methotrexate
Regulatory sources consulted
Approved indications
- Oncologic treatment of solid tumors and hematologic malignancies through multiple routes and regimens, plus selected non-oncologic indications.
Contraindications
Absolute
- Hypersensitivity; bilirubin >5 mg/dL; alcoholism; CrCl <30 mL/min; blood dyscrasias or immunodeficiency.
- Severe acute or chronic infections; stomatitis, oral ulcers, or active gastrointestinal ulcerative disease; breastfeeding; live vaccines; pregnancy for non-oncologic indications.
Clinical warnings
- For arthritis, JIA, psoriasis, and psoriatic arthritis it is given once weekly. Daily-dosing errors have caused fatal toxicity. — CIMA/AEMPS, ficha técnica 62121
- For high doses, provide folinic-acid rescue when indicated, hydration, and urinary alkalinization to prevent tubular precipitation. Monitor blood counts, kidneys, liver, lungs, and mucosa. — CIMA/AEMPS, ficha técnica 62121
Drug interactions
- HighNSAIDs, salicylates, TMP-SMX, or sulfonamides
Mechanism: They may reduce elimination, displace binding, or add hematologic and renal toxicity.
Recommendation: Avoid especially with high doses or monitor exposure, renal function, and blood counts.
CIMA/AEMPS, ficha técnica 62121
- HighPenicillins or other antibiotics that reduce clearance
Mechanism: They may increase methotrexate exposure and toxicity.
Recommendation: Avoid or closely monitor concentrations and toxicity.
CIMA/AEMPS, ficha técnica 62121
- HighHepatotoxic drugs or cyclosporine
Mechanism: They may increase hepatic, renal, or immunosuppressive toxicity.
Recommendation: Avoid when possible or intensify monitoring.
CIMA/AEMPS, ficha técnica 62121
Pregnancy and lactation
It may cause fetal harm. Exclude pregnancy before treatment and repeat testing when clinically indicated. In non-oncologic indications it is contraindicated during pregnancy. Women must use contraception during treatment and for at least 6 months afterward. Men must use contraception and not donate semen during treatment or for at least 3 months afterward. Do not breastfeed.
Recent literature (PubMed)
Rheumatoid arthritis is the most common autoimmune, destructive, inflammatory arthritis in adults. Effective treatments include oral conventional synthetic disease-modifying antirheumatic drugs (DMARDs; eg, methotrexate), injectable biologic DMARDs, and targeted synthetic DMARDs (oral). Key recommendations are to start effective treatment immediately with DMARDs to reduce disability; use effective doses of methotrexate (oral or subcutaneous) with folic acid as the initial treatment; rapidly escalate treatment with various DMARDs, if methotrexate alone is not effective in controlling rheumatoid arthritis; and aim for a treat-to-target strategy with a goal of low disease activity or remission by frequently monitoring disease activity and escalating treatment.
Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. We sought to systematically synthesize the benefits and harms of AD systemic treatments. For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna). The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among
Prednisone is currently recommended as the first-line treatment for pulmonary sarcoidosis but is associated with many side effects. Methotrexate, which is recommended as a second-line treatment, appears to have fewer side effects than prednisone but a slower onset of action. Data are needed on the efficacy and side-effect profile of methotrexate as compared with prednisone as first-line treatment for pulmonary sarcoidosis. In this multicenter, open-label, noninferiority trial involving patients with pulmonary sarcoidosis who had not previously received treatment, we randomly assigned patients, in a 1:1 ratio, to receive prednisone or methotrexate according to a prespecified treatment schedule. The primary end point was the mean change from baseline to week 24 in the percentage of the predicted forced vital capacity (FVC), as estimated with the use of mixed models for repeated measures. The noninferiority margin for the primary end point was 5 percentage points. Of the 138 patients who underwent randomization, 70 were assigned to receive prednisone and 68 to receive methotrexate. The unadjusted mean change from baseline to week 24 in the percentage of the predicted FVC was 6.75 percentage points (95% confidence interval [CI], 4.50 to 8.99) in the prednisone group and 6.11 percentage points (95% CI, 3.72 to 8.50) in the methotrexate group. Methotrexate was noninferior to prednisone with regard to the primary end point, with an adjusted between-group difference of -1.17 percentage points (95% CI, -4.27 to 1.93). Adverse events occurred in a similar percentage of patients in the two trial groups. Weight gain, insomnia, and increased appetite were the most common adverse events with prednisone, and nausea, fatigue, and any abnormal liver-function test were among the most common adverse events with methotrexate. In patients with pulmonary sarcoidosis, initial treatment with methotrexate was noninferior to that with prednisone with regard to the change from baseline to wee
Ectopic pregnancy occurs in 2% of all pregnancies and is a potentially life-threatening emergency. A high level of clinical suspicion is required for any pregnant patient who presents with vaginal bleeding and/or pelvic pain. Workup should begin with immediate triage based on vital signs, a pregnancy test, and transvaginal ultrasound. Ectopic pregnancy can be treated either medically with methotrexate or surgically with either salpingectomy or salpingostomy. Carefully counseled, asymptomatic patients may be candidates for expectant management. This sheet is about exposure to methotrexate in pregnancy and while breastfeeding. This information is based on available research studies. It should not take the place of medical care and advice from your healthcare provider.