Methotrexate dosage
Methotrexate for rheumatoid arthritis and psoriasis is taken ONCE A WEEK — on one day, not every day. This is not a nuance; it is the single most important fact about the drug. The FDA label carries a dedicated warning section (5.9, "Risk of Serious Adverse Reactions with Medication Error") that states plainly: "Deaths occurred in patients as a result of medication errors. Most commonly, these errors occurred in patients who were taking methotrexate daily when a weekly dosing regimen was prescribed." The patient labeling repeats it in plain English: "Take your methotrexate tablets dose 1 time each week, not every day. Severe side effects and death have happened in people who mistakenly have taken methotrexate tablets every day instead of 1 time each week." Because the reference tablet is only 2.5 mg, a normal weekly dose is several tablets swallowed together on a single day — a bottle that looks like a daily medicine but is not. If you are ever unsure which day is your methotrexate day, or whether you have taken a dose twice, call your prescriber or pharmacist before taking another tablet. Everything below is the labeled oral weekly regimen for RA and psoriasis; oncology protocols and the subcutaneous autoinjectors use different doses and are out of scope for this page.
This is reference, not a dosing instruction. Methotrexateis prescription-only and the dose is individualized and titrated by a prescriber to your condition, response, kidney/liver function and other medicines. The figures below are the FDA label’s — do not start, change or stop a dose based on this page.
Approved for: Oral methotrexate tablets are FDA-approved for rheumatoid arthritis in adults, polyarticular juvenile idiopathic arthritis (pJIA), and severe psoriasis in adults, plus several neoplastic indications (acute lymphoblastic leukemia, mycosis fungoides, relapsed/refractory non-Hodgkin lymphoma). This page covers ONLY oral once-weekly dosing for rheumatoid arthritis and psoriasis. Oncology dosing is a different regimen entirely, and the subcutaneous autoinjector products (Otrexup, Rasuvo) have their own separate labels and dose ranges — do not read this page across to either.
Available as: Tablets, 2.5 mg (the FDA label for methotrexate tablets, USP states: "Methotrexate Tablets, USP are available containing 2.5 mg methotrexate, USP equivalent to 2.74 mg methotrexate sodium." Higher labeled strengths — 5 mg, 7.5 mg, 10 mg, 15 mg — exist from other manufacturers; the 2.5 mg tablet is the reference strength, which is why a 15 mg weekly dose is often six tablets taken together on one day.)
| Use | What the label says |
|---|---|
| Rheumatoid arthritis (oral, ONCE WEEKLY) | Current FDA label, section 2.3: "The recommended starting dosage of methotrexate tablets is 7.5 mg orally once weekly with escalation to achieve optimal response." The same section sets the toxicity threshold: "Dosages of more than 20 mg once weekly result in an increased risk of serious adverse reactions, including myelosuppression." Response is not immediate — the label notes: "When responses are observed, the majority occurred between 3 and 6 weeks from initiation of treatment; however, responses have occurred up to 12 weeks after treatment initiation." Older-format methotrexate tablet labeling also listed a split-day option for the same weekly total, and it is still used in practice: "Adult Rheumatoid Arthritis: Recommended Starting Dosage Schedules 1. Single oral doses of 7.5 mg once weekly. 2. Divided oral dosages of 2.5 mg at 12 hour intervals for 3 doses given as a course once weekly." Read that second option carefully: three 2.5 mg tablets spaced 12 hours apart is still ONE weekly course (7.5 mg total over about 24 hours), then nothing until the following week. It is not a daily schedule. |
| Psoriasis (oral, ONCE WEEKLY) | Current FDA label, section 2.5: "The recommended dosage of methotrexate tablets is 10 to 25 mg orally once weekly until an adequate response is achieved. Adjust the dose gradually to achieve optimal clinical response; do not exceed a dose of 30 mg per week. Once optimal clinical response has been achieved, reduce the dosage to the lowest possible dosing regimen." Older-format labeling gave the same weekly range plus the split-day variant: "Psoriasis: Recommended Starting Dose Schedules 1. Weekly single oral, IM or IV dose schedule: 10 to 25 mg per week until adequate response is achieved. 2. Divided oral dose schedule: 2.5 mg at 12-hour intervals for three doses," with "30 mg/week should not ordinarily be exceeded." Again, the divided schedule is one weekly course, not daily dosing. |
