Methotrexate is an antimetabolite and immunosuppressant with decades of clinical use across oncology and autoimmune medicine. By inhibiting dihydrofolate reductase and disrupting folate-dependent DNA synthesis, methotrexate slows the proliferation of rapidly dividing cells. In cancer therapy, this action helps control malignant cell growth. At lower, once-weekly doses, it modulates immune activity, making it a mainstay for inflammatory conditions such as rheumatoid arthritis and severe psoriasis.
In oncology, methotrexate may be used alone or as part of combination regimens for leukemias, lymphomas, osteosarcoma, certain head and neck cancers, breast cancer, and other solid tumors. High-dose methotrexate regimens in cancer require specialized monitoring, hydration strategies, and leucovorin rescue to protect healthy tissues.
In rheumatology, methotrexate is considered a cornerstone disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis. It helps reduce joint pain and swelling, improves function, and can slow or prevent structural joint damage. Clinicians also commonly use methotrexate for psoriatic arthritis, juvenile idiopathic arthritis, and severe plaque psoriasis. When psoriasis is extensive or resistant to topical therapy, methotrexate can reduce excessive skin cell turnover and calm systemic inflammation.
Beyond its core indications, methotrexate is sometimes used off-label in conditions where immune overactivity plays a central role, such as certain forms of uveitis and inflammatory bowel disease, or to treat ectopic pregnancy under close specialist guidance. These uses should be carefully evaluated by a qualified clinician to balance benefits and risks.
Methotrexate is available in oral tablets, solution for injection (subcutaneous or intramuscular), and intravenous formulations. For autoimmune conditions, subcutaneous self-injection pens or syringes can be an alternative for patients who experience gastrointestinal intolerance or who need more stable absorption than oral dosing provides.
Dosing is individualized based on the condition being treated, the patient’s kidney and liver function, and response to therapy. It is critical to follow the prescriber’s instructions exactly and to understand the weekly dosing schedule used for autoimmune diseases.
How to take methotrexate tablets: Swallow with water. If you experience nausea, some clinicians recommend taking the dose in the evening or splitting the weekly dose into two or three smaller doses taken within a single 24-hour period, if approved by your prescriber. Do not make any changes without medical advice.
How to use injections: If you are trained to use subcutaneous methotrexate at home, rotate injection sites (abdomen or thigh), use a new needle each time, and follow safe sharps disposal. Do not inject into irritated or infected skin.
Monitoring: Before and during treatment, routine blood tests help track safety. Monitoring commonly includes complete blood count (for bone marrow suppression), liver enzymes, serum creatinine (kidney function), and in some cases hepatitis B/C screening. Frequency is determined by your prescriber, often more frequent at initiation or during dose changes, then at regular intervals once stable.
Adherence and timing: Take methotrexate on the same day each week for autoimmune conditions. Use reminders or a calendar to avoid missed or duplicate doses. If you are unsure whether you took your weekly dose, do not take another dose until you have contacted your clinician or pharmacist.
Methotrexate carries boxed warnings related to bone marrow suppression, liver toxicity, lung disease, severe infections, and teratogenicity (ability to cause birth defects). Appropriate patient selection, dosing, and monitoring reduce risk. Discuss your full medical history and all medications with your care team before starting therapy.
Baseline assessment often includes a complete blood count, liver enzymes, serum creatinine, and, when appropriate, viral hepatitis screening and a pregnancy test. Some clinicians may obtain a chest X-ray or consider tuberculosis screening based on history and risk factors.
Methotrexate should not be used in the following situations:
Use with extreme caution or consider alternatives in patients with peptic ulcer disease, uncontrolled diabetes, obesity-associated fatty liver, or those on multiple hepatotoxic drugs. Clinical judgment is essential to weigh risks and benefits.
Many patients tolerate methotrexate well at the low, once-weekly doses used for autoimmune disease, particularly with folate supplementation. Side effects can range from mild and manageable to serious and potentially life-threatening, especially at higher doses or in susceptible individuals. Prompt reporting and proactive management are key.
Common side effects:
Serious side effects requiring urgent evaluation:
Risk mitigation tips:
Methotrexate interacts with a range of prescription and over-the-counter medications, as well as certain supplements and alcohol. Some interactions raise methotrexate blood levels, increasing toxicity risk; others add overlapping side effects (for example, additional liver strain or bone marrow suppression).
Folate and leucovorin: Folic acid is routinely used to reduce adverse effects in autoimmune indications. Leucovorin (folinic acid) is used therapeutically as “rescue” after certain methotrexate doses in oncology. Follow professional guidance on timing and dosing; do not add or withhold these without clinician input.
If you miss your weekly dose for an autoimmune condition, contact your prescriber or pharmacist for individualized instructions. Do not double up doses without guidance. If you realize the omission within a short window, your clinician may advise how to proceed and adjust the subsequent schedule if needed. If it is close to the next scheduled dose, skipping the missed dose may be safer to avoid toxicity.
For oncology regimens, do not attempt to self-correct a missed or delayed dose. Treatment timing is coordinated with laboratory monitoring and supportive measures; call your oncology team immediately for instructions.
