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METHOTREXATE SHOULD BE USED ONLY BY PHYSICIANS WHOSE KNOWLEDGE AND EXPERIENCE INCLUDE THE USE OF ANTIMETABOLITE THERAPY.
BECAUSE OF THE POSSIBILITY OF SERIOUS TOXIC REACTIONS (WHICH CAN BE FATAL):
- METHOTREXATE SHOULD BE USED ONLY IN LIFE THREATENING NEOPLASTIC DISEASES, OR IN PATIENTS WITH PSORIASIS OR RHEUMATOID ARTHRITIS WITH SEVERE, RECALCITRANT, DISABLING DISEASE WHICH IS NOT ADEQUATELY RESPONSIVE TO OTHER FORMS OF THERAPY.
- DEATHS HAVE BEEN REPORTED WITH THE USE OF METHOTREXATE IN THE TREATMENT OF MALIGNANCY, PSORIASIS, AND RHEUMATOID ARTHRITIS.
- PATIENTS SHOULD BE CLOSELY MONITORED FOR BONE MARROW, LIVER, LUNG AND KIDNEY TOXICITIES. (See PRECAUTIONS.)
- PATIENTS SHOULD BE INFORMED BY THEIR PHYSICIAN OF THE RISKS INVOLVED AND BE UNDER A PHYSICIAN'S CARE THROUGHOUT THERAPY.
- Methotrexate has been reported to cause fetal death and/or congenital anomalies. Therefore, it is not recommended for women of childbearing potential unless there is clear medical evidence that the benefits can be expected to outweigh the considered risks. Pregnant women with psoriasis or rheumatoid arthritis should not receive methotrexate. (See CONTRAINDICATIONS.)
- Methotrexate elimination is reduced in patients with impaired renal function, ascites, or plural effusions. Such patients require especially careful monitoring for toxicity, and require dose reduction or, in some cases, discontinuation of methotrexate administration.
- Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and gastrointestinal toxicity have been reported with concomitant administration of methotrexate (usually in high dosage) along with some nonsteroidal anti-inflammatory drugs (NSAIDs). (See PRECAUTIONS: Drug Interactions.)
- Methotrexate causes hepatotoxicity, fibrosis, and cirrhosis, but generally only after prolonged use. Acutely, liver enzyme elevations are frequently seen. These are usually transient and asymptomatic, and also do not appear predictive of subsequent hepatic disease. Liver biopsy after sustained use often shows histologic changes, and fibrosis and cirrhosis have been reported; these latter lesions may not be preceded by symptoms or abnormal liver function tests in the psoriasis population. For this reason, periodic liver biopsies are usually recommended for psoriatic patients who are under long-term treatment. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in the rheumatoid arthritis population. (See PRECAUTIONS; Organ System Toxicity: Hepatic)
- Methotrexate-induced lung disease is a potentially dangerous lesion, which may occur acutely at any time during therapy and which has been reported at doses as low as 7.5 mg/week. It is not always fully reversible. Pulmonary symptoms (especially a dry, nonproductive cough) may require interruption of treatment and careful investigation.
- Diarrhea and ulcerative stomatitis require interruption of therapy; otherwise, hemorrhagic enteritis and death from intestinal perforation may occur.
- Malignant lymphomas, which may regress following withdrawal of methotrexate, may occur in patients receiving low-dose methotrexate and, thus, may not require cytotoxic treatment. Discontinue methotrexate first and, if the lymphoma does not regress, appropriate treatment should be instituted.
- Like other cytoxic drugs, methotrexate may induce “tumor lysis syndrome” in patients with rapidly growing tumors. Appropriate supportive and pharmacologic measures may prevent or alleviate this complication.
- Severe, occasionally fatal, skin reactions have been reported following single or multiple doses of methotrexate. Reactions have occurred within days of oral, intramuscular, intravenous, or intrathecal methotrexate administration. Recovery has been reported with discontinuation of therapy. (See PRECAUTIONS; Organ System Toxicity: Skin.)
- Potentially fatal opportunistic infections, especially Pneumocystis carinii pneumonia, may occur with methotrexate therapy.
- Methotrexate given concomitantly with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis.
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METHOTREXATE SUMMARY
METHOTREXATE Tablets USP, 2.5 mg
Each tablet contains methotrexate sodium equivalent to:
Methotrexate. .. .. .. .. . 2.5 mg
Methotrexate is an antimetabolite used in the treatment of certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis.
Neoplastic Diseases
Methotrexate is indicated in the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole.
Methotrexate is used in maintenance therapy in combination with other chemotherapeutic agents.
Methotrexate is used alone or in combination with other anticancer agents in the treatment of breast cancer, epidermoid cancers of the head and neck, advanced mycosis fungoides (cutaneous T cell lymphoma) and lung cancer, particularly squamous cell and small cell types. Methotrexate is also used in combination with other chemotherapeutic agents in the treatment of advanced stage non-Hodgkin’s lymphomas.