| Folic acid alongside (taken DAILY, unlike the methotrexate) | For RA and psoriasis, folate supplementation is part of the labeled regimen, not an optional add-on. Label section 5.10, Non-neoplastic Diseases: "Folate deficiency may increase methotrexate adverse reactions. Administer folic acid or folinic acid for patients with rheumatoid arthritis, pJIA," and psoriasis. Both the RA and psoriasis dosing sections repeat the instruction: "Administer folic acid or folinic acid to reduce the risk of methotrexate adverse reactions." The patient labeling specifies the schedule and the benefit: "Take a folic acid or folinic acid supplement every day during treatment with methotrexate tablets, as instructed by your healthcare provider, to help reduce the chance of developing certain side effects, such as mouth sores." Note the deliberate asymmetry patients find confusing: the folic acid is the daily pill, the methotrexate is the weekly one. The opposite is true in cancer treatment — for neoplastic indications the label says to "instruct patients not to take products containing folic acid or folinic acid unless directed to do so by their healthcare provider," because folate "may decrease the clinical effectiveness of methotrexate." Your prescriber decides the dose and form. |
Maximum dose
Rheumatoid arthritis: the label does not set a hard ceiling but marks the risk threshold — "Dosages of more than 20 mg once weekly result in an increased risk of serious adverse reactions, including myelosuppression" (section 2.3). Psoriasis: an explicit cap — "do not exceed a dose of 30 mg per week" (section 2.5); older labeling phrased it as "30 mg/week should not ordinarily be exceeded." Polyarticular juvenile idiopathic arthritis, for reference: starting dose "10 mg/m2 orally once weekly," with "Dosages of more than 30 mg/m2 once weekly result in an increased risk of serious adverse reactions." Every one of these numbers is a PER-WEEK total, not a per-day amount. There is no labeled daily dose of methotrexate for RA or psoriasis at any level.
Dose adjustments
Renal impairment (section 8.6): "Methotrexate elimination is reduced in patients with renal impairment. Patients with renal impairment are at increased risk for methotrexate adverse reactions. Closely monitor patients with renal impairment [creatinine clearance (CLcr) less than 90 mL/min, Cockcroft-Gault] for adverse reactions. Reduce the dosage or discontinue methotrexate tablets as appropriate." Note how early that threshold sits — CLcr under 90 mL/min captures a great many ordinary older adults. Hepatic impairment (section 8.7): "The pharmacokinetics and safety of methotrexate in patients with hepatic impairment is unknown. Patients with hepatic impairment may be at increased risk for methotrexate adverse reactions... Closely monitor patients with hepatic impairment for adverse reactions. Reduce the dosage or discontinue methotrexate tablets as appropriate." Older adults (section 8.5): "Clinical studies of methotrexate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects" — no age-specific dose is given, but declining renal function with age makes the renal caution above the practical driver. Monitoring: blood counts — "Obtain blood counts at baseline, periodically during treatment, and as clinically indicated" (5.3); liver — "Monitor liver tests at baseline, periodically during treatment and as clinically indicated" (5.5); kidneys — "Monitor renal function at baseline, periodically during treatment and as clinically indicated" (5.8). The label also warns of a silent form of liver damage in psoriasis: "In patients with psoriasis, fibrosis or cirrhosis may occur in the absence of symptoms or abnormal liver tests; the risk of hepatotoxicity appears to increase with total cumulative dose and generally occurs after receipt of a total cumulative dose of 1.5 g or more." Swallowing: "Do not administer to patients who are unable to swallow a tablet."