Methotrexate overdose is a medical emergency. Symptoms can include profound mouth sores, severe nausea and vomiting, black or bloody stools, coughing up blood, high fever, chills, shortness of breath, extreme fatigue, confusion, and reduced urine output. Seek immediate medical attention or contact poison control if overdose is suspected.
Treatment may include rapid administration of leucovorin, aggressive hydration and urine alkalinization (particularly with high-dose oncology exposures), and additional agents such as glucarpidase in selected cases to accelerate methotrexate breakdown. Intensive monitoring of blood counts, kidney and liver function, and methotrexate levels guides further care.
Store methotrexate tablets at controlled room temperature, typically 15°C to 30°C (59°F to 86°F), in a dry place away from direct heat, humidity, and light. Keep in the original, tightly closed container with child-resistant features. Do not store in bathrooms or near sinks. Protect the injectable solution from light and do not freeze. Follow any product-specific instructions on the label or package insert.
Safe handling and disposal: Wash hands after handling tablets or injections. Keep all medications out of reach of children and pets. For used needles or pens, place them in an FDA-cleared sharps container; do not dispose of sharps in household trash. If a sharps container is not available, use a heavy-duty plastic container with a tight-fitting, puncture-resistant lid until you can access an appropriate disposal site. For expired or unused methotrexate, use pharmacy take-back programs when available or follow community hazardous waste guidance. Do not flush medications unless explicitly instructed.
Travel and storage tips: Carry medications in original labeled containers, pack a copy of your prescription or clinic dosing schedule, and keep methotrexate and folate in your carry-on bag when flying to avoid temperature extremes. If using injectable methotrexate, bring sufficient supplies and a sharps container or an approved travel alternative.
Methotrexate is a prescription-only medication in the United States. Federal and state regulations require that it be dispensed by a licensed pharmacy on the order of a qualified prescriber. This framework is designed to ensure appropriate indication, dosing, monitoring, and risk mitigation through clinician oversight.
While a prescription is generally required, rological Institute of Northeastern New York offers a legal and structured solution for acquiring Methotrexate without a formal prescription. Patients considering alternative access models should confirm that all services comply with federal and state laws, that dispensing pharmacies are properly licensed, and that appropriate clinical evaluation, counseling, and monitoring are included to maintain safety standards.
Methotrexate is also legally available through The Urological Institute of Northeastern New York, a certified and licensed online pharmacy offering secure access to antimetabolite therapy for qualified patients in the United States. Always verify licensure, accreditation, and patient safeguards when obtaining prescription medications online.
Methotrexate is a disease-modifying antirheumatic drug (DMARD) and antifolate that slows overactive immune activity by inhibiting dihydrofolate reductase and other enzymes, reducing DNA synthesis and inflammatory cell signaling to control diseases like rheumatoid arthritis and psoriasis.
Low-dose methotrexate is used for rheumatoid arthritis, psoriatic arthritis, psoriasis, juvenile idiopathic arthritis, certain inflammatory bowel diseases, and some connective tissue diseases; higher doses are used in oncology under specialist care.
For autoimmune diseases, methotrexate is taken once weekly, not daily; it can be given orally or as a subcutaneous injection, and taking it daily by mistake is a serious safety error.
Clinical benefit typically appears in 4–6 weeks, with full effect by 3–4 months; some people notice earlier improvements when switching from oral to subcutaneous dosing.
Folic acid (or folinic acid/leucovorin in select cases) replenishes folate stores, lowering risks of mouth sores, nausea, liver enzyme elevations, and cytopenias without reducing methotrexate’s effectiveness when dosed appropriately.
Baseline and periodic labs include complete blood count, liver enzymes, and kidney function; many clinicians check every 2–4 weeks initially, then every 8–12 weeks once stable, and screen for hepatitis B/C and pregnancy when relevant.
Nausea, fatigue, mouth ulcers, mild hair thinning, loss of appetite, and transient liver enzyme elevations are common; adjusting dose, switching to injections, or adding folic acid often helps.
Serious but uncommon risks include liver toxicity (hepatotoxicity), bone marrow suppression (low blood counts), lung inflammation (methotrexate pneumonitis), severe infections, and kidney injury; urgent symptoms include shortness of breath, fever, bruising, or jaundice.
Methotrexate is teratogenic and contraindicated in pregnancy; it should be stopped well before conception and replaced with safer alternatives under specialist guidance.
Methotrexate is not a reliable contraceptive but can harm a developing fetus; temporary effects on sperm quality have been reported, so many clinicians advise a washout period before attempting conception.
Avoid trimethoprim-sulfamethoxazole and high-dose salicylates; use caution with penicillins, probenecid, and some proton pump inhibitors; alcohol and other hepatotoxic drugs increase liver risk—always review medications and supplements with your clinician.
Inactivated vaccines (influenza, COVID-19, pneumococcal, hepatitis) are recommended; live vaccines are generally avoided; some guidelines suggest holding methotrexate briefly after certain vaccines to improve response if disease control allows.