Psoriasis
Methotrexate is indicated in the symptomatic control of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy, but only when the diagnosis has been established, as by biopsy and/or after dermatologic consultation. It is important to ensure that a psoriasis “flare” is not due to an undiagnosed concomitant disease affecting immune responses.
Rheumatoid Arthritis including Polyarticular-Course Juvenile Rheumatoid Arthritis
Methotrexate is indicated in the management of selected adults with severe, active, rheumatoid arthritis (ACR criteria), or children with active polyarticular-course juvenile rheumatoid arthritis, who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose nonsteroidal anti-inflammatory agents (NSAIDs).
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.) Steroids may be reduced gradually in patients who respond to methotrexate. Combined use of methotrexate with gold, penicillamine, hydroxychloroquine, sulfasalazine, or cytotoxic agents, has not been studied and may increase the incidence of adverse effects. Rest and physiotherapy as indicated should be continued.
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NEWS HIGHLIGHTSMedia Articles Related to Methotrexate
ACR: Tocilizumab Protects Joints Better than Methotrexate Alone (CME/CE)
Source: MedPage Today Rheumatology [2009.10.23]
PHILADELPHIA (MedPage Today) -- The investigational biologic agent tocilizumab appeared to prevent joint erosion among rheumatoid arthritis patients better than treatment with methotrexate alone, researchers said here.
Adalimumab plus methotrexate effective for rheumatoid arthritis
Source: The Doctors Lounge - Rheumatology
Adalimumab and methotrexate is about five times more effective than methotrexate alone, according to a new systematic review of studies.
Tocilizumab Shows Sustained Efficacy In Rheumatoid Arthritis
Source: Arthritis / Rheumatology News From Medical News Today [2009.10.23]
PHILADELPHIA - Investigators are reporting that tolicizumab is an effective, long-term treatment option in multiple subgroups of rheumatoid arthritis (RA) patients. These include patients who have an inadequate response to disease-modifying anti-rheumatic drugs (DMARD-IR), patients who have an inadequate response to anti-TNF inhibitors (TNF-IR), and patients who have not failed methotrexate.
EADV: Benefit of Methrotrexate in Psoriasis Will Show Up Early (CME/CE)
Source: MedPage Today Dermatology [2009.10.14]
BERLIN (MedPage Today) -- A suboptimal response to methotrexate at 12 weeks identified psoriasis patients who were unlikely to benefit from continued therapy at higher doses, a retrospective analysis of clinical-trial data showed.
Published Studies Related to Methotrexate
Evaluation of two strategies (initial methotrexate monotherapy vs its combination with adalimumab) in management of early active rheumatoid arthritis: data from the GUEPARD trial. [2009.11]
Objectives. In early and active RA despite MTX, continuous treatment with TNF blockers in combination with MTX is recommended.Initial combination of MTX and ADA and then an adjusted based on the disease activity status achieved a faster control of disease activity but did not increase the number of patients for whom anti-TNF-alpha treatment was not needed after 12 weeks nor a better subsequent clinical or radiological outcome than a 3-month delayed initiation of anti-TNF in patients with still active disease despite MTX.
Uracil-tegafur and tamoxifen vs cyclophosphamide, methotrexate, fluorouracil, and tamoxifen in post-operative adjuvant therapy for stage I, II, or IIIA lymph node-positive breast cancer: a comparative study. [2009.08.18]
BACKGROUND: It has been reported that treatment with uracil-tegafur (UFT) has shown significantly better survival and relapse-free survival (RFS) than surgery alone. Therefore, we compared UFT with a combination therapy of cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients who had undergone curative surgery for axillary lymph node-positive breast cancer... CONCLUSION: UFT administered in combination with TAM holds promise in the treatment of lymph node-positive early breast cancer. On stratified analysis, the recurrence rate in the UFT group was found to be better in oestrogen receptor (ER)-positive patients. Tegafur-based treatment should be evaluated by a prospective randomised trial conducted in ER-positive patients.
Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. [2009.08.08]
BACKGROUND: New treatment strategies for early rheumatoid arthritis are evolving rapidly. We aimed to compare addition of conventional disease-modifying antirheumatic drugs (sulfasalazine and hydroxychloroquine) with addition of a tumour necrosis factor antagonist (infliximab) to methotrexate in patients with early rheumatoid arthritis... INTERPRETATION: In patients with early rheumatoid arthritis in whom methotrexate treatment failed, addition of a tumour necrosis factor antagonist to methotrexate monotherapy is clinically superior to addition of conventional disease-modifying antirheumatic drugs. FUNDING: Swedish Rheumatism Association, Schering-Plough.
Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. [2009.08]
OBJECTIVE: To assess the safety and efficacy of golimumab in methotrexate (MTX)-naive patients with active rheumatoid arthritis (RA)... CONCLUSION: Although the primary end point was not met, the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than, and the efficacy of golimumab alone is similar to, the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients, with no unexpected safety concerns.
Uterine artery embolization compared with methotrexate for the management of pregnancy implanted within a cesarean scar. [2009.08]
OBJECTIVE: The objective of the study was to compare the efficacy and safety of uterine artery embolization (UAE) vs systemic methotrexate (MTX) for pregnancy within a cesarean scar... CONCLUSION: For pregnancy within a cesarean scar, UAE followed by suction curettage appears to have more advantage and may be a priority option.
