Methotrexate: uses, dosing, side effects & brands

Xatmep (Methotrexate Sodium) is a folate analog metabolic inhibitor used to treat Juvenile Arthritis, Rheumatoid Arthritis, Breast Neoplasms, Choriocarcinoma.

The FDA classifies methotrexate as a folate analog metabolic inhibitor. Folate analog metabolic inhibitors like methotrexate block the enzyme that converts folate into its usable form, starving fast-dividing cells of the building blocks for DNA. At low doses they also calm an overactive immune system and reduce inflammation. If you are checking whether it is safe to combine with something else, the class is what matters — two drugs from the same class usually should not be stacked.

The elimination half-life of methotrexate is about 3 to 10 hours — that is how long the body takes to clear half of a dose. The 3-to-10-hour figure is for the low weekly doses used in rheumatoid arthritis, psoriasis, and low-dose cancer therapy (under 30 mg/m2). After high-dose intravenous methotrexate the terminal half-life is longer, 8 to 15 hours. Methotrexate leaves the bloodstream faster than it leaves the body's tissues: inside cells it is converted to methotrexate polyglutamates, active metabolites that the FDA label says "may remain in tissues for extended periods," with retention varying by tissue and tumor — the label gives no half-life number for them. A second active metabolite, 7-hydroxymethotrexate, is also formed in smaller amounts; the label states no half-life for it either. The drug is cleared mainly by the kidneys, and the label states that the elimination half-life increases with the severity of kidney impairment, with wide variation between individuals — relevant to older adults, whose kidney function declines with age. The effect of liver impairment on methotrexate pharmacokinetics is unknown per the label. There is no extended-release form of methotrexate; oral tablets, oral solution, and subcutaneous auto-injectors are all immediate-release. Half-life is not the same as how long a drug test can detect the drug, and it varies with age, kidney and liver function.

It depends on the medicine. We check it against the FDA labels rather than guessing: our interaction checker searches each drug's own label for the other and quotes what it says, naming the section it came from. Run methotrexate against whatever else you take — and remember that a label not naming a drug is not the same as that combination being safe.

We track 10 methotrexate-containing products in the U.S.: Xatmep, Methotrexate Lpf, Methotrexate Preservative Free, Abitrexate, Jylamvo, Methotrexate Sodium, Otrexup and Otrexup Pfs, and 2 more. They are the same active ingredient; they differ in form, manufacturer, price and FDA recall record.

Across the brands we track, methotrexate is currently marketed as solution, injectable and tablet, per the FDA's National Drug Code Directory. Each form is dosed differently — follow the label for the exact product you were prescribed.

Yes. Our catalog lists 2 generic methotrexate products alongside the brand versions. A generic has the same active ingredient and must meet the FDA's bioequivalence standard; it usually costs less. Ask your pharmacist which one your plan covers.

The FDA's Enforcement database lists 1 recall record whose product description mentions methotrexate. The most recent: Methotrexate Tablets (Aug 1, 2024). A recall applies to specific lots, not to the drug as a whole — check the record for the affected lot numbers.

For rheumatoid arthritis, juvenile idiopathic arthritis, and psoriasis, methotrexate tablets are dosed ONCE WEEKLY, and the FDA boxed warning states plainly that patients who took it daily by mistake have died. The label's recommended starting dose is 7.5 mg once weekly for adult rheumatoid arthritis and 10 to 25 mg once weekly for psoriasis (not to exceed 30 mg per week). Pick one weekday, write it on the calendar, and keep the bottle away from your daily pills. If you have taken more than one weekly dose by accident, contact your prescriber or poison control immediately — do not wait for symptoms.

The label's overall common reactions are mouth ulcers (ulcerative stomatitis), low white blood cells, nausea, and abdominal discomfort. In 12- to 18-week rheumatoid arthritis trials at 7.5 to 15 mg once weekly, elevated liver tests occurred in 15% and nausea/vomiting in 10%; stomatitis and low platelets in 3% to less than 10%; rash/itch/dermatitis, diarrhea, hair thinning, low white cells, pancytopenia, and dizziness in 1% to under 3%. Interstitial pneumonitis, a serious lung reaction, occurred in about 1%. In children with pJIA, elevated liver tests were 14% and GI reactions 11%. Your prescriber should also give you folic acid or folinic acid, which the label says reduces methotrexate adverse reactions.

Four items. First, embryo-fetal toxicity including fetal death — for non-cancer conditions like rheumatoid arthritis and psoriasis, methotrexate is contraindicated in pregnancy, and for cancer use both women and men of reproductive potential need effective contraception. Second, it is contraindicated in anyone with a history of severe hypersensitivity to methotrexate, including anaphylaxis. Third, serious reactions including death have been reported, so you must be monitored for toxicity of the bone marrow, gut, liver, lungs, skin, and kidneys, with the drug held or stopped when they appear. Fourth, medication errors — daily dosing instead of the prescribed weekly dosing has killed patients.

Two absolute contraindications in the current label: pregnant women taking it for non-cancer conditions such as rheumatoid arthritis or psoriasis, and anyone with a history of a severe hypersensitivity reaction, including anaphylaxis, to methotrexate. The label also instructs prescribers to verify pregnancy status in females of reproductive potential before starting, and says not to give the tablets to anyone who cannot swallow a tablet. If you become pregnant or plan to, tell your prescriber before the next weekly dose, not at your next scheduled visit.

Call promptly for mouth sores or ulcers, a new dry cough or shortness of breath (the label reports interstitial pneumonitis in about 1% of rheumatoid arthritis patients), fever or any sign of infection, unusual bruising or bleeding, severe diarrhea or abdominal pain, yellowing of the skin or eyes or dark urine, a spreading or blistering rash, or a drop in urine output. These map to the exact organ systems the boxed warning says to monitor — bone marrow, gastrointestinal tract, liver, lungs, skin, and kidneys — and the label's instruction is to withhold or discontinue methotrexate when they occur. Do not skip the routine blood tests and liver tests; they are how the serious reactions get caught before they become dangerous.