Dosing safety — read before you rely on any number
WEEKLY, NOT DAILY — this comes first because it is what kills people. FDA label section 5.9: "Deaths occurred in patients as a result of medication errors. Most commonly, these errors occurred in patients who were taking methotrexate daily when a weekly dosing regimen was prescribed. For patients prescribed a once weekly dosing regimen, instruct patients and caregivers to take the recommended dosage as directed, because medication errors have led to death." The Dosage and Administration section leads with the same instruction: "Instruct patients and caregivers to take the recommended dosage as directed, because medication errors have led to deaths." BOXED WARNING — "EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, and SEVERE ADVERSE REACTIONS": (1) "Methotrexate tablets can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, methotrexate tablets are contraindicated in pregnancy." Pregnancy is a flat contraindication for RA and psoriasis use, listed in section 4 as "Pregnant women receiving methotrexate tablets for treatment of non-neoplastic diseases." Section 5.1 adds contraception timing: "Advise females of reproductive potential to use effective contraception during treatment with methotrexate tablets and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during methotrexate tablets treatment and for 3 months after the final dose." (2) "Methotrexate tablets are contraindicated in patients with a history of severe hypersensitivity reactions to methotrexate, including anaphylaxis." (3) "Serious adverse reactions, including death, have been reported with methotrexate. Closely monitor for adverse reactions of the bone marrow, gastrointestinal tract, liver, lungs, skin, and kidneys. Withhold or discontinue methotrexate tablets as appropriate." Those six organ systems map to the labeled severe toxicities: myelosuppression — "severe and life-threatening pancytopenia, anemia, leukopenia, neutropenia, and thrombocytopenia" (5.3); gastrointestinal toxicity including mucositis and stomatitis, with "Hemorrhagic enteritis and fatal intestinal perforation have been reported" (5.4); hepatotoxicity (5.5); pulmonary toxicity — "acute or chronic interstitial pneumonitis and irreversible or fatal cases" (5.6), reported at 1% incidence in RA trials; severe dermatologic reactions including "toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin necrosis" (5.7); and renal toxicity "including irreversible acute renal failure" (5.8). NSAIDs and aspirin: section 7.1 lists "Aspirin and other nonsteroidal anti-inflammatory drugs" among products that "may increase methotrexate plasma concentrations, which may increase the risk of methotrexate severe adverse reactions," with the instruction: "If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions." This matters because NSAIDs are exactly what many RA patients are already taking — in the RA trials, "Most patients received concomitant nonsteroidal anti-inflammatory drugs (NSAIDs)." The combination is common and managed, not forbidden, but it is not a decision to make on your own with an over-the-counter bottle. Other listed interactions that raise methotrexate exposure include proton pump inhibitors, penicillins and sulfonamide antibiotics, probenecid, and other antifolate drugs. Alcohol: "The risk of hepatotoxicity is increased with heavy alcohol consumption." Nitrous oxide: "Avoid nitrous oxide anesthesia in patients receiving methotrexate" — worth telling a dentist or surgeon. Live vaccines and breastfeeding are also restricted per the label.
Bottom line
For rheumatoid arthritis and psoriasis, oral methotrexate is a once-a-week medicine. RA typically starts at 7.5 mg once weekly, with more than 20 mg weekly flagged for increased serious toxicity. Psoriasis runs 10 to 25 mg once weekly, never exceeding 30 mg per week. Daily folic or folinic acid goes alongside it. Taking the methotrexate itself daily by mistake has killed patients — the FDA label says so in a warning section written for exactly that error. Know your dosing day, keep the weekly total on your medication list in writing, ask before adding any NSAID or new antibiotic, and keep the scheduled blood, liver, and kidney tests. If you are or could become pregnant, methotrexate is contraindicated for these uses. Oncology methotrexate and the subcutaneous autoinjectors follow different rules and none of the numbers above transfer to them.
Frequently asked questions
Is methotrexate taken daily or weekly?
Weekly, for rheumatoid arthritis and psoriasis. The FDA patient labeling is unusually direct about it: "Take your methotrexate tablets dose 1 time each week, not every day." You take the whole dose on one chosen day and take none on the other six. Because the reference tablet is 2.5 mg, a 15 mg weekly dose means six tablets swallowed together on your dosing day — a quantity that can look like a week's worth of daily pills but is a single dose. Some regimens split that weekly dose into tablets taken 12 hours apart, but that split still covers about one day and is followed by a full week off. Oncology use of methotrexate follows different schedules; if you are taking it for cancer, follow that prescription instead.
What happens if you take methotrexate daily by mistake?
