 (RR 1.15, 95% CI 1.05 to 1.25) and lowered gut adverse events (RR 0.58, 95% CI 0.40 to 0.83) and diarrhea (RR 0.42), with no difference in ACR70 or disease activity scores [5].
Population
375 adults with active RA new to methotrexate [3]; 1,335 patients in 7 studies [4]; 974 patients in 9 RCTs [5].
Sources
[3], [4], [5]
Caveats
The ACR50 benefit was not robust in [5] and not significant in [4]. Most trials were short.
ModerateVery common

Plaque psoriasis

Shown to raise 75% skin clearing against placebo in moderate to severe psoriasis, 41% against 10% at 16 weeks with injection under the skin, though biologics cleared more.

Compared with placebo injections [6]; placebo, biologics and other systemic drugs in a network analysis [7]

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In the METOP trial, PASI 75 at week 16 was reached by 41% on methotrexate under the skin starting at 17.5 mg a week and 10% on placebo (RR 3.93, 95% CI 1.31 to 11.81), with folic acid 5 mg a week in both arms. No one died or had serious infections, cancers or major cardiovascular events, and 3% had serious adverse events over 52 weeks [6]. In a network meta-analysis of 179 RCTs, non-biological systemic drugs including methotrexate reached PASI 90 more often than placebo, biologics more often than the non-biological drugs, and methotrexate did not differ from ciclosporin or apremilast [7].
Population
120 adults with moderate to severe plaque psoriasis new to methotrexate [6]; 62,339 adults in 179 RCTs [7].
Sources
[6], [7]
Caveats
METOP was small and funded by Medac, which makes an injectable methotrexate [6].
Moderate

Crohn's disease, injected into a muscle

Shown to raise remission against placebo when injected into a muscle weekly, while low-dose tablets did not differ from placebo in small trials.

Compared with placebo [10][11]; mercaptopurine, azathioprine and 5-ASA [10]

The numbers and sources
Effect
In one large trial, methotrexate 25 mg a week into a muscle lowered failure to enter remission and stop steroids, 61% against 81% on placebo (RR 0.75, 95% CI 0.61 to 0.93, number needed to treat 5). Three small trials of 12.5 to 15 mg a week by mouth found no difference from placebo or mercaptopurine [10]. For keeping remission, 65% on methotrexate into a muscle stayed in remission at 40 weeks against 39% on placebo (RR 1.67, 95% CI 1.05 to 2.67, number needed to treat 4) [11].
Population
495 adults with active refractory Crohn's disease in 7 studies [10]; 333 patients in 5 maintenance studies, 76 in the muscle-injection comparison [11].
Sources
[10], [11]
Caveats
The induction benefit rests on one trial, and the reviews judged most evidence low to moderate quality from sparse data [10][11]. Withdrawals for adverse events were 17% on methotrexate and 2% on placebo in that trial [10].
Moderate

Fewer side effects with added folic acid

Shown to cut nausea and other gut side effects by about 26% and liver enzyme rises by about 77% when folic or folinic acid is added in rheumatoid arthritis.

Compared with placebo added to methotrexate [12]

The numbers and sources
Effect
Adding low-dose folic or folinic acid (starting at 7 mg a week or less) lowered gut side effects such as nausea, vomiting or abdominal pain (RR 0.74, 95% CI 0.59 to 0.92, 9% absolute), abnormal serum transaminase rises (RR 0.23, 95% CI 0.15 to 0.34, 16% absolute) and withdrawal from methotrexate for any reason (RR 0.39, 95% CI 0.28 to 0.53). The fall in mouth sores was not significant (RR 0.72, 95% CI 0.49 to 1.06), and blood count effects could not be judged. Disease activity did not differ [12].
Population
624 adults with rheumatoid arthritis on methotrexate 25 mg a week or less in 6 double-blind RCTs [12].
Sources
[12]
Caveats
Moderate quality evidence, low for blood effects [12]. The labels direct folic or folinic acid for rheumatoid arthritis, juvenile arthritis and psoriasis, and say folate may reduce methotrexate's effect in cancer [13].

Mixed results1

Limited

Psoriatic arthritis

Mixed results: one trial found no joint benefit over placebo at 6 months but better skin and global scores, and another found fewer responders than on etanercept.