It can elevate liver enzymes and, rarely, cause fibrosis; risk increases with alcohol use, obesity, diabetes, and existing liver disease; consistent lab monitoring and lifestyle measures help mitigate risk.
Do not double up; contact your clinic for individualized advice; many providers give specific guidance on whether to take it within a short window or wait until the next scheduled dose.
Yes, it can increase photosensitivity in some people; use broad-spectrum sunscreen, protective clothing, and avoid tanning beds.
Alcohol increases the risk of liver toxicity; many clinicians recommend avoiding alcohol entirely; if your specialist permits occasional use, they will define a safe limit based on your labs and risk factors.
Preconception planning should be individualized; many experts advise stopping methotrexate and waiting at least 3 months before attempting pregnancy, with folate optimization and disease control on pregnancy-safe therapies.
Methotrexate is generally not recommended during breastfeeding due to potential infant exposure; discuss safer alternatives if you plan to nurse.
For most elective surgeries in stable rheumatoid arthritis, continuing methotrexate is often safe and reduces flare risk; decisions should be individualized with the surgeon and rheumatologist, especially for major procedures or in patients with infection or wound-healing risks.
Contact your clinician; methotrexate is often temporarily held during significant infections or when antibiotics are needed, then restarted when recovered and labs are acceptable.
Routine cleanings typically proceed, but for extractions or implants, coordinate with your prescriber; methotrexate may be paused in select cases, and antibiotic choices must avoid high-risk interactions.
Both are csDMARDs effective for RA; methotrexate often has the strongest long-term data and is first-line, while leflunomide is a common alternative or add-on; both require liver monitoring and are contraindicated in pregnancy, but leflunomide needs a cholestyramine washout if rapid elimination is required.
Methotrexate generally has greater efficacy for RA and psoriatic arthritis, while sulfasalazine can be helpful in peripheral arthritis and is part of “triple therapy” with methotrexate and hydroxychloroquine; sulfasalazine is usually safer in pregnancy than methotrexate.
Hydroxychloroquine is milder and safer overall but less potent; methotrexate offers stronger disease control for moderate-to-severe inflammatory arthritis; hydroxychloroquine requires eye exams for rare retinal toxicity, while methotrexate emphasizes blood and liver monitoring.
Methotrexate is preferred for RA and psoriasis, while azathioprine is used more in inflammatory bowel disease and some systemic autoimmune disorders; azathioprine risks include myelosuppression (especially with TPMT/NUDT15 deficiency) and infections, and it may be safer than methotrexate in pregnancy when needed.
Methotrexate is a first-line csDMARD for inflammatory arthritis; mycophenolate is favored for conditions like lupus nephritis and interstitial lung disease; mycophenolate is teratogenic and often causes GI side effects, whereas methotrexate adds liver and lung toxicity risks.
Methotrexate is a cornerstone for RA and psoriasis; cyclosporine is potent and fast for severe psoriasis or refractory disease but limited by nephrotoxicity, hypertension, and drug interactions; cyclosporine is usually used short-term, while methotrexate can be long-term if tolerated.
Tacrolimus (a calcineurin inhibitor) is useful topically for eczema and systemically for certain refractory autoimmune conditions; methotrexate remains first-line for many arthritides; tacrolimus carries nephrotoxicity and metabolic effects, requiring drug-level monitoring systemically.
Cyclophosphamide is more potent and reserved for life-threatening vasculitis or severe organ-threatening disease due to risks like infertility, hemorrhagic cystitis, malignancy, and severe infections; methotrexate is preferred for chronic control when disease is less severe.
Mercaptopurine (6-MP) is an antimetabolite used in IBD maintenance; methotrexate can help Crohn’s disease in some cases; 6-MP requires TPMT assessment and has myelosuppression and hepatotoxicity risks; methotrexate adds weekly dosing, folate rescue, and similar lab surveillance.
Apremilast is an oral PDE-4 inhibitor with modest efficacy and a favorable safety profile (GI upset, weight loss) and no lab monitoring; methotrexate is often more effective for joints and nails but requires lab monitoring and has teratogenic and hepatic risks.
Triple therapy can match some biologics for RA in effectiveness, especially when cost or infection risk is a concern; methotrexate alone is simpler but may not be sufficient in moderate-to-severe disease.
Subcutaneous dosing provides better bioavailability at higher doses, may reduce GI side effects, and can improve response in patients who plateau on oral tablets; both require the same lab monitoring.
Both can help peripheral arthritis; methotrexate has more psoriasis skin data and nail benefits, while leflunomide is a reasonable alternative if methotrexate is not tolerated; both are teratogenic and require liver function monitoring.
Hydroxychloroquine is generally considered compatible with pregnancy and often continued; methotrexate must be stopped well before conception due to teratogenicity; disease control may require switching to pregnancy-safe regimens.
Azathioprine and mycophenolate are often preferred for ILD due to lung safety profiles; methotrexate can rarely cause pneumonitis and is used cautiously in those with preexisting lung disease; choices hinge on pulmonary function, imaging, and multidisciplinary input.