It can be fatal. The FDA label devotes a warning section to it (5.9): "Deaths occurred in patients as a result of medication errors. Most commonly, these errors occurred in patients who were taking methotrexate daily when a weekly dosing regimen was prescribed." Cumulative daily dosing overwhelms the body's folate pathways and produces the severe toxicities in the boxed warning — bone marrow suppression (dangerously low blood counts), mucositis and mouth ulcers, gastrointestinal bleeding, liver and kidney injury. The label's overdose section notes that "Overdosage, including fatal overdosage, has occurred with methotrexate," with manifestations including "leukopenia, thrombocytopenia, anemia, pancytopenia, myelosuppression, mucositis, stomatitis, oral ulceration." If you realize you have taken methotrexate on more than one day in a week, do not wait for symptoms and do not simply skip ahead — contact your prescriber or Poison Control (1-800-222-1222 in the US) immediately. There is a rescue treatment (leucovorin/folinic acid) and it works best early. Warning signs to report urgently: mouth sores, unexplained fever, sore throat, easy bruising or bleeding, extreme fatigue, or a new cough or shortness of breath.
What is the methotrexate dose for rheumatoid arthritis?
The FDA label states: "The recommended starting dosage of methotrexate tablets is 7.5 mg orally once weekly with escalation to achieve optimal response." Doses are then adjusted upward by the prescriber, with the label marking where risk rises: "Dosages of more than 20 mg once weekly result in an increased risk of serious adverse reactions, including myelosuppression." An alternative in older labeling, still seen in practice, splits the same weekly total into "2.5 mg at 12 hour intervals for 3 doses given as a course once weekly." Do not expect a fast answer — the label notes most responses appear "between 3 and 6 weeks from initiation of treatment," and some take up to 12 weeks. Your specific dose is set by your rheumatologist based on response, kidney function, and other medicines.
Why do you take folic acid with methotrexate?
Methotrexate works by blocking dihydrofolate reductase, an enzyme in the folate pathway, and that same blockade causes many of its side effects. Supplementing folate reduces the side effects without abandoning the treatment. The FDA label instructs for RA, pJIA, and psoriasis: "Folate deficiency may increase methotrexate adverse reactions. Administer folic acid or folinic acid." The patient labeling names the payoff: take it "every day during treatment... to help reduce the chance of developing certain side effects, such as mouth sores." Note the schedule difference that trips people up — folic acid is the daily pill, methotrexate is the weekly one. Important exception: for cancer treatment the label says the opposite, instructing patients "not to take products containing folic acid or folinic acid unless directed to do so by their healthcare provider," because folate "may decrease the clinical effectiveness of methotrexate." Let your prescriber set the dose, timing, and form.
Can you drink alcohol while taking methotrexate?
The FDA label does not ban alcohol outright, but it flags the specific hazard: "The risk of hepatotoxicity is increased with heavy alcohol consumption." Methotrexate can cause serious liver injury on its own, and in psoriasis the label warns the damage can be invisible: "fibrosis or cirrhosis may occur in the absence of symptoms or abnormal liver tests," with risk rising with cumulative dose. Because of that, the label asks patients to tell their provider if they "drink alcohol-containing beverages and, during treatment with methotrexate tablets, if there are any changes in the amount of alcoholic beverages you drink." Many rheumatologists advise avoiding alcohol or keeping intake minimal, and the answer depends on your liver tests, dose, and other medications — this is a conversation to have with your own prescriber rather than a number to look up.
Can you take methotrexate while pregnant?
No. For rheumatoid arthritis and psoriasis, pregnancy is an absolute contraindication. The boxed warning states: "Methotrexate tablets can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, methotrexate tablets are contraindicated in pregnancy." The label instructs prescribers to "Verify pregnancy status in females of reproductive potential before starting methotrexate tablets." Contraception is required beyond the last dose for both sexes: "Advise females of reproductive potential to use effective contraception during treatment with methotrexate tablets and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during methotrexate tablets treatment and for 3 months after the final dose." Breastfeeding is also off the table — the patient labeling says "Do not breastfeed during treatment and for 1 week after your last dose." The label further notes methotrexate "Can cause impairment of fertility, oligospermia, and menstrual dysfunction." If you are planning a pregnancy or think you may be pregnant, contact your prescriber before your next dose — do not just stop and hope.
Sources
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Doses are transcribed from the FDA-approved label and are general reference information, not medical advice or a personal dose. Only a prescriber can set or change your dose. If you think you took too much, contact Poison Control (1-800-222-1222) or 911.