Compared with placebo tablets [8]; etanercept injections, with placebo [9]

The numbers and sources
Effect
In the MIPA trial, methotrexate 15 mg a week by mouth did not differ from placebo at 6 months on psoriatic arthritis response (OR 1.77, 95% CI 0.97 to 3.23), ACR20 (OR 2.00, 95% CI 0.65 to 6.22) or disease activity, joint counts, ESR or CRP. Patient and assessor global scores and skin scores improved [8]. In SEAM-PsA, ACR20 at 24 weeks was reached by 50.7% on oral methotrexate 20 mg a week, 60.9% on etanercept 50 mg weekly under the skin and 65.0% on both, and x-ray progression was greater on methotrexate alone [9].
Population
221 adults with active psoriatic arthritis [8]; 851 adults with psoriatic arthritis [9].
Sources
[8], [9]
Caveats
In [8], 44 people were lost to follow-up and missing data were imputed. SEAM-PsA had no placebo arm, so it cannot show the size of methotrexate's own effect [9].

Not shown to help1

Moderate

Rheumatoid arthritis, compared with combinations and biologics

Shown in a network analysis to give less major improvement alone than combined with other DMARDs or most biologics, about 41% against 56 to 67% in people new to methotrexate.

Compared with methotrexate with sulfasalazine and hydroxychloroquine, and methotrexate with biologics or tofacitinib [2]

The numbers and sources
Effect
In people new to methotrexate, the estimated chance of an ACR50 response was 41% on oral methotrexate alone and 56% to 67% on triple therapy (methotrexate with sulfasalazine and hydroxychloroquine), several biologics with methotrexate, or tofacitinib. After an inadequate response to methotrexate, triple therapy gave a 61% chance. Methotrexate with a TNF inhibitor slowed x-ray damage more than methotrexate alone, but by less than the smallest clinically important difference. Triple therapy led to fewer withdrawals for adverse events than methotrexate plus infliximab [2].
Population
158 randomized or quasi-randomized trials in adults with rheumatoid arthritis [2].
Sources
[2]
Caveats
Network estimates rest partly on indirect comparisons [2]. Most combinations include methotrexate itself.

Doses studied

The rheumatoid arthritis trials used 5 to 25 mg once a week [1], and the route trial used 15 mg once a week under the skin or by mouth [3]. The psoriasis trial used 17.5 mg a week under the skin, raised to 22.5 mg if needed, with folic acid 5 mg a week [6]. The psoriatic arthritis trials used 15 and 20 mg a week by mouth [8][9]. The Crohn's disease trials that found a benefit used 25 mg a week into a muscle for induction [10] and 15 mg a week into a muscle for maintenance [11]. The tablet label starts rheumatoid arthritis at 7.5 mg once weekly, says doses above 20 mg once weekly raise the risk of serious reactions including bone marrow suppression, and gives 10 to 25 mg once weekly for psoriasis, not above 30 mg [13]. Otrexup is a once-weekly auto-injector under the skin for rheumatoid arthritis, juvenile arthritis and psoriasis, not for cancer [14].

Risks

Reported risks9

LimitedStudied in pregnancyVery common

FDA boxed warning: harm to an unborn baby

The label warns methotrexate can cause embryo-fetal toxicity and fetal death and is contraindicated in pregnancy for non-cancer uses. One study found 42% miscarriage after exposure.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
First-trimester exposure is linked to miscarriage and to skull, face, brain, limb and sometimes heart defects. In a prospective study of women taking 30 mg a week or less after conception, miscarriage occurred in 42% (95% CI 29 to 59), against 22% in unexposed women with autoimmune disease and 17% in women without it. Major birth defects among live births were higher than in unexposed women with autoimmune disease (adjusted OR 1.8, 95% CI 0.6 to 6) and without it (adjusted OR 3.1, 95% CI 1 to 10). The label calls for pregnancy testing before starting and warns against breastfeeding during treatment and for 1 week after [13].
Population
Case reports, reviews and a prospective multicenter study summarized on the label [13].
Sources
[13]
Caveats
The label does not give the study's size or citation. Some birth defects after exposure did not match the known methotrexate pattern [13].
ModerateVery common

Raised liver enzymes and liver damage

Shown to raise liver enzymes about 2 to 2.6 times as often as other drugs in trials, with no rise in liver failure, cirrhosis or death over trial periods.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Across 32 double-blind trials, methotrexate raised total liver adverse events (RR 2.19, 95% CI 1.73 to 2.77), minor liver enzyme rises up to 3 times normal (RR 2.16) and major rises above 3 times normal or leading to withdrawal (RR 2.63, 95% CI 1.90 to 3.64). Liver failure, cirrhosis or death did not rise (RR 0.12, 95% CI 0.01 to 1.09) [18]. In placebo-controlled RA trials of 7.5 to 15 mg a week, elevated liver tests occurred in 15%. The label warns of fibrosis, cirrhosis and fatal liver failure, more likely with heavy alcohol use and higher cumulative doses, and that in psoriasis fibrosis may appear without symptoms or abnormal liver tests [13].
Population
13,177 participants with rheumatoid arthritis, psoriasis, psoriatic arthritis or bowel disease in 32 RCTs of at least 24 weeks [18]; 128 people with RA in 12- to 18-week placebo-controlled trials [13].
Sources
[18], [13]
Caveats
Heterogeneity was high for total and minor liver events (I² 68%), and trials were too short to judge long-term damage [18]. The label's 15% figure lacks a placebo rate in the text [13]. Added folic acid lowered transaminase rises [12].
ModerateCommon