Clinical Trials Related to Methotrexate
Treatment of Early RA: Minocycline in Combination With Methotrexate vs Methotrexate Alone [Completed]
The purpose of this study is to determine if a combination of methotrexate and minocycline
works better than methotrexate alone in early Rheumatoid Arthritis
Abatacept and Infliximab in Combination With Methotrexate in Subjects With Rheumatoid Arthritis [Completed]
The purpose of this clinical research study is to learn if Abatacept in combination with
Methotrexate and Infliximab demonstrate a greater reduction in disease activity over
placebo.
Study Comparing Etanercept and Methotrexate vs. Methotrexate Alone in Rheumatoid Arthritis [Active, not recruiting]
To compare the effects of the combination of ETN and MTX to MTX alone on radiographic change
and clinical disease activity in subjects with early RA over 12 months.
A Study of the Safety and Efficacy of Golimumab in Subjects With Rheumatoid Arthritis That Are Methotrexate-Naive [Active, not recruiting]
The purpose of this study is to evaluate the efficacy and safety of golimumab, alone or in
combination with methotrexate, as compared to methotrexate alone in rheumatoid arthritis
subjects who have not been previously treated with methotrexate.
Remicade Study in Psoriatic Arthritis Patients Of Methotrexate-Naïve Disease (RESPOND) (Study P04422AM1)(COMPLETED) [Completed]
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PATIENT REVIEWS / RATINGS / COMMENTSBased on a total of 10 ratings/reviews, Methotrexate has an overall score of 7.60. The effectiveness score is 9 and the side effect score is 7.20. The scores are on ten point scale: 10 - best, 1 - worst. Below are selected reviews: the highest, the median and the lowest rated.
| | Methotrexate review by 64 year old female patient | | | Rating |
| Overall rating: | |  |
| Effectiveness: | | Considerably Effective |
| Side effects: | | No Side Effects | | |
Treatment Info |
| Condition / reason: | | Rheumatoid Arthritis |
| Dosage & duration: | | 20 mg. taken 1 x week for the period of 2 years to present |
| Other conditions: | | none |
| Other drugs taken: | | Remicade | | |
Reported Results |
| Benefits: | | The combination of weekly 20mg. Methotrexate with an infusion (at the doctor's office) of Remicade has almost completely controlled my rheumatoid arthritis.
I have had no further joint damage, and the initial symptoms of extreme fatigue and pain in the small joints of my hands, wrists, feet and ankles has abated. |
| Side effects: | | None that I am aware of |
| Comments: | | I was diagnosed with rheumatoid arthritis about two years ago and began treatment with a combination of Remicade (infused once every eight weeks over a period of about 2 hours in my doctor's office) and Methotrexate 20 mg. once a week. I take 8 tablets every Friday, 2.r mg. each. I have had no negative side effects from either medication. |
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| | Methotrexate review by care giver of 17 year old male patient | | | Rating |
| Overall rating: | |  |
| Effectiveness: | | Highly Effective |
| Side effects: | | Moderate Side Effects | | |
Treatment Info |
| Condition / reason: | | psoriasis |
| Dosage & duration: | | 15mg per week taken 1 x per week for the period of continuing for past 22 mos. |
| Other conditions: | | Down syndrome, hypothyroidism |
| Other drugs taken: | | tegratol, synthroid, topical steroid | | |
Reported Results |
| Benefits: | | Relieved the plaque psoriasis which was over 90% of skin and extremely uncomfortable. |
| Side effects: | | Vomiting and nausea on days the drug was ingested, rebound effect(return of plaque) when attempting to decrease the medication; liver blood levels need monitoring while on the drug. |
| Comments: | | Patient had onset of psoriasis and was treated with topical steroids. Psoriasis quickly spread over entire body and methotrexate was recommended. It worked quickly to eliminate the plaque on the trunk of body, but patient has been unable to wean from the drug because psoriasis has never completely gon away on arms and legs. We are now looking at Enbrol. |
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| | Methotrexate review by 58 year old female patient | | | Rating |
| Overall rating: | | |
| Effectiveness: | | Considerably Effective |
| Side effects: | | Severe Side Effects | | |
Treatment Info |
| Condition / reason: | | psoraitic arthritis |
| Dosage & duration: | | 6 tabs taken daily for the period of 4 years |
| Other conditions: | | psoriasis |
| Other drugs taken: | | none | | |
Reported Results |
| Benefits: | | the treatment masked the psoriasis and what was considered arthritis |
| Side effects: | | increasing all over body pain |
| Comments: | | I started with 4 tabs and increased to 6 as the all over body pain increased and then they were going to put me on prednisone. I opted to turn to homeopathic treatment and weaned off the methotrexate. The all over body pain went completely away but the psoriasis was exacerbated. I'd rather have that than not be able to walk or move. |
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Page last updated: 2009-10-23
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