This guide explains how methotrexate works, who it helps, how it’s taken safely, and what to know about side effects, monitoring, and U.S. access policies. It is educational and not a substitute for your clinician’s advice.
Common uses of Methotrexate
Methotrexate is a cornerstone therapy in rheumatology and dermatology and is also used in oncology. As a disease-modifying antirheumatic drug (DMARD), it is commonly prescribed for rheumatoid arthritis to reduce pain, stiffness, and joint damage. It is also used for psoriatic arthritis, plaque psoriasis, and juvenile idiopathic arthritis. In inflammatory bowel disease, methotrexate may serve as a steroid-sparing option for Crohn’s disease when other therapies are unsuitable.
In oncology, methotrexate is part of multi-drug regimens for leukemias, lymphomas, osteosarcoma, and certain solid tumors. Dosing and rescue strategies in cancer care are specialized and managed by oncology teams. Methotrexate may also be used to medically manage ectopic pregnancy in select, carefully evaluated cases, avoiding surgery by targeting rapidly dividing trophoblastic cells.
Across these indications, methotrexate’s antifolate action slows fast-dividing cells and tempers overactive immune responses. The goal is symptom relief, disease control, and long-term protection of organ and joint function.
Dosage and direction: weekly dosing, forms, and folic acid
For autoimmune conditions, methotrexate is usually taken once weekly—never daily—an essential safety point that prevents serious toxicity. Typical starting doses for rheumatoid arthritis range from 7.5 to 15 mg once weekly, titrated up in 2.5–5 mg increments to a common maximum of 20–25 mg weekly based on response and tolerability. Psoriasis dosing is similar, often 10–25 mg once weekly. Your clinician will individualize the regimen, considering age, kidney function, liver health, and other medications.
Methotrexate is available as oral tablets, an oral solution, and as injections (subcutaneous, intramuscular, or intravenous). For rheumatologic and dermatologic use, subcutaneous self-injection can improve bioavailability and reduce gastrointestinal upset when higher doses are needed or when pills are poorly tolerated. Take the dose on the same day each week to build a routine, and use reminders to avoid errors.
Folic acid supplementation is standard to reduce mouth sores, nausea, and blood abnormalities. Many clinicians recommend folic acid 1 mg daily (or 5 mg once weekly, separated from methotrexate by at least a day). Follow your prescriber’s exact plan. Blood tests (CBC, liver enzymes, creatinine) are checked regularly to guide safe dosing. Oncology protocols vary widely and may involve high doses, leucovorin rescue, hydration, and close methotrexate level monitoring—these regimens are strictly managed by oncology specialists.
Precautions: pregnancy, liver and kidney health, infections, and vaccines
Methotrexate is contraindicated in pregnancy due to serious risk of fetal harm. People who can become pregnant should use effective contraception during treatment and for a period after the last dose (often at least one full ovulatory cycle for low-dose rheumatology use; oncology guidance differs). Those who can cause pregnancy should also use reliable contraception for a clinician-advised interval after the last dose. Do not use methotrexate while breastfeeding unless your specialist confirms a circumstance where benefits outweigh risks and timing strategies are clearly defined.
Liver health is critical. Avoid heavy alcohol use; many clinicians advise avoiding alcohol altogether to minimize the risk of hepatotoxicity. Methotrexate may be unsuitable for people with chronic liver disease, uncontrolled diabetes with fatty liver, or persistently elevated liver enzymes. Kidney function affects methotrexate clearance; reduced kidney function increases toxicity risk and may require dose adjustments or alternative therapy.
Methotrexate can lower immune defenses. Report fevers, persistent cough, unexplained bruising, or unusual fatigue promptly. Pre-treatment screening may include hepatitis B and C, TB risk assessment, and baseline labs. Avoid live vaccines during therapy (e.g., MMR, varicella, intranasal flu). Inactivated vaccines (like flu shot or COVID-19 mRNA vaccines) are generally allowed and recommended, but discuss timing to optimize response. Rarely, methotrexate can cause lung inflammation (pneumonitis) presenting with dry cough, shortness of breath, and fever—seek urgent evaluation if respiratory symptoms develop.
Contraindications to Methotrexate
Do not use methotrexate if you are pregnant or planning pregnancy, have a known hypersensitivity to the drug, severe liver disease, significant renal impairment without specialist oversight, active alcohol use disorder, preexisting blood dyscrasias (e.g., severe anemia, leukopenia, thrombocytopenia), or active serious infections. Caution or alternative therapy is advised for uncontrolled pleural or peritoneal effusions, immunodeficiency states, and in the frail elderly. Oncology teams may use methotrexate in complex scenarios with intensive monitoring; outside of those settings, these contraindications typically preclude use.
Possible side effects of Methotrexate
Common dose‑related effects include nausea, reduced appetite, abdominal discomfort, diarrhea, fatigue, headache, and mouth sores (stomatitis). Folic acid supplementation often improves these symptoms. Mild hair thinning and skin sensitivity may occur. Many patients find switching from oral to subcutaneous dosing reduces gastrointestinal issues.
More serious adverse effects include bone marrow suppression (leading to low white cells, anemia, or low platelets), liver enzyme elevations or hepatotoxicity, lung inflammation (pneumonitis), and heightened infection risk. Warning signs that require urgent evaluation include fever, chills, sore throat, easy bruising or bleeding, severe or persistent cough, shortness of breath, jaundice, dark urine, severe abdominal pain, confusion, or profound fatigue. Rarely, severe skin reactions (Stevens–Johnson syndrome/toxic epidermal necrolysis), kidney injury (particularly with high-dose oncology regimens), or neurotoxicity can occur.
Long-term use in autoimmune disease is generally well tolerated with proper monitoring. Your clinician will schedule routine blood tests to catch early signals of toxicity, adjust dosing, and evaluate the need for folic acid, folinic acid rescue in special cases, or route changes to optimize benefit and minimize risk.
Drug interactions with Methotrexate
Some medicines increase methotrexate levels or amplify toxicity. Notable interactions include trimethoprim–sulfamethoxazole (Bactrim) and trimethoprim alone, which can dangerously boost bone marrow suppression—these are usually avoided. High-dose or frequent NSAIDs, salicylates, and aspirin may reduce renal clearance of methotrexate; clinical judgment is used in rheumatology, but concurrent use requires caution and monitoring. Probenecid and penicillins can decrease methotrexate elimination. Certain proton pump inhibitors (e.g., omeprazole) have been associated with impaired clearance, particularly in high-dose oncology settings.
Other interactions include loop diuretics, sulfonylureas, phenytoin, and retinoids, which may alter toxicity profiles. Alcohol increases liver risk. Live vaccines should be avoided during therapy; inactivated vaccines are generally acceptable but plan timing with your clinician. Folate supplements reduce side effects and do not diminish the clinical efficacy of methotrexate for autoimmune disease when used appropriately. Always provide a complete list of prescription drugs, over-the-counter medicines, vitamins, and herbal products to your care team before starting or adjusting methotrexate.
Missed dose: what to do safely
If you miss your once-weekly dose and remember within one to two days, take it as soon as you remember and resume your usual weekly schedule. If it is closer to your next scheduled dose, skip the missed dose—do not double up. If you miss more than one dose, or if you are unsure, contact your clinician for guidance. For oncology protocols, do not self-correct; call your oncology team for exact instructions.
Overdose: urgent steps and clinical management
Taking methotrexate daily instead of weekly is a common and dangerous error that can lead to severe mouth ulcers, gastrointestinal injury, profound bone marrow suppression, and organ toxicity. If an overdose is suspected, seek emergency care immediately and contact Poison Control (1-800-222-1222 in the U.S.). Clinicians may use folinic acid (leucovorin) “rescue,” aggressive hydration, urine alkalinization, and serial methotrexate level monitoring. In select cases with delayed clearance due to kidney injury, glucarpidase may be considered. Early recognition and treatment are critical.
Storage and safe handling
Store tablets and oral solution at room temperature, away from moisture and direct light, and out of reach of children and pets. For injections, follow labeling regarding temperature and light; do not freeze unless specifically indicated. Because methotrexate is cytotoxic, handle tablets and solution with dry hands, keep in original containers, and dispose of sharps and unused medication through approved take-back or hazardous waste programs—do not flush or discard in household trash.
U.S. sale and prescription policy: access, legality, and Geisinger HealthSouth
In the United States, methotrexate is a prescription-only medication. It is not legal to buy methotrexate without a prescription, and reputable pharmacies will require one. This safeguard exists to ensure proper diagnosis, dosing, lab monitoring, pregnancy prevention counseling, and management of drug interactions and side effects.
Geisinger HealthSouth offers a legal and structured pathway to access methotrexate through clinician-led evaluation, shared decision-making, and coordinated pharmacy fulfillment. Patients can schedule in-person or telehealth visits, complete baseline labs, review contraception needs and vaccine status, and receive an e-prescription when appropriate—fully compliant with U.S. laws and safety standards. This integrated model supports ongoing monitoring, dose optimization, and rapid support for side effects or flare management. If you have questions about eligibility, costs, or care pathways, contact Geisinger HealthSouth to begin with a licensed clinician who can determine whether methotrexate is right for you and arrange safe, timely access through partnered pharmacies.