Low blood counts

The label warns methotrexate can cause severe, life-threatening low blood counts. Low platelets occurred in 3 to under 10% in placebo-controlled arthritis trials.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In 12- to 18-week placebo-controlled RA trials of 7.5 to 15 mg a week, reactions above the placebo rate included thrombocytopenia (platelets under 100,000) at 3% to under 10%, and leukopenia (white cells under 3,000) and pancytopenia at 1% to under 3%. The label warns of severe and life-threatening pancytopenia, anemia, leukopenia, neutropenia and thrombocytopenia and calls for blood counts at baseline and during treatment [13].
Population
128 people with RA in placebo-controlled trials [13].
Sources
[13]
Caveats
Small, short trials with most people also taking NSAIDs [13].
ModerateCommon

Nausea, mouth sores and other gut effects

Shown to cause nausea or vomiting in about 10% and mouth sores in 3 to under 10% in arthritis trials. Injection under the skin lowered gut side effects against tablets.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In placebo-controlled RA trials, nausea or vomiting occurred in 10% and stomatitis in 3% to under 10%, and diarrhea, rash and hair loss in 1% to under 3%, all above placebo. The label reports hemorrhagic enteritis and fatal intestinal perforation [13]. Against tablets, injection under the skin lowered gut adverse events (RR 0.58, 95% CI 0.40 to 0.83) [5]. Added folic or folinic acid lowered gut side effects (RR 0.74) [12].
Population
128 people with RA [13]; 974 patients in 9 RCTs [5]; 624 patients in 6 RCTs [12].
Sources
[13], [5], [12]
Caveats
The label groups rates in bands, not exact figures [13].
ModerateCommon

Lung disease and pneumonitis

Shown to raise respiratory adverse events slightly, about 10%, and pneumonitis about 8-fold in RA trials, with no rise in deaths from lung disease.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Against other DMARDs and biologics, methotrexate raised all respiratory adverse events (RR 1.10, 95% CI 1.02 to 1.19) and respiratory infections (RR 1.11). In studies that described pneumonitis, risk rose (RR 7.81, 95% CI 1.76 to 34.72). Deaths from lung disease (RR 1.53, 95% CI 0.46 to 5.01) and noninfectious respiratory events did not rise [19]. In two RA trials of 680 people on 7.5 to 15 mg a week, interstitial pneumonitis occurred in 1%, and the label warns of irreversible or fatal pneumonitis [13].
Population
8,584 participants with RA in 22 double-blind RCTs of at least 24 weeks [19]; 680 people with RA [13].
Sources
[19], [13]
Caveats
The pneumonitis estimate rests on few events and a wide interval [19].
LimitedHow often is not known

FDA boxed warning: fatal errors from daily instead of weekly dosing

The label warns that methotrexate taken once daily by mistake has resulted in death, mostly when weekly dosing was prescribed. Reported errors often ended in serious harm.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The boxed warning states that methotrexate tablets inadvertently taken once daily have resulted in death, and the label says these errors most often occurred in people taking it daily when a weekly regimen was prescribed [13]. Of 106 medication errors reported to FDA from 1997 to 2001, 25 (24%) ended in death and 48 (45%) in other serious outcomes, and confusion about the once-weekly schedule was the most common error (30%) [15]. In 74 French cases, 70 people took it daily for a mean 11.7 days, 62.2% had severe complications and 9 of 61 with complications died [16]. Of 111 calls to a US poison center, most dosing errors came from taking it more often than prescribed, 36% were admitted and 2 people died [17].
Population
Reports to FDA [15]; French poison control and pharmacovigilance cases [16]; a US poison center, 2009 to 2019 [17].
Sources
[13], [15], [16], [17]
Caveats
Case series of reported errors cannot give a rate among people taking methotrexate. The European Medicines Agency's 2019 measures on dosing errors could not be read, because its site refused the request.
ModerateHow often is not known

