Methotrexate is a medication used to treat a wide range of conditions, from rheumatoid arthritis and psoriasis to certain cancers and ectopic pregnancies. It works by slowing down rapidly dividing cells and suppressing an overactive immune system. What makes methotrexate unusual is just how different it looks depending on the condition being treated: a person with arthritis might take a small weekly pill, while a cancer patient could receive hundreds of times that dose through an IV infusion.
Rheumatoid Arthritis
Rheumatoid arthritis is by far the most common reason methotrexate is prescribed. It’s typically the first drug doctors reach for when someone is diagnosed with RA, and it remains a cornerstone of treatment even as newer biologics have entered the market. The standard starting dose is 7.5 mg taken by mouth once per week, with gradual increases until symptoms improve. Doses above 20 mg per week raise the risk of serious side effects, so most people stay within that range.
Methotrexate doesn’t work overnight. Most people notice reduced joint pain, swelling, and stiffness within 3 to 6 weeks, but it can take up to 12 weeks at an effective dose to feel the full benefit. That delay can be frustrating, but it’s normal. The drug works by dialing down the immune system’s attack on joint tissue, which takes time to translate into symptom relief.
Psoriasis and Other Autoimmune Conditions
Methotrexate is also used for severe psoriasis, particularly when the condition covers large areas of the body or hasn’t responded to creams and light therapy. It slows the rapid skin cell turnover that causes thick, scaly plaques. The dosing is similar to what’s used in rheumatoid arthritis: a low weekly dose, usually taken as a pill or injection.
Beyond psoriasis, methotrexate is prescribed for a number of other autoimmune and inflammatory conditions. These include psoriatic arthritis, lupus, inflammatory bowel disease (especially Crohn’s disease), and some forms of vasculitis. In all of these cases, the goal is the same: to calm an immune system that’s mistakenly attacking the body’s own tissues.
Cancer Treatment
Methotrexate has a notable place in cancer history. It was the first drug shown to cure a cancer when used on its own, specifically a rare pregnancy-related cancer called gestational trophoblastic disease, for which it remains a primary treatment today. It’s also an important part of modern chemotherapy for acute lymphoblastic leukemia (ALL), the most common childhood cancer.
The doses used in cancer treatment are dramatically higher than those for autoimmune conditions. High-dose methotrexate, defined as 500 mg per square meter of body surface area or more, is given as an IV infusion over 4 to 36 hours. At these levels, the drug would be lethal without a “rescue” medication called leucovorin, which is given for two to three days afterward to shut down methotrexate’s toxic effects on healthy cells.
High-dose protocols are used for cancers that are hard for drugs to reach, particularly those involving the brain and central nervous system. This includes primary central nervous system lymphoma, osteosarcoma (a bone cancer most common in teenagers), and as preventive treatment to stop leukemia and high-risk lymphoma from spreading to the brain and spinal fluid.
Ectopic Pregnancy
When a fertilized egg implants outside the uterus, usually in a fallopian tube, methotrexate can resolve the pregnancy without surgery. It stops the rapidly dividing cells of the early pregnancy from growing, allowing the body to reabsorb the tissue over the following weeks.
The standard protocol is a single injection of 50 mg per square meter of body surface area. After the injection, blood levels of the pregnancy hormone hCG are checked on days 4 and 7 to confirm they’re dropping. If the hormone level hasn’t declined by at least 15% between those two checks, a second injection is given. Candidates for this approach need to be medically stable, with normal liver and kidney function. Women with a ruptured ectopic pregnancy or heavy internal bleeding need surgery instead.
How It’s Taken for Autoimmune Conditions
For arthritis, psoriasis, and similar conditions, methotrexate is taken once a week, not daily. This is a critical distinction that causes confusion. Taking it daily instead of weekly can lead to a dangerous overdose. Most people take it as a tablet, though a subcutaneous injection is available for those who experience nausea with the oral form or need better absorption.
Folic acid is almost always prescribed alongside methotrexate. The British Society for Rheumatology recommends at least 5 mg of folic acid once a week, taken on a different day than the methotrexate dose. If side effects like nausea or mouth sores develop, the folic acid dose can be increased to 10 mg per week, though evidence doesn’t support going higher than that. Folic acid helps replenish a vitamin that methotrexate depletes, which is what causes many of its common side effects.
Side Effects and Monitoring
At the low doses used for autoimmune conditions, the most common side effects are nausea, fatigue, and mouth sores. These are often manageable with folic acid supplementation and sometimes resolve as your body adjusts. Some people experience mild hair thinning. More serious but less common risks include liver damage, reduced blood cell counts (which can lower your ability to fight infections), and lung inflammation.
Because of these risks, regular blood tests are part of the deal when you’re on methotrexate long-term. The typical monitoring schedule starts with blood work by week 6 after starting or changing the dose, checking a complete blood count and liver enzymes. If those results are normal, another set is drawn at week 12, then again at week 24 with the addition of kidney function tests. After that initial period, blood tests settle into a routine of every 3 months for as long as you’re on the medication.
Pregnancy and Methotrexate
Methotrexate causes birth defects and miscarriage. This applies to both women and men taking the drug. Anyone who could become pregnant, or whose partner could become pregnant, needs reliable contraception while on methotrexate. After stopping the medication, both men and women are advised to wait before trying to conceive, with the recommended waiting period typically being at least three months. This is one of the most important safety considerations with the drug, regardless of why it’s being prescribed.
Methotrexate also passes into breast milk, so it’s not compatible with breastfeeding.