Infections

Shown to raise infections about 25% against placebo in rheumatoid arthritis, but not in other inflammatory diseases, and serious infections did not rise.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Against placebo, methotrexate raised infections in RA (RR 1.25, 95% CI 1.01 to 1.56). Across all included diseases, total infections (RR 1.14, 95% CI 0.98 to 1.34) and serious infections (RR 0.76, 95% CI 0.11 to 5.15) did not rise [20]. The label warns of life-threatening or fatal infections, including Pneumocystis pneumonia, hepatitis B reactivation, tuberculosis and disseminated shingles, and advises against live vaccines during treatment [13].
Population
1,146 adults with inflammatory rheumatic diseases in 12 RCTs, 906 for serious infection [20].
Sources
[20], [13]
Caveats
Few trials and short follow-up [20].
LimitedHow often is not known

Severe skin reactions and allergic reactions

The label warns of severe and sometimes fatal skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, and of anaphylaxis.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label lists toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin necrosis and erythema multiforme, radiation recall and sunburn reactivation. A history of severe hypersensitivity, including anaphylaxis, is a contraindication in the boxed warning [13].
Population
Postmarketing and trial reports on the label [13].
Sources
[13]
Caveats
The label gives no rate [13].
LimitedHow often is not known

With antibiotics, NSAIDs and acid reducers

The label warns that some antibiotics, NSAIDs, aspirin and proton pump inhibitors can raise methotrexate levels and toxicity. Reviews found few major problems with NSAIDs at low doses.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label lists oral antibiotics, penicillins and sulfonamides including trimethoprim-sulfamethoxazole, aspirin and other NSAIDs, proton pump inhibitors, probenecid and other drugs that may raise methotrexate levels, and warns against nitrous oxide anesthesia [13]. An FDA review of adverse event reports and case reports found proton pump inhibitors such as omeprazole may slow methotrexate clearance, mainly at high doses, and FDA added this to the label [22]. A Cochrane review of 17 studies in RA found no added lung, liver or kidney harm or major toxic reactions with NSAIDs and low-dose methotrexate, transient low platelets in 1 study, and liver and kidney effects with anti-inflammatory doses of aspirin [23].
Population
Label [13]; FDA adverse event reports and case reports [22]; 17 publications in people with RA [23].
Sources
[13], [22], [23]
Caveats
The proton pump inhibitor evidence is mostly case reports at high doses [22].

Mixed results1

ModerateHow often is not known

Skin cancer and lymphoma

Linked to a small rise in melanoma, about 15%, that did not hold when the largest study was removed. The label warns of lymphoma that may regress after stopping.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Against unexposed people, low-dose methotrexate was linked to melanoma (pooled RR 1.15, 95% CI 1.08 to 1.22), falling to 1.11 (95% CI 1.00 to 1.24) without the largest study, with a number needed to harm of 18,630 in Australia [21]. The label warns of secondary cancers, says lymphoproliferative disease during low-dose treatment has sometimes regressed fully after withdrawal, and says skin cancer risk rises further with ciclosporin after methotrexate in psoriasis [13].
Population
12 studies with 16,642 melanoma cases, from 8 RCTs, 5 cohort and 4 case-control studies [21]; label [13].
Sources
[21], [13]
Caveats
Mostly observational, and the result was sensitive to one study [21].

Claims tested and not found

  1. That folic acid blunts methotrexate's effect in rheumatoid arthritis. Disease activity, including tender and swollen joint counts, did not differ with folic or folinic acid against placebo in 6 RCTs [12].
  2. That low-dose methotrexate tablets bring Crohn's disease into remission. Three small trials of 12.5 to 15 mg a week by mouth found no difference from placebo or mercaptopurine [10].
  3. That methotrexate eases joint inflammation in psoriatic arthritis. In a 221-person placebo-controlled trial, response criteria, ACR20, joint counts, ESR and CRP did not differ at 6 months [8].

Sources

  1. Lopez-Olivo MA, Siddhanamatha HR, Shea B, et al. Methotrexate for treating rheumatoid arthritis. Cochrane Database of Systematic Reviews. 2014. https://doi.org/10.1002/14651858.cd000957.pub2
  2. Hazlewood GS, Barnabe C, Tomlinson G, et al. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis. BMJ. 2016. https://doi.org/10.1136/bmj.i1777
  3. Braun J, Kästner P, Flaxenberg P, et al. Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthritis & Rheumatism. 2008. https://doi.org/10.1002/art.23144
  4. Li D, Yang Z, Kang P, Xie X. Subcutaneous administration of methotrexate at high doses makes a better performance in the treatment of rheumatoid arthritis compared with oral administration of methotrexate: A systematic review and meta-analysis. Seminars in Arthritis and Rheumatism. 2016. https://doi.org/10.1016/j.semarthrit.2015.11.004
  5. Li G, Xie W, Liu J, et al. Subcutaneous methotrexate compared with oral methotrexate in rheumatoid arthritis: a systematic review and meta-analysis. Frontiers in Immunology. 2026. https://doi.org/10.3389/fimmu.2026.1816269
  6. Warren RB, Mrowietz U, von Kiedrowski R, et al. An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2017. https://doi.org/10.1016/s0140-6736(16)32127-4
  7. Sbidian E, Chaimani A, Guelimi R, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database of Systematic Reviews. 2023. https://doi.org/10.1002/14651858.cd011535.pub6
  8. Kingsley GH, Kowalczyk A, Taylor H, et al. A randomized placebo-controlled trial of methotrexate in psoriatic arthritis. Rheumatology. 2012. https://doi.org/10.1093/rheumatology/kes001
  9. Mease PJ, Gladman DD, Collier DH, et al. Etanercept and Methotrexate as Monotherapy or in Combination for Psoriatic Arthritis: Primary Results From a Randomized, Controlled Phase III Trial. Arthritis & Rheumatology. 2019. https://doi.org/10.1002/art.40851
  10. McDonald JW, Wang Y, Tsoulis DJ, et al. Methotrexate for induction of remission in refractory Crohn's disease. Cochrane Database of Systematic Reviews. 2014. https://doi.org/10.1002/14651858.cd003459.pub4
  11. Patel V, Wang Y, MacDonald JK, et al. Methotrexate for maintenance of remission in Crohn's disease. Cochrane Database of Systematic Reviews. 2014. https://doi.org/10.1002/14651858.cd006884.pub3
  12. Shea B, Swinden MV, Tanjong Ghogomu E, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database of Systematic Reviews. 2013. https://doi.org/10.1002/14651858.cd000951.pub2
  13. Trexall (methotrexate) tablets, for oral use, prescribing information (Teva Women's Health). 2026. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e942f8db-510f-44d6-acb5-b822196f5e8c
  14. Otrexup (methotrexate) injection, for subcutaneous use, prescribing information (Antares Pharma). 2025. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9ab8ce16-f7de-41d4-a4c8-1c742621b6d5
  15. Moore TJ, Walsh CS, Cohen MR. Reported medication errors associated with methotrexate. American Journal of Health-System Pharmacy. 2004. https://doi.org/10.1093/ajhp/61.13.1380
  16. Vial T, Patat AM, Boels D, et al. Adverse consequences of low-dose methotrexate medication errors: data from French poison control and pharmacovigilance centers. Joint Bone Spine. 2019. https://doi.org/10.1016/j.jbspin.2018.09.006
  17. Thompson JA, Love JS, Hendrickson RG. Methotrexate Toxicity from Unintentional Dosing Errors: Calls to a Poison Center and Death Descriptions. Journal of the American Board of Family Medicine. 2021. https://doi.org/10.3122/jabfm.2021.06.210120
  18. Conway R, Low C, Coughlan RJ, et al. Risk of liver injury among methotrexate users: A meta-analysis of randomised controlled trials. Seminars in Arthritis and Rheumatism. 2015. https://doi.org/10.1016/j.semarthrit.2015.05.003
  19. Conway R, Low C, Coughlan RJ, et al. Methotrexate and lung disease in rheumatoid arthritis: a meta-analysis of randomized controlled trials. Arthritis & Rheumatology. 2014. https://doi.org/10.1002/art.38322
  20. Ibrahim A, Ahmed M, Conway R, Carey JJ. Risk of Infection with Methotrexate Therapy in Inflammatory Diseases: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2018. https://doi.org/10.3390/jcm8010015
  21. Yan MK, Wang C, Wolfe R, et al. Association Between Low-Dose Methotrexate Exposure and Melanoma: A Systematic Review and Meta-analysis. JAMA Dermatology. 2022. https://doi.org/10.1001/jamadermatol.2022.3337
  22. Bezabeh S, Mackey AC, Kluetz P, et al. Accumulating evidence for a drug-drug interaction between methotrexate and proton pump inhibitors. The Oncologist. 2012. https://doi.org/10.1634/theoncologist.2011-0431
  23. Colebatch AN, Marks JL, van der Heijde DM, Edwards CJ. Safety of nonsteroidal antiinflammatory drugs and/or paracetamol in people receiving methotrexate for inflammatory arthritis: a Cochrane systematic review. The Journal of Rheumatology Supplement. 2012. https://doi.org/10.3899/jrheum.120